Diagnosis is traditionally based on the clinical findings above in combination with excessive analgesic use. It is estimated that between 2 and 3 kg each of phenacetin or aspirin must be consumed before evidence of analgesic nephropathy becomes clinically apparent.

Once suspected, analgesic nephropathy can be confirmed with relative accuracy using computed tomography (CT) imaging without contrast. One trial demonstrated that the appearance of papillary calcifications on CT imaging was 92% sensitive and 100% specific for the diagnosis of analgesic nephropathy.

Complications of analgesic nephropathy include pyelonephritis and end-stage kidney disease. Risk factors for poor prognosis include recurrent urinary tract infection and persistently elevated blood pressure. Analgesic nephropathy also appears to increase the risk of developing cancers of the urinary system.

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.

Guidelines for referral to a nephrologist vary between countries. Though most would agree that nephrology referral is required by Stage 4 CKD (when eGFR/1.73m is less than 30 ml/min; or decreasing by more than 3 ml/min/year); and may be useful at an earlier stage (e.g. CKD3) when urine albumin-to-creatinine ratio is more than 30 mg/mmol, when blood pressure is difficult to control, or when hematuria or other findings suggest either a primarily glomerular disorder or secondary disease amenable to specific treatment. Other benefits of early nephrology referral include proper patient education regarding options for renal replacement therapy as well as pre-emptive transplantation, and timely workup and placement of an arteriovenous fistula in those patients opting for future hemodialysis

Screening those who have neither symptoms nor risk factors for CKD is not recommended. Those who should be screened include: those with hypertension or history of cardiovascular disease, those with diabetes or marked obesity, those aged > 60 years, subjects with indigenous racial origin, those with a history of kidney disease in the past and subjects who have relatives who had kidney disease requiring dialysis. Screening should include calculation of estimated GFR from the serum creatinine level, and measurement of urine albumin-to-creatinine ratio (ACR) in a first-morning urine specimen (this reflects the amount of a protein called albumin in the urine), as well as a urine dipstick screen for hematuria. The GFR (glomerular filtration rate) is derived from the serum creatinine and is proportional to 1/creatinine, i.e. it is a reciprocal relationship (the higher the creatinine, the lower the GFR). It reflects one aspect of kidney function: how efficiently the glomeruli (filtering units) work. But as they make up <5% of the mass of the kidney, the GFR does not indicate all aspects of kidney health and function. This can be done by combining the GFR level with the clinical assessment of the patient (especially fluid state) and measuring the levels of hemoglobin, potassium, phosphate and parathyroid hormone (PTH). Normal GFR is 90-120 mLs/min. The units of creatinine vary from country to country.

The definitive diagnosis of HN requires morphological examination. Common histological features can be identified in the renal and glomerular vasculature. Glomerulosclerosis is often present, either focally or globally, which is characterized by hardening of the vessel walls. Also, luminal narrowing or the arteries and arterioles of the kidney system. However, this type of procedure is likely to be preceded with a provisional diagnosis based on laboratory investigations.

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

The standard diagnostic workup of suspected kidney disease is history & examination, as well as a urine test strip. Also, renal ultrasonography is essential in the diagnosis and management of kidney-related diseases.

Patients at risk for acute uric acid nephropathy can be given allopurinol or rasburicase (a recombinant urate oxidase) prior to treatment with cytotoxic drugs.

For an adult patient with isolated hematuria, tests such as ultrasound of the kidney and cystoscopy are usually done first to pinpoint the source of the bleeding. These tests would rule out kidney stones and bladder cancer, two other common urological causes of hematuria. In children and younger adults, the history and association with respiratory infection can raise the suspicion of IgA nephropathy. A kidney biopsy is necessary to confirm the diagnosis. The biopsy specimen shows proliferation of the mesangium, with IgA deposits on immunofluorescence and electron microscopy. However, patients with isolated microscopic hematuria (i.e. without associated proteinuria and with normal kidney function) are not usually biopsied since this is associated with an excellent prognosis. A urinalysis will show red blood cells, usually as red cell urinary casts. Proteinuria, usually less than 2 grams per day, also may be present. Other renal causes of isolated hematuria include thin basement membrane disease and Alport syndrome, the latter being a hereditary disease associated with hearing impairment and eye problems.

Other blood tests done to aid in the diagnosis include CRP or ESR, complement levels, ANA, and LDH. Protein electrophoresis and immunoglobulin levels can show increased IgA in 50% of all patients.

The sensitivity of an abnormal gallium scan has been reported to range from 60% to 100%.

The osmolality of the contrast agent was previously believed to be an important factor in contrast-induced nephropathy. Today it has become increasingly clear that other physicochemical properties play a greater role, such as viscosity. Attention should be paid to using contrast agents of low viscosity. Moreover, sufficient fluids should be supplied to limit fluid viscosity of urine. Modern iodinated contrast agents are non-ionic, the older ionic types caused more adverse effects, and their use has diminished.

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.

Evidence supports the use of N-acetylcysteine with intravenous saline among those getting low molecular weight contrast. The use of statins with N-acetylcysteine and intravenous saline is also supported.

The diagnosis can be confirmed on a blood sample using a genetic test.

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.

It is diagnosed by micturating cystography; scarring can be demonstrated by ultrasound or DMSA.

Urinary findings include:

- Eosinophiluria: Original studies with Methicillin-induced AIN showed sensitivity of 67% and specificity of 83%. The sensitivity is higher in patients with interstitial nephritis induced by methicillin or when the Hansel's stain is used. However, a 2013 study showed that the sensitivity and specificity of urine eosinophil testing are 35.6% and 68% respectively.

- Isosthenuria

- Blood in the urine and occasional RBC casts

- Sterile pyuria: white blood cells and no bacteria

- Nephrotic-range amount of protein in the urine may be seen with NSAID-associated AIN

Nephrotoxicity is usually monitored through a simple blood test. A decreased creatinine clearance indicates poor renal function. Normal creatinine level is between 80 - 120 μmol/L. In interventional radiology, a patient's creatinine clearance levels are all checked prior to a procedure.

Serum creatinine is another measure of renal function, which may be more useful clinically when dealing with patients with early kidney disease.

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.

Over time, kidney failure can develop and most men with the disease will eventually require dialysis or kidney transplantation. For reasons which are not understood, women with the disease, although they often have blood in their urine, only rarely develop kidney failure. The disease has been shown to recur following kidney transplantation, however in most cases the kidney transplant has a normal lifespan.

Treatment is focused on preventing deposition of uric acid within the urinary system by increasing urine volume with potent diuretics such as furosemide. Raising the urinary pH to a level higher than 7 (alkalinization) is often difficult to attain, although sodium bicarbonate and/or acetazolamide are sometimes used in an attempt to increase uric acid solubility.

Dialysis (preferably hemodialysis) is started if the above measures fail.

Individuals with renal papillary necrosis due to excess use of analgesic have an elevated risk of epithelial tumors, hence a urine cytology exam is useful. In terms of imaging this condition can be identified by retrograde pyelography (RGP). The diagnosis of renal papillary necrosis is therefore done via:

Male gender, proteinuria (especially > 2 g/day), hypertension, smoking, hyperlipidemia, older age, familial disease and elevated creatinine concentrations are markers of a poor outcome. Frank hematuria has shown discordant results with most studies showing a better prognosis, perhaps related to the early diagnosis, except for one group which reported a poorer prognosis. Proteinuria and hypertension are the most powerful prognostic factors in this group.

There are certain other features on kidney biopsy such as interstitial scarring which are associated with a poor prognosis. ACE gene polymorphism has been recently shown to have an impact with the DD genotype associated more commonly with progression to kidney failure.

Some forms of glomerulonephritis are diagnosed clinically, based on findings on history and examination. Other tests may include:

- Urine examination

- Blood tests investigating the cause, including FBC, inflammatory markers and special tests including (ASLO, ANCA, Anti-GBM, Complement levels, Antinuclear antibodies

- Biopsy of the kidney

- Renal ultrasonography is useful for prognostic purposes in finding signs of chronic kidney disease, which however may be caused by many other diseases than glomerulonephritis.