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A urinalysis is a test of your urine. It's used to detect and manage a wide range of disorders, such as urinary tract infections, kidney disease and diabetes.

A urinalysis involves checking the appearance, concentration and content of urine. For example, a urinary tract infection can make urine look cloudy instead of clear. Increased levels of protein in urine can be a sign of kidney disease.

Unusual urinalysis results often require more testing to find the source of the problem.

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Why it's done

A urinalysis is a common test that's done for several reasons:

• To check your overall health. A urinalysis might be part of a routine medical exam, pregnancy checkup or pre-surgery preparation. Or it might be used to screen for a variety of disorders, such as diabetes, kidney disease or liver disease, when you're admitted to a hospital.
• To diagnose a medical condition. A urinalysis might be requested if you have abdominal pain, back pain, frequent or painful urination, blood in your urine, or other urinary problems. A urinalysis can help diagnose the cause of these signs and symptoms.
• To monitor a medical condition. If you've been diagnosed with a medical condition, such as kidney disease or a urinary tract infection, your doctor might recommend testing your urine regularly to monitor your condition and treatment.

Other tests, such as pregnancy testing and drug screenings, might rely on a urine sample, but these tests look for substances that aren't included in a typical urinalysis.

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How you prepare

If you're having only a urinalysis, you can eat and drink before the test. If you're having other tests, you might need to fast before the test. Your health care provider will give you specific instructions.

Many drugs, including nonprescription medications and supplements, can affect the results of a urinalysis. Before a urinalysis, tell your doctor about medications, vitamins or other supplements you take.

What you can expect

You might collect a urine sample at home or at your health care provider's office. Providers typically give out containers for urine samples. You might be asked to collect the sample at home first thing in the morning, when your urine is more concentrated.

You might be instructed to collect the sample midstream, using a clean-catch method. This method involves the following steps:

• Cleanse the urinary opening. Women should spread the labia and clean from front to back. Men should wipe the tip of the penis.
• Begin to urinate into the toilet.
• Pass the collection container into your urine stream.
• Urinate at least 1 to 2 ounces (30 to 60 milliliters) into the collection container.
• Finish urinating into the toilet.
• Deliver the sample as directed by your health care provider.
• If you can't deliver the sample to the designated area within 60 minutes of collection, refrigerate the sample, unless your provider has told you otherwise.

In some cases, if needed, your provider can insert a thin, flexible tube (catheter) through the urinary tract opening and into the bladder to collect the urine sample.

The urine sample is sent to a lab for analysis. You can return to your usual activities immediately.

For a urinalysis, your urine sample is evaluated in three ways: visual exam, dipstick test and microscopic exam.

Visual exam

A lab technician examines the urine's appearance. Urine is typically clear. Cloudiness or an unusual odor can indicate a problem, such as an infection. Protein in urine can make it appear foamy.

Blood in the urine can make it look red or brown. Urine color can be influenced by what you've just eaten or by certain drugs you're taking. For example, beets or rhubarb might tint your urine red.

Dipstick test

A dipstick — a thin, plastic stick with strips of chemicals on it — is placed in the urine. The chemical strips change color if certain substances are present or if their levels are above typical levels. A dipstick test checks for:

• Acidity (pH). The pH level indicates the amount of acid in urine. The pH level might indicate a kidney or urinary tract disorder.
• Concentration. A measure of concentration shows how concentrated the particles are in your urine. A higher than normal concentration often is a result of not drinking enough fluids.
• Protein. Low levels of protein in urine are typical. Small increases in protein in urine usually aren't a cause for concern, but larger amounts might indicate a kidney problem.
• Sugar. The amount of sugar (glucose) in urine is typically too low to be detected. Any detection of sugar on this test usually calls for follow-up testing for diabetes.
• Ketones. As with sugar, any amount of ketones detected in your urine could be a sign of diabetes and requires follow-up testing.
• Bilirubin. Bilirubin is a product of red blood cell breakdown. Usually, bilirubin is carried in the blood and passes into your liver, where it's removed and becomes part of bile. Bilirubin in your urine might indicate liver damage or disease.
• Evidence of infection. Either nitrites or leukocyte esterase — a product of white blood cells — in your urine might indicate a urinary tract infection.
• Blood. Blood in your urine requires additional testing. It may be a sign of kidney damage, infection, kidney or bladder stones, kidney or bladder cancer, or blood disorders.

Microscopic exam

Sometimes performed as part of a urinalysis, this test involves viewing drops of concentrated urine — urine that's been spun in a machine — under a microscope. If any of the following levels are above average, you might need more tests:

• White blood cells (leukocytes) might be a sign of an infection.
• Red blood cells (erythrocytes) might be a sign of kidney disease, a blood disorder or another underlying medical condition, such as bladder cancer.
• Bacteria, yeast or parasites can indicate an infection.
• Casts — tube-shaped proteins — can be a result of kidney disorders.
• Crystals that form from chemicals in urine might be a sign of kidney stones.

A urinalysis alone usually doesn't provide a definite diagnosis. Depending on the reason your provider recommended this test, you might need follow-up for unusual results. Evaluation of the urinalysis results with other tests can help your provider determine next steps.

Getting standard test results from a urinalysis doesn't guarantee that you're not ill. It might be too early to detect disease or your urine could be too diluted. Tell your provider if you still have signs and symptoms.

For specifics about what your urinalysis results mean, talk with your health care provider.

• Lab Tests Online. Urinalysis. https://labtestsonline.org/tests/urinalysis. Accessed Aug. 14, 2021.
• What is a urinalysis (also called a "urine test")? National Kidney Foundation. https://www.kidney.org/atoz/content/what-urinalysis. Accessed Aug. 14, 2021.
• Evaluation of the renal patient. Merck Manual Professional Version. https://www.merckmanuals.com/professional/genitourinary-disorders/approach-to-the-genitourinary-patient/evaluation-of-the-renal-patient?query=urinalysis#v1152664. Accessed Aug. 14, 2021.
• Wald R. Urinalysis in the diagnosis of kidney disease. https://www.uptodate.com/contents/search. Accessed Aug. 14, 2021.
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Urinalysis (urine test).

A urinalysis is a simple test that looks at a small sample of your urine.  It can help find problems that need treatment, including infections or kidney problems.  It can also help find serious diseases in the early stages, like kidney disease , diabetes , or liver disease.  A urinalysis is also called a “urine test.”

A urine test can include three parts:

Visual exam.   The urine will be looked at for color and clearness. Blood may make urine look red or the color of tea or cola. An infection may make urine look cloudy. Foamy urine can be a sign of kidney problems.

Microscopic exam.   A small amount of urine will be looked at under a microscope to check for things that do not belong in normal urine that cannot be seen with the naked eye, including red blood cells, white blood cells (or pus cells), bacteria (germs), or crystals (which are formed from chemicals in the urine and may eventually get bigger and become kidney stones).

Dipstick test.   A dipstick is a thin, plastic stick with strips of chemicals on it.  It is dipped into the urine.  The strips change color if a substance is present at a level that is above normal.  . Some of the things a dipstick examination can check for include:

• Acidity (pH) is a measure of the amount of acid in the urine. A pH that is above normal may be a sign of kidney stones, urinary infections, kidney problems, or other disorders.
• Protein is an important building block in the body. Everyone has protein in their blood.  But it should only be in your blood, not your urine.  Your kidneys play a role in this process.  Healthy kidneys remove waste products and extra water from your blood, but leave behind the things your body needs, like protein.  When kidneys are injured, protein leaks into your urine. Having protein in your urine suggests that your kidney's filtering units are damaged by kidney disease.
• Glucose (sugar) is usually a sign of diabetes.
• White blood cells (pus cells) are signs of infection.
• Bilirubin is a waste product from the breakdown of old red blood cells.  It is normally removed from the blood by the liver.  Its presence in the urine may be a sign of liver disease. 
• Blood can It can be a sign of an infection, a kidney problem, certain medicines, or even heavy exercise.  Finding blood in the urine requires further testing.  It does not mean you have a serious medical problem.

A urinalysis can help to detect many diseases before you feel symptoms. Finding and treating a problem early can help keep serious diseases from getting worse.

  For More Information

Urinalysis and Kidney Disease: What You Need to Know

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What Is a Urinalysis?

What to expect when undergoing this test

Purpose of Test

Risks and contraindications, before the test, taking the test, interpreting the results.

A urinalysis is a common test used to analyze the content and chemical makeup of your urine. A urinalysis may be used at a healthcare provider's office if kidney disease, a urinary tract infection, or other urinary-related disorder is suspected. 

A urinalysis should not be confused with a urine drug screening, used to check for recent illicit drug use, or a home pregnancy test, used to detect the pregnancy hormone hCG in urine.

The urinary tract is composed of the kidneys, ureter, bladder, and urethra. Its primary role is to filter waste and regulate the balance of water, electrolytes, proteins, acids, and other substances in the body.

If any part of this system is damaged or impaired, it will alter the chemical composition and/or volume of urine. The urinalysis is a direct means of assessing these changes.

While a urinalysis is not diagnostic (meaning that it cannot determine the cause of a disease), it can suggest the nature of a disease and may be used to support a diagnosis.

A urinalysis can also be used to monitor and manage a wide range of disorders, most specifically kidney (renal) disorders. Among its applications, a urinalysis may be used to:

• Help diagnose medical conditions such as a urinary tract infection (UTI) ,  kidney stones , uncontrolled diabetes , chronic kidney disease (CKD) , acute renal failure , polycystic kidney disease (PKD) , and kidney inflammation ( glomerulonephritis )
• Screen for diseases such as kidney disease, diabetes, high blood pressure ( hypertension ),  liver disease , and other conditions in which the urinary tract is involved
• Monitor disease progression  and your response to treatment for kidney failure , diabetic nephropathy , lupus nephritis , and hypertension-related renal impairment , among others
• Provide a preoperative assessment of your renal function prior to undergoing surgery
• Monitor for pregnancy abnormalities , including bladder or kidney infection, dehydration, preeclampsia , and gestational diabetes, among others

A urinalysis is also often included as a part of a routine physical.

When we refer to a urinalysis, we typically assume that to mean peeing in a cup at your healthcare provider's office. In truth, that is just one of the ways urinalysis is performed in clinical practice.

A urinalysis may refer to:

• A complete microscopic urinalysis  performed in a lab to assess the physical, chemical, and microscopic characteristics of your urine
• A rapid urinalysis  performed at your healthcare provider's office using test strips to routinely check for common renal abnormalities
• A 24-hour urine collection  in which urine is collected over 24 hours to provide your healthcare provider a clearer picture of your overall renal function, including output and composition

While a urine culture (in which a urine sample is placed in a growth medium to check for bacteria or fungi) is not technically a form of urinalysis, it may be an extension of the test if a UTI is suspected. It can even be performed using the same urine sample.

A urinalysis is considered a safe and non-invasive form of testing. The only risk it may pose is for those who require catheterization to obtain a urine sample. The risks of urinary catheterization include infection, bleeding, or pain.

While the preparations for a urinalysis are minimal, there are a few things you should know before delivering a sample.

An optimal urine sample is usually obtained in the early morning when the concentration is at its highest. If possible, try to schedule the collection for this time and "hold it in" until you get there if you can. The collection itself only takes a couple of minutes.

For a 24-hour urine collection, you should ideally pick a 24-hour period when you can stay at home so that you don't have to carry the samples with you or miss a collection.

A urinalysis may be performed at your healthcare provider's office, clinic, or lab, or upon admission to hospital. In some instances, you may be provided a sterile plastic cup and lid to collect the sample at home, after which you would deliver the sample to the lab within an hour. (If performing a 24-hour urine collection, ask your healthcare provider when samples should be dropped off.)

Food and Drink

Typically, no fasting is required before the collection of a urine sample. The only exception would be if other tests are being performed that do require fasting, such as a cholesterol test or fasting plasma glucose test . Check with your healthcare provider if you are unsure about the dietary restrictions. The test is obviously easier with a full bladder, so some like to drink liquids beforehand.

Medications

Most routine medications can be taken before a urinalysis unless your healthcare provider tells you otherwise. It is important, however, to advise your healthcare provider about any and all drugs you may be taking, whether they be prescription, over-the-counter, traditional, homeopathic, or recreational.

Since the test involves a visual, chemical, and microscopic examination of the collected urine, certain substances may throw off the results. Examples include:

• Anthraquinone laxatives
• Azulfidine (sulfasalazine), used to treat ulcerative colitis and rheumatoid arthritis
• Levodopa (L-Dopa), a Parkinson's disease drug
• Metronidazole, an antibiotic
• Nitrofurantoin, an antibiotic
• Phenazopyridine, used to treat UTIs
• Robaxin (methocarbamol), a muscle relaxant
• Vitamin B2 (riboflavin) 
• Vitamin C supplements

Ask your healthcare provider if you need to stop any of these before taking the test.

Cost and Health Insurance

A urinalysis is a common and relatively inexpensive test. Standard testing panels can range in price from $5 of $30, which may be covered in part or in full by health insurance. If you're enrolled in a plan, check the terms of your policy or speak with a customer service representative at your insurance company for complete details, including your deductible and co-pay costs. 

On the day of the test, bring identification and your insurance card to register. You may also be asked to fill out a patient information form if it is your first visit, detailing any health problems or medications you may be taking. If you are taking the test as part of a healthcare provider's appointment, this may not be necessary.

You will then led to a private bathroom and provided a sterile plastic cup and lid, a sanitary cleansing wipe, and instructions on how to obtain a "midstream clean-catch" sample. The clean-catch technique prevents bacteria or fungus from the penis or vagina from accidentally getting into the urine.

How to Obtain a Clean Catch

• Women should clean around the urethra by spreading the labia and wiping from front to back (toward the anus).
• Men need to clean the tip of the penis and retract the foreskin.
• After cleansing, urinate for a few seconds to ensure that any contaminants in the urethra are cleared.
• Place the cup under the urine stream and collect at least 30 to 60 milliliters (roughly three to five tablespoons).
• Empty the rest of your bladder into the toilet.

Once filled, place the lid on the cup, wash your hands, and deliver the sample to the nurse or attendant. Some facilities may ask you to deposit the cup in a designated cabinet.

If you collected the sample at home and cannot bring it to the lab within an hour, you may be able to refrigerate it. Speak with the lab to ensure this is okay. If it is, place the sealed cup in a sealed plastic bag to prevent contamination.

A urine sample should not be refrigerated for more than 24 hours. It should never be frozen or kept on ice but rather stored at temperatures of around 39 degrees.

Though evaluation of a urinalysis involves three separate steps, you will generally get your results in just a few days. Understanding the process used to come to your results can help you better understand them and what they might mean.

Visual Examination

During the visual exam, the lab technician will characterize the color and clarity of the urine. Any variations may be signs of an abnormality.

Urine color  is considered normal if it is described as yellow, straw color, or near colorless. Abnormal colors may be the result of a disease, something you've eaten, or something you've taken.

Examples include:

• Dark yellow urine may be an indication of dehydration.
• Bright yellow urine is often caused by multivitamin supplements.
• Red or pink urine may be a sign of bleeding or simply a result of having eaten beets.
• Brown or greenish-brown urine may be a sign of hepatitis or other liver problems.
• Green urine is sometimes seen in people who have been on the sedative Diprivan (propofol) for a long period of time.

Urine clarity refers to how clear the urine is. Under normal circumstances, urine is expected to be relatively clear or only slightly cloudy. Overt cloudiness is often caused by abnormal or excessive substances in the urine, such as:

• Bacteria, including sexually transmitted bacteria
• Calcium crystals, a possible sign of kidney stones
• Excess protein ( proteinuria )
• Fungus, including yeast (Candida)
• Semen, a sign of retrograde ejaculation
• Red blood cells (RBCs), a possible sign of bleeding
• White blood cells (WBCs), a possible sign of infection
• Uric acid crystals, a possible sign of gout

Chemical Examination

To perform the chemical exam, the lab uses commercially prepared test strips (called reagent strips) impregnated with reactive chemicals. The technician dips each strip into the urine. Any abnormality in the urine composition triggers a color change within seconds or minutes. There are also machines able to do this all at once and deliver an automated result within minutes. 

The 10 most commonly performed reagent tests are:

• Bilirubin , a yellowish pigment associated liver problems
• Erythrocytes (red blood cells), a sign of bleeding 
• Glucose, elevations that suggest diabetes
• Ketones , elevations that also suggest diabetes
• Leukocytes (white blood cells), a sign of infection
• Nitrites, suggestive of a bacterial infection
• pH, which measures how acidic the urine is
• Protein, elevations that suggest kidney impairment
• Specific gravity (SG), which measures urine concentration 
• Urobilinogen , seen with hepatitis and liver disease

Vitamin C (ascorbic acid) reagent strips are sometimes used to see if any abnormality in the results is caused by disease or a vitamin supplement you may have taken.

Microscopic Examination

A microscopic exam may or may not be performed if the results of the visual and chemical exams are normal. If it is used, the urine sample is prepared by placing it in a centrifuge and spinning it at a rapid speed so that all of the contents are sedimented on the bottom of the tube.

A drop or two of the sediment is then placed on a slide under the microscope. Cells, crystals, and other substances are counted and reported as either "per low power field" (LPF) or "per high power field" (HPF). Other, smaller substances may be reported as "few," "moderate," or "many."

Some of the substances found either abnormally or in abnormal quantities may include:

• Bacteria, fungi, or parasites
• Crystals (calcium, uric acid, etc.)
• Epithelial cells, possibly due to an infection or malignancy
• RBCs or WBCs
• Urinary casts, multicolored particles produced by the kidney in response to disease

Three or more RBCs per high power field with microscopic urinalysis requires a workup for microhematuria, according to the American Urological Association. This includes urine studies, imaging, and cystoscopy.  

Reference Ranges

Your healthcare provider should review the results with you. The lab values can be difficult to decipher but are generally evaluated on a scale called a laboratory reference range (RR).

The RR delineates the numeric values between which a test result is considered normal. The RR differs for each substance being tested and is based on the expected value within a specific population. Those values higher than the RR are often marked "H" for high, while values lower than the RR may be marked "L" for low.

In reviewing your results, your healthcare provider will explain which values are normal, borderline, and/or abnormal. Oftentimes, a healthcare provider can explain an abnormality based on your medical history and offer a treatment plan. In other cases, further testing will be needed.

There will be conditions by which a urinalysis may need to be repeated, either to monitor your response to therapy or the progression of your disease. Two such examples include chronic kidney disease (CKD), in which the amount of protein in urine reveals how rapidly the disease is advancing, and an acute kidney injury (AKI), in which urine test reveals how well the kidneys are recovering.

The same may apply to monitoring gestational diabetes during pregnancy. Routine urinalysis may be ordered to check to see if glucose, not commonly found in urine, is detected. The findings may help direct prenatal treatment and care.

If you have symptoms of a urinary tract infection but the causal agent (pathogen) cannot be identified in the initial urinalysis, a bacterial or fungal culture may be performed along with pathogen-specific blood tests. (Negative urine culture results are sometimes suggestive of a less common viral UTI).

Imaging tests, such as an ultrasound, computed tomography (CT) , or magnetic resonance imaging (MRI) , may be also be used to determine whether the problem is located before the kidneys (pre-renal), in the kidneys (renal), or after the kidneys (post-renal).

A flexible fiber-optic tool called a cystoscope may be used to check for benign or malignant bladder tumors . The narrow, tube-like device is fed into the bladder through the urethra, providing direct visualization of injuries that other imaging and blood tests sometimes miss.

A Word From Verywell 

A urinalysis with all normal values is generally a strong indication that your kidneys and urinary tract are functioning normally. Beyond that, there are limitations as to what can be interpreted from the test.

The absence of abnormal values is neither the "all clear" sign nor an indication that your symptoms are all in your head. It simply means that the lab was unable to detect any abnormalities based on this one test. 

Similarly, a urinalysis with abnormal values could mean any number of things, both consequential and inconsequential. It is only when used with other tests—such as a complete blood count , liver function , or renal function test —that a urinalysis can provide fuller insights into what is going on. A urinalysis is almost never used as the sole form of diagnosis.

While a urinalysis is an important tool for diagnosis, remember that the values need to be taken in context. Try not to make assumptions until an experienced clinician is able to review your results in their entirety. If an explanation cannot be found, you can seek a second opinion or ask for a referral to a specialist who may have better insights into a possible cause.

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A more recent article on  office-based urinalysis  is available.

Am Fam Physician. 2014;90(8):542-547

Author disclosure: No relevant financial affiliations.

Urinalysis is useful in diagnosing systemic and genitourinary conditions. In patients with suspected microscopic hematuria, urine dipstick testing may suggest the presence of blood, but results should be confirmed with a microscopic examination. In the absence of obvious causes, the evaluation of microscopic hematuria should include renal function testing, urinary tract imaging, and cystoscopy. In a patient with a ureteral stent, urinalysis alone cannot establish the diagnosis of urinary tract infection. Plain radiography of the kidneys, ureters, and bladder can identify a stent and is preferred over computed tomography. Asymptomatic bacteriuria is the isolation of bacteria in an appropriately collected urine specimen obtained from a person without symptoms of a urinary tract infection. Treatment of asymptomatic bacteriuria is not recommended in nonpregnant adults, including those with prolonged urinary catheter use.

Urinalysis with microscopy has proven to be an invaluable tool for the clinician. Urine dipstick testing and microscopy are useful for the diagnosis of several genitourinary and systemic conditions. 1 , 2 In 2005, a comprehensive review of urinalysis was published in this journal. 3 This article presents a series of case scenarios that illustrate how primary care physicians can utilize the urinalysis in common clinical situations.

Microscopic Hematuria: Case 1

Microscopic hematuria is common and has a broad differential diagnosis, ranging from completely benign causes to potentially invasive malignancy. Causes of hematuria can be classified as glomerular, renal, or urologic 3 – 5 ( Table 1 6 ) . The prevalence of asymptomatic microscopic hematuria varies among populations from 0.18% to 16.1%. 4 The American Urological Association (AUA) defines asymptomatic microscopic hematuria as three or more red blood cells per high-power field in a properly collected specimen in the absence of obvious causes such as infection, menstruation, vigorous exercise, medical renal disease, viral illness, trauma, or a recent urologic procedure. 5 Microscopic confirmation of a positive dipstick test for microscopic hematuria is required. 5 , 7

DIAGNOSTIC APPROACH

Case 1: microscopic hematuria.

A 58-year-old truck driver with a 30-year history of smoking one pack of cigarettes per day presents for a physical examination. He reports increased frequency of urination and nocturia, but does not have gross hematuria. Physical examination reveals an enlarged prostate. Results of his urinalysis with microscopy are shown in Table 2 .

Based on this patient's history, symptoms, and urinalysis findings, which one of the following is the most appropriate next step?

A. Repeat urinalysis in six months.

B. Obtain blood urea nitrogen and creatinine levels, perform computed tomographic urography, and refer for cystoscopy.

C. Treat with an antibiotic and repeat the urinalysis with microscopy.

D. Inform him that his enlarged prostate is causing microscopic hematuria, and that he can follow up as needed.

E. Perform urine cytology to evaluate for bladder cancer.

The correct answer is B .

For the patient in case 1 , because of his age, clinical history, and lack of other clear causes, the most appropriate course of action is to obtain blood urea nitrogen and creatinine levels, perform computed tomographic urography, and refer the patient for cystoscopy. 5 An algorithm for diagnosis, evaluation, and follow-up of patients with asymptomatic microscopic hematuria is presented in Figure 1 . 5 The AUA does not recommend repeating urinalysis with microscopy before the workup, especially in patients who smoke, because tobacco use is a risk factor for urothelial cancer ( Table 3 ) . 5

A previous article in American Family Physician reviewed the American College of Radiology's Appropriateness Criteria for radiologic evaluation of microscopic hematuria. 8 Computed tomographic urography is the preferred imaging modality for the evaluation of patients with asymptomatic microscopic hematuria. 5 , 8 It has three phases that can detect various causes of hematuria. The non–contrast-enhanced phase is optimal for detecting stones in the urinary tract; the nephrographic phase is useful for detecting renal masses, such as renal cell carcinoma; and the delayed phase outlines the collecting system of the urinary tract and can help detect urothelial malignancies of the upper urinary tract. 9 Although the delayed phase can detect some bladder masses, it should not replace cystoscopy in the evaluation for bladder malignancy. 9 After a negative microscopic hematuria workup, the patient should continue to be followed with yearly urinalysis until at least two consecutive normal results are obtained. 5

In patients with microscopic hematuria, repeating urinalysis in six months or treating empirically with antibiotics could delay treatment of potentially curable diseases. It is unwise to assume that benign prostatic hyperplasia is the explanation for hematuria, particularly because patients with this condition typically have risk factors for malignancy. Although urine cytology is typically part of the urologic workup, it should be performed at the time of cystoscopy; the AUA does not recommend urine cytology as the initial test. 5

Dysuria and Flank Pain After Lithotripsy: Case 2

After ureteroscopy with lithotripsy, a ureteral stent is often placed to maintain adequate urinary drainage. 10 The stent has one coil that lies in the bladder and another that lies in the renal pelvis. Patients with ureteral stents may experience urinary frequency, urgency, dysuria, flank pain, and hematuria. 10 They may have dull flank pain that becomes sharp with voiding. This phenomenon occurs because the ureteral stent bypasses the normal nonrefluxing uretero-vesical junction, resulting in transmission of pressure to the renal pelvis with voiding. Approximately 80% of patients with a ureteral stent experience stent-related pain that affects their daily activities. 11

POTENTIALLY MISLEADING URINALYSIS

Case 2: dysuria and flank pain after lithotripsy.

A 33-year-old woman with a history of nephrolithiasis presents with a four-week history of urinary frequency, urgency, urge incontinence, and dysuria. She recently had ureteroscopy with lithotripsy of a 9-mm obstructing left ureteral stone; she does not know if a ureteral stent was placed. She has constant dull left flank pain that becomes sharp with voiding. Results of her urinalysis with microscopy are shown in Table 4 .

A. Treat with three days of ciprofloxacin (Cipro), and tailor further antibiotic therapy according to culture results.

B. Treat with 14 days of ciprofloxacin, and tailor further antibiotic therapy according to culture results.

C. Obtain a urine culture and perform plain radiography of the kidneys, ureters, and bladder.

D. Perform a 24-hour urine collection for a metabolic stone workup.

E. Perform computed tomography.

The correct answer is C .

The presence of a ureteral stent causes mucosal irritation and inflammation; thus, findings of leukocyte esterase with white and red blood cells are not diagnostic for urinary tract infection, and a urine culture is required. In this setting, plain radiography of the kidneys, ureters, and bladder would be useful to determine the presence of a stent. If a primary care physician identifies a neglected ureteral stent, prompt urologic referral is indicated for removal. Retained ureteral stents may become encrusted, and resultant stone formation may lead to obstruction. 10

Flank discomfort and recent history of urinary tract manipulation suggest that this is not an uncomplicated urinary tract infection; therefore, a three-day course of antibiotics is inadequate. Although flank pain and urinalysis suggest possible pyelonephritis, this patient should not be treated for simple pyelonephritis in the absence of radiography to identify a stent. A metabolic stone workup may be useful for prevention of future kidney stones, but it is not indicated in the acute setting. Finally, although computed tomography would detect a ureteral stent, it is not preferred over radiography because it exposes the patient to unnecessary radiation. Typically, microscopic hematuria requires follow-up to ensure that there is not an underlying treatable etiology. In this case , the patient's recent ureteroscopy with lithotripsy is likely the etiology.

Urinalysis in a Patient Performing Clean Intermittent Catheterization: Case 3

Case 3: urinalysis in a patient performing clean intermittent catheterization.

A 49-year-old man who has a history of neurogenic bladder due to a spinal cord injury and who performs clean intermittent catheterization visits your clinic for evaluation. He reports that he often has strong-smelling urine, but has no dysuria, urge incontinence, fever, or suprapubic pain. Results of his urinalysis with microscopy are shown in Table 5 .

A. Inform the patient that he has a urinary tract infection, obtain a urine culture, and treat with antibiotics.

B. Refer him to a urologist for evaluation of a complicated urinary tract infection.

C. Perform computed tomography of the abdomen and pelvis to evaluate for kidney or bladder stones.

D. Inform him that no treatment is needed.

E. Obtain a serum creatinine level to evaluate for chronic kidney disease.

The correct answer is D .

Although the urinalysis results are consistent with a urinary tract infection, the clinical history suggests asymptomatic bacteriuria. Asymptomatic bacteriuria is the isolation of bacteria in an appropriately collected urine specimen obtained from a person without symptoms of a urinary tract infection. 12 The presence of bacteria in the urine after prolonged catheterization has been well described; one study of 605 consecutive weekly urine specimens from 20 chronically catheterized patients found that 98% contained high concentrations of bacteria, and 77% were polymicrobial. 13

Similar results have been reported in patients who perform clean intermittent catheterization; another study of 1,413 urine cultures obtained from 407 patients undergoing clean intermittent catheterization found that 50.6% contained bacteria. 14 Guidelines from the Infectious Diseases Society of America recommend against treatment of asymptomatic bacteriuria in nonpregnant patients with spinal cord injury who are undergoing clean intermittent catheterization or in those using a chronic indwelling catheter. 12

In the absence of symptoms of a urinary tract infection or nephrolithiasis, there is no need to culture the urine, treat with antibiotics, refer to a urologist, or perform imaging of the abdomen and pelvis. There is no reason to suspect acute kidney injury in this setting; thus, measurement of the serum creatinine level is also unnecessary.

Data Sources : Literature searches were performed in PubMed using the terms urinalysis review, urinalysis interpretation, microscopic hematuria, CT urogram, urinary crystals, indwelling ureteral stent, asymptomatic bacteriuria, and bacteriuria with catheterization. Guidelines from the American Urological Association were also reviewed. Search dates: October 2012 and June 2013.

Wu X. Urinalysis: a review of methods and procedures. Crit Care Nurs Clin North Am. 2010;22(1):121-128.

Hardy PE. Urinalysis interpretation. Neonatal Netw. 2010;29(1):45-49.

Simerville JA, Maxted WC, Pahira JJ. Urinalysis: a comprehensive review [published correction appears in Am Fam Physician . 2006;74(7):1096]. Am Fam Physician. 2005;71(6):1153-1162.

Cohen RA, Brown RS. Clinical practice. Microscopic hematuria. N Engl J Med. 2003;348(23):2330-2338.

American Urological Association. Diagnosis, evaluation and follow-up of asymptomatic microhematuria (AMH) in adults. http://www.auanet.org/education/asymptomatic-microhematuria.cfm . Accessed June 6, 2014.

Ahmed Z, Lee J. Asymptomatic urinary abnormalities. Hematuria and proteinuria. Med Clin North Am. 1997;81(3):641-652.

Rao PK, Jones JS. How to evaluate ‘dipstick hematuria’: what to do before you refer. Cleve Clin J Med. 2008;75(3):227-233.

Choyke PL. Radiologic evaluation of hematuria: guidelines from the American College of Radiology's Appropriateness Criteria. Am Fam Physician. 2008;78(3):347-352.

Sadow CA, Wheeler SC, Kim J, Ohno-Machado L, Silverman SG. Positive predictive value of CT urography in the evaluation of upper tract urothelial cancer. AJR Am J Roentgenol. 2010;195(5):W337-W343.

Haleblian G, Kijvikai K, de la Rosette J, Preminger G. Ureteral stenting and urinary stone management: a systematic review. J Urol. 2008;179(2):424-430.

Joshi HB, Stainthorpe A, MacDonagh RP, Keeley FX, Timoney AG, Barry MJ. Indwelling ureteral stents: evaluation of symptoms, quality of life and utility. J Urol. 2003;169(3):1065-1069.

Nicolle LE, Bradley S, Colgan R, Rice JC, Schaeffer A, Hooton TM Infectious Diseases Society of America; American Society of Nephrology; American Geriatric Society. Infectious Diseases Society of America guidelines for the diagnosis and treatment of asymptomatic bacteriuria in adults [published correction appears in Clin Infect Dis . 2005;40(10):1556]. Clin Infect Dis. 2005;40(5):643-654.

Warren JW, Tenney JH, Hoopes JM, Muncie HL, Anthony WC. A prospective microbiologic study of bacteriuria in patients with chronic indwelling urethral catheters. J Infect Dis. 1982;146(6):719-723.

Bakke A, Digranes A. Bacteriuria in patients treated with clean intermittent catheterization. Scand J Infect Dis. 1991;23(5):577-582.

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Tests & procedures, microscopic urinalysis, does this test have other names.

Microscopic urine analysis, microscopic examination of urine

What is this test?

This test looks at a sample of your urine under a microscope. It can see cells from your urinary tract, blood cells, crystals, bacteria, parasites, and cells from tumors.

This test is often used to confirm the findings of other tests or add information to a diagnosis.

Why do I need this test?

You may need this test to help diagnose:

Kidney disease

Urinary tract infection

Reactions to medicines

Prostate infection

Liver disease

Viral infection

Yeast infection

Parasitic infection

What other tests might I have along with this test?

You may have other tests on your urine sample. These may include:

Checking the color and odor

Measuring the level of dissolved solid substances in the urine

Checking the acidity

Testing for protein, sugar, bilirubin, and other substances that may be a sign of different diseases

You may also have blood tests.

What do my test results mean?

Test results may vary depending on your age, gender, health history, and other things. Your test results may be different depending on the lab used. They may not mean you have a problem. Ask your healthcare provider what your test results mean for you.

Here is a sample of what certain results may mean:

A high number of red blood cells may mean that you have kidney disease, urinary tract infection, a drug reaction, or cancer.

A high number of white blood cells may mean that you have an infection or inflammation in your urinary tract.

A high number of cells called eosinophils may mean that you have problems in your urinary tract.

A high number of certain kidney cells may mean that you have kidney damage.

Substances created in the kidney, called casts, can suggest different diseases.

Abnormal crystals formed from amino acids and certain medicines can be a sign of a variety of health problems.

How is this test done?

This test is done with a urine sample. Your healthcare provider may ask you to provide a sample at a specific time of day, such as first thing in the morning. Or you may collect a sample at random. For this test, you may also need to collect all the urine you make over a certain period, such as 24 hours. For this sample, you empty your bladder completely first thing in the morning without collecting it. Note the time. Then collect your urine every time you go to the bathroom over the next 24 hours. You will collect it in a container that your healthcare provider or the lab gives you.

Does this test pose any risks?

This test poses no known risks.

What might affect my test results?

Certain medicines can alter the appearance of urine under the microscope, including:

Sulfamethoxazole

Dyes used in imaging tests

High doses of medicines that contain salicylate

Your results may also be affected by:

Stool in your urine sample

Menstrual blood

Vaginal medicine

How do I get ready for this test?

You don't need to prepare for this test. But be sure your healthcare provider knows about all medicines, herbs, vitamins, and supplements you are taking. This includes medicines that don't need a prescription and any illegal drugs you may use.

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Urine Analysis

Nov 14, 2014

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Urine Analysis. 1- Physical Examination 2- Chemical Examination 3- Microscopic Examination 4- Microbiological Examination. Collection of urine. Early morning sample-qualitative Random sample- routine 24hrs sample- quantitative Midstream sample-UTI Post prandial sample-D.M.

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Urine Analysis 1- Physical Examination 2- Chemical Examination 3- Microscopic Examination 4- Microbiological Examination

Collection of urine Early morning sample-qualitative Random sample- routine 24hrs sample- quantitative Midstream sample-UTI Post prandial sample-D.M

24 hour urine sample For quantitative estimation of proteins For estimation of vanillyl mandelic acid, 5-hydroxyindole acetic acid, metanephrines For detection of microalbuminuria

Urine Analysis Collection of Urine for Analysis • Urine is collected over a period of 24 hours. • A preservative (as toluene, chloroform, thymol & formalin) is added to prevent contamination of the urine • keeping urine in refrigerator is greatly advisable especially in hot weather.

URINE ANALYSISPhysical Examination 1- Volume 2- Specific Gravity 3- Aspect 4- Color 5- Odor 6- Deposit 7- Reaction (pH)

URINE ANALYSISPhysical Examination 1- Volume: Normal urine volume in 24 hours is 600-2000 ml. The night urine is generally < 400 ml. In pregnancy the usual diurnal variation is reversed causing nocturnia & excretion of dilute urine 1-Urine volume increases (Polyuria) in the following conditions: Physiological: • Increased fluid intake • Diuretic Pathological: • Diabetes mellitus (type-1 & type-2) • Diabetes insipidus(due to decrease of ADH) • Chronic renal failure 2- Urine volume decreases (Oliguria or anuria) in the following conditions: • Dehydration • Acute renal failure • Obstruction

URINE ANALYSISPhysical Examination 2- Specific gravity (SG): • Specific gravity measures solute concentration (urea and sodium). • Normally the specific gravity ranges between 1.015-1.025. 1- Increased in • Dehydration (with oliguria) • Diabetes Mellitus (with polyuria) • Acute renal failure (with oliguria) 2- Decreased in • Diabetes insipidus (with polyuria) • Fixed specific gravity (isosthenuria)=1.010 Seen in chronic renal disease when kidney has lost the ability to concentrate or dilute

URINE ANALYSISPhysical Examination 3- Appearance: Normal fresh urine: clear (transparent) Abnormal : Cloudy urine may indicate possible abnormal constituents such as white cells, epithelial cells, crystals and bacteria. N.B. Stored urine with no preservative & no cooling may turn clear urine samples into cloudy. ( d.t. pptn of amorphous crystals, (urates in acidic pH and phosphates in alkaline pH), mucus or growth of bacteria.)

URINE ANALYSISPhysical Examination 4-Color: Normal color: pale yellow (amber yellow) due to the presence of pigments of urobilinor urobilinogen Abnormal colors of urine: • Colorless • Orange • Greenish yellow • Red • Black • Smoky

URINE ANALYSISPhysical Examination Color (cont.) 1- Colorless Urine: • Chronic renal failure • Diabetes insipidus. 2- Orange Urine: • Ingestion of large amount of carotenoids (vitamin A) 3- Yellowish brown urine: due to presence of billirubinin cases of: • Obstructive Jaundice • Hepatic Jaundice

URINE ANALYSISPhysical Examination Color(cont.) 4- Red urine: due to presence of blood,hemoglobin & RBCs. 5- Black urine: • Methemoglobin • Homogentisic acid in alkaptonuria • Malignant malaria (black water fever due to Malaria falciparum). • Melanin(melanoma) 6- Smoky urine: • presence RBCs. in the urine, in cases of acute glomerulonephritis

URINE ANALYSISPhysical Examination 5- Odor: Normal Urineferous odor: The normal odor of fresh voided urine sample Abnormal Odors 1- Fruity odor due to presence of acetone in the urine as in diabetic ketoacidosis 2- Ammonia odor due to release of ammonia as result of: the bacterial action on urea in the contaminated urine or long standing exposed urine samples. 3-Putrid or foul odor : In fresh urine is due to urinary tract infection Other specific abnormal odors are associated with rare disorders of amino acid metabolism 4- Sweet odor : glucose

URINE ANALYSISPhysical Examination 6- Foam • Normal urine will foam slightly when stopped and shaken, and the foam will be white. • The formation of abundant white foam indicates the presence of large concentrations of protein. • A characteristic abundant vivid yellow color foam is shown by urine containing bilirubin

URINE ANALYSISPhysical Examination 7- Deposits: • Normally the urine is devoid of deposits. • The presence of deposits is mainly due to various types of crystals, salts and cells.

URINE ANALYSISPhysical Examination 8- Reaction (pH): Normally: The pH of urine varies from 4.6 - 8.0 1- Acidic urine: • Large intake of meat & certain fruits (cranberries) • Metabolic & respiratory acidosis • Starvation • Severe diarrhea( together with acidosis) 2- Alkaline urine: • Vegetarians • Metabolic & respiratory alkalosis • Urinary tract infection by urea splitting bacteria which spliturea to ammonia (alkaline) • Severe vomiting

Glucose Bilirubin Ketones Specific Gravity Blood pH Protein Urobilinogen Nitrite Leukocyte Esterase Chemical Analysis Urine Dipstick

URINE ANALYSISChemical Examination Normal Constituents of Urine Normal urine contains about 50g of solids dissolved in about 1.5 liters of water per day. Urine contains organic and inorganic solids. A) Chief Inorganic Solids • Sodium, potassium & chlorides • Smaller amounts of calcium, magnesium, sulfate & phosphates • Traces of iron, copper, zinc and iodine. B) Chief Organic Solids: 1- Non-protein nitrogen: • amino acids, ammonia, urea, uric acid , creatine & creatinine 2- Organic acids: • lactic acid, citric acid & oxalic acid • ketone bodies (few amounts) 3- Sugars: • Normally not more than 1g of sugars is excreted in the urine per day. • Sugars cannot be detected by ordinary tests. • Very small amounts of glucose not exceeding 150 mg of glucose are normally excreted per day. • Other sugars present in urine are: pentose and lactose . • Lactosuria occurs in infant and in women during the late months of pregnancy and during lactation

URINE ANALYSISChemical Examination Abnormal Constituents of Urine 1- Proteins (proteinuria) 2- Sugars (glucosuria, fructosuria & galactosuria) 3- ketone Bodies (ketonuria) 4- Billirubin (billirubinuria) & Bile Salts 5- Nitrites

URINE ANALYSISChemical Examination 1- Proteins:(proteinuria) Proteinuria Presence of more than 150 mg proteins in urine in 24 hours detected by ordinary laboratory means heavy proteinuria : ＞4 gm/24 hours moderate proteinuria: 1 - 4 gm/24 hours minimal proteinuria: ＜ 1.0 gm/24 hours

URINE ANALYSISChemical Examination 1- Proteins: (proteinuria) Proteinuria is divided into prerenal, renal and postrenal proteinuria. 1-Prerenal proteinuria: • Bence-Jones protein: This abnormal gamma globulin (light chains only) is synthesized by malignant plasma cells (multiple myeloma). It precipitates at 60oC, redidssolves at 100oC and reprecipitates on cooling. • Heart failure 2-Renal proteinuria: • Severe muscular exercise • After prolonged standing • Acute glomerulonephritis • Nephrotic syndrome 3-Postrenal proteinuria: • Lower urinary tract inflammation, tumors or stones.

Tests for proteins Test – HEAT & ACETIC ACID TEST Principle-proteins are denatured & coagulated on heating to give white cloud precipitate. Method-take 2/3 of test tube with urine, heat only the upper part keeping lower part as control. Presence of phosphates, carbonates, proteins gives a white cloud formation. Add acetic acid 1-2 drops, if the cloud persists it indicates it protein (acetic acid dissolves the carbonates/phosphates)

URINE ANALYSISChemical Examination Negative Trace (100 mg/dL) + (250 mg/dL) ++ (500 mg/dL) +++ (1000 mg/dL) ++++ (2000+ mg/dL) Glucose Chemical Principle Glucose Oxidase Glucose + 2 H2O+ O2---> Gluconic Acid + 2 H2O2 Horseradish Peroxidase 3 H2O2 + KI ---> KIO3 + 3 H2O Read at 30 seconds

URINE ANALYSISChemical Examination 2- Sugars: (glycosuria) Glucose (Glucosuria); Presence of detectable amount of glucose in urine which occurs in the following conditions: Glycosuria with hyperglycaemia- Uncontrolled Diabetes Mellitus (DM) ,acromegaly, cushing’s disease, hyperthyroidism, drugs like corticosteroids.) - Glycosuria without hyperglycaemia- Renal glucosuria with lowering of renal threshold : e.g. during pregnancy (gestational diabetes). Fructose(Fructosuria): Presence of fructose in urine & may be due to: • - Alimentary causes following the ingestion of large amounts of fructose Fructosemia & herditary fructose intolerance (Metabolic disorders of fructose). Galactose (Galactosuria): Presence of galactose in urine& may be due to: - Alimentary causes following the ingestion of large amount of galactose. - Galactosemia

URINE ANALYSISChemical Examination 3- Ketone Bodies (Ketonuria): Presence of acetone, acetoacetic acid and βhydroxybutyricacid in urine due to: • Diabetic ketoacidosis(uncontrolled DM) • Starvation • Unbalanced diet: high fat & low carbohydrates diet.

URINE ANALYSISChemical Examination 4- Bilirubin (bilirubinuria) Billirubin appears in urine in cases of: • Hepatocellular Jaundice: as in viral hepatitis • Obstructive Jaundice as any cause of obstruction of bile duct

URINE ANALYSISChemical Examination 5-Nitrites • In bacteruria in urine (in cases of Urinary Tract Infection, UTI) • ( nitrate will change to nitrite by some bacteria which are generally gram-negative bacteria)

MICROSCOPIC URINALYSIS a)Crystals :urates andoxalates (acid urine), tripple phosphate (ammonium magnesium phosphate [NH2MgPO4]) (alkaline urine) b)Casts : albuminoid substances released from epithelial c)Parasiticova ; and d)Cells :Pus cells or RBCs.

MICROSCOPIC URINALYSIS • A first morning , midstream, clean catch specimen is generally the specimen of choice. • This specimen is preferred since it is most concentrated and thus small amounts of abnormal constituents are more likely to be detected • Specimen should be centrifuged and examined within 2 hours of collection as RBCs, WBCs and casts disintegrate rapidly especially in dilute ( sp gr.<1010 ) urine of an alkaline pH

Microscopic examination Microscopic urinalysis is done simply pouring the urine sample into a test tube and centrifuging it (spinning it down in a machine) for a few minutes. The top liquid part (the supernatant) is discarded. The solid part left in the bottom of the test tube (the urine sediment) is mixed with the remaining drop of urine in the test tube and one drop is analyzed under a microscope

MICROSCOPIC URINALYSIS 1.Red Blood Cells( N < 3/HPF) Hematuria is the presence of abnormal numbers of red cells in urine due to: a. Glomerular damage b. Tumors c. Urinary tract stones d. Upper and lower urinary tract infections Two Types of Hematuria Gross hematuria means that the blood can be seen by the naked eye. The urine may look pinkish, brownish, or bright red. Microscopic hematuria means that the urine is clear, but blood cells can be seen when urine is looked at under a microscope or tested ina lab. When blood is present in chemical screen , it is important to differentiate between haematuria from hemoglobinuria and myoglobinuria. With haematuria, red blood cells are present /HPF but absent in the others

RBC's may appear normally shaped, • Swollen by dilute urine (in fact, only cell ghosts and free hemoglobin may remain) or crenated by concentrated urinein dilute or hypotonic ( low specific gravity ) • In concentrated urine( high specific gravity) the red cells appear crenated

White Blood Cells N < 5/HPF, Pyuriarefers to the presence of abnormal numbers of leukocytes that may appear with infection in either the upper or lower urinary tract or with acute glomerulonephritis. -Repeated sterile cultures in presence of pyuria may indicate: -The patient is on antibiotic therapy -The presence of an organism that does not grow on ordinary media as T.B. -Non- bacterial uretheritis or cystitis as viral infection

Epithelial Cells • Renal tubular epithelial cells, contain a large round or oval nucleus and normally slough into the urine in small numbers. • However, with nephrotic syndrome and in conditions leading to tubular degeneration, the number sloughed is increased

Casts • Urinary casts are formed only in the distal convoluted tubule (DCT) or the collecting duct (distal nephron). • The proximal convoluted tubule (PCT) and loop of Henle are not locations for cast formation. Hyaline casts are composed primarily of a mucoprotein (Tamm-Horsfall protein) secreted by tubule cells. The Tamm-Horsfall protein secretion (green dots) is illustrated in the diagram below, forming a hyaline cast in the collecting duct:

The factors which favor protein cast formation are: *low flow rate, *high salt concentration, *and low pH, all of which favor protein denaturation and precipitation, particularly that of the Tamm-Horsfall protein. Protein casts with long, thin tails formed at the junction of Henle's loop and the distal convoluted tubule are called cylindroids. Hyaline casts can be seen even in healthy patients

Red blood cells may stick together and form red blood cell casts. Such casts are indicative of glomerulonephritis, with leakage of RBC's from glomeruli, or severe tubular damage White blood cell casts are most typical for acute pyelonephritis, but they may also be present with glomerulonephritis. Their presence indicates inflammation of the kidney, because such casts will not form except in the kidney.

Types of casts Acellular casts Hyaline casts Granular casts Waxy casts Fatty casts Pigment casts Crystal casts Cellular casts Red cell casts White cell casts Epithelial cell cast

Hyaline casts The most common type of cast, hyaline casts are solidified Tamm-Horsfall mucoprotein secreted from the tubular epithelial cells Seen in fever, strenuous exercise, damage to the glomerular capillary

Granular casts Granular casts can result either from the breakdown of cellular casts or the inclusion of aggregates of plasma proteins (e.g., albumin) or immunoglobulin light chains indicative of chronic renal disease

Waxy casts waxy casts suggest severe, longstanding kidney disease such as renal failure(end stage renal disease).

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Many of these substances can be found only in certain amounts in urine, so their higher or lower concentration indicates disease in different organs. Urine testing (for protein, pathogen, WBCs) not only can help detect and monitor diseases of the kidney and urethra, but also can be seen as indication of liver diseases (testing for bilirubin, urobilinogen) and other metabolic diseases (testing for glucose, ketone).

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Urine Culture

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Chemical – Bio Estimation and Analysis of Urine

Chemical – Bio Estimation and Analysis of Urine. By Dr.G.Srinivasagan Rajapalayam Rajus College. Urine consists of:. (96%) water. Inorganic: Cl - , Na, K. trace amounts of: sulfate, HCO 3 etc.). Urine:

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Red urine. Hemoglobinuria Myoglobinuria Drugs (rifampicin),food Inborn errors of metabolism(porphyria) Urate crystals Hematuria Do dipstick,microscopy ( &gt; 5cells/ul in fresh uncentrifuged urine, &gt;3 cells/HPF in centrifuged sediment.

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urine culture

urine culture. Pathophysiology of urinary tract infection. Ascending route of infection is the most common. Hospital infection associated with lower urinary tract instrumentation (catheterization, cystoscopy).

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I- URINE. Physical properties of urine : 1-Color of urine : Normal urine ordinary possesses an amber yellow The color of normal urine is due to a pigment called – urochrome (oxidative product of colourless urochromogen - urobilin , riboflavin, uroerythrine

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Article Contents

Introduction, case report, acknowledgements, conflicts of interest.

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Isolated gastrointestinal histoplasmosis with a negative urine antigen test mimicking ulcerative colitis flare: a case report

The authors wish it to be known that, in their opinion, J.Y. and N.B. should be regarded as joint First Authors.

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Jianyi Yin, Neeraja Balachandar, Dipti Karamchandani, Roopa Vemulapalli, David I Fudman, Isolated gastrointestinal histoplasmosis with a negative urine antigen test mimicking ulcerative colitis flare: a case report, Gastroenterology Report , Volume 12, 2024, goae013, https://doi.org/10.1093/gastro/goae013

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Histoplasmosis is a mycotic infection caused by Histoplasma capsulatum . The usual clinical presentation is pulmonary disease. Disseminated disease can occur and involve multiple organs [ 1 ]. Gastrointestinal (GI) involvement can be seen in 70% of autopsy cases, but only 3%–12% are symptomatic [ 1 ]. Moreover, isolated GI histoplasmosis without accompanying pulmonary symptoms is exceedingly rare. Recognizing this rare entity can be difficult, especially in patients with pre-existing GI disorders such as inflammatory bowel disease (IBD).

Here, we present a case of isolated GI histoplasmosis with negative urine antigen in a patient with ulcerative colitis (UC) treated with infliximab. Our case illustrates the importance of considering histoplasmosis as a differential diagnosis and using endoscopic tissue sampling rather than relying on lab tests alone for prompt diagnosis. Our case also highlights the need for further studies to determine the optimal IBD pharmacotherapy following the treatment of histoplasmosis.

A 21-year-old woman with a history of UC was admitted for progressively worsening abdominal pain, nausea, vomiting, low-grade fever and weight loss. Her symptoms began 8 weeks prior to presentation. She did not report any pulmonary symptoms or new skin lesions. Her symptoms were similar to those during her prior index flare of UC, but lacked the diarrhea and hematochezia she previously experienced. Her original diagnosis of UC was made 1 year prior during a hospitalization for acute severe UC, when she required rescue therapy with infliximab. She subsequently achieved endoscopic and histologic remission 4 months later after discharge.

Before this admission, her new symptoms did not improve despite increasing infliximab from 10 mg/Kg every 8 weeks to every 4 weeks and a 4-week trial of budesonide. She worked as a medical technologist in a microbiology lab in North Texas. She attended college in Oklahoma (USA) and traveled to Missouri (USA) 2 months prior to presentation.

On admission, she had a temperature of 38.1°C and mild tenderness to palpation in the mid-epigastric abdomen. Her labs were notable for C-reactive protein of 660 nmol/L and fecal calprotectin of 604 µg/g. Computed tomography revealed mild wall thickening with surrounding fat stranding in the duodenum, jejunum and proximal colon. Antegrade enteroscopy and ileocolonoscopy showed numerous superficial ulcers in the duodenum, jejunum, cecum and transverse colon ( Figure 1A and 1 B ), without inflammation in the ileum, left colon and rectum. Of note, jejunal biopsy revealed granulomatous inflammation with fungal organisms on Grocott's methenamine silver stain, consistent with Histoplasma infection ( Figure 1C and 1 D ). Her urine antigen test for Histoplasma by enzyme immunoassay was negative.

Endoscopic findings of ulcerations (arrows) in the jejunum ( A ) and colon ( B ), and histological findings of jejunal biopsy, notable for granulomatous inflammation on hematoxylin and eosin stain ( C , 100 × magnification, circle), with fungal organisms on Grocott's methenamine silver stain ( D , 400 × magnification, arrow).

Due to Histoplasma infection, infliximab was discontinued, and she was treated with amphotericin B followed by itraconazole. Her symptoms improved significantly over a few days. Then, she started mesalamine for maintenance therapy for UC. Three months later, repeat endoscopic evaluation showed resolution of duodenal, jejunal and colonic ulcers without histologic evidence of Histoplasma infection, and her UC condition remained in remission. However, a new jejunal stricture was noted, for which she underwent serial dilations. A year later, she completed anti-fungal treatment and opted to continue mesalamine as maintenance therapy.

In retrospect, the clinical improvement and persistent histologic remission following anti-fungal therapy and de-escalation of IBD pharmacotherapy suggested GI histoplasmosis over UC flare as the cause of her presentation. For the same reason, the jejunal stricture was more likely a sequela of GI histoplasmosis [ 2 ] rather than a manifestation of possibly unrecognized Crohn’s disease.

Here, we describe a patient treated with infliximab for UC who developed isolated GI histoplasmosis. This case is unusual in several aspects. First, this patient presented with isolated GI histoplasmosis without any pulmonary symptoms. Secondly, the partial overlap in clinical manifestations between GI histoplasmosis and UC flare made differential diagnosis difficult. Thirdly, her urine antigen test for Histoplasma was falsely negative, and the final diagnosis was established based on endoscopic tissue sampling.

Early diagnosis of histoplasmosis is crucial, as untreated cases can be fatal. Recognizing isolated GI histoplasmosis without pulmonary involvement in patients with pre-existing IBD can be difficult, due to their overlapping clinical manifestations. Urine antigen test is widely used in the USA for diagnosing histoplasmosis, with a sensitivity reportedly greater than 90% in patients with disseminated disease [ 3 ]. However, the test is highly dependent on the fungal burden and may be falsely negative, as in our case and a few others in the literature [ 4 , 5 ]. In addition, the test is not readily available in many parts of the world outside the USA. Our case suggests the importance of not relying solely on the urine antigen test for distinguishing GI histoplasmosis from IBD flare. Rather, early endoscopic evaluation with tissue sampling can be useful in promptly establishing the diagnosis.

Anti-tumor necrosis factor (anti-TNF) therapy is known as a risk factor for Histoplasma infection. Discontinuation of anti-TNF therapy is considered standard of care upon diagnosis of histoplasmosis. However, limited evidence is available to guide the re-initiation of IBD pharmacotherapy. In a single-center retrospective study, 19 of 49 patients continued or resumed anti-TNF therapy for IBD after Histoplasma infection [ 5 ]. No recurrence of histoplasmosis was observed except in a patient who self-discontinued itraconazole. In another single-center study, immunosuppressive therapy was re-introduced in 10 out of 17 patients with IBD, including two patients who resumed anti-TNF therapy, and no recurrence of histoplasmosis was reported [ 6 ]. Despite these data, non-anti-TNF therapies are often favored as an alternative regimen in patients with history of severe infections on anti-TNF therapy, as they are considered safer with respect to the risk of opportunistic infection. However, case reports of patients who developed histoplasmosis on ustekinumab [ 7 , 8 ], vedolizumab [ 9 , 10 ] or tofacitinib [ 6 ] have been described, and it remains unclear which non-anti-TNF therapy has the best safety profile in such cases. T cell-mediated adaptive immunity is a major immune mechanism to clear Histoplasma infection. Mechanistically, vedolizumab may greatly affect the T cell-mediated response in the GI tract, whereas ustekinumab theoretically may have a less profound effect. Therefore, we speculated that ustekinumab might be more favorable than vedolizumab in this case of isolated GI histoplasmosis if escalation of IBD pharmacotherapy was needed, but this needs to be evaluated by further studies.

Informed consent was obtained for this case report.

D.I.F. has served on advisory boards for Janssen, Fresenius Kabi and Pfizer. Other authors declare that there are no conflicts of interest in this study.

Kahi CJ , Wheat LJ , Allen SD et al.  Gastrointestinal histoplasmosis . Am J Gastroenterol 2005 ; 100 : 220 – 31 .

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Rowe KM , Green M , Nehme F et al.  Isolated ileal stricture secondary to antigen-negative GI histoplasmosis in a patient on immunosuppressive therapy . ACG Case Rep J 2017 ; 4 : e10 .

Hage CA , Ribes JA , Wengenack NL et al.  A multicenter evaluation of tests for diagnosis of histoplasmosis . Clin Infect Dis 2011 ; 53 : 448 – 54 .

Escobar B , Maldonado VN , Ansari S et al.  Antigen negative gastrointestinal histoplasmosis in an AIDS patient . Am J Case Rep 2014 ; 15 : 90 – 3 .

Jansson-Knodell CL , Harris CE , Loftus EV Jr , et al.  Histoplasmosis in inflammatory bowel disease with tumor necrosis factor-alpha inhibitors: safe to continue biologics? Dig Dis Sci 2021 ; 66 : 190 – 8 .

Pabla BS , Scoville EA , Sarker S et al.  Histoplasmosis as a complication of inflammatory bowel disease therapy: a case series . Inflamm Bowel Dis 2019 ; 25 : e69 – 70 .

Huang YH , Magleby R , Rao R et al.  Histoplasmosis in an off-trail Hiker receiving ustekinumab: Implications for Preventive and diagnostic strategies for patients receiving anti-IL-12/23 therapy . Med Mycol Case Rep 2021 ; 32 : 43 – 6 .

Sandborn WJ , Feagan BG , Danese S et al.  Safety of ustekinumab in inflammatory bowel disease: pooled safety analysis of results from phase 2/3 studies . Inflamm Bowel Dis 2021 ; 27 : 994 – 1007 .

Murskyj I. Disseminated histoplasmosis after vedolizumab treatment for ulcerative colitis . Case Rep 2020 ; 45 . https://scholarlycommons.henryford.com/merf2020caserpt/45/ .

Zahiruddin F , Nan X , Zimmerman J. Pulmonary histoplasmosis during vedolizumab therapy for Crohn's disease . Am J Respir Crit Care Med 2017 ; 195 : A2161 .

Author notes

• ulcerative colitis
• histoplasmosis
• urinary antigen tests

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• Continuing Education Activity

Cystine stones are due to an inherited defect in the transport of the amino acid cystine leading to excessive excretion in the kidney, causing cystinuria. Cystinuria causes supersaturation in the kidney, predisposing to the development of stones. This activity outlines the evaluation and management of cystine stones and explains the role of the interprofessional team in improving care for patients with this condition.

• Review the etiology of cystine stones.
• Describe the development of hematuria and acute flank pain in the history and physical examination of patients with cystine stones.
• Summarize the use of the sodium cyanide-nitroprusside test and other, newer tests in the laboratory screening and evaluation of cystinuria.
• Explain the importance of collaboration and communication among the interprofessional team to enhance care delivery for patients affected by cystine stones.
• Introduction

Cystine stones account for only about 1% to 2% of all kidney stones but represent roughly 6% to 8% of all pediatric calculi. Eighty percent of cystinuria patients will have their first stone during their first two decades of life. [1]

The name "cystine" comes from its original description as "bladder calculi" in 1833.

Kidney stones are the singular clinical manifestation of this condition. The primary treatment is the optimization of urinary volume and pH with hydration and oral alkalinizing medications. Second-line medical therapy consists of thiol-based drugs and is used in patients where conservative measures alone are insufficient.

While most cystine stone formers will make pure cystine stones, up to 40% may develop mixed calculi also containing calcium oxalate, calcium phosphate, or struvite. [2]

Compared to calcium stone formers, cystine nephrolithiasis patients will tend to make larger stones, require more urological procedures, make stones more often, and start at an earlier age. They also face a greater risk of eventual kidney damage and chronic renal failure compared to calcium nephrolithiasis patients. [2] [3] [4] [5]  Cystinuria patients also report relatively poor health-related quality of life scores due to multiple recurrent stone episodes and related surgical procedures although these scores can be improved with optimized prophylactic therapy. [6] [7]

The cause of cystinuria is an inheritable, autosomal recessive genetic defect that affects the proximal renal tubular reabsorption of cystine. This same problem also affects ornithine, lysine, and arginine (COLA), but only cystine is clinically significant as it is the only amino acid in this group that will form stones. Cystine is the least soluble of all the essential amino acids. Interestingly, intestinal transport and absorption of cystine in patients with cystinuria also tend to be impaired, but other factors significantly offset this benefit. [8] [9]

Cystinuria would not be a problem except for its relative insolubility in urine at physiological pH levels and normal body temperatures. Cystine solubility is highly pH-dependent because it substantially increases as the urine becomes more alkaline, especially above a pH of 7.

Cystine solubility is also affected by urinary macromolecules, electrolytes, and ions, all of which increase cystine's solubility.

The specific genetic cause has been identified as mutations in the SLC3A1 gene on chromosome 2, the SLC7A9 gene on chromosome 19, or rarely both. [10]

Various genotypic and phenotypic types have been identified, but they appear to have relatively little effect on the clinical course.  No difference in the number of stones, age at the time of the first stone event, nor the total number of stone episodes has been observed between the different genetic types. [11] [12] [13]  For this reason, genetic testing is not usually performed for cystinuria patients. However, it has been suggested that genetic testing can be useful by confirming the diagnosis, helping with disease classification, and assisting in counseling family members. [11]  

• Epidemiology

Cystinuria is the most common inheritable cause of kidney stone disease. Worldwide and United States incidence is about 1 in 7,000 population. Prevalence is 1 per 100,000 in Sweden, 1 per 18,000 in Japan, 1 per 4,000 in Australia, 1 per 2,500 in Israel, and 1 per 2,000 in Great Britain and Spain. In cystinuric stone formers, the typical patient makes about one stone every one to two years, has one surgical procedure every three years, and has undergone seven surgeries by the time they are middle-aged. [14] [15]  The 5-year recurrence rate for cystine stones is higher than for any other stone type at 83%. [10]  More than 25% of cystine stone formers can develop non-cystine urinary calculi; this is found most often in patients following shock wave lithotripsy who may become over-alkalinized with urinary antacid therapy, which predisposes them to calcium phosphate stone formation. [2]

• Men are affected about twice as often as women. The peak age of presentation of the first cystine stone is 22 years of age, although 22% of cystinuria patients will start making calculi as children.
• The overall risk of some degree of renal injury or failure is high at up to 70%, but end-stage renal failure is relatively low in cystinuria patients at less than 5%.
• Twenty to forty percent of cystinuria patients have other kidney stone-related urinary chemical abnormalities such as hypocitraturia (44%), hypercalciuria (19%), or hyperuricosuria (22%).
• Infrequently, cystinuria is associated with hemophilia, muscular dystrophy, mongolism, hereditary pancreatitis, and retinitis pigmentosa.
• Recurrence rates after surgical intervention approach 45% at three months without prophylactic medical treatment. With treatment, the average recurrence rate drops to 25% at three years.
• Pathophysiology

The solubility of cystine in urine is about 250 mg/L at a pH of 7. This solubility increases as the urine becomes more alkaline, especially above pH 7. For example, 500 mg of cystine will dissolve in a liter of urine at a pH of 7.5. Cystine solubility goes up to 750 mg/L at a pH of 8, but it sometimes becomes challenging to achieve and maintain a urinary pH above 7.5 in clinical practice. There is also an increased risk of calcium phosphate precipitation in very alkaline urines. [10]

The actual solubility of cystine in urine is actually somewhat greater than the standard solubility guidelines would suggest. This is due to the actions of various electrolytes, ions, and macromolecules. So while standard solubility estimates can be a guide, the actual solubility in an individual patient's urine can only be roughly estimated from the published data. [16]  However, a specialized laboratory can measure relative solubility with a urinary cystine supersaturation ratio or a "cystine capacity" test (for patients on thiol medications). (See below)

• History and Physical

The initial presentation of a patient with cystine stones is identical to any patient with obstructing urolithiasis except that they will often present at a younger age or even as children. They typically will develop acute flank pain with hematuria, often associated with nausea and vomiting. The pain will radiate around the flank towards the groin, and they often have costovertebral angle (CVA) tenderness. Microscopic or gross hematuria is frequently present, but up to 15% of patients with obstructing stones may not have microscopic hematuria. The strongest element in the patient's history is a positive personal or family history of cystinuria or cystine stone formation.

Since cystine contains sulfur, the urine of hypercystinuric individuals may have a rotten egg odor. Typical hexagonal cystine crystals can sometimes be seen on urinalysis in affected patients. When these hexagonal crystals appear on urinalysis, it suggests supersaturation of the urine with cystine. [10] [17]  Characteristic hexagonal crystals of cystine will appear in 25% of cases on early morning urinalyses and are considered diagnostic of cystinuria. [1]

The sodium cyanide-nitroprusside test is often the initial laboratory screening test for cystinuria as it is fast, simple, and provides a reasonably reliable, qualitative assessment of urinary cystine levels. The cyanide converts cystine to cysteine, which then binds to the nitroprusside creating an intense purple color in just a few minutes. The test typically turns positive at cystine levels above 75 mg/gm creatinine. [18]  False positives can occur in patients with Fanconi syndrome or those taking sulfur-based medications, ampicillin, or N-acetylcysteine. [6]  Overall sensitivity is 72%, with a specificity of 95%. [10]  The test is considered outdated due to its relatively low sensitivity and the need to use unstable, hazardous reagents. The sodium nitroprusside test is not recommended in known cystine stone-forming patients as the more reliable, quantitative 24-hour total cystine level is preferred. Accepted methodologies for quantitative urinary cystine measurements include ion-exchange chromatography or liquid chromatography-tandem mass spectrometry. Both are now considered acceptable clinical reference methodologies. [11]

A definitive diagnosis of cystinuria requires a quantitative 24-hour urine test for cystine and a positive stone chemical composition analysis (preferably using X-ray diffraction and infrared spectroscopy). [19]  In younger children who cannot perform 24-hour collections, there are age-related standards for first-morning urine cystine concentration per gram of creatinine. In older children, cystinuria is usually defined as >315 mg cystine/gram creatinine. Normal cystine concentrations in younger children are as follows: [20] [21]

• Age <1 month: <80 mg cystine/gram creatinine
• Age   1 month - 1 year: <52 mg cystine/gram creatinine
• Age >1 year:    <35 mg cystine/gram creatinine

Regular 24-hour urine tests are recommended to monitor therapy results and modify treatment as a change in stone composition is common. [22]  However, standard laboratory testing cannot differentiate between free and bound cystine for patients on thiol therapy. [22]  (See "cystine capacity" test below.)

Cystine Supersaturation  is a very useful laboratory measurement that evaluates the cystine crystallization potential as well as the efficacy of prophylactic therapy, except for those on thiol-based medications where the test is not considered reliable as it looks at total cystine whether complexed with thiol or not. To perform this test, the patient's urine sample is incubated with additional cystine crystals for 48 hours at 37 degrees C. At this point, the urine is completely saturated with cystine. Dividing the original sample's cystine concentration by the concentration of the fully saturated sample provides a supersaturation ratio. The optimal ratio to prevent cystine stone formation is not known, but a supersaturation ratio of 0.6 or less has been suggested as a goal.

The "Cystine Capacity"   test  is recommended for cystinuria patients on thiol-based medications where the supersaturation test cannot be used reliably. The "cystine capacity" test measures the ability of a patient's urine to dissolve a solid cystine sample. A pre-determined amount of solid cystine is added to a measured sample of the patient's urine. The sample is incubated for 48 hours at 37 degrees C, and then all solid cystine is removed. If the recoverable solid cystine weighs less than the original sample, the urine is undersaturated. If it weighs more, then it is supersaturated. A "positive" test means that the solid cystine sample has gained additional cystine after incubation, so the test urine was supersaturated. A "negative" test indicates that the solid sample has partially dissolved, and therefore the test sample was undersaturated with cystine. While "cystine capacity" is a very reasonable test for cystine saturation, it is relatively insensitive and somewhat labor-intensive, which limits its practicality and availability, although it does allow an accurate determination of cystine saturation even for patients who are on medical (thiol) therapy. [6]  In the US, both of these tests (cystine supersaturation and "cystine capacity") are available through a specialized laboratory such as Litholink (litholink.labcorp.com or 1-800-338-4333).  

The definitive diagnosis of obstructing cystine calculi will require imaging, including plain abdominal X-rays (KUB), ultrasound, and CT scans.

Plain X-rays of the abdomen will not show cystine stones well as they are only faintly radio-opaque. If visible, they will tend to have a ground-glass appearance. [10]

Ultrasound can identify cystine stones in the kidney if they are sufficiently large (usually >4 mm) and can detect hydronephrosis, but it cannot distinguish cystine from other stone chemical compositions. It is the preferred initial imaging study for stones in children and in pregnancy. Ultrasound can measure the renal resistive index, which is elevated in cases of obstruction. The resistive index is defined as (peak systolic velocity - end-diastolic velocity) / peak systolic velocity.  This value is usually 0.50 to 0.70. If one side has a higher resistive index, it suggests obstruction on the affected (elevated) side.  (In medical renal disease, the resistive indices on both sides are elevated equally.)

The finding of a hyperechoic fetal colon on routine ultrasound at <36 weeks gestation has been shown to indicate fetal cystinuria with a very high positive predictive value of 89%. [23] [24]  The explanation for this is a cystinuric fetus will have high cystine levels in the amniotic fluid. As this fluid is naturally ingested by the fetus, it overloads the fetal intestinal absorbing ability resulting in cystine precipitation in the colon. [25]  In these rare cases, genetic testing can be recommended to confirm the early diagnosis of cystinuria as tubular immaturity interferes with urinary cystine excretion in very young children. [11]

CT scans without contras t remain the "gold standard" for diagnosing urolithiasis and will show cystine stones clearly. Such calculi will typically demonstrate a relatively low density of <800 Hounsfield units. [26] (Stones with a density of >1,000 Hounsfield units are unlikely to be pure cystine.)  Unfortunately, Hounsfield units alone cannot easily distinguish between cystine and uric acid stones since their Hounsfield densities overlap. [26]  Uric acid stones will also have low Hounsfield units of <500 on CT, but they will demonstrate very low urinary pH levels, which is not typical of cystine stones. Dual-energy CT scans use information from two separate beams to help distinguish the stone chemical composition, but these machines are more costly, are not universally available, and are still unable to definitively distinguish between uric acid and cystine stone compositions where the densities overlap. [27] [28]

• Treatment / Management

The currently recommended treatment strategy for cystine stone formers is based on a progressive approach starting with the most conservative measures. Initial therapy involves dietary measures, hydration, and alkalinization. In refractory cases, treatment is extended to thiol-based medications. Existing cystine stones are treated similarly to other urinary calculi of similar size, with consideration being given to the high stone recurrence rate and relative resistance to extracorporeal shockwave lithotripsy (ESWL) fragmentation.  

Medical Management

Dietary measures alone for cystinuria have shown only relatively minor clinical benefits. Nevertheless, a "bad" diet can certainly increase stone risk. Patients on various supplements high in cystine and methionine have shown rapid growth and production of cystine stones. [29]  The best evidence for dietary risk reduction may be sodium, where a low salt diet appears to reduce urinary cystine excretion. [30] [31] [32]  Dietary sodium should be limited to less than 2 grams/day. A low methionine/low protein diet is still typically recommended, although its overall effectiveness is still considered somewhat limited. [33]  High methionine foods include turkey, beef, fish, pork, tofu, milk, cheese, nuts, beans, and whole grains like quinoa. A normal daily dietary methionine intake of 1,200 to 1,400 mg per day is recommended. [34]  High animal protein consumption will also raise urinary acidity, decrease pH and increase hydrogen ion excretion. Protein restrictions should not extend to children who are still growing, although the amount of very high methionine foods should be limited. [10] [11] [34]  Alkalinizing beverages (such as lemonade, orange juice, and mineral water with high bicarbonate levels) are recommended. [6] [10]

Hydration is usually the first step in medical management, along with dietary measures. Increasing fluid intake sufficiently to reliably generate 3,000 ml or more of urine per day is recommended. The goal is to dilute the urine sufficiently to get the urinary cystine content to the recommended concentration level of 250 mg/L or less; this frequently requires having the patient wake up in the middle of the night to void and drink extra water. Drinking 240 ml of water every hour during the day and 480 ml before bed and at least once overnight is a standard strategy for maximizing oral hydration therapy and urinary volume. Hydration can be monitored by following the specific gravity, which should always be 1.010 or less. Since some cystinuric patients can generate up to 1,400 mg of cystine per day, hydration alone may not be sufficient, but it is always the initial step in management along with dietary measures. Up to one-third of cystine stone patients can manage their stone recurrences with fluid management alone. Optimal hydration will depend on the patient's individual cystine excretion. [10]  

Clinicians should be aware that maintenance of high fluid intake is often difficult for patients, especially at the much higher than usual levels required of cystine stone formers. Maintenance of fluid is so critical that patients are typically advised to drink extra water before bedtime and each time they awaken. In refractory cases, particularly in the pediatric age group, using a nocturnal nasogastric or gastrostomy tube to provide additional overnight fluid can be considered. [11]  Periodic, regular review and monitoring of the patient's daily urinary output volume by the clinical team are necessary to maintain the effectiveness of this important treatment modality in managing this challenging disorder.

Acceptable levels of urinary cystine are 250 mg/L or less at a urinary pH of 7 or more. Some experts have recommended cystine concentrations of 150 mg/L, and possibly even lower at 90 mg/L, as "optimal." [10]  This level can often be reached through increasing fluid intake. The use of thiol-based medications to reduce urinary cystine levels is discouraged unless hydration and alkalinization treatments alone are insufficient to achieve the desired "optimal" cystine concentration levels (less than 250 mg/L) at an acceptable, achievable pH of at least 7. A sustained urinary pH of 7.5 or more can be useful to attempt dissolution of existing cystine stones, although such high pH levels can be difficult to maintain clinically and may tend to precipitate calcium phosphate. 

Urinary alkalinization can not only prevent cystine precipitation and stone formation but may also dissolve existing calculi. For prophylaxis, the urinary pH should be targeted at 7.5, but a urinary pH higher than 7.5 needs to be maintained for stone dissolution. However, at this high pH level (above 7.5), calcium phosphate stones can precipitate. In such cases, hypercalciuria needs to be controlled tightly with diet and thiazide therapy, while hydration should be optimized. Cystine solubility increases dramatically above a urine pH of 7 at body temperature. At a pH of 7.5, cystine solubility is 500 mg/L, almost double its solubility at a pH of 7.

Mineral water and citrus juices can help increase pH levels, but potassium citrate supplementation is the mainstay of urinary alkalinization therapy. The usual daily potassium citrate dosage in cystinuria is 60 to 90 mEq total in 3 or 4 divided doses and then titrated as needed to optimize the pH at 7.5. A large bedtime dose is suggested as well. Patients should be warned that they may see tablets in their stool and that this is normal. (The tablets are wax-based and designed to pass through the gastrointestinal tract and be expelled in the stool.) Serum potassium should be checked periodically in patients on high dosages of potassium citrate and those with renal failure to detect hyperkalemia early. [10]  

Cystinuria patients on alkalinization therapy often need very high doses of urinary antacids. Unfortunately, potassium citrate tablets are notorious for poor long-term patient compliance as they require frequent daily dosing, tend to have significant gastrointestinal side effects, and can be physically difficult to swallow for many patients due to their large size. Liquid potassium citrate formulations can be quite concentrated and offer a relatively large urinary alkalinization effect, but they also often taste exceedingly bad or are unavailable. [35]  If hyperkalemia is limiting potassium citrate administration, urinary alkalinizing medications with lower potassium content are available. These would include various prescription and OTC combinations of sodium citrate, sodium bicarbonate, citric acid, magnesium citrate, and potassium citrate. [35] [36]

A low potassium OTC urinary alkalinizer is available online that overcomes the problems with most urinary antacid products. Each 10 mEq citrate packet contains 5 mEq of potassium citrate, 2.5 mEq of sodium bicarbonate, and 2.5 mEq of magnesium citrate. (This is equivalent in urinary alkalinizing ability to a standard 10 mEq potassium citrate tablet but is better absorbed, has fewer intestinal side effects, is less expensive, and contains half the potassium content.) It has been formulated to have no taste when mixed with water, juice, or other beverages, requires no prescription, and the cost is nominal. [36]

Sodium bicarbonate can also be used to help with pH issues, especially in patients at risk for hyperkalemia with potassium citrate therapy, but it tends to have a relatively short-term alkalinizing effect, and the extra sodium intake may actually increase urinary cystine excretion. High animal protein diets are also discouraged in cystinuric patients for the same reason. [10]  

Acetazolamide is a carbonic anhydrase inhibitor that increases urinary bicarbonate excretion and raises urinary pH levels. While not a first-line therapy (it can cause hypocitraturia and metabolic acidosis), it may occasionally help maintain high urinary pH levels in addition to the other therapies mentioned. Acetazolamide can be particularly useful in maintaining a high nighttime urinary pH without the need for multiple awakenings or additional overnight alkalinization dosing. [37]  However, it is not always well-tolerated and can cause metabolic acidosis. Potassium citrate is still preferred for urinary alkalinization, but acetazolamide can occasionally be helpful in selected patients.

Alpha-lipoic acid , a nutritional supplement, has been shown to increase cystine solubility in urine without affecting concentration or pH in both animal models and humans. Studies are very limited, but anecdotal case reports are quite promising. [38] Given its very high safety profile, alpha-lipoic acid may be worth using in cases where hydration and alkalinization therapy alone have not been adequate. The dosage used was 300 - 600 mg PO BID, but an optimal dose has not been established for cystinuria. When used for diabetes or neuropathy, dosages of 600 mg to 1,800 mg per day of alpha-lipoic acid have been used safely. A formal clinical trial on the use of alpha-lipoic acid in cystinuria stone formers is underway. 

The goal of all the above therapies is to achieve a cystine concentration of no more than 250 mg/L at a urinary pH of at least 7. To reduce the urinary cystine concentration, additional fluid intake will be necessary. If the pH is not at least 7, additional alkalinizing therapy should be utilized. The optimal urine pH in cystine stone-forming patients is 7.5. When these target goals cannot be achieved, or such conservative measures are insufficient to control stone formation after a three-month trial period, a thiol-based drug regimen will be the next step in treatment for active cystine stone formers. [10]

Thiol-Based Agents

Cystine is composed of two cysteine molecules bound together by a disulfide bond. Thiol-based drugs have sulfhydryl groups that can reduce this disulfide bond, producing a mixed cysteine disulfide compound that is far more soluble than the original cystine molecule. As a general guide, most patients with a 24-hour urinary cystine excretion of 500 mg or more are likely to need a thiol medication in addition to hydration therapy and urinary alkalinization. [10]  It is generally recommended that a higher dose be given at bedtime. Thiol-based drugs are contraindicated during pregnancy. 

Thiol-based treatment is thought to have the extra benefit of possibly making cystine stones more amenable to ESWL treatment. This may occur because of the mixing of calcium phosphate along with the cystine creating a more fragile stone that is easier to fragment with ESWL therapy. All patients on thiol-based drug therapy should have routine blood and platelet counts, serum albumin, liver function tests, and 24-hour urine tests for cystine, "cystine capacity" (if available), and protein. [39]

Penicillamine, a penicillin derivative,   was the first thiol drug used for cystinuria. Penicillamine-cysteine disulfide is 50 times more soluble in urine than cystine. Each 250 mg penicillamine tablet can reduce urinary cystine levels by about 75 mg to 100 mg per day. The problem with penicillamine is that there is a high incidence of side effects, including fever, rash, loss of taste, arthritis, leukopenia, aplastic anemia, gastrointestinal (GI) disturbances, renal membranous nephropathy with proteinuria, and pyridoxine (vitamin B-6) deficiency. The incidence of significant side effects is about 50% but could be as high as 84%, limiting long-term compliance. Almost 70% of patients discontinued the drug due to these adverse side effects in one study. Penicillamine can suppress the immune system, which will increase the risk of infection, but these patients need close monitoring for renal function, heart effects, liver toxicity, abnormal blood counts, and neurological defects. [40]  For these reasons, penicillamine use is limited in favor of other thiol-based drugs. [41]

Tiopronin (Thiola, alpha-mercaptopropionylglycine, or alpha-MPG) is a second-generation thiol drug that works similarly to penicillamine but is roughly 30% more effective (higher dissolution rate) with significantly fewer side effects (approximately 20% to 50%). It received approval for use in the United States in 1988, so there is ample experience with the medication. The typical dose is 300 mg three times per day but can be upwardly adjusted to 1,500 mg/day. (For pediatric patients, the recommended dosage is 20 to 40 mg/kg/day, split into two doses.) [1]  Long-term compliance is about 70%, and the discontinuation rate is half that of penicillamine. [42]  An enteric-coated formulation has recently become available. For these reasons, tiopronin is currently the thiol drug of choice for cystinuria when hydration and urinary alkalinization therapy fail to achieve optimal cystine concentration levels at an acceptable pH. [43]

Captopril is an angiotensin-converting enzyme (ACE) inhibitor normally used for hypertension, but it is also a unique thiol-based drug that can form captopril-cysteine mixed disulfides that are highly soluble in cystinuric patients. While safe with few side effects, captopril's clinical effectiveness in cystinuric stone-forming patients is uncertain as various studies have produced conflicting results. It may be most useful in patients who have chronic renal failure, hypertension, and proteinuria.  It is not recommended as monotherapy for cystinuria. Pending a more rigorous, definitive study, it should be considered a reasonable treatment option only in cystinuric patients where other thiols are overly toxic or unavailable. [39] [44]

Bucillamine is a third-generation, thiol-based drug that is currently available only in Japan and South Korea. Even there, it is only approved for use in rheumatoid arthritis. As a di-thiol compound, it would theoretically be more effective than tiopronin and better tolerated since lower dosages of the drug would be needed. Experience in Asia over 30 years has demonstrated a low toxicity profile. Bucillamine has been shown to be more effective than tiopronin in at least one small cystinuria study. [22]   A phase 2 study is currently underway in the United States to determine its potential clinical usefulness in treating hypercystinuria. (It is also being investigated for a possible role in treating COVID-19.)

Surgical Management

The surgical treatment of cystine stones is similar to that of other stones except that cystine is notoriously resistant to extracorporeal shock wave lithotripsy (ESWL) unless the stones are less than 1 cm in size. Cystine stones appear to be more fragile and more amenable to ESWL in patients taking oral thiol medications. [10] Retrograde pyelography and the use of indwelling ureteral catheters with intermittent diluted retrograde contrast injections will help to visualize stones that otherwise would be difficult to target for ESWL therapy. Cystine calculi will also likely require more shocks than calcium oxalate or calcium phosphate stones. For these reasons, ureteroscopy with laser lithotripsy is preferable for most cystinuria patients with obstructing or non-obstructing cystine stones that require surgery. Surgical therapy for cystine stones is usually a bit more aggressive than for other urinary calculi meaning that surgery is recommended earlier and for smaller stones than other stone types. Nevertheless, ESWL may be considered even for relatively resistant cystine stones in children and others wishing to avoid more invasive procedures as much as possible. Percutaneous procedures should be limited and used only when absolutely necessary to minimize renal damage over time. Miniaturized equipment should be utilized when possible. [45] [46]

Total removal of all cystine stones and fragments has demonstrated reduced recurrence rates and better preservation of renal function. This is particularly important in pediatric cystinuric patients, where prophylactic measures should be emphasized to avoid new stone production and the need for additional future surgeries. When carefully and appropriately performed, stone surgery does not generally cause any measurable decrease in overall renal function. [45] [47] [48]

When ureteral double J stents are used, their time in place should be minimized as complete stent encrustation, and blockage in cystinuria patients can occur in less than two weeks. [49]

The spontaneous passage rate is similar for all stone types, although cystinuria patients may be able to pass larger stones due to their greater average number of prior episodes. A maximum of 30 days is recommended for conservative management and spontaneous passage, after which surgical intervention should be performed to prevent further symptoms and complications. [50] [51] A recent large, worldwide real-life study of calculi managed conservatively showed overall stone passage rates for proximal ureteral calculi were 52% compared to 83% for distal stones. The spontaneous stone passage rate for various stone sizes (diameters) was as follows: [52]

• Stone diameter <5 mm  = 89% stone passage rate
• Stone diameter 5-7 mm = 49% stone passage rate
• Stone diameter >7 mm  = 29% stone passage rate

Patient Monitoring

Urinary cystine is found in both soluble (free) and insoluble (bound) forms. [49]  How much cystine is soluble vs. insoluble depends on many factors, including concentration, temperature, ionic strength, pH, macromolecules, etc. [16]  This is why the total daily urinary cystine is not always a good indicator of the patient's true clinical status or propensity for stone production. Separate measurements of free and bound cystine levels have clinical significance in treating patients on thiol and other cystine-binding drugs, but these values are not readily available, and results need to be verified, standardized, and published. [19] [53] [54]

Regular renal ultrasounds are recommended in all active cystine stone-forming patients every 6 to 12 months. [6]  This has been shown to be an effective way to monitor stone production while minimizing ionizing radiation exposure. The timing of these ultrasounds should be modified based on each patient's individual clinical history, response to prophylactic therapy, daily urinary cystine production, and pH, as well as stone production. For patients with infrequent stones (<1 stone a year), annual monitoring may be sufficient. For more active stone formers, monitoring frequency should be increased accordingly.

Routine 24-hour urine tests for total cystine excretion, supersaturation, and urinary cystine capacity are recommended for monitoring and optimizing therapy. Regular 24-hour urine testing for protein is recommended for patients on thiol medications and those with renal failure.

There appears to be a correlation between new cystine stone production and the presence of crystalluria on urinalysis. [55] [56]  The optimal timing and frequency of urinalyses for cystine crystalluria monitoring have not been determined, and no prospective studies have yet been done. In addition, there is no generally accepted, standardized methodology for assessing the degree of cystine crystalluria. In Europe, many centers already use some form of urinary crystal detection and quantification for routine monitoring of cystinuria patients. Theoretically, monitoring of cystine crystalluria may allow for better optimization of ultrasound and CT examinations for early stone detection. [11]  There is also no standardization for assessing cystine stone activity.  Should we use the number of stones made per year, the number of urological stone procedures, the increase in the number or size of calculi, or some combination of these factors to determine cystine stone activity for both clinical and research purposes? The answer remains yet to be determined.

It is well established that increased patient compliance with therapy, particularly alkalinizing agents, is associated with fewer urological surgery procedures. [57]  Achieving this is not always easy. Besides education, support, and reinforcement, there are now cellphone apps that include gentle reminders to patients to drink more water, check their urine pH, and take their prescribed alkalinizing medications.  All cystine stone-forming patients should monitor their urinary pH regularly with dipsticks, pH paper, or electronic meters. Optimal urinary pH is generally considered to be 7.5, but this is not always easy to achieve in the real world. However, cystine is twice as soluble at a pH of 7.5 compared to 7.0 (500 mg/L vs. 250 mg/L), so the extra effort is well worth it.

• Differential Diagnosis
• Constipation
• Diverticulitis
• Emergent management of pancreatitis
• Fungus ball in renal pelvis or ureter
• Inflammatory bowel disease
• Liver abscess
• Nephrolithiasis (calcium, uric acid, struvite)
• Nutcracker syndrome
• Peptic ulcer disease
• Prostate or cervical cancer
• Pyelonephritis
• Pyonephrosis
• Renal cell carcinoma 
• Splenic abscess
• Sloughed papilla
• Ureteral urothelial carcinoma
• Ureteropelvic junction obstruction
• Urinary tract infection and cystitis in females

Cystinuria patients generally have a lower quality of life compared to the general population. [58] [59] Treatment is frequently difficult to tolerate or maintain, unpleasant, and often ineffective. Patients with cystine stones require more surgeries than other nephrolithiasis patients and are at considerably higher risk of chronic kidney disease, although the incidence of end-stage renal failure is relatively low at <5%. This risk is related to the degree of renal tissue damage, age, comorbidities, and prior renal surgeries. Most adult cystinuria patients will have an estimated glomerular filtration rate (GFR) of <90 ml/min. and hypertension is reported in 29% to 51%. [60] [61]  The risk of hypertension was associated with the male sex, increasing age, and the degree of renal failure.

• Complications

The complications from cystinuria are all related to the effects of multiple kidney stones, resulting in renal and ureteral damage, scarring, pain, repeated surgeries, and eventual renal failure. For these reasons, aggressive prophylactic measures, focusing on increasing fluid intake and optimizing urinary pH, are utilized.

• Deterrence and Patient Education

Patient education is mandatory in cystinuria.  The consequences of inadequate prophylactic measures causing eventual renal deterioration and possibly even renal failure need to be repeated and reinforced to patients to achieve optimal hydration and urinary pH levels. Teaching patients how to check urine specific gravity, pH values, and 24-hour urine volumes can be extremely helpful in fine-tuning and optimizing therapy to maintain a daily target urinary volume of 3 liters with a pH of 7.5.  

• Pearls and Other Issues

A quantum dot assay to measure cystine concentration has been described.  It uses a complicated hydrothermal method with several benefits compared to conventional chemical means, including high sensitivity, stability, rapid results, low cost, and the ability to reliably measure cystine even in the presence of chemicals and compounds that would otherwise interfere. [62]

Urinary dipsticks or chemically treated test paper to check urine pH are readily available at nominal cost at most pharmacies or online. These products change color when dipped in urine, based on the urinary pH. This can then be matched to a color guide on the bottle or dispenser, corresponding to a particular pH level. Unfortunately, most urinary home pH products do not have a very clear color differentiation between a pH of 6 and 8. Another problem is that pH paper and many urinary dipsticks do not include specific gravity, which is a test for urine concentration and hydration status. The typical recommendation is for a product for patients with a relatively limited pH range (usually 4.5 to 9) which makes it visually easier to read the correct pH level. A specific dipstick for kidney stone formers and cystinuria patients to use at home that has an optimized pH range and includes a specific gravity reading is under development. It would be ideal for urinary pH and hydration monitoring in uric acid and cystine stone-forming patients on alkalinization and fluid therapy.

About 25% of cystine stone formers will have non-cystine chemical components in their stones. For this reason, complete stone chemical composition analyses and 24-hour urine tests for nephrolithiasis risk factors are recommended for optimal stone prophylaxis. [10]

Some high protein dietary supplements have enough cystine and methionine (a cystine precursor) to increase cystine stone formation. [29]  Such high protein supplements should be strictly avoided in cystinuric patients. 

Selenium, at a dosage of 200 mg/day for six weeks, was shown in a 2018 double-blinded study to significantly reduce cystine crystal volume, but this finding has not yet been confirmed by other investigators. [19]

Alpha-lipoic acid has been shown to increase urinary cystine solubility in mice. It also has prevented cystine stones in 2 human patients. [38]  A phase 2 clinical trial is assessing the effectiveness of a daily administration of 1,200 mg of alpha-lipoic acid over a three-year period in controlling stone formation in hypercystinuric patients.

A vasopressin receptor antagonist (tolvaptan) has been shown to prevent the growth of cystine stones in animal models by drastically increasing urinary volume. [63]  A pilot study is being done to evaluate its safety and tolerability in human subjects (ClinicalTrials.gov Identifier: NCT02538016 ). [64]  Tolvaptan works to increase urinary output by enhancing renal free water excretion. It was tested in 4 young adults with cystinuria. All of the subjects tested noted dramatically improved urinary volumes and increased cystine carrying capacity. There were no liver enzyme or serum electrolyte problems. The only side effect noted was significantly increased thirst. [64]  Such an approach has the potential to significantly reduce stone recurrences in cystinuria patients as well as in other kidney stone formers who find it otherwise difficult to increase their fluid intake and urinary volumes. While it appears to be safe and effective for cystinuric and other kidney stone formers, there are concerns about possible hepatic toxicity as 3 cases of potentially serious liver injuries have been noted. Liver toxicity appears to be related to dosage and to the presence of pre-existing liver problems or autosomal dominant polycystic kidney disease. For now, usage is currently limited to 30 days per FDA guidelines.

A combination of potassium citrate and potassium bicarbonate is being evaluated for efficacy and safety in cystine stone-forming children.

Besides bucillamine, other new cystine binding agents or crystal growth inhibitors are under evaluation. For example, L-cystine dimethyl esters (L-CDME) and L-cystine methyl esters (L-CME) have shown promising results with good therapeutic effects at relatively low concentrations, which suggest better tolerability and fewer side effects than similar agents. [3] [65]  Several other new, investigational thiol compounds, such as thiophosphate and meso-2-3-dimercaptosuccinic acid, are undergoing testing and also appear promising. [66]

Stem cell transplants have shown positive activity in reducing cystinuria in the mouse model, and a human phase 1 and 2 study is currently underway (ClinicalTrials.gov Identifier: NCT03897361 ). [67]

Experimentally, real-time in situ atomic force microscopy has suggested that L-cystine dimethyl ester (L-CDME) and L-cystine methyl ester (L-CME) can dramatically reduce the growth rate of cystine stones and crystals. They interfere with specific receptor sites on crystal surfaces that block cystine molecule binding. [3] [65] [68]

Crystal growth inhibitors may be the next new wave of prophylactic treatments for cystine stone patients. L-cystine bismorpholide and L-cystine bis(N'-methylpiperazide) appear to be the most potent potential cystine crystalization inhibitors, but they have not yet been tested in any published clinical trials. [3] [66]

A recombinant human enzyme ( ACN00107 ) that can degrade cysteine and cystine and reduce urinary cystine levels while inhibiting cystine stone formation has been shown to be effective in mice and is awaiting human trials. [22]

Chaperone therapy, where various agents are used to correct protein and enzymatic misfolding, is a new approach to various heritable diseases. Since several mutations result in protein misfolding in cystinuria, chaperone therapy is a potentially promising new treatment for cystinuric patients in the future. [22]   

Treatment Summary

Initial or First-Line Therapy

• Reduce dietary methionine (animal protein).
• Lower the dietary salt intake.
• Increase fluid intake sufficient to generate 3,000 ml of urine daily.
• Start alkalinization therapy with the goal of raising and maintaining the urinary pH up to 7.5, if possible.
• Routine patient self-monitoring of pH and specific gravity is recommended, along with appropriate adjustments in therapy.
• Potassium citrate is the preferred alkalinizing medication, but sodium bicarbonate may also be used.
• Liquid forms of urinary alkalinizers are more quickly absorbed than tablets. They are more appropriate for patients with rapid intestinal transit times, irritable bowel syndrome, chronic diarrhea, or post gastric bypass surgery.
• Use low potassium urinary antacid treatments in patients requiring high doses of alkalinizing therapy, develop hyperkalemia or have renal failure.
• Acetazolamide can be effective in raising urinary pH, but its use is discouraged except in carefully selected patients.
• Avoid routine urinary alkalinization beyond pH 7.5 to minimize calcium phosphate precipitation, although this may help attempt cystine stone dissolution.
• Cystine concentration should be <250 mg/L, and the urine pH should be maintained optimally at 7.5 but should be at least 7. If this cannot be achieved and maintained, additional second-line (thiol) therapy should be used.
• Routine laboratory testing should include a quantitative 24-hour total urinary cystine, serum potassium, and a cystine supersaturation ratio as well as the total daily urine volume and pH.

Second-Line Therapy

• Thiol-based treatment should use tiopronin, which is currently the preferred agent.
• "Cystine Capacity" testing should be used for monitoring treatment efficacy for patients on thiol therapy.

Optional Therapies

• Alpha-lipoic acid is readily available, well-tolerated, safe, and might be of real value based on very good results in limited studies.
• Selenium is cheap and easy to administer, but its role is unproven and untested except for a single study showing a benefit.
• Bucillamine might be a better, more effective, and less toxic thiol drug for cystinuria, but it remains mostly untested for this indication. Availability is also an issue. 
• Enhancing Healthcare Team Outcomes

An interprofessional team should educate patients that treatment for cystinuria starts with diet (low meat protein, low sodium) and hydration sufficient to generate 3,000 mL or more of urine daily. Urinary alkalinization with mineral water, fruit juices, sodium bicarbonate, and potassium citrate will significantly increase cystine solubility. The goal is to achieve a cystine concentration of 250 mg/L or less at a pH of at least 7 and optimally 7.5. An "optimal" cystine level is generally considered to be 150 mg/L or less, but some reports suggest that a cystine concentration goal of 90 mg/L may be "optimal." If this is not achievable or possible for any reason (tolerability, compliance issues, side effects), then the use of a thiol-based cystine lowering medication is warranted. Currently, tiopronin is the preferred thiol medication of choice based on its efficacy and reduced side effect profile.  

It has been shown that a dedicated multi-disciplinary clinic for cystinuria patients reduces the surgical intervention rate by 50%, enhances patient education, increases the quality of life scores, and improves treatment compliance. [69]  Each healthcare team member should take every opportunity to support and reinforce the value of continuing medical prophylactic therapy, especially after urological procedures. [70]

Excellent clinical practice guidelines and management updates for treating cystinuria have recently been published in the US and Europe. [6] [19] [22]  These guidelines, as outlined earlier, provide a reasonable approach and framework for the evaluation and treatment of cystinuric patients with the goal of improving overall outcomes for this uncommon but frequently relapsing form of urolithiasis.  

All members of the interprofessional team treating cystinuria patients, including urologists, nurses, dietitians, and clinicians, should remind and educate patients that the optimal preservation of renal function with the best quality of life and the lowest stone recurrence rates are found in those with early and continuing prophylactic medical management of their cystinuria along with complete surgical stone removal whenever possible. [71]  [Level 5] Maintaining optimal preventive therapy with fluids and alkalinizing medications should be encouraged and reinforced with patients at every opportunity by all healthcare team members. 

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Disclosure: Stephen Leslie declares no relevant financial relationships with ineligible companies.

Disclosure: Hussain Sajjad declares no relevant financial relationships with ineligible companies.

Disclosure: Lama Nazzal declares no relevant financial relationships with ineligible companies.

This book is distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) ( http://creativecommons.org/licenses/by-nc-nd/4.0/ ), which permits others to distribute the work, provided that the article is not altered or used commercially. You are not required to obtain permission to distribute this article, provided that you credit the author and journal.

• Cite this Page Leslie SW, Sajjad H, Nazzal L. Cystinuria. [Updated 2023 May 30]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-.

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