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Diagnostic approach to adult patients with subacute kidney injury in an outpatient setting
Authors:
Pedram Fatehi, MD, MPH
Chi-yuan Hsu, MD, MSc
Section Editor:
Paul M Palevsky, MD
Deputy Editor:
Alice M Sheridan, MD
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Feb 2018. | This topic last updated: Mar 05, 2018.

INTRODUCTION — Patients with kidney disease may have a variety of different clinical presentations. Some have symptoms or signs that are directly referable to the kidney (such as hematuria) or to associated extrarenal manifestations (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 hospitalized patients or following a procedure. Subacute kidney injury defines a presentation that develops more slowly than AKI but generally results in worsening creatinine in less than three months. Chronic kidney disease (CKD) is defined by an elevated creatinine, or other evidence of kidney damage, that is relatively stable for greater than three months.

Although not all presentations fit within these narrowly defined categories, knowledge of the duration and acuity of onset of disease often narrows the differential diagnosis among patients who may present similar clinical findings related to the kidney.

This topic reviews the evaluation of patients who present with subacute kidney injury [1]. Most patients are evaluated as outpatients, but, in some cases, the trend of gradually rising creatinine is recognized upon hospital admission. The evaluation of hospitalized patients who develop an increase in creatinine within hours to days is discussed elsewhere [1]. (See "Evaluation of acute kidney injury among hospitalized adult patients".)

The evaluation of patients with newly identified CKD is discussed elsewhere [1]. (See "Diagnostic approach to the patient with newly identified chronic kidney disease".)

OVERVIEW

Major components of evaluation — The major components to the evaluation of patients with an elevated creatinine involve:

Careful history and physical examination. An important part of the history is the duration of the increased creatinine.

Assessment of renal function by estimation of the glomerular filtration rate (GFR). Estimation of the GFR requires that the patient is in steady state. (See 'Evaluation' below and "Assessment of kidney function".)

Careful examination of the urine by both qualitative chemical tests and microscopic examination. The urinary findings narrow the differential (table 1). (See 'Urinalysis' below.)

Radiographic imaging of the kidneys. (See 'Radiologic studies' below.)

Serologic testing and tissue diagnosis with renal biopsy if noninvasive evaluation is not sufficient for diagnosis. (See 'Serologic testing and role of renal biopsy' below.)

Determination of disease duration — The determination of disease duration is an important aspect of the evaluation. Making this determination accurately requires the availability of older data for comparison. Knowing the disease duration helps to narrow the differential diagnosis of cause and to provide prognostic information to guide management.

The distinction among acute kidney injury (AKI), subacute injury, and chronic kidney disease (CKD) is arbitrary, but the following definitions have been established by consensus panels:

Acute – AKI is defined by a rise in the serum creatinine concentration or an abnormal urinalysis that has developed within hours to days. Consensus criteria for AKI include an increase in serum creatinine by ≥0.3 mg/dL (27 micromol/L) relative to a known baseline value within 48 hours, or an increase to ≥1.5 times the known or presumed baseline value within seven days, or a decrease in urine volume to <3 mL/kg over six hours (Kidney Disease: Improving Global Outcomes [KDIGO]-AKI) (table 2).

AKI is most commonly diagnosed in hospitalized patients. (See "Definition and staging criteria of acute kidney injury in adults".)

Chronic – The National Kidney Foundation Kidney Disease Outcomes Quality Initiative (NKF-KDOQI) and the KDIGO CKD guidelines define CKD as being present if reduced GFR (ie, <60 mL/min/1.73 m2) or evidence of kidney damage, such as albuminuria or abnormal findings on renal imaging, have been present for three months or more and have implications for health. (See "Definition and staging of chronic kidney disease in adults", section on 'Definition of CKD' and "Diagnostic approach to the patient with newly identified chronic kidney disease".)

Subacute – KDIGO guidelines proposed the term "acute kidney diseases and disorders" (AKD) to encompasses any decrement in renal function occurring in less than three months [1]. Disorders that evolve over more than 48 hours but generally in under three months are informally referred to here as subacute kidney injury. AKD includes both AKI and subacute kidney injury, and there is considerable overlap in an acute and subacute presentation.

We emphasize that these categories are less important in the clinical setting than having a clear understanding of the natural history of the underlying diseases. Many signs and symptoms of disease may be present before there is a decline in clearance function. As an example, glomerular diseases referred to as rapidly progressive glomerulonephritides (RPGNs) often cause subtle signs and symptoms for weeks to months before the patient develops overt manifestations of nephritic syndrome, including a decline in clearance. In two case-series reports of antineutrophil cytoplasmic antibody (ANCA) vasculitis, for example, an average time of ≥10 weeks elapsed between reported, initial symptoms and the diagnosis of glomerulonephritis [2,3].

The assessment of disease duration is best performed by comparing the current serum creatinine concentration and/or urinalysis with previous results. As an example, a patient with a current serum creatinine concentration of 4 mg/dL (354 micromol/L) and a creatinine of 0.6 mg/dL (53 micromol/L) one month previously has acute or subacute disease. In contrast, the same patient with a prior serum creatinine concentration of 3.5 mg/dL (309 micromol/L) two years ago almost certainly has slowly progressive CKD.

When a previous urinalysis, serum creatinine concentration, and/or radiographic study are unavailable, certain findings from the history and physical examination may suggest the duration of disease. As examples [4]:

The recent onset of symptoms or signs, such as sudden onset of anasarca and discolored urine, suggests an acute process.

Marked oliguria (urine output <500 mL/day) or anuria indicates an acute process since prolonged oliguria/anuria does not occur in slowly progressive CKD (even if advanced) prior to initiation of maintenance dialysis.

A daily progressive increase in the serum creatinine concentration indicates an acute process, while a stable value suggests CKD.

Imaging showing small kidneys provides definitive evidence of chronicity. However, the presence of normal-sized kidneys does not exclude chronic disease. Markedly increased renal echogenicity coupled with small, atrophic kidneys strongly suggest CKD [5-7]. (See "Radiologic assessment of renal disease".)

Radiologic evidence of renal osteodystrophy such as subperiosteal bone resorption or loss of bone density at the distal third of the clavicles strongly suggests CKD. (See "Overview of chronic kidney disease-mineral and bone disorder (CKD-MBD)".)

Other findings are less helpful. As an example, anemia due to erythropoietin deficiency is a common (though not absolute) finding in CKD, but many conditions can cause both hemolysis or bleeding and AKI or subacute injury. Hyperphosphatemia also does not distinguish acute from chronic disease. Although hyperphosphatemia commonly affects CKD patients, serum phosphorus levels can also rise quickly in AKI or subacute kidney injury.

MAJOR CAUSES AND PATHOGENESIS OF KIDNEY DISEASE — The traditional approach to kidney disease has been to categorize the clinical etiology as prerenal (decreased renal perfusion pressure), intrinsic renal (pathology of the vessels, glomeruli, or tubulointerstitium), or postrenal (obstructive).

However, diseases often cross these nosological boundaries. As examples, prolonged prerenal azotemia can lead to intrinsic acute tubular necrosis (ATN) and possibly to chronic fibrosis and progressive chronic kidney disease (CKD), and untreated urinary tract obstruction eventually causes fibrosis and atrophy of the obstructed kidney(s). In addition, many diseases that initially damage the glomeruli eventually result in tubulointerstitial fibrosis. Another example is cholesterol emboli syndrome, which affects both small vessels and the glomeruli and ultimately causes tubulointerstitial fibrosis.

Conditions that cause prerenal, intrinsic, or postrenal subacute kidney injury are discussed below.

Prerenal disease — Prerenal conditions that cause subacute kidney injury include overdiuresis, decreased oral intake, diarrhea, or unreplenished insensible losses. Renal perfusion pressure may also be low in hypervolemic states with low effective circulating (arterial) volume, such as heart failure with reduced ejection fraction or decompensated liver disease with portal hypertension. (See "Cardiorenal syndrome: Definition, prevalence, diagnosis, and pathophysiology" and "Hepatorenal syndrome".)

Alterations in renal vascular autoregulation, such as afferent arteriole vasoconstriction caused by nonsteroidal anti-inflammatory drugs (NSAIDs), and inhibition of efferent vasoconstriction by renin-angiotensin system (RAS) blockade may cause a propensity for prerenal kidney injury. (See "NSAIDs: Acute kidney injury (acute renal failure)".)

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

Subacute intrinsic diseases that involve small blood vessels include small vessel vasculitides affecting glomerular capillaries, atheroembolic disease, and diseases that cause microangiopathy and hemolytic anemia (MAHA) such as thrombotic thrombocytopenic purpura-hemolytic uremic syndrome (TTP/HUS), scleroderma, and malignant hypertension. (See "Clinical presentation, evaluation, and treatment of renal atheroemboli" and "Moderate to severe hypertensive retinopathy and hypertensive encephalopathy in adults", section on 'Clinical manifestations and diagnosis' and "Renal disease in systemic sclerosis (scleroderma), including scleroderma renal crisis" and "Glomerular disease: Evaluation and differential diagnosis in adults".)

Intrinsic renal vascular diseases that involve larger vessels include renal infarction from aortic dissection, systemic thromboembolism, or renal artery abnormalities (such as aneurysm). Renal vein thrombosis is most frequently associated with massive proteinuria in the setting of nephrotic syndrome. (See "Renal infarction" and "Renal vein thrombosis and hypercoagulable state in nephrotic syndrome".)

Intrinsic 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) (table 1):

A nephritic (proliferative) pattern produces an active urine microscopy with red blood cell (RBC) casts, dysmorphic red cells, and a variable degree of albuminuria [8,9]. (See "Glomerular disease: Evaluation and differential diagnosis in adults".)

A nephrotic (nonproliferative) pattern is associated with proteinuria, usually in the nephrotic range (>3.5 g per 24 hours or on spot/random protein-to-creatinine ratio), and an inactive urine microscopy with few cells or casts. (See "Glomerular disease: Evaluation and differential diagnosis in adults".)

The quantification of protein excretion is discussed elsewhere. (See "Assessment of urinary protein excretion and evaluation of isolated non-nephrotic proteinuria in adults".)

Both patterns can present with an acute or more chronic time course, and elements of both may be observed simultaneously or sequentially in the same patient. The differential diagnosis of glomerular disease is discussed elsewhere. (See "Glomerular disease: Evaluation and differential diagnosis in adults".)

Intrinsic tubular and interstitial disease — Subacute tubulointerstitial diseases include interstitial nephritis (which is often drug induced and commonly called acute interstitial nephritis), cast nephropathy in multiple myeloma, and acute phosphate nephropathy following a phosphate-containing bowel preparation [10]. (See "Etiology and diagnosis of prerenal disease and acute tubular necrosis in acute kidney injury in adults" and "Clinical manifestations and diagnosis of acute interstitial nephritis" and "Epidemiology, pathogenesis, and etiology of kidney disease in multiple myeloma and other monoclonal gammopathies" and "Clinical manifestations of hypercalcemia", section on 'Renal insufficiency' and "Tumor lysis syndrome: Definition, pathogenesis, clinical manifestations, etiology and risk factors" and "Acute phosphate nephropathy".)

ATN never causes subacute kidney injury but rather always presents as AKI. However, AKI, especially if severe or frequently recurrent, may not recover completely, resulting in irreversible CKD. In such patients, if the elevated creatinine is identified within three months, it may be erroneously "classified" as subacute kidney injury. Causes of AKI are often easily identified in the history, such as cardiac surgery or severe sepsis, and chronicity can be established by close follow-up of the patient.

Obstructive nephropathy — Obstruction may occur anywhere in the urinary tract. Among patients who do not have underlying CKD, a substantial reduction in 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) or metastatic cancer. Retroperitoneal fibrosis is a rare cause of chronic ureteral obstruction. (See "Clinical manifestations and diagnosis of retroperitoneal fibrosis".)

Acute obstruction of the urinary tract usually causes symptoms of pain (renal colic or suprapubic fullness), but gradual, severe obstruction may cause renal dysfunction without obvious symptoms. If untreated, obstructive nephropathy leads to irreversible tubulointerstitial fibrosis (ie, intrinsic disease). (See "Clinical manifestations and diagnosis of urinary tract obstruction and hydronephrosis", section on 'Symptoms and signs'.)

CLINICAL MANIFESTATIONS — Patients with subacute kidney injury may present with symptoms and signs resulting directly from diminished kidney function. These include edema, hypertension, and/or decreased urine output. Patients with rheumatologic diseases affecting the kidney may have subtle joint or skin manifestations. However, many patients have no clinical symptoms. In such patients, kidney injury is detected by laboratory tests that are obtained, potentially as part of an evaluation of an unrelated disorder.

Symptoms and/or signs of prolonged renal failure, including weakness and easy fatigability, anorexia, vomiting, mental status changes, and seizures, are generally not present in patients with subacute injury, although exceptions may occur. Such symptoms suggest severe acute kidney injury (AKI) or advanced chronic kidney disease (CKD).

The total absence of urine (anuria) is never observed with subacute injury and always indicates AKI. Anuria occurs as a result of shock, bilateral urinary tract obstruction, pregnancy-related cortical necrosis, or any process that causes severe, prolonged loss of renal perfusion. (See "Evaluation of acute kidney injury among hospitalized adult patients".)

The major, and occasionally the only, laboratory finding in patients with subacute kidney injury is an increased serum creatinine concentration. Increased urea (blood urea nitrogen [BUN]) and hyperkalemia may also be present. Albuminuria and/or abnormal urine microscopy may be present. (See 'Urinalysis' below.)

Incidental findings (eg, multiple renal cysts suggestive of polycystic kidney disease [PKD]) may be observed on radiographic imaging performed for some other reason.

EVALUATION

Overview — Once kidney disease is discovered and determined to be subacute in onset, the underlying cause should be identified, if possible. Frequently helpful are a careful history, review of medications, and physical examination (eg, signs of volume contraction).

The presence of certain symptoms or signs may suggest an underlying diagnosis. As examples:

Systemic symptoms and findings, such as fever, arthralgias, and pulmonary lesions, are suggestive of a systemic disease such as vasculitis or lupus. (See "Diagnosis and differential diagnosis of systemic lupus erythematosus in adults".)

Livedo reticularis and distal microemboli suggest atheroembolic disease. (See "Embolism from atherosclerotic plaque: Atheroembolism (cholesterol crystal embolism)".)

Unilateral flank pain is most consistent with obstruction, renal infarction, or infection. (See "Renal infarction", section on 'Differential diagnosis'.)

A constellation of symptoms and signs may suggest a particular set of disorders. As examples, hypertension, hematuria with red cell casts, and a rapidly rising serum creatinine concentration are almost certainly due to acute glomerulonephritis or renal vasculitis. Edema, heavy proteinuria, and little or no hematuria are indicative of a nonproliferative (nephrotic) glomerular disease such as diabetic nephropathy, membranous nephropathy, or minimal change disease. Some other urinary findings are relatively nonspecific (eg, a normal or near-normal urinalysis) and can be observed in a variety of disorders (table 1). (See "Urinalysis in the diagnosis of kidney disease", section on 'Correlation of urinary findings with kidney diseases'.)

The approach to evaluation varies among clinicians and depends on the degree of creatinine change and the corresponding change in the glomerular filtration rate (GFR), which is estimated from the serum creatinine. We define mild injury as a serum creatinine that is increased to <0.5 mg/dL above baseline and moderate to severe injury as a serum creatinine that is increased to ≥0.5 mg/dL above baseline. However, the absolute change in creatinine should be evaluated in the context of the baseline creatinine. For patients with chronic kidney disease (CKD) and thus a higher creatinine at baseline, small fluctuations in creatinine are common. For such patients, mild injury may be better defined as a less than 50 percent change in creatinine and moderate to severe injury defined as a greater than 50 percent change in creatinine. Among patients with a relatively low baseline serum creatinine, smaller changes may reflect a significant reduction in kidney function. For example, if a patient has a baseline serum creatinine of 0.6 mg/dL, an increase of 0.3 mg/dL is significant.

For most patients with mild injury, we follow a stepwise approach that begins with assessment of volume status and the exclusion of drugs that are nephrotoxins or cause prerenal azotemia (algorithm 1). Common examples of such agents are nonsteroidal anti-inflammatory agents (NSAIDs), angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs), and diuretics. We repeat the serum creatinine in one to two weeks.

If, on repeat testing, the creatinine remains elevated, we perform laboratory and radiographic tests as described below. (See 'Initial testing' below.)

For patients who have moderate or severe injury, we initiate the laboratory and radiographic evaluation immediately (ie, concurrent with holding potential nephrotoxins and restoring euvolemia). (See 'Initial testing' below.)

Initial testing — Initial testing should include a reagent strip urinalysis (dipstick) with automated urine microscopy, the quantification of urine protein or albumin (by random [or "spot"] protein-to-creatinine ratio or albumin-to-creatinine ratio), and a renal ultrasound. Some clinicians also send a serum and urine protein electrophoresis (SPEP and UPEP) at the time of the initial evaluation and, if these are abnormal, a free light chain assay.

Among all patients who are considered at higher risk for multiple myeloma based on key clinical features, we obtain a SPEP and UPEP, with immunofixation, and a serum light chain assay at the time of the initial evaluation. Patients who are considered at higher risk for myeloma include all patients who are >40 years of age who have a documented increase in the serum creatinine within three to six months and no other obvious cause for increased creatinine, such as NSAID use or contrast exposure. Patients who have other manifestations consistent with myeloma are also considered at high risk regardless of whether the creatinine increase is documented to be within three to six months; such manifestations include hypercalcemia, bone pain or radiographic lesions, or anemia that is disproportionate to CKD and otherwise unexplained. (See "Clinical features, evaluation, and diagnosis of kidney disease in multiple myeloma and other monoclonal gammopathies", section on 'Patients presenting with acute or subacute kidney injury'.)

The utility of measuring total urine protein versus albumin is debatable. A more detailed discussion is presented elsewhere (see "Assessment of urinary protein excretion and evaluation of isolated non-nephrotic proteinuria in adults"). Manual urine microscopy for the assessment of urine sediment is best performed by an experienced operator.

We perform imaging in all patients with subacute injury and in those with an increased serum creatinine of unclear duration. In most patients, we perform a renal ultrasound rather than other imaging modalities. However, patients who are suspected of renal or ureteral calculi often undergo non-contrast computed tomography (CT) as an initial imaging test. (See 'Clinical manifestations' above and "Diagnosis and acute management of suspected nephrolithiasis in adults", section on 'Noncontrast CT'.)

The urgency with which the kidney imaging is performed depends upon the rate of creatinine rise or onset of clinical symptoms. Among patients with a rapid rate of creatinine rise or marked symptoms, a referral to the emergency department may be warranted for measurement of post-void residual by ultrasound, placement of a bladder catheter for strict urine volume monitoring, and further evaluation (see "Clinical manifestations and diagnosis of urinary tract obstruction and hydronephrosis"). Even patients with a subjectively normal amount of urine production at home may have severe bladder outlet obstruction, as is observed among patients with slowly progressive prostatic hypertrophy.

The results of the urinalysis and ultrasound generally direct the remainder of the diagnostic evaluation (algorithm 1):

Patients who have evidence of obstruction on ultrasound require further investigation and usually intervention to relieve the obstruction and determine the cause. (See "Clinical manifestations and diagnosis of urinary tract obstruction and hydronephrosis".)

Patients who have a urinalysis and/or albumin-to-creatinine ratio that suggests a glomerular or interstitial lesion should be further evaluated based upon the specific finding on urinalysis or based upon determination of abnormal proteinuria. Among patients with evidence of glomerular bleeding (ie, red blood cell [RBC] casts or dysmorphic RBCs), it is important to perform an expedient evaluation, even if this requires an inpatient work-up. Some glomerular diseases may be rapidly progressive, and timely serology and biopsy evaluations followed by appropriate immunosuppression can drastically improve morbidity associated with them. (See "Urinalysis in the diagnosis of kidney disease" and "Overview of the classification and treatment of rapidly progressive (crescentic) glomerulonephritis".)

Patients with granular casts and renal tubular epithelial cells should be evaluated for acute tubular necrosis (ATN). (See "Etiology and diagnosis of prerenal disease and acute tubular necrosis in acute kidney injury in adults".)

Patients with sterile pyuria should be evaluated for interstitial nephritis. (See "Clinical manifestations and diagnosis of acute interstitial nephritis".)

Patients who have normal renal imaging (no obstruction or other apparent intrinsic process such as polycystic kidney disease [PKD]), minimal proteinuria, and benign urinalysis and microscopy should be evaluated with a SPEP and UPEP, if this has not yet been performed. If either the SPEP or UPEP is abnormal, we obtain immunofixation and a serum free light chain assay. Because of its improved sensitivity over spot UPEP in detecting light chain disease, some clinicians obtain a serum free light chain assay initially rather than SPEP or UPEP [11,12].

The recognition of monoclonal gammopathy by serum or urine electrophoresis or by abnormal ratio of light chains in a patient with kidney disease of uncertain etiology may prompt renal biopsy for definitive diagnosis. Discussion of monoclonal gammopathy of undetermined significance (MGUS), myeloma, and amyloidosis are presented elsewhere. (See "Clinical presentation, classification, and causes of membranoproliferative glomerulonephritis", section on 'Monoclonal gammopathies' and "Clinical features, evaluation, and diagnosis of kidney disease in multiple myeloma and other monoclonal gammopathies" and "Epidemiology, pathogenesis, and etiology of kidney disease in multiple myeloma and other monoclonal gammopathies" and "Renal amyloidosis".)

For patients with an unremarkable initial work-up (including benign urinalysis and absent abnormal proteinuria), further evaluation is determined by the severity of disease and rate of further decline of kidney function. Among patients who have mild injury, the serum creatinine may be repeated in one to two weeks. If the creatinine remains stable, we generally continue to follow it intermittently, until a clear temporal pattern is established. Among patients who have signs and symptoms of rapidly progressive or unexplained systemic disease, a renal biopsy may be warranted, even if the estimated GFR (eGFR) is near normal.

If the creatinine is markedly elevated on initial evaluation without a clear explanation or if an initially mild increase in the creatinine worsens over the course of weeks to months, then a kidney biopsy should be performed, providing there is no clear evidence of chronicity on imaging. A biopsy generally provides more definitive tissue diagnosis and may allow a therapeutic intervention to stave off progression to end-stage renal disease (ESRD).

In some cases, even without kidney biopsy, the etiology of kidney disease can be ascertained with reasonable certainty with tissue diagnosis from other sites. As an example, a bone marrow biopsy among patients with monoclonal gammopathy or a fat pad biopsy among those with amyloidosis may avert the need for a kidney biopsy. Renal biopsy is discussed below and in more detail elsewhere (see "Indications for and complications of renal biopsy"). Additional testing prior to biopsy may also be suggested by the history. As an example, determining lead levels may be indicated among patients with a history of lead exposure. (See "Lead nephropathy and lead-related nephrotoxicity".)

Estimation of glomerular filtration rate — The most common methods utilized to estimate the GFR in adults are the serum creatinine concentration, the creatinine clearance, and GFR estimation equations based upon the serum creatinine concentration and variables such as age, sex, and race. (See "Assessment of kidney function", section on 'Estimation of GFR'.)

The equations that use serum creatinine concentration to estimate GFR were derived in patients with stable kidney function. The use of these equations may lead to errors in estimation of kidney function among patients who are not in steady state, such as those with acute kidney injury (AKI), in whom the GFR is often markedly reduced upon presentation, but there has not yet been adequate time for creatinine concentration to equilibrate. Measuring the serum creatinine over time often allows one to determine whether there is sufficient stability to use estimation equations. (See "Assessment of kidney function".)

Urinalysis — The urinalysis involves both use of a urine dipstick and microscopic examination of the urine sediment. The dipstick can test for protein (albumin), pH, glucose, hemoglobin (or myoglobin), leukocyte esterase and nitrites (reflecting pyuria), and specific gravity. (See "Urinalysis in the diagnosis of kidney disease", section on 'Urine dipstick'.)

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 1). (See "Urinalysis in the diagnosis of kidney disease", section on 'Urine sediment' and "Etiology and diagnosis of prerenal disease and acute tubular necrosis in acute kidney injury in adults", section on 'Urinalysis'.)

Urine volume — The absolute volume of urine production is most helpful in evaluation if it is very low or if it is significantly changing in a single direction (increasing or decreasing). Normal urine output can be maintained even with an abnormally low GFR, as in nonoliguric ATN or in many patients with CKD. As noted above, clear evidence that a patient has become oliguric or anuric, whether by reliable history or by physical exam of volume overload, should prompt more urgent (or emergent) evaluation since oliguria and certainly anuria suggest an AKI or the late stages of a subacute kidney injury. (See 'Overview' above and "Evaluation of acute kidney injury among hospitalized adult patients", section on 'Urine volume'.)

Radiologic studies — A number of radiologic studies are used to evaluate the patient with kidney disease.

Because of safety, ease of use, and the information provided, the most commonly used radiographic technique in patients presenting with kidney disease is renal ultrasonography. Increasing emphasis on controlling catheter-associated urinary tract infections has led to lower utilization of bladder catheters and more common use of bedside bladder scans. (See "Radiologic assessment of renal disease".)

Intravenous contrast agents should be avoided, if possible, in patients with kidney injury of any duration because these contrast media are known to be potentially nephrotoxic. This issue is discussed separately. (See "Prevention of contrast nephropathy associated with angiography".)

Among patients with moderate to advanced kidney disease with eGFR <30 mL/min/1.73 m2, the administration of gadolinium has been associated with the potentially severe syndrome of nephrogenic systemic fibrosis (NSF). Most reported cases have been in chronic dialysis patients, but the syndrome may also occur in those with acute or subacute injury. In such patients, gadolinium-based imaging should be avoided, if possible. This issue is discussed separately. (see "Nephrogenic systemic fibrosis/nephrogenic fibrosing dermopathy in advanced renal failure")

Serologic testing and role of renal biopsy — Depending on the history, physical, radiographic, and urine findings, particularly those which suggest nephritic or nephrotic glomerular disease, serologic testing is ordered to further characterize the etiology of kidney disease (see "Glomerular disease: Evaluation and differential diagnosis in adults"). A native (nontransplanted) kidney biopsy is most commonly obtained when noninvasive evaluation of subacute kidney injury has been unable to establish the correct diagnosis [13,14].

Biopsy may be deferred if other findings and serologic testing strongly support diagnostic and therapeutic decision making and the risk outweighs the benefit. A pregnant woman with nephritic syndrome, positive serologic markers for lupus, and hypocomplementemia, for example, may be treated with immunosuppression for lupus nephritis and the biopsy reconsidered postpartum.

Biopsy may also be deferred if the duration of the increased creatinine is not known and may have been present for longer than three months duration, particularly if imaging suggests chronicity (see 'Overview' above). In addition, as noted above, some patients who have stable CKD resulting from an episode of AKI may be erroneously classified as having subacute kidney injury just because an increased creatinine is detected within three months from a previously normal baseline. Such patients almost always have a history of intervening illness and hospitalization. Such patients should not undergo biopsy, since the biopsy would be unrevealing and specific intervention is not required.

Issues related to renal biopsy, including indications, when biopsy may not be necessary, prebiopsy evaluation, technique, and complications, are discussed separately. (See "Indications for and complications of renal 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 5th to 6th 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 10th to 12th 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: Chronic kidney disease (The Basics)" and "Patient education: Acute kidney injury (The Basics)")

Beyond the Basics topics (see "Patient education: Chronic kidney disease (Beyond the Basics)" and "Patient education: Dialysis or kidney transplantation — which is right for me? (Beyond the Basics)" and "Patient education: Hemodialysis (Beyond the Basics)" and "Patient education: Peritoneal dialysis (Beyond the Basics)" and "Patient education: Protein in the urine (proteinuria) (Beyond the Basics)" and "Patient education: Split urine collection for orthostatic proteinuria (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

Knowledge of the duration of kidney disease often narrows the differential diagnosis of the underlying cause. Subacute kidney injury generally develops over more than 48 hours but in under three months. (See 'Introduction' above and 'Overview' above.)

Subacute kidney injury may be categorized as prerenal (decreased renal perfusion pressure), intrinsic renal (pathology of the vessels, glomeruli, or tubules-interstitium), or postrenal (obstructive). However, diseases often cross these nosologic boundaries. (See 'Major causes and pathogenesis of kidney disease' above.)

Once kidney disease is discovered and duration determined, the underlying cause should be identified. Review of medications and physical examination are very helpful. Initial testing should include reagent strip urinalysis (dipstick) with automated urine microscopy and the quantification of urine protein or albumin (by random or "spot" protein-to-creatinine ratio or albumin-to-creatinine ratio) and a renal ultrasound. The results of the urine studies and ultrasound generally direct the remainder of the diagnostic evaluation (algorithm 1). (See 'Evaluation' above.)

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REFERENCES

  1. Kidney Disease: Improving Global Outcomes (KDIGO) Acute Kidney Injury Work Group. KDIGO Clinical Practice Guideline for Acute Kidney Injury. Kidney Int Suppl 2012; 2:1.
  2. Harper L, Savage CO. ANCA-associated renal vasculitis at the end of the twentieth century--a disease of older patients. Rheumatology (Oxford) 2005; 44:495.
  3. Hedger N, Stevens J, Drey N, et al. Incidence and outcome of pauci-immune rapidly progressive glomerulonephritis in Wessex, UK: a 10-year retrospective study. Nephrol Dial Transplant 2000; 15:1593.
  4. Rose BD. Pathophysiology of Renal Disease, 2nd ed., McGraw-Hill, New York 1987. p.41.
  5. Moghazi S, Jones E, Schroepple J, et al. Correlation of renal histopathology with sonographic findings. Kidney Int 2005; 67:1515.
  6. Manley JA, O'Neill WC. How echogenic is echogenic? Quantitative acoustics of the renal cortex. Am J Kidney Dis 2001; 37:706.
  7. Platt JF, Rubin JM, Bowerman RA, Marn CS. The inability to detect kidney disease on the basis of echogenicity. AJR Am J Roentgenol 1988; 151:317.
  8. Kitamoto Y, Tomita M, Akamine M, et al. Differentiation of hematuria using a uniquely shaped red cell. Nephron 1993; 64:32.
  9. Köhler H, Wandel E, Brunck B. Acanthocyturia--a characteristic marker for glomerular bleeding. Kidney Int 1991; 40:115.
  10. Esson ML, Schrier RW. Diagnosis and treatment of acute tubular necrosis. Ann Intern Med 2002; 137:744.
  11. Holding S, Spradbery D, Hoole R, et al. Use of serum free light chain analysis and urine protein electrophoresis for detection of monoclonal gammopathies. Clin Chem Lab Med 2011; 49:83.
  12. Katzmann JA. Screening panels for monoclonal gammopathies: time to change. Clin Biochem Rev 2009; 30:105.
  13. Madaio MP. Renal biopsy. Kidney Int 1990; 38:529.
  14. Appel GB. Renal biopsy: How effective, what technique, and how safe. J Nephrol 1993; 6:4.
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