The microscopic examination of tissue (histology) gives the definitive diagnosis. The diagnostic histopathologic finding is intravascular cholesterol crystals, which are seen as cholesterol clefts in routinely processed tissue (embedded in paraffin wax). The cholesterol crystals may be associated with macrophages, including giant cells, and eosinophils.

The sensitivity of small core biopsies is modest, due to sampling error, as the process is often patchy. Affected organs show the characteristic histologic changes in 50-75% of the clinically diagnosed cases. Non-specific tissue findings suggestive of a cholesterol embolization include ischemic changes, necrosis and unstable-appearing complex atherosclerotic plaques (that are cholesterol-laden and have a thin fibrous cap). While biopsy findings may not be diagnostic, they have significant value, as they help exclude alternate diagnoses, e.g. vasculitis, that often cannot be made confidently based on clinical criteria.

Tests for inflammation (C-reactive protein and the erythrocyte sedimentation rate) are typically elevated, and abnormal liver enzymes may be seen. If the kidneys are involved, tests of renal function (such as urea and creatinine) are elevated. The complete blood count may show particularly high numbers of a type of white blood cell known as "eosinophils" (more than 0.5 billion per liter); this occurs in only 60-80% of cases, so normal eosinophil counts do not rule out the diagnosis. Examination of the urine may show red blood cells (occasionally in casts as seen under the microscope) and increased levels of protein; in a third of the cases with kidney involvement, eosinophils can also be detected in the urine. If vasculitis is suspected, complement levels may be determined as reduced levels are often encountered in vasculitis; complement is a group of proteins that forms part of the innate immune system. Complement levels are frequently reduced in cholesterol embolism, limiting the use of this test in the distinction between vasculitis and cholesterol embolism.

It is critical to diagnose CRS at an early stage in order to achieve optimal therapeutic efficacy. However, unlike markers of heart damage or stress such as troponin, creatine kinase, natriuretic peptides, reliable markers for acute kidney injury are lacking. Recently, research has found several biomarkers that can be used for early detection of acute kidney injury before serious loss of organ function may occur. Several of these biomarkers include neutrophil gelatinase-associated lipocalin (NGAL), N-acetyl-B-D-glucosaminidase (NAG), Cystatin C, and kidney injury molecule-1 (KIM-1) which have been shown to be involved in tubular damage. Other biomarkers that have been shown to be useful include BNP, IL-18, and fatty acid binding protein (FABP). However, there is great variability in the measurement of these biomarkers and their use in diagnosing CRS must be assessed.

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.

The diagnosis of renal artery stenosis can use many techniques to determine if the condition is present, a clinical prediction rule is available to guide diagnosis.

Among the diagnostic techniques are:

- Doppler ultrasound study of the kidneys

- refractory hypertension

- auscultation (with stethoscope) - bruit ("rushing" sound)

- captopril challenge test

- captopril test dose effect on the differential renal function as measured by MAG3 scan.

- renal artery arteriogram.

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.

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.

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.)

Kidney failure is very common in patients suffering from congestive heart failure. It was shown that kidney failure complicates one-third of all admissions for heart failure, which is the leading cause of hospitalization in the United States among adults over 65 years old. These complications led to longer hospital stay, higher mortality, and greater chance for readmission. Another study found that 39% of patients in NYHA class 4 and 31% of patients in NYHA class 3 had severely impaired kidney function. Similarly, kidney failure can have deleterious effects on cardiovascular function. It was estimated that about 44% of deaths in patients with end-stage kidney failure (ESKF) are due to cardiovascular disease.

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

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.

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.

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

Angioplasty with or without stenting is the best option for the treatment of renal artery stenosis due to fibromuscular dysplasia.

Usually, the diagnosis of ADPKD is initially performed by renal imaging using ultrasound, CT scan, or MRI. However, molecular diagnostics can be necessary in the following situations: 1- when a definite diagnosis is required in young individuals, such as a potential living related donor in an affected family with equivocal imaging data; 2- in patients with a negative family history of ADPKD, because of potential phenotypic overlap with several other kidney cystic diseases; 3- in families affected by early-onset polycystic kidney disease, since in this cases hypomorphic alleles and/or oligogenic inheritance can be involved; and 4- in patients requesting genetic counseling, especially in couples wishing a pre-implantation genetic diagnosis.

The findings of large echogenic kidneys without distinct macroscopic cysts in an infant/child at 50% risk for ADPKD are diagnostic. In the absence of a family history of ADPKD, the presence of bilateral renal enlargement and cysts, with or without the presence of hepatic cysts, and the absence of other manifestations suggestive of a different renal cystic disease provide presumptive, but not definite, evidence for the diagnosis. In some cases, intracranial aneurysms can be an associated sign of ADPKD, and screening can be recommended for patients with a family history of intracranial aneurysm.

Molecular genetic testing by linkage analysis or direct mutation screening is clinically available; however, genetic heterogeneity is a significant complication to molecular genetic testing. Sometimes a relatively large number of affected family members need to be tested in order to establish which one of the two possible genes is responsible within each family. The large size and complexity of PKD1 and PKD2 genes, as well as marked allelic heterogeneity, present obstacles to molecular testing by direct DNA analysis. The sensitivity of testing is nearly 100% for all patients with ADPKD who are age 30 years or older and for younger patients with PKD1 mutations; these criteria are only 67% sensitive for patients with PKD2 mutations who are younger than age 30 years.

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.

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.

The risk of death in hepatorenal syndrome is very high; consequently, there is a significant emphasis on the identification of patients who are at risk for HRS, and prevention of triggers for onset of HRS. As infection (specifically spontaneous bacterial peritonitis) and gastrointestinal hemorrhage are both complications in individuals with cirrhosis, and are common triggers for HRS, specific care is made in early identification and treatment of cirrhotics with these complications to prevent HRS. Some of the triggers for HRS are induced by treatment of ascites and can be preventable. The aggressive use of diuretic medications should be avoided. In addition, many medications that are either used to treat cirrhotic complications (such as some antibiotics) or other conditions may cause sufficient impairment in kidney function in the cirrhotic to lead to HRS. Also, large volume paracentesis—which is the removal of ascites fluid from the abdomen using a needle or catheter in order to relieve discomfort—may cause enough alteration in hemodynamics to precipitate HRS, and should be avoided in individuals at risk. The concomitant infusion of albumin can avert the circulatory dysfunction that occurs after large-volume paracentesis and may prevent HRS. Conversely, in individuals with very tense ascites, it has been hypothesized that removal of ascitic fluid may improve kidney function if it decreases the pressure on the renal veins.

Individuals with ascites that have become infected spontaneously (termed spontaneous bacterial peritonitis or SBP) are at an especially high risk for the development of HRS. In individuals with SBP, one randomized controlled trial found that the administration of intravenous albumin on the day of admission and on the third day in hospital reduced both the rate of kidney insufficiency and the mortality rate.

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.

Management of sickle nephropathy is not separate from that of overall patient management. In addition, however, the use of ACE inhibitors has been associated with improvement of the hyperfiltration glomerulopathy. Three-year graft and patient survival in kidney transplant recipients with sickle nephropathy is lower when compared to those with other causes of end-stage kidney disease.

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.

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.