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.

The "RIFLE criteria", proposed by the Acute Dialysis Quality Initiative (ADQI) group, aid in assessment of the severity of a person's acute kidney injury. The acronym RIFLE is used to define the spectrum of progressive kidney injury seen in AKI:

- Risk: 1.5-fold increase in the serum creatinine, or glomerular filtration rate (GFR) decrease by 25 percent, or urine output <0.5 mL/kg per hour for six hours.

- Injury: Two-fold increase in the serum creatinine, or GFR decrease by 50 percent, or urine output <0.5 mL/kg per hour for 12 hours

- Failure: Three-fold increase in the serum creatinine, or GFR decrease by 75 percent, or urine output of <0.3 mL/kg per hour for 24 hours, or no urine output (anuria) for 12 hours

- Loss: Complete loss of kidney function (e.g., need for renal replacement therapy) for more than four weeks

- End-stage kidney disease: Complete loss of kidney function (e.g., need for renal replacement therapy) for more than three months

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

Chronic kidney failure is measured in five stages, which are calculated using a patient’s GFR, or glomerular filtration rate. Stage 1 CKD is mildly diminished renal function, with few overt symptoms. Stages 2 and 3 need increasing levels of supportive care from their medical providers to slow and treat their renal dysfunction. Patients in stages 4 and 5 usually require preparation of the patient towards active treatment in order to survive. Stage 5 CKD is considered a severe illness and requires some form of renal replacement therapy (dialysis) or kidney transplant whenever feasible.

- Glomerular filtration rate

A normal GFR varies according to many factors, including sex, age, body size and ethnic background. Renal professionals consider the glomerular filtration rate (GFR) to be the best overall index of kidney function. The National Kidney Foundation offers an easy to use on-line GFR calculator for anyone who is interested in knowing their glomerular filtration rate. (A serum creatinine level, a simple blood test, is needed to use the calculator.)

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.

Before the advancement of modern medicine, renal failure was often referred to as uremic poisoning. Uremia was the term for the contamination of the blood with urine. It is the presence of an excessive amount of urea in blood. Starting around 1847, this included reduced urine output, which was thought to be caused by the urine mixing with the blood instead of being voided through the urethra. The term "uremia" is now used for the illness accompanying kidney failure.

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.

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.

Nephrocalcinosis is diagnosed for the most part by imaging techniques. The imagings used are ultrasound (US), abdominal plain film and CT imaging. Of the 3 techniques CT and US are the more preferred. Nephrocalcinosis is considered present if at least two radiologists make the diagnosis on US and/or CT. In some cases a renal biopsy is done instead if imaging is not enough to confirm nephrocalcinosis. Once the diagnosis is confirmed additional testing is needed to find the underlying cause because the underlying condition may require treatment for reasons independent of nephrocalcinosis. These additional tests will measure serum, electrolytes, calcium, and phosphate, and the urine pH. If no underlying cause can be found then urine collection should be done for 24 hours and measurements of the excretion of calcium, phosphate, oxalate, citrate, and creatinine are looked at.

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

Patients will require dialysis to compensate for the function of their kidneys.

Nephrotic syndrome can affect any age, although it is mainly found in adults with a ratio of adults to children of 26 to 1.

The syndrome presents in different ways in the two groups: the most frequent glomerulopathy in children is minimal change disease (66% of cases), followed by focal segmental glomerulosclerosis (8%) and mesangiocapillary glomerulonephritis (6%). In adults the most common disease is mesangiocapillary glomerulonephritis (30-40%), followed by focal and segmental glomeruloesclerosis (15-25%) and minimal change disease (20%). The latter usually presents as secondary and not primary as occurs in children. Its main cause is diabetic nephropathy. It usually presents in a patient’s 40s or 50s.

Of the glomerulonephritis cases approximately 60% to 80% are primary, while the remainder are secondary.

There are also differences in epidemiology between the sexes, the disease is more common in men than in women by a ratio of 2 to 1.

The epidemiological data also reveals information regarding the most common way that symptoms develop in patients with nephrotic syndrome: spontaneous remission occurs in up to 20% or 30% of cases during the first year of the illness. However, this improvement is not definitive as some 50% to 60% of patients die and / or develop chronic renal failure 6 to 14 years after this remission. On the other hand, between 10% and 20% of patients have continuous episodes of remissions and relapses without dying or jeopardizing their kidney. The main causes of death are cardiovascular, as a result of the chronicity of the syndrome, and thromboembolic accidents.

While the only diagnostic "gold standard" mechanism of diagnosis en vivo is via kidney biopsy, the clinical conditions and blood clotting disorder often associated with this disease may make it impractical in a clinical setting. Alternatively, it is diagnosed clinically, or at autopsy, with some authors suggesting diagnosis by contrast enhanced CT.

A 24-hour urine collection for determination of creatinine clearance may be an alternative, although not a very accurate test due to the collection procedure. Another laboratory test that should be considered is urinalysis with microscopic examination for the presence of protein, casts, blood and pH.

A detailed and accurate history and physical will help determine if uremia is acute or chronic. In the cases of acute uremia, causes may be identified and eliminated, leading to higher chance for recovery of normal renal function, if treated correctly.

Prompt treatment of some causes of azotemia can result in restoration of kidney function; delayed treatment may result in permanent loss of renal function. Treatment may include hemodialysis or peritoneal dialysis, medications to increase cardiac output and increase blood pressure, and the treatment of the condition that caused the azotemia.

Millions of people across the world suffer from kidney disease. Of those millions, several thousand will eventually or do need kidney transplants. Out of those millions in the world, 16,500 in the United States needed a kidney transplant in 2008. Of those 16,500 people, 5,000 died while waiting for a transplant. Currently, there is a shortage of donors, and in 2007 there were only 64,606 kidney transplants in the world. This shortage of donors is causing countries to place monetary value on kidneys. Countries such as Iran and Singapore are eliminating their lists by paying their citizens to donate. Also, the black market accounts for 5-10 percent of transplants that occur worldwide. The act of buying an organ through the black market is illegal in the United States. To be put on the waiting list for a kidney transplant, patients must first be referred by a physician, then they must choose and contact a donor hospital. Once they choose a donor hospital, patients must then receive an evaluation to make sure they are sustainable to receive a transplant. In order to be a match for a kidney transplant, patients must match blood type and human leukocyte antigen factors with their donors. They must also have no reactions to the antibodies from the donor’s kidneys.

Increasing fluid intake to yield a urine output of greater than 2 liters a day can be advantageous for all patients with nephrocalcinosis. Patients with hypercalciuria can reduce calcium excretion by restricting animal protein, limiting sodium intake to less than 100 meq a day and being lax of potassium intake. If changing ones diet alone does not result in an suitable reduction of hypercalciuria, a thiazide diuretic can be administered in patients who do not have hypercalcemia. Citrate can increase the solubility of calcium in urine and limit the development of nephrocalcinosis. Citrate is not given to patients who have urine pH equal to or greater than 7.

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.

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

As the majority of individuals with hepatorenal syndrome have cirrhosis, much of the epidemiological data on HRS comes from the cirrhotic population. The condition is quite common: approximately 10% of individuals admitted to hospital with ascites have HRS. A retrospective case series of cirrhotic patients treated with terlipressin suggested that 20.0% of acute kidney failure in cirrhotics was due to type 1 HRS, and 6.6% was due to type 2 HRS. It is estimated that 18% of individuals with cirrhosis and ascites will develop HRS within one year of their diagnosis with cirrhosis, and 39% of these individuals will develop HRS within five years of diagnosis. Three independent risk factors for the development of HRS in cirrhotics have been identified: liver size, plasma renin activity, and serum sodium concentration.

The prognosis of these patients is grim with untreated patients having an extremely short survival. The severity of liver disease (as evidenced by the MELD score) has been shown to be a determinant of outcome. Some patients without cirrhosis develop HRS, with an incidence of about 20% seen in one study of ill patients with alcoholic hepatitis.

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.

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.

If an underlying muscle disease is suspected, for instance if there is no obvious explanation or there have been multiple episodes, it may be necessary to perform further investigations. During an attack, low levels of carnitine in the blood and high levels of acylcarnitine in blood and urine may indicate a lipid metabolism defect, but these abnormalities revert to normal during convalescence. Other tests may be used at that stage to demonstrate these disorders. Disorders of glycolysis can be detected by various means, including the measurement of lactate after exercise; a failure of the lactate to rise may be indicative of a disorder in glycolysis, while an exaggerated response is typical of mitochondrial diseases. Electromyography (EMG) may show particular patterns in specific muscle diseases; for instance, McArdle's disease and phosphofructokinase deficiency show a phenomenon called "cramp-like contracture". There are genetic tests available for many of the hereditary muscle conditions that predispose to myoglobinuria and rhabdomyolysis.

Muscle biopsy can be useful if an episode of rhabdomyolysis is thought to be the result of an underlying muscle disorder. A biopsy sample taken during an episode is often uninformative, as it will show only evidence of cell death or may appear normal. Taking the sample is therefore delayed for several weeks or months. The histopathological appearance on the biopsy indicates the nature of the underlying disorder. For instance, mitochondrial diseases are characterized by "ragged red fibers". Biopsy sites may be identified by medical imaging, such as magnetic resonance imaging, as the muscles may not be uniformly affected.