Evaluation of acute kidney injury among hospitalized adult patients

INTRODUCTION — 

Patients with kidney disease have a variety of different clinical presentations. Some have symptoms or signs that are directly related to the kidney (such as gross hematuria) or to reduced kidney function (edema, hypertension, signs of uremia). Many patients are asymptomatic and are incidentally found to have an elevated serum creatinine concentration, abnormal urine studies (such as proteinuria or microscopic hematuria), or abnormal radiologic imaging of the kidneys.

Specific disorders generally cause acute, subacute, or chronic kidney injury. Acute kidney injury (AKI) develops over hours to days and is usually diagnosed in the emergency department, in hospitalized patients, or following a procedure. Occasionally, AKI is incidentally noted on outpatient laboratory evaluation as an abrupt rise in serum creatinine.

This topic reviews the evaluation of hospitalized patients with AKI. Patients who present to the emergency department with a creatinine above the recent baseline value may be acute or subacute. If recent baseline is not known, the kidney disease may be chronic in nature.

The evaluations of subacute kidney injury, newly identified chronic kidney disease (CKD), and AKI in pregnancy are discussed elsewhere:

●(See "Diagnostic approach to adult patients with subacute kidney injury in an outpatient setting".)

●(See "Chronic kidney disease (newly identified): Clinical presentation and diagnostic approach in adults".)

●(See "Acute kidney injury in pregnancy".)

DEFINITION — 

AKI is defined as a reduction in kidney function that has developed within hours to days and is commonly manifested by a rise in the serum creatinine concentration or a decline in urine output. Impaired kidney function results in the retention of uremic toxins and the dysregulation of extracellular volume and electrolytes.

Commonly accepted criteria for AKI include an increase in serum creatinine by ≥0.3 mg/dL (27 micromol/L) within 48 hours or an increase to ≥1.5 times the baseline value that is known or presumed to have occurred within the prior seven days, or a decrease in urine volume to <0.5 mL/kg/hour for more than six hours (Kidney Disease: Improving Global Outcomes [KDIGO]-AKI) (table 1) [1]. (See "Definition and staging criteria of acute kidney injury in adults".)

CLINICAL MANIFESTATIONS

●Symptoms and signs – Patients with AKI may present with symptoms and signs resulting directly from diminished kidney function. These typically include decreased urine output, hypertension, and edema. However, many patients with early or mild AKI have no clinical symptoms, and an increase in creatinine is detected by the frequent laboratory testing common among hospitalized patients.

●Laboratory tests – In addition to an elevated serum creatinine, laboratory tests may also reveal increased urea (blood urea nitrogen [BUN]) and hyperkalemia. Some patients, particularly those who are fluid overloaded, may be hyponatremic. A urinalysis may show albuminuria and/or an abnormal urine sediment. (See 'Laboratory tests' below.)

ETIOLOGY AND CLASSIFICATION — 

Our approach to evaluation of AKI in the hospitalized patient (see 'Diagnostic evaluation' below) is based on our understanding of the major causes.

Major etiologies of AKI — The causes of AKI are traditionally classified according to renal anatomy [2], with etiologies categorized as prerenal, intrinsic renal, or postrenal/obstructive. In contrast to intrinsic and obstructive AKI, the acute decrease in kidney function in a purely prerenal disorder occurs in the absence of structural problems within the kidney or urinary drainage system. Unfortunately, some clinicians interpret the term "prerenal" as a state requiring treatment with fluids, which in many cases is not appropriate. As such, rather than "prerenal," we prefer the term "hemodynamic" to denote AKI in an unobstructed patient with preserved, or at least unchanged, kidney vasculature and parenchyma.

Hemodynamic ("prerenal") — Hemodynamically mediated AKI, historically called "prerenal" AKI, may result from the following:

●Reduced renal arterial perfusion – Reductions in renal arterial perfusion that lead to AKI may occur in states of volume depletion, euvolemia, or volume excess:

•Total body volume depletion – Total body volume depletion, or true volume depletion, can result from diarrhea, vomiting, acute bleeding, unreplenished insensible losses, excessive diuretic therapy, third-space sequestration (eg, crush injury or acute pancreatitis), or some combination of these factors. (See "Etiology, clinical manifestations, and diagnosis of volume depletion in adults", section on 'Etiology'.)

•Normal or variable total body volume – Euvolemic patients may have reduced kidney perfusion due to low arterial blood pressure, which occurs in different types of distributive shock (eg, sepsis or anaphylaxis), or any loss of arteriolar vasomotor tone (eg, overtreatment with antihypertensive medication).

•Total body volume overload – Patients with total body volume overload may have reduced kidney perfusion due to a low effective circulating volume. Examples include severe heart failure with reduced ejection fraction or decompensated liver disease with portal hypertension and ascites (ie, hepatorenal syndrome). (See "Hepatorenal syndrome: Clinical presentation and diagnosis" and "Cardiorenal syndrome: Definition, prevalence, diagnosis, and pathophysiology".)

●Renal venous congestion – Since perfusion to any capillary bed depends on the difference between arterial and venous pressures, markedly elevated renal venous pressures (with or without arterial hypotension) will compromise normal perfusion to renal parenchyma and may cause AKI. Examples of such venous congestion include severe heart failure with preserved ejection fraction or abdominal compartment syndrome. (See "Abdominal compartment syndrome in adults" and "Cardiorenal syndrome: Definition, prevalence, diagnosis, and pathophysiology".)

●Drugs affecting glomerular hemodynamics – Drug-induced alterations in renal vascular autoregulation, such as afferent arteriole vasoconstriction caused by nonsteroidal anti-inflammatory drugs (NSAIDs) or iodinated radiocontrast media, may cause or contribute to AKI. (See "NSAIDs: Acute kidney injury" and "Contrast-associated and contrast-induced acute kidney injury: Clinical features, diagnosis, and management".)

Angiotensin blockade (as with an angiotensin-converting enzyme [ACE] inhibitor or angiotensin receptor blocker) or sodium-glucose cotransporter 2 (SGLT2) inhibitors also alter the kidney's ability to autoregulate blood flow during states of decreased kidney perfusion; these medications thus commonly exacerbate hemodynamically mediated AKI. (See "Major side effects of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers".)

Intrinsic — Intrinsic kidney disorders may involve the blood vessels, glomeruli, tubules, or interstitium.

●Renal vascular disease – Intrinsic renal vascular diseases directly affect both small- and large-sized blood vessels within the kidneys.

•Acute intrinsic diseases that primarily involve small blood vessels include small vessel vasculitides, atheroembolic disease, and thrombotic microangiopathies, such as thrombotic thrombocytopenic purpura-hemolytic uremic syndrome (TTP/HUS), scleroderma, and malignant hypertension. (See "Glomerular disease: Evaluation and differential diagnosis in adults" and "Clinical presentation, evaluation, and treatment of renal atheroemboli" and "Diagnostic approach to suspected TTP, HUS, or other thrombotic microangiopathy (TMA)" and "Kidney disease in systemic sclerosis (scleroderma), including scleroderma renal crisis" and "Moderate to severe hypertensive retinopathy and hypertensive encephalopathy in adults", section on 'Clinical manifestations and diagnosis'.)

•Diseases that affect larger vessels and cause AKI include renal infarction from aortic dissection, systemic thromboembolism, renal artery abnormality (such as aneurysm), and acute renal vein thrombosis (see "Renal infarction" and "Renal vein thrombosis in adults"). Severe AKI from renal vascular catastrophe suggests bilateral involvement or involvement of a solitary functioning kidney.

●Glomerular disease – Disorders that produce glomerular disease can be classified as being primary (idiopathic, not associated with systemic disease) or secondary (such as paraneoplastic, drug-induced, or part of a systemic rheumatologic disease). Two general patterns are observed (with considerable overlap in some diseases):

•A nephritic pattern (proliferative glomerulonephritis) produces an active urine sediment, classically with dysmorphic red cells, red blood cell casts, and a variable degree of proteinuria [3,4]. Rapidly progressive glomerulonephritis (RPGN), which causes AKI or subacute kidney injury, always presents with a nephritic pattern. (See "Glomerular disease: Evaluation and differential diagnosis in adults".)

•A nephrotic pattern (nonproliferative glomerulopathy) is a rare cause of AKI in the hospitalized patient but may occur in patients with very large amounts of proteinuria. (See "Acute kidney injury (AKI) in minimal change disease and other primary forms of nephrotic syndrome" and "Glomerular disease: Evaluation and differential diagnosis in adults".)

The quantification of protein excretion is discussed elsewhere. (See "Evaluation of proteinuria in adults".)

●Tubular and interstitial diseases – Tubular and interstitial diseases commonly cause AKI.

•Acute tubular necrosis – The most common acute tubulointerstitial disease is acute tubular necrosis (ATN) from ischemia or a nephrotoxic exposure. ATN often occurs in the setting of cardiac (or other major) surgery, sepsis, and/or shock. ATN also may occur in conjunction with the use of NSAIDs or radiocontrast media (especially in patients with decreased kidney perfusion), in the setting of myoglobinuria or hemoglobinuria (ie, pigment nephropathy in rhabdomyolysis or severe hemolysis), or after exposure to nephrotoxic medications (eg, amphotericin or cisplatin). (See "Etiology and diagnosis of prerenal disease and acute tubular necrosis in acute kidney injury in adults" and "NSAIDs: Acute kidney injury" and "Contrast-associated and contrast-induced acute kidney injury: Clinical features, diagnosis, and management" and "Clinical features and diagnosis of heme pigment-induced acute kidney injury".)

•Acute interstitial nephritis – Other tubulointerstitial diseases that cause AKI include acute interstitial nephritis (AIN) that is often drug-induced. A large variety of drugs can produce AIN, including NSAIDs, various antibiotics, and checkpoint inhibitors for cancer immunotherapy. Infections and autoimmune processes also may cause AIN. (See "Clinical manifestations and diagnosis of acute interstitial nephritis" and "Overview of toxicities associated with immune checkpoint inhibitors", section on 'Kidney'.)

•Less common causes – Less common causes of tubulointerstitial AKI that should be considered in the appropriate setting include tumor lysis syndrome (acute uric acid nephropathy), which occurs among patients with lymphomas and other cancers with high tumor burdens, often following chemotherapy; cast nephropathy in multiple myeloma or other monoclonal gammopathies; crystalline nephropathy associated with oxalate, intravenous acyclovir, or other medications; acute phosphate nephropathy following a phosphate-containing bowel preparation; and anticoagulant-related nephropathy. (See "Tumor lysis syndrome: Pathogenesis, clinical manifestations, definition, etiology and risk factors" and "Kidney disease in multiple myeloma and other monoclonal gammopathies: Etiology and evaluation" and "Crystalline-induced acute kidney injury" and "Acute phosphate nephropathy" and "Anticoagulant-related nephropathy".)

Obstructive — Obstruction may occur anywhere in the urinary tract. Among patients who do not have underlying chronic kidney disease (CKD), a substantial reduction in the glomerular filtration rate (GFR) suggests bilateral obstruction (or unilateral obstruction of a single functioning kidney). This is most commonly due to prostatic disease (hyperplasia or cancer), urothelial carcinoma, or gynecologic/metastatic cancer. Retroperitoneal fibrosis is a rare cause of progressive ureteral obstruction (see "Clinical manifestations and diagnosis of retroperitoneal fibrosis"). If untreated, obstructive nephropathy leads to irreversible tubulointerstitial fibrosis (ie, intrinsic kidney disease).

Relative frequency of AKI etiologies — The most detailed epidemiologic data on AKI are in hospitalized patients in resource-rich countries. Most of the relevant studies were published prior to the most recent proposed definitions of AKI (see "Definition and staging criteria of acute kidney injury in adults"). Nonetheless, those studies do provide guidance about the relative frequency of AKI causes. Among hospitalized patients, ATN and hemodynamic (prerenal) disease are the most common. A study from Spain evaluated all 748 cases of AKI at 13 tertiary hospital centers [5] and reported that the most frequent causes were as follows:

●ATN – 45 percent

●Hemodynamic ("prerenal") – 21 percent

●Acute superimposed on CKD – 13 percent (mostly due to ATN and prerenal disease)

●Urinary tract obstruction – 10 percent (most often older men with prostatic disease)

●Glomerulonephritis or vasculitis – 4 percent

●AIN – 2 percent

●Atheroemboli – 1 percent

A study from the Program to Improve Care in Acute Renal Disease (PICARD) examined the etiology of AKI in a more acutely ill population of 618 patients in five intensive care units (ICUs) in the United States [6]. Many patients had more than one possible cause. Over 70 percent of cases were thought to be due to ATN related to sepsis and hypotension. Other causes included hemodynamically mediated AKI (eg, hypovolemia, heart failure, and hepatorenal syndrome), contrast-induced nephropathy, and rhabdomyolysis. Some patients had two or more causes of AKI.

Of note, more recent studies attributed a higher proportion of AKI cases to AIN. A study of native kidney biopsies in a Spanish registry that included 120 hospitals and over 3000 cases of AKI reported that 13 percent of patients had a diagnosis of AIN, with the prevalence increasing over time [7]. An increasing trend of AIN may be due to greater use of medications such as antibiotics, NSAIDs, proton pump inhibitors, and immunomodulators such as checkpoint inhibitors.

Common causes of AKI differ somewhat in resource-poor compared with resource-rich settings. AKI in resource-poor countries often occurs in younger patients with a single disease process such as a diarrheal illness or malarial infection, among others; in resource-rich countries, AKI is more frequently associated with complex surgery, sepsis, and multiorgan diseases [8,9].

INITIAL ASSESSMENT AND TRIAGE — 

The initial assessment for all patients with AKI includes triage of those who may need urgent dialysis based upon symptoms or life-threatening laboratory abnormalities.

Identification of acute kidney injury — As noted above, AKI is occasionally accompanied by the onset of symptoms or signs related to reduced kidney function, all of which suggest the diagnosis. (See 'Clinical manifestations' above.)

Among hospitalized patients who generally have frequent monitoring of serum creatinine levels and urine quantity, the diagnosis of AKI is easily established by demonstrating an increase in serum creatinine concentration and/or a decrease in urine output (table 1) (see 'Definition' above). Serum cystatin C and several other biomarkers have been used to identify AKI (see "Investigational biomarkers and the evaluation of acute kidney injury"), but serum creatinine remains the only laboratory value used in formal definitions of AKI and is the laboratory test most used in clinical practice. All subsequent evaluation is directed at determining the underlying cause of AKI in order to allow for prompt management. (See 'Diagnostic evaluation' below.)

Early diagnosis of AKI may allow for intervention to improve outcomes, and some studies have suggested that early nephrologist involvement in hospital-acquired AKI confers benefits [10]. However, a randomized, controlled trial of an electronic alert system to promote early recognition of AKI resulted in neither reduced severity of injury nor improved clinical outcomes [11].

Identification of patients needing urgent dialysis — Infrequently, hospitalized patients with AKI may have absolute or relative indications for dialysis at the time that their kidney disease is recognized. Those who have refractory pulmonary edema, life-threatening hyperkalemia or metabolic acidosis, encephalopathy, or a pericardial rub should be rapidly evaluated for the possible initiation of dialysis. These indications are discussed at length elsewhere. (See "Kidney replacement therapy (dialysis) in acute kidney injury in adults: Indications, timing, and dialysis dose".)

Limitations of estimated GFR — Commonly used equations that use serum creatinine and/or cystatin C concentrations to estimate glomerular filtration rate (GFR) were derived in nonhospitalized patients with stable kidney function (see "Assessment of kidney function", section on 'Estimation of GFR') [12]. Although more complex formulas have been proposed to estimate GFR from the change in creatinine values among patients with AKI [13,14], any equation that uses creatinine (or cystatin C) may lead to errors among patients who are not in steady state.

The following examples illustrate common problems encountered when interpreting estimated GFR in patients with AKI:

●Early in the course of AKI, the serum creatinine may remain in the normal range because there has not yet been adequate time for accumulation; in such cases, estimating equations that use creatinine (and/or cystatin C) will overestimate kidney function.

●The serum creatinine also may be falsely low (and estimated GFR misleadingly high) immediately after the administration of large volumes of intravenous fluid, which expands the extracellular fluid volume and the volume of distribution for creatinine (and cystatin C) [15].

DIAGNOSTIC EVALUATION — 

It is important to quickly establish the cause of AKI. In many cases, AKI is reversible if the underlying cause is quickly identified and addressed.

Initial evaluation — We take a systematic approach to the evaluation of patients with AKI. Even if the cause of AKI seems obvious, skipping steps in the diagnostic evaluation risks missing important causes of or contributors to AKI. Our initial diagnostic approach to hospitalized patients with AKI is outlined below (algorithm 1).

History — For all patients, we carefully review the history, particularly the timing of AKI onset, the presence of concurrent illnesses, and the use of potentially nephrotoxic medications.

●Timing of onset – The timing of onset often suggests the underlying etiology. The date of onset can very often be precisely timed if the serum creatinine concentration has been measured frequently as part of interval blood testing or if there is accurate documentation of urine output. As an example, suppose that a patient has had a stable serum creatinine concentration, which then begins to rise progressively starting on hospital day 5. Careful study of the patient's chart may identify the precipitating event on day 3 or 4 (eg, surgery or hypotension) or identify cumulative insults (eg, iodinated contrast) prior to the increase in creatinine.

There are two important caveats to consider when examining the timing of AKI onset:

•Patients who receive aggressive volume resuscitation may have the increase in serum creatinine blunted due to dilution in a larger volume of distribution [15].

•A substantial time gap may exist between the precipitant of AKI and the identification of AKI. For example, coronary angiography or cardiac/aortic surgery may precede the onset of atheroembolic AKI by several days to weeks (see "Clinical presentation, evaluation, and treatment of renal atheroemboli"). The onset of drug-induced acute interstitial nephritis (AIN) following drug exposure may range from three to five days (as occurs with a second exposure to an offending drug) to as long as several weeks. (See "Clinical manifestations and diagnosis of acute interstitial nephritis".)

●Concurrent illness – A review of concurrent illnesses and comorbidities often provides important clues to the etiology of AKI. Some examples are as follows:

•Sepsis or hemorrhage suggests acute tubular necrosis (ATN).

•Crush injury or compartment syndrome suggests pigment nephropathy. (See "Clinical features and diagnosis of heme pigment-induced acute kidney injury".)

•A malignancy associated with a high risk of tumor lysis syndrome suggests acute uric acid nephropathy (table 2). (See "Overview of kidney disease in patients with cancer".)

●Medication review – A careful review of medications is imperative. Often, nephrotoxic medications (eg, nonsteroidal anti-inflammatory drugs [NSAIDs]) were started just prior to the onset of AKI, which suggests an etiology. In addition, other medications (eg, angiotensin-converting enzyme [ACE]-inhibitors, angiotensin receptor blockers [ARBs], or sodium-glucose cotransporter 2 [SGLT2-inhibitors]) may render patients vulnerable to AKI in the setting of hemodynamic compromise. (See 'Hemodynamic ("prerenal")' above.)

The use of electronic medical records with tools to show clearly and graphically the temporal relationships between decreasing urine output, creatinine elevation, changes in vital signs, and medication exposures can be most helpful in these investigations.

Physical examination — A physical examination may reveal the etiology. Special attention should be paid to volume status, since hemodynamically mediated AKI often responds promptly to the correction of volume depletion or volume overload.

Common examples of salient physical examination findings include:

●Signs of volume contraction suggest hemodynamically mediated AKI. (See "Etiology and diagnosis of prerenal disease and acute tubular necrosis in acute kidney injury in adults", section on 'History and physical examination'.)

●A typical "drug rash" suggests AIN. (See "Clinical manifestations and diagnosis of acute interstitial nephritis", section on 'Clinical manifestations'.)

●Significant volume overload and signs of heart failure suggest hemodynamic AKI, as seen in cardiorenal syndrome. (See "Cardiorenal syndrome: Definition, prevalence, diagnosis, and pathophysiology".)

●Ascites and jaundice suggest liver disease with portal hypertension and hepatorenal syndrome. (See "Hepatorenal syndrome: Clinical presentation and diagnosis".)

●Blue toes and/or livedo reticularis suggest cholesterol emboli. (See "Clinical presentation, evaluation, and treatment of renal atheroemboli", section on 'History and physical examination'.)

Urine output — Trending and comparing volumes of fluid going in and coming out of a patient (including urine output) are helpful physiologic parameters in patients with AKI.

●Oliguria versus normal urine output – Oliguria (typically defined as <0.3 mL/kg per hour or <500 mL/day of urine output) often but not always occurs in AKI with rising creatinine. Normal urine output can be maintained even with an abnormally low glomerular filtration rate (GFR) in patients with nonoliguric ATN. The prognosis of nonoliguric AKI is generally better than oliguric or anuric disease [16-19]. (See "Nonoliguric versus oliguric acute kidney injury (AKI)".)

An abrupt decline in urine volume may suggest new obstruction (such as an obstructed bladder catheter) or another new, superimposed cause of AKI. Conversely, increasing urine output often reflects kidney recovery.

●Response to diuretics – Although the administration of diuretics in AKI has not been shown to improve kidney function or creatinine trajectory, the increase of urine output (ie, the conversion of anuric or oliguric AKI to nonoliguric AKI) spontaneously or with the use of diuretics often reflects kidney function recovery or less severe injury [20]. Furthermore, increasing urine output will mitigate the risk of volume overload and pulmonary edema, thus potentially allowing the patient to be managed without dialysis. (See "Nonoliguric versus oliguric acute kidney injury (AKI)".)

●Anuria – In contrast to oliguria, which is common in patients with AKI, anuria (<50 mL/day) is rare. Anuria reflects severe AKI, which will likely require dialytic therapy unless there is prompt recovery. Anuria generally occurs as a result of the following conditions:

•Severe ATN due to prolonged shock

•Bilateral urinary tract obstruction, or unilateral obstruction with an absent or nonfunctional contralateral kidney

•Bilateral renal artery obstruction, as seen in abdominal aortic dissection

•Pregnancy-related cortical necrosis

Oliguria may progress to genuine anuria in other cases of severe AKI, such as untreated thrombotic microangiopathy and rapidly progressive (crescentic) glomerulonephritis.

Laboratory tests

●Urine tests – The urinalysis and quantification of urinary protein excretion are key components of the AKI evaluation. By contrast, the measurement of urine sodium is often of limited utility.

•Urinalysis

-The urine dipstick can test for protein (albumin), pH, glucose, hemoglobin (or myoglobin), leukocyte esterase (reflecting pyuria), and specific gravity. (See "Urinalysis in the diagnosis of kidney disease", section on 'Urine dipstick analysis'.)

-Microscopic examination of the urine sediment by an experienced operator is an important component of the diagnostic evaluation since characteristic findings strongly suggest certain diagnoses (table 3).

•Protein excretion – Urinary protein excretion should be quantified by random "spot" urine protein-to-creatinine ratio (uPCR) or albumin-to-creatinine ratio (uACR). However, in AKI, these ratios may provide substantial overestimates of 24-hour urinary protein or albumin excretion due to reduced urine creatinine, among other factors. (See "Evaluation of proteinuria in adults".)

•Sodium excretion – We believe that the evaluation of AKI is best guided by history, physical, and the incorporation of laboratory findings other than urine sodium values. However, in an oliguric patient without baseline chronic kidney disease (CKD) whose effective circulating volume is difficult to assess, the calculation of fractional urine excretion (FENa) may help to distinguish hemodynamic AKI from ATN. The fractional excretion of urea (FEUrea) also may provide information in some patients. Unfortunately, there are many instances where the FENa is not helpful. (See "Fractional excretion of sodium, urea, and other molecules in acute kidney injury" and "Etiology and diagnosis of prerenal disease and acute tubular necrosis in acute kidney injury in adults", section on 'Fractional excretion of sodium and urine sodium concentration'.)

●Blood tests – In addition to serum creatinine, electrolytes, glucose, and blood urea nitrogen (BUN), initial blood tests should include the following:

•Serum calcium to evaluate for hypercalcemia

•Complete blood count with white blood cell differential to assess for anemia, thrombocytopenia, and eosinophilia

●Additional tests for patients at higher risk for multiple myeloma – Among patients who are considered at higher risk for multiple myeloma and cast nephropathy based on key clinical features, we obtain the following tests at the time of the initial evaluation:

•Serum protein electrophoresis (SPEP) with immunofixation

•Urine protein electrophoresis (UPEP) with immunofixation

•Serum free light chain assay

Patients who are considered at higher risk for myeloma include all patients who are >40 years of age who have no other obvious cause for increased creatinine. Other features, such as hypercalcemia, unexplained anemia, and increased gamma globulin concentration may increase suspicion of monoclonal gammopathy. (See "Kidney disease in multiple myeloma and other monoclonal gammopathies: Etiology and evaluation", section on 'Patients with acute or subacute kidney injury'.)

Imaging

●When to obtain – Radiographic imaging is generally performed in patients with AKI when the underlying cause is not immediately apparent. The major reason for performing kidney imaging in AKI is to assess for urinary tract obstruction. In some cases in which the duration of kidney dysfunction is not clear, small, echogenic kidneys indicate a chronic component of kidney disease.

Patients who have an obvious cause of AKI do not necessarily require imaging. As an example, we do not initially perform imaging for an elevated creatinine in a patient admitted with septic shock who has muddy brown granular casts on urine microscopy. If, however, the cause of AKI is not clear after initial evaluation or if the trajectory of kidney function impairment is unexpected, and if concurrent incidental kidney imaging (eg, abdominal computed tomography [CT] scan) is unavailable, then we obtain kidney imaging for additional clues to etiology.

●Preferred modality – Kidney ultrasound is an ideal modality to evaluate for obstruction: it is safe, easy to perform, and highly sensitive. However, helical CT scan without contrast is generally preferred among patients with possible urolithiasis. Such patients usually, though not always, present with flank pain and hematuria. (See "Radiologic assessment of kidney disease" and "Kidney stones in adults: Diagnosis and acute management of suspected nephrolithiasis", section on 'Diagnostic imaging'.)

For older males with AKI in whom benign prostatic hyperplasia and concomitant bladder outlet obstruction are common, postvoid bladder ultrasound is an easily obtained and reasonable initial imaging modality. However, the lack of urinary retention on bladder scan does not rule out upper urinary tract obstruction. (See "Clinical manifestations and diagnosis of urinary tract obstruction (UTO) and hydronephrosis".)

Subsequent evaluation — The subsequent diagnostic evaluation, including the need for additional testing, is guided by the clinical presentation and results of the initial evaluation.

Targeted additional assessment — Additional testing depends on clinical features and/or abnormal test results.

●Clinical features

•Volume depletion, hypotension, or shock – Hospitalized patients with AKI who have volume depletion, hypotension, or shock usually have hemodynamic AKI or ATN.

-Hemodynamic AKI – Hemodynamic AKI caused by volume depletion and/or hypotension is suggested by the history and physical examination (eg, severe vomiting and signs of volume depletion) and a urinalysis that is generally bland with minimal proteinuria. The diagnosis is confirmed when AKI rapidly corrects with the administration of volume and/or treatment of hypotension.

-ATN – A clinical diagnosis of ATN is usually made when the history and physical examination demonstrate a clear precipitant (eg, sepsis, hemorrhage, major surgery, or cardiovascular collapse) and there is no evidence for another cause of AKI (eg, hematuria or obstruction). A urinary sediment showing pigmented ("muddy brown") granular casts and/or renal tubular epithelial cells supports the diagnosis of ATN, but the absence of these classic urinary findings does not rule out the diagnosis. (See "Etiology and diagnosis of prerenal disease and acute tubular necrosis in acute kidney injury in adults".)

•Heart and liver failure – AKI due to decompensated heart failure or advanced hepatic impairment with portal hypertension is suggested by the history and physical examination and a urinalysis that is generally bland with minimal proteinuria. Because hospital-acquired AKI is frequently multifactorial, such patients should be evaluated for other AKI etiologies while being treated for their heart or liver disease. (See "Cardiorenal syndrome: Prognosis and treatment" and "Hepatorenal syndrome: Clinical presentation and diagnosis".)

•Cancer – AKI caused solely by cancer is relatively uncommon; in such patients, AKI is more likely to be caused by other etiologies such as volume depletion, ATN, or heart failure. However, the presence of specific cancers in a patient with AKI may prompt additional testing (see "Overview of kidney disease in patients with cancer"). As examples:

-For patients with a malignancy associated with tumor lysis syndrome (table 2), we obtain serum levels of uric acid and phosphorus to evaluate for acute uric acid nephropathy. (See "Tumor lysis syndrome: Pathogenesis, clinical manifestations, definition, etiology and risk factors" and "Tumor lysis syndrome: Prevention and treatment".)

-For patients with multiple myeloma, we measure serum levels of calcium, uric acid, and phosphorus and quantify the burden of circulating monoclonal protein with serum and urine protein electrophoresis and immunofixation and a serum free light chain (SFLC) assay. (See "Kidney disease in multiple myeloma and other monoclonal gammopathies: Etiology and evaluation".)

•Recent intra-aortic procedure – In patients with AKI, a diagnosis of atheroembolic kidney disease can be made if there was both a precipitating event (eg, coronary angiography, cardiac or aortic surgery) that preceded the onset of AKI by several days to weeks, and if there are consistent skin findings (ie, blue toe syndrome, livedo reticularis, or both) or Hollenhorst plaques on retinal examination. Eosinophilia and hypocomplementemia are consistent, but nonspecific findings. (See "Clinical presentation, evaluation, and treatment of renal atheroemboli".)

●Abnormal laboratory findings

•Hematuria – Patients who have hematuria without recent urinary tract instrumentation, especially in conjunction with an abnormally increased uACR and physical examination findings such as hypertension or edema, should be evaluated for glomerulonephritis. (See "Glomerular disease: Evaluation and differential diagnosis in adults".)

•Sterile pyuria – Patients who have sterile pyuria should be evaluated for interstitial nephritis. Only a minority of patients with drug-induced acute interstitial nephritis have the classic triad of rash, fever, and eosinophilia. (See "Clinical manifestations and diagnosis of acute interstitial nephritis".)

•Myoglobinuria or hemoglobinuria – In patients who may have either hemoglobinuria or myoglobinuria, as suggested by a heme-positive urine dipstick in the absence of visible red cells by microscopy, we evaluate for pigment nephropathy caused by rhabdomyolysis or hemolysis. (See "Clinical features and diagnosis of heme pigment-induced acute kidney injury".)

•Hypercalcemia – Moderate to severe hypercalcemia (ie, serum calcium values greater than 12 mg/dL [3 mmol/L]) can produce hypovolemia and renal vasoconstriction resulting in reversible AKI. If hypercalcemia is the sole cause of AKI, then lowering of the serum calcium will quickly improve the kidney function. However, hypercalcemia is frequently not the sole cause of AKI; instead, another underlying disorder (eg, multiple myeloma or sarcoidosis) may be responsible for both conditions. (See "Diagnostic approach to hypercalcemia" and "Treatment of hypercalcemia".)

•New, unexplained anemia and/or thrombocytopenia – In patients without a more common cause of AKI, the presence of new, unexplained anemia, thrombocytopenia, or both should prompt an evaluation for thrombotic microangiopathy, including a peripheral blood smear to evaluate for schistocytes and serum levels of unconjugated bilirubin, haptoglobin, and lactate dehydrogenase to evaluate for hemolysis. (See "Thrombotic microangiopathies (TMAs) with acute kidney injury (AKI) in adults: CM-TMA and ST-HUS".)

●Obstruction – In patients with AKI who have ultrasound findings consistent with urinary tract obstruction, additional imaging with CT may be required for definitive diagnosis and subsequent management. This is discussed in detail elsewhere. (See "Clinical manifestations and diagnosis of urinary tract obstruction (UTO) and hydronephrosis".)

Unexplained AKI — For patients who have normal kidney imaging, minimal proteinuria, benign urine sediment on urinalysis/microscopy (no red cells or cellular casts), and no clear explanation for AKI, further evaluation is determined by the severity of disease and rate of further decline as follows:

●If the creatinine is markedly elevated or if an initially mild increase in the creatinine worsens over the course of days, then a kidney biopsy is usually performed. A biopsy frequently provides a more definitive tissue diagnosis and may allow a therapeutic intervention to prevent end-stage kidney disease (ESKD).

In some cases, even without kidney biopsy, the etiology of kidney disease can be ascertained with reasonable certainty with tissue diagnosis from other sites. For example, a bone marrow biopsy in a patient with suspected multiple myeloma or a fat pad biopsy in a patient with suspected amyloidosis may avert the need for a kidney biopsy. The indications for kidney biopsy are discussed in more detail elsewhere. (See "The kidney biopsy".)

●Among patients who have signs and symptoms of rapidly progressive or unexplained systemic disease, a kidney biopsy is usually warranted, even if the estimated GFR (eGFR) remains stable after initial increase.

●Among patients who have a mild decrease in eGFR (eg, down to 45 to 60 mL/min/1.73 m²) that subsequently remains stable, we often just follow the serum creatinine. If the creatinine remains stable, we generally continue to follow creatinine, urine studies (urinalysis/microscopic studies, urine protein/creatinine), and blood pressure until a clear temporal pattern is established.

Role of kidney biopsy — A kidney biopsy is most commonly obtained when noninvasive evaluation has been unable to establish the correct diagnosis [21,22].

Biopsy may be deferred if other findings strongly support diagnostic and therapeutic decision making or if the risk of biopsy outweighs the expected benefit. Issues related to kidney biopsy, including indications, when biopsy may not be necessary, prebiopsy evaluation, technique, and complications, are discussed separately. (See "The kidney biopsy".)

SOCIETY GUIDELINE LINKS — 

Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Acute kidney injury in adults".)

INFORMATION FOR PATIENTS — 

UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topics (see "Patient education: Acute kidney injury (The Basics)")

●Beyond the Basics topics (see "Patient education: Kidney (renal) biopsy (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

●Definition of acute kidney injury – Acute kidney injury (AKI) refers to a decrease in kidney function that has developed within hours to days. Commonly accepted criteria for AKI include an increase in serum creatinine by ≥0.3 mg/dL (27 micromol/L) within 48 hours or an increase to ≥1.5 times the baseline value that is known or presumed to have occurred within the prior seven days, or a decrease in urine volume to <3 mL/kg over six hours. (See 'Definition' above.)

●Clinical manifestations – Patients with AKI may present with symptoms and signs resulting directly from diminished kidney function. These include edema, hypertension, and/or decreased urine output. However, many patients with early or mild AKI have no clinical symptoms, and an increase in creatinine is detected incidentally by the frequent laboratory testing common among hospitalized patients. (See 'Clinical manifestations' above.)

●Etiology and classification – AKI may be caused by hemodynamic factors (eg, volume depletion, hypotension, low effective circulating volume, or venous congestion), intrinsic kidney disorders (eg, acute tubular necrosis [ATN]), or urinary tract obstruction. In many hospitalized patients, the cause of AKI is multifactorial. (See 'Etiology and classification' above.)

●Initial assessment and triage – Among hospitalized patients who generally have frequent monitoring of serum creatinine levels and urine production, the diagnosis of AKI is easily established by demonstrating an increase in serum creatinine concentration and/or a decrease in urine output. Infrequently, hospitalized patients with AKI may have absolute or relative indications for dialysis at the time that their kidney disease is recognized. (See 'Initial assessment and triage' above.)

●Diagnostic evaluation – The major components to the initial diagnostic evaluation of patients with AKI include a careful history and physical examination, assessment of urine output, laboratory tests including microscopic examination of the urine, and radiographic imaging of the kidneys in select patients (algorithm 1). The subsequent diagnostic evaluation, including the need for additional testing, is guided by the clinical presentation and results of the initial evaluation. (See 'Initial evaluation' above and 'Subsequent evaluation' above.)