Diagnosis is made by history and examination.

In immunocompromised patients, pus is present in the urine but often no organism can be cultured. In children, polymerase chain reaction sequencing of urine can detect fragments of the infectious agent.

The procedure differs somewhat for women and men. Laboratory testing of urine samples now can be performed with dipsticks that indicate immune system responses to infection, as well as with microscopic analysis of samples. Normal human urine is sterile. The presence of bacteria or pus in the urine usually indicates infection. The presence of hematuria, or blood in the urine, may indicate acute UTIs, kidney disease, kidney stones, inflammation of the prostate (in men), endometriosis (in women), or cancer of the urinary tract. In some cases, blood in the urine results from athletic training, particularly in runners.

In people with microscopic hematuria, it is important to rule out any possible confounders such as menstruation in women, possible presence of semen in sample or recent rigorous exercise. In menstruating women, tests should be repeated during non-bleeding parts of their cycles. In individuals with history of recent rigorous exercise, urinalysis should be repeated 4–6 weeks following cessation of exercise. All women of child-bearing age should undergo a pregnancy test, and if positive should receive an ultrasound of their kidneys and bladder with further invasive diagnostic work-up deferred until completion of pregnancy.

If diagnostic work-up has been unyielding so far or the aforementioned risk factors are present, it is important to begin a thorough work-up for possible malignancy especially of the bladder and kidney by referring to a Urologist to look at the urethra and bladder with a cystoscopy and also performing additional imaging using CT urography, which provides a thorough view of the complete urinary system.

For individuals with persistent hematuria with no immediate identifiable cause, urinalysis should be repeated once a year, and if it is negative for 2 years then you can stop repeating the tests. However, if it is positive for 3 years, repeat anatomic evaluation should be done.

For people with visible hematuria and evidence of blood clots, further imaging with an abdominal CT scan should be done and an urgent referral to a urologist made. Otherwise, the next step involves determining if source of bleeding is glomerular in nature as evidenced by presence of inappropriately shaped/dysmorphic red blood cells, presence of protein in the urine, new or worsening hypertension or swelling. If source is glomerular patients should be referred to a nephrologist for further evaluation. Non-glomerular source of bleeding will usually require further work-up by a urologist.

Testing for bacteriuria is often performed in those with symptoms of a urinary tract infection. Testing is often done in other scenarios as in failure to thrive of a newborn or confusion in the elderly. Screening for bacteriuria is recommended in pregnancy as there is evidence that asymptomatic bacteriuria can lead to low birth weight and preterm delivery.

- Bacteriuria can be detected by urine dipstick test. The urinary nitrite test will be able to detect any nitrate-reducing bacteria in the urine. The leukocyte esterase test detects the presence of leukocytes (white blood cells) in the urine which can be associated with a urinary tract infection.The urine dipstick test is readily available and provides fast results.

- Microscopy can also be used to detect bacteriuria. It is more specific, especially when used with gram staining, but requires more time and equipment.

- The gold standard for detecting bacteriuria is a bacterial culture which identifies the actual organism. This test is more specific but can take several days to obtain a result. As a result, clinicians will often treat a bacteriuria based on the results of the urine dipstick test while waiting for the culture results. The culture will often provide antibiotic sensitivity.

Bacteriuria can be confirmed if a single bacterial species is isolated in a concentration greater than 100,000 colony forming units per millilitre of urine in clean-catch midstream urine specimens (one for men, two consecutive specimens with the same bacterium for women). For urine collected via bladder catheterization in men and women, a single urine specimen with greater than 100,000 colony forming units of a single species per millilitre is considered diagnostic. The threshold is also 100 colony forming units of a single species per millilitre for women displaying UTI symptoms.

Unfortunately mesna is ineffective as a treatment once hemorrhagic cystitis has developed. Although rare, once a case of radiation-induced hemorrhagic cystitis is diagnosed there is no empirically-proven treatments to heal this type of condition, which can severely degrade a patient's quality of life and might possibly lead to renal failure with risk of death.

Viral hemorrhagic cystitis in children generally spontaneously resolves within a few days.

The first step in the treatment of HC should be directed toward clot evacuation. Bladder outlet obstruction from clots can lead to urosepsis, bladder rupture, and renal failure. Clot evacuation can be performed by placing a wide-lumen bladder catheter at bedside. The bladder can be irrigated with water or sodium chloride solution. The use of water is preferable because water can help with clot lysis. Care must be taken to not overdistend the bladder and cause a perforation.. Hyperbaric oxygen (HBO2) therapy has been proven to be effective in treating radiation-induced hemorrhagic cystitis.

The decision to treat bacteriuria depends on the presence of accompany symptoms and comorbidities.

If left untreated, complications may arise including abscess formation, peritonitis, sepsis, and damage to the urinary tract by fibrosis and granuloma formation. It is recommended, as a first step, to drain the lesion with ultrasound or CT guidance. If a patient has an underlying obstructive problem it needs to be addressed according to its cause.

Biochemical blood tests determine the amount of typical markers of renal function in the blood serum, for instance serum urea and serum creatinine. Biochemistry can also be used to determine serum electrolytes. Special biochemical tests (arterial blood gas) can determine the amount of dissolved gases in the blood, indicating if pH imbalances are acute or chronic.

Urinalysis is a test that studies urine for abnormal substances such as protein or signs of infection.

- A Full Ward Test, also known as dipstick urinalysis, involves the dipping of a biochemically active test strip into the urine specimen to determine levels of tell-tale chemicals in the urine.

- Urinalysis can also involve MC&S microscopy, culture and sensitivity

Urodynamic tests evaluate the storage of urine in the bladder and the flow of urine from the bladder through the urethra. It may be performed in cases of incontinence or neurological problems affecting the urinary tract.

Ultrasound is commonly performed to investigate problems of the kidney and/or urinary tract.

Radiology:

- KUB is plain radiography of the urinary system, e.g. to identify kidney stones.

- An intravenous pyelogram studies the shape of the urinary system.

- CAT scans and MRI can also be useful in localising urinary tract pathology.

- A voiding cystogram is a functional study where contrast "dye" is injected through a catheter into the bladder. Under x-ray the radiologist asks the patient to void (usually young children) and will watch the contrast exiting the body on the x-ray monitor. This examines the child's bladder and lower urinary tract. Typically looking for vesicoureteral reflux, involving urine backflow up into the kidneys.

Treatment is dependent on the underlying cause of this symptom. The most easily treatable cause is obstruction of urine flow, which is often solved by insertion of a urinary catheter into the urinary bladder.

Mannitol is a medicine that is used to increase the amount of water removed from the blood and thus improve the blood flow to the kidneys. However, mannitol is contraindicated in anuria secondary to renal disease, severe dehydration, intracranial bleeding (except during craniotomy), severe pulmonary congestion, or pulmonary edema.

Dextrose and Dobutamine are both used to increase blood flow to the kidney and act within 30 to 60 minutes.

In people with a history of stones, those who are less than 50 years of age and are presenting with the symptoms of stones without any concerning signs do not require helical CT scan imaging. A CT scan is also not typically recommended in children.

Otherwise a noncontrast helical CT scan with sections is the diagnostic modality of choice in the radiographic evaluation of suspected nephrolithiasis. All stones are detectable on CT scans except very rare stones composed of certain drug residues in the urine, such as from indinavir. Calcium-containing stones are relatively radiodense, and they can often be detected by a traditional radiograph of the abdomen that includes the kidneys, ureters, and bladder (KUB film). Some 60% of all renal stones are radiopaque. In general, calcium phosphate stones have the greatest density, followed by calcium oxalate and magnesium ammonium phosphate stones. Cystine calculi are only faintly radiodense, while uric acid stones are usually entirely radiolucent.

Where a CT scan is unavailable, an intravenous pyelogram may be performed to help confirm the diagnosis of urolithiasis. This involves intravenous injection of a contrast agent followed by a KUB film. Uroliths present in the kidneys, ureters or bladder may be better defined by the use of this contrast agent. Stones can also be detected by a retrograde pyelogram, where a similar contrast agent is injected directly into the distal ostium of the ureter (where the ureter terminates as it enters the bladder).

Renal ultrasonography can sometimes be useful, as it gives details about the presence of hydronephrosis, suggesting the stone is blocking the outflow of urine. Radiolucent stones, which do not appear on KUB, may show up on ultrasound imaging studies. Other advantages of renal ultrasonography include its low cost and absence of radiation exposure. Ultrasound imaging is useful for detecting stones in situations where X-rays or CT scans are discouraged, such as in children or pregnant women. Despite these advantages, renal ultrasonography in 2009 was not considered a substitute for noncontrast helical CT scan in the initial diagnostic evaluation of urolithiasis. The main reason for this is that compared with CT, renal ultrasonography more often fails to detect small stones (especially ureteral stones), as well as other serious disorders that could be causing the symptoms. A 2014 study confirmed that ultrasonography rather than CT as an initial diagnostic test results in less radiation exposure and did not find any significant complications.

It is possible to analyze urine samples in determining albumin, hemoglobin and myoglobin with an optimized MEKC method.

Laboratory investigations typically carried out include:

- microscopic examination of the urine, which may show red blood cells, bacteria, leukocytes, urinary casts and crystals;

- urine culture to identify any infecting organisms present in the urinary tract and sensitivity to determine the susceptibility of these organisms to specific antibiotics;

- complete blood count, looking for neutrophilia (increased neutrophil granulocyte count) suggestive of bacterial infection, as seen in the setting of struvite stones;

- renal function tests to look for abnormally high blood calcium blood levels (hypercalcemia);

- 24 hour urine collection to measure total daily urinary volume, magnesium, sodium, uric acid, calcium, citrate, oxalate and phosphate;

- collection of stones (by urinating through a StoneScreen kidney stone collection cup or a simple tea strainer) is useful. Chemical analysis of collected stones can establish their composition, which in turn can help to guide future preventive and therapeutic management.

Diagnosis is made by patient history of passing air or a sputtering urine stream. CT scans may show air in the urinary bladder or bladder walls.

Extravasation of urine due to blunt renal trauma or ureteral obstruction can lead to the formation of an urinoma.

Extravasation of urine refers to the condition where an interruption of the urethra leads to a collection of urine in other cavities, such as the scrotum or the penis in males. It can be associated with a calculus.

The amount of protein being lost in the urine can be quantified by collecting the urine for 24 hours, measuring a sample of the pooled urine, and extrapolating to the volume collected.

Also a urine dipstick test for proteinuria can give a rough estimate of albuminuria. This is because albumin is by far the dominant plasma protein, and bromophenol blue the agent used in the dipstick is specific to albumin.

To make the diagnosis of a urinary tract infection in children, a positive urinary culture is required. Contamination poses a frequent challenge depending on the method of collection used, thus a cutoff of 10 CFU/mL is used for a "clean-catch" mid stream sample, 10 CFU/mL is used for catheter-obtained specimens, and 10 CFU/mL is used for suprapubic aspirations (a sample drawn directly from the bladder with a needle). The use of "urine bags" to collect samples is discouraged by the World Health Organization due to the high rate of contamination when cultured, and catheterization is preferred in those not toilet trained. Some, such as the American Academy of Pediatrics recommends renal ultrasound and voiding cystourethrogram (watching a person's urethra and urinary bladder with real time x-rays while they urinate) in all children less than two years old who have had a urinary tract infection. However, because there is a lack of effective treatment if problems are found, others such as the National Institute for Health and Care Excellence only recommends routine imaging in those less than six months old or who have unusual findings.

In straightforward cases, a diagnosis may be made and treatment given based on symptoms alone without further laboratory confirmation. In complicated or questionable cases, it may be useful to confirm the diagnosis via urinalysis, looking for the presence of urinary nitrites, white blood cells (leukocytes), or leukocyte esterase. Another test, urine microscopy, looks for the presence of red blood cells, white blood cells, or bacteria. Urine culture is deemed positive if it shows a bacterial colony count of greater than or equal to 10 colony-forming units per mL of a typical urinary tract organism. Antibiotic sensitivity can also be tested with these cultures, making them useful in the selection of antibiotic treatment. However, women with negative cultures may still improve with antibiotic treatment. As symptoms can be vague and without reliable tests for urinary tract infections, diagnosis can be difficult in the elderly.

A urinoma is the result of a breach of the integrity of the pelvis or calices of the kidney or of the ureter. The urine collection in the perirenal fat causes an inflammatory response with lipolysis resulting in its fibrous encapsulation. Urinomas are usually caused by blunt trauma to the kidneys. While extravasation of urine is common as a result a severe blunt trauma (2-18%), spontaneous resolution is typical, and urinoma formation develops only in few instances. Less common causes of urinoma development are ureteral obstructions due to cancer, calculus formation, pregnancy, or congenital causes.

Urinomas tend to develop gradually. Symptoms depend on size and location of the lesion. Eventually local pain and pressure symptoms may become apparent. Biochemical testing of renal function is indicated. Imaging (IVP, ultrasonography, CT scan) will identify the lesion. Image-guided percutaneous needle aspiration is both diagnostic and therapeutic.

Conventionally, proteinuria is diagnosed by a simple dipstick test, although it is possible for the test to give a false negative reading, even with nephrotic range proteinuria if the urine is dilute. False negatives may also occur if the protein in the urine is composed mainly of globulins or Bence Jones proteins because the reagent on the test strips, bromophenol blue, is highly specific for albumin. Traditionally, dipstick protein tests would be quantified by measuring the total quantity of protein in a 24-hour urine collection test, and abnormal globulins by specific requests for protein electrophoresis. Trace results may be produced in response to excretion of Tamm–Horsfall mucoprotein.

More recently developed technology detects human serum albumin (HSA) through the use of liquid crystals (LCs). The presence of HSA molecules disrupts the LCs supported on the AHSA-decorated slides thereby producing bright optical signals which are easily distinguishable. Using this assay, concentrations of HSA as low as 15 µg/mL can be detected.

Alternatively, the concentration of protein in the urine may be compared to the creatinine level in a spot urine sample. This is termed the protein/creatinine ratio. The 2005 UK Chronic Kidney Disease guidelines states protein/creatinine ratio is a better test than 24-hour urinary protein measurement. Proteinuria is defined as a protein/creatinine ratio greater than 45 mg/mmol (which is equivalent to albumin/creatinine ratio of greater than 30 mg/mmol or approximately 300 mg/g) with very high levels of proteinuria having a ratio greater than 100 mg/mmol.

Protein dipstick measurements should not be confused with the amount of protein detected on a test for microalbuminuria which denotes values for protein for urine in mg/day versus urine protein dipstick values which denote values for protein in mg/dL. That is, there is a basal level of proteinuria that can occur below 30 mg/day which is considered non-pathology. Values between 30–300 mg/day are termed microalbuminuria which is considered pathologic. Urine protein lab values for microalbumin of >30 mg/day correspond to a detection level within the "trace" to "1+" range of a urine dipstick protein assay. Therefore, positive indication of any protein detected on a urine dipstick assay obviates any need to perform a urine microalbumin test as the upper limit for microalbuminuria has already been exceeded.

The deterioration of kidney function may be signaled by a measurable decrease in urine output. Often, it is diagnosed on the basis of blood tests for substances normally eliminated by the kidney: urea and creatinine. Additionally, the ratio of BUN to creatinine is used to evaluate kidney injury. Both tests have their disadvantages. For instance, it takes about 24 hours for the creatinine level to rise, even if both kidneys have ceased to function. A number of alternative markers has been proposed (such as NGAL, KIM-1, IL18 and cystatin C), but none of them is currently established enough to replace creatinine as a marker of kidney function.

Once the diagnosis of AKI is made, further testing is often required to determine the underlying cause. It is useful to perform a bladder scan or a post void residual to rule out urinary retention. In post void residual, a catheter is inserted into the urinary tract immediately after urinating to measure fluid still in the bladder. 50–100 ml suggests neurogenic bladder dysfunction.

These may include urine sediment analysis, renal ultrasound and/or kidney biopsy. Indications for kidney biopsy in the setting of AKI include the following:

1. Unexplained AKI, in a patient with two non-obstructed normal sized kidneys

2. AKI in the presence of the nephritic syndrome

3. Systemic disease associated with AKI

4. Kidney transplant dysfunction

In medical imaging, the acute changes in the kidney are often examined with renal ultrasonography as the first-line modality, where CT scan and magnetic resonance imaging (MRI) are used for the follow-up examinations and when US fails to demonstrate abnormalities. In evaluation of the acute changes in the kidney, the echogenicity of the renal structures, the delineation of the kidney, the renal vascularity, kidney size and focal abnormalities are observed. CT is preferred in renal traumas, but US is used for follow-up, especially in the patients suspected for the formation of urinomas. A CT scan of the abdomen will also demonstrate bladder distension or hydronephrosis. However, in AKI, the use of IV contrast is contraindicated as the contrast agent used is nephrotoxic.

Pyuria is the condition of urine containing white blood cells or pus. Defined as the presence of 6-10 or more neutrophils per high power field of unspun, voided mid-stream urine. It can be a sign of a bacterial urinary tract infection. Pyuria may be present in the people with sepsis, or in an older people with pneumonia.

Sterile pyuria, is urine which contains white blood cells while appearing sterile by standard culturing techniques. It is often caused by sexually transmitted infections, such as gonorrhea, or viruses which will not grow in bacterial cultures. Sterile pyuria is listed as a side effect from some medications such as paracetamol (acetaminophen). Its occurrence is also associated with certain disease processes, such as Kawasaki disease and genitourinary tuberculosis. However, there are many known causes, including systemic or infectious disease, structural and physiological reasons, intrinsic kidney pathology, or drugs.

The level of albumin protein produced by microalbuminuria can be detected by special albumin-specific urine dipsticks, which have a lower detection threshold than standard urine dipsticks. A microalbumin urine test determines the presence of the albumin in urine. In a properly functioning body, albumin is not normally present in urine because it is retained in the bloodstream by the kidneys.

Microalbuminuria can be diagnosed from a 24-hour urine collection (between 30–300 mg/24 hours) or, more commonly, from elevated concentration in a spot sample (20 to 200 mg/L). Both must be measured on at least two of three measurements over a two- to three-month period.

An albumin level above the upper limit values is called "macroalbuminuria", or sometimes just albuminuria. Sometimes, the upper limit value is given as one less (such as 300 being given as 299) to mark that the higher value (here 300) is defined as macroalbuminuria.

To compensate for variations in urine concentration in spot-check samples, it is helpful to compare the amount of albumin in the sample against its concentration of creatinine. This is termed the albumin/creatinine ratio (ACR) and microalbuminuria is defined as ACR ≥3.5 mg/mmol (female) or ≥2.5 mg/mmol (male), or, with both substances measured by mass, as an ACR between 30 and 300 µg albumin/mg creatinine.

For the diagnosis of microalbuminuria, care must be taken when collecting sample for the urine ACR. An early morning sample is preferred. The patient should refrain from heavy exercises 24 hours before the test. A repeat test should be done 3 to 6 months after the first positive test for microalbuminuria. Lastly, the test is inaccurate in a person with too much or too little muscle mass. This is due to the variation in creatinine level which is produced by the muscle.

Increasing access to, and use of, genome profiling may provide opportunity for diagnosis based on presentation and genetic risk factors, by identifying ApoL1 gene variants on chromosome 22.

Along with obtaining a complete medical history, a series of biochemical tests are required in order to arrive at an accurate diagnosis that verifies the presence of the illness. In addition, imaging of the kidneys (for structure and presence of two kidneys) is sometimes carried out, and/or a biopsy of the kidneys. The first test will be a urinalysis to test for high levels of proteins, as a healthy subject excretes an insignificant amount of protein in their urine. The test will involve a 24-hour bedside urinary total protein estimation. The urine sample is tested for proteinuria (>3.5 g per 1.73 m per 24 hours). It is also examined for urinary casts, which are more a feature of active nephritis. Next a blood screen, comprehensive metabolic panel (CMP) will look for hypoalbuminemia: albumin levels of ≤2.5 g/dL (normal=3.5-5 g/dL). Then a Creatinine Clearance C test will evaluate renal function particularly the glomerular filtration capacity. Creatinine formation is a result of the breakdown of muscular tissue, it is transported in the blood and eliminated in urine. Measuring the concentration of organic compounds in both liquids evaluates the capacity of the glomeruli to filter blood. Electrolytes and urea levels may also be analysed at the same time as creatinine (EUC test) in order to evaluate renal function.

A lipid profile will also be carried out as high levels of cholesterol (hypercholesterolemia), specifically elevated LDL, usually with concomitantly elevated VLDL, is indicative of nephrotic syndrome.

A kidney biopsy may also be used as a more specific and invasive test method. A study of a sample’s anatomical pathology may then allow the identification of the type of glomerulonephritis involved. However, this procedure is usually reserved for adults as the majority of children suffer from minimum change disease that has a remission rate of 95% with corticosteroids. A biopsy is usually only indicated for children that are "corticosteroid resistant" as the majority suffer from focal and segmental glomeruloesclerosis.

Further investigations are indicated if the cause is not clear including analysis of auto-immune markers (ANA, ASOT, C3, cryoglobulins, serum electrophoresis), or ultrasound of the whole abdomen.