Acute Renal Failure Workup

Several laboratory tests are useful for assessing the etiology of AKI, and the findings can aid in proper management. These tests include complete blood count (CBC), serum biochemistries, urine analysis with microscopy, and urine electrolytes.

In some cases, renal imaging is useful, especially if renal failure is secondary to obstruction. The American College of Radiology recommends ultrasonography, preferably with Doppler methods, as the most appropriate imaging method in AKI.^[10]

Although increased levels of BUN and creatinine are the hallmarks of renal failure, the rate of rise is dependent on the degree of renal insult as well as on protein intake with respect to BUN.

The ratio of BUN to creatinine is an important finding, because the ratio can exceed 20:1 in conditions in which enhanced reabsorption of urea is favored (eg, in volume contraction); this suggests prerenal acute kidney injury (AKI).

BUN may be elevated in patients with GI or mucosal bleeding, steroid treatment, or protein loading.

Assuming no renal function, the rise in BUN over 24 hours can be roughly predicted using the following formula: 24-hour protein intake in milligrams X 0.16 divided by total body water in mg/dL added to the BUN value.

Assuming no renal function, the rise in creatinine can be predicted using the following formulas:

• For males: weight in kilograms X [28 - 0.2(age)] divided by total body water in mg/dL added to the creatinine value
• For females: weight in kilograms X [23.8 - 0.17(age)] divided by total body water added to the creatinine value

As a general rule, if serum creatinine increases to more than 1.5 mg/dL/d, rhabdomyolysis must be ruled out.

The peripheral smear may show schistocytes in conditions such as HUS or TTP.

A finding of increased rouleaux formation suggests multiple myeloma, and the workup should be directed toward immunoelectrophoresis of serum and urine.

The presence of myoglobin or free hemoglobin (eg, pigment nephropathy), increased serum uric acid level (eg, tumor lysis syndrome), serum lactate dehydrogenase (LDH) (eg, renal infarction), and other related findings may help to further define the etiology of acute kidney injury (AKI).

Serologic tests for antinuclear antibody (ANA), ANCA, anti-GBM antibody, hepatitis, and antistreptolysin (ASO) and complement levels may help to include and exclude glomerular disease.

Although serologic tests can be informative, the costs can be prohibitive if these tests are not ordered judiciously.

Findings of granular, muddy-brown casts are suggestive of tubular necrosis (see the image below). The presence of tubular cells or tubular cell casts also supports the diagnosis of ATN. Often, oxalate crystals are observed in cases of ATN.

Reddish brown or cola-colored urine suggests the presence of myoglobin or hemoglobin, especially in the setting of a positive dipstick for heme and no red blood cells (RBCs) on the microscopic examination.

The dipstick assay may reveal significant proteinuria as a result of tubular injury.

The presence of RBCs in the urine is always pathologic. Eumorphic RBCs suggest bleeding along the collecting system. Dysmorphic RBCs or RBC casts indicate glomerular inflammation, suggesting glomerulonephritis is present.

The presence of WBCs or WBC casts suggests pyelonephritis or acute interstitial nephritis. The presence of urine eosinophils is helpful in establishing a diagnosis but is not necessary for allergic interstitial nephritis to be present.

The presence of eosinophils, as visualized with Wright stain or Hansel stain, suggests interstitial nephritis but can also be seen in urinary tract infections, glomerulonephritis, and atheroembolic disease.

The presence of uric acid crystals may represent ATN associated with uric acid nephropathy.

Calcium oxalate crystals are usually present in cases of ethylene glycol poisoning.

Urine electrolyte findings also can serve as valuable indicators of functioning renal tubules. The fractional excretion of sodium (FENa) is the commonly used indicator. However, the interpretation of results from patients in nonoliguric states, those with glomerulonephritis, and those receiving or ingesting diuretics can lead to an erroneous diagnosis.

FENa can be a valuable test for helping to detect extreme renal avidity for sodium in conditions such as hepatorenal syndrome. The formula for calculating the FENa is as follows:

FENa = (U_Na/P_Na) / (U_Cr/P_Cr) X 100

Calculating the FENa is useful in acute kidney injury (AKI) only in the presence of oliguria.

In patients with prerenal azotemia, the FENa is usually less than 1%. In ATN, the FENa is greater than 1%. Exceptions to this rule are ATN caused by radiocontrast nephropathy, severe burns, acute glomerulonephritis, and rhabdomyolysis.

In the presence of liver disease, FENa can be less than 1% in the presence of ATN. On the other hand, because administration of diuretics may cause the FENa to be greater than 1%, these findings cannot be used as the sole indicators in AKI.

In patients who are receiving diuretics, a fractional excretion of urea (FEUrea) can be obtained, since urea transport is not affected by diuretics. The formula for calculating the FEUrea is as follows:

FEUrea = (U_urea/P_urea) / (U_Cr/P_Cr) X 100

FEUrea of less than 35% is suggestive of a prerenal state.

An intra-abdominal pressure of less than 10 mm Hg is considered normal and suggests that abdominal compartment syndrome is not the cause of AKI. Patients with an intra-abdominal pressure below 15-25 mm Hg are at risk for abdominal compartment syndrome, and those with bladder pressures above 25 mm Hg should be suspected of having AKI as a result of abdominal compartment syndrome.

A number of biomarkers are being investigated to risk stratify and predict acute kidney injury (AKI) in patients at risk for the disease. The reason for this is because creatinine is a late marker for renal dysfunction and, once elevated, reflects a severe reduction in GFR. The most promising biomarker to date is urinary neutrophil gelatinase-associated lipocalin (NGAL), which has been shown to predict AKI in children undergoing cardiopulmonary bypass surgery.

Breidthardt et al studied a model that combined the markers plasma B-type natriuretic peptide and NGAL and found it to be a strong predictor of early AKI in patients with lower respiratory tract infection.^[11]

A study of adults on the first day of meeting AKI criteria found that urine protein biomarkers and microscopy findings significantly improve upon clinical determination of prognosis.^[12]

A study by Mancini et al has found that extracorporeal cardiopulmonary bypass time did not predict acute renal failure requiring dialysis, suggesting that an risk assessment may be a more reliable marker.^[13]

Renal ultrasonography is useful for evaluating existing renal disease and obstruction of the urinary collecting system. The degree of hydronephrosis does not necessarily correlate with the degree of obstruction. Mild hydronephrosis may be observed with complete obstruction if found early.

Obtaining images of the kidneys can be technically difficult in patients who are obese or in those with abdominal distension due to ascites, gas, or retroperitoneal fluid collection.

Ultrasonographic scans or other imaging studies showing small kidneys suggest chronic renal failure.

Doppler ultrasonography

Doppler scans are useful for detecting the presence and nature of renal blood flow.

Because renal blood flow is reduced in prerenal or intrarenal AKI, test findings are of little use in the diagnosis of AKI. However, Doppler scans can be quite useful in the diagnosis of thromboembolic or renovascular disease.

Increased resistive indices can be observed in patients with hepatorenal syndrome.

Radionuclide imaging with technetium-99m-mercaptoacetyltriglycine (^99m Tc-MAG3),^99m Tc-diethylenetriamine penta-acetic acid (^99m Tc-DTPA), or iodine-131 (¹³¹ I)-hippurate can be used to assess renal blood flow and tubular functions.

Because of a marked delay in tubular excretion of radionuclide in prerenal disease and intrarenal disease, the value of these scans is limited.

This can be helpful in establishing the diagnosis of renal vascular diseases, including renal artery stenosis, renal atheroembolic disease, and atherosclerosis with aortorenal occlusion, and in certain cases of necrotizing vasculitis (eg, polyarteritis nodosa).

A renal biopsy can be useful in establishing the diagnosis of intrarenal causes of acute kidney injury (AKI) and can be justified if it will change management (eg, initiation of immunosuppressive medications). A renal biopsy may also be indicated when renal function does not return for a prolonged period and a prognosis is required to develop long-term management.

In as many as 40% of cases, renal biopsy results reveal an unexpected diagnosis.

Acute cellular or humoral rejection in a transplanted kidney can be definitively diagnosed only by performing a renal biopsy.