Azotemia Workup
- Author: Moro O Salifu, MD, MPH, FACP; Chief Editor: Vecihi Batuman, MD, FACP, FASN more...
Laboratory Studies
- Obtain CBC count, biochemical profile, urinalysis, and urine electrolytes for the initial evaluation. In addition to establishing the presence of systemic disease, clues for the origin of azotemia may emerge from these tests. Diagnostic indices commonly used to differentiate prerenal from intrarenal or postrenal azotemia are summarized in the image below.
Diagnostic Images in Azotemia: Although these indices are helpful, it is not necessary to perform all these tests on a particular patient. Comparison should always be made with the patients baseline values to identify trends consistent with increase or decrease in effective circulating volume. It should be noted that use of some of these indices may be limited in certain clinical conditions, such as in anemia (hematocrit), hypocalcemia (serum calcium), decreased mucle mass (serum creatinine), liver disease (BUN, total protein, albumin), poor nutritional state (BUN, total protein, albumin) and use of diuretics (urine Na). FEUrea and FELi appear to be better in assessing prerenal status in patients on diuretics. - Prerenal azotemia
- In prerenal azotemia, hemoconcentration results in elevation of hematocrit, total protein/albumin, calcium, bicarbonate, and uric acid from their baselines.
- Oliguria (urine volume is < 500 mL/d), anuria (< 100 mL/d), high urine specific gravity (>1.015), normal urinary sediment, and low urinary sodium (< 20 fractional excretion of sodium [FENa] < 1.0%) are seen.
- When volume depletion is predominant, exaggerated proximal tubular reabsorption results in azotemia, hypernatremia, elevated levels of calcium, uric acid, and bicarbonate, while hemoconcentration results in the elevation of total protein, albumin, and hematocrit levels from their baselines. When hypoperfusion due to decreased cardiac output or effective arterial volume is present, patients exhibit edema, hyponatremia, and hypoalbuminemia. The hematocrit, calcium, uric acid, and bicarbonate levels vary widely in this category. These patients often are critically ill.
- The FENa has traditionally been used to differentiate prerenal azotemia from ATN. An FENa below 1% is suggestive of a prerenal cause (eg, volume depletion), while an FENa above 2% is suggestive of ATN. Since the FENa is based on the fact that sodium reabsorption is enhanced in the setting of volume depletion, active use of diuretics may elevate the FENa even when volume depletion is present. The fractional excretion of urea or fractional excretion of urea nitrogen (FEUrea), or the fractional excretion of uric acid (FEUA), are the alternatives, because urea and uric acid excretion are not influenced by diuretics. An FEUrea of less than 35% or an FEUA of less than 25% is suggestive of a prerenal etiology of ARF, while an FEUrea of more than 50% or an FEUA above 25% suggests ATN.[3]
- Intrarenal azotemia
- Anemia, thrombocytopenia, hypocalcemia, and high anion gap metabolic acidosis may suggest intrarenal azotemia.
- Low urine specific gravity (< 1.015), active urinary sediment (see Pathophysiology), high urinary sodium (>40 mEq/L), FENa (>5%), plasma BUN–creatinine ratio (< 20), and low urine osmolality may suggest intrarenal azotemia.
- For patients with long-standing CKD, a renal sonogram usually shows small, contracted kidneys. Some causes of CKD can be associated with normal or large-sized kidneys, such as HIV nephropathy, diabetes, and renal amyloidosis. The renal sonogram usually is diagnostic for patients with polycystic kidney disease. In patients with active urinary sediment, progressive azotemia, proteinuria, and/or normal-sized kidneys on sonogram, a renal biopsy should be considered. Consultation with a nephrologist is imperative in all such patients.
- Postrenal azotemia
- Urinary indices in postrenal azotemia due to complete bilateral obstruction are usually nondiagnostic. The prima facie finding here is anuria and, occasionally, hypertension. Urine output still may be present if overflow (in bladder outlet obstruction) or partial ureteral obstruction is present.
- A Foley catheter should be inserted as part of the initial evaluation to rule out obstruction below the bladder outlet. Unilateral ureteral obstruction rarely leads to azotemia; it occurs acutely (due to obstruction from calculi, papillary necrosis, or hematoma), producing renal colic, or may be chronic and asymptomatic, producing hydronephrosis.
- Bilateral partial obstruction may be associated with azotemia in the presence of normal urine output. When patients are subjected to maneuvers that increase urinary flow (eg, diuretic renogram, perfusion pressure flow studies), they may exhibit an increase in size or pressure of the collecting system or experience pain.
- In addition to azotemia, polyuria due to loss of concentrating ability and type 1 renal tubular acidosis, with hyperkalemia, hypercalcemia from metastatic pelvic tumor, and elevated prostate-specific antigen (PSA), may be clues to postrenal azotemia. Hydronephrosis in the absence of hydroureter may be seen in early (< 3 d) obstruction, retroperitoneal process, or partial obstruction. Renal sonogram is the test of choice to rule out obstructive uropathy. If renal sonogram is equivocal, a Lasix washout scan, as discussed below in Imaging Studies, should be performed.
Imaging Studies
- Plain film of abdomen
- If symptoms suggest nephrolithiasis, a plain film of the abdomen is performed to screen for presence of a radiopaque stone.
- Calcium-containing, struvite, and cystine stones can be identified, but radiolucent ones, such as uric acid stones, will be missed.
- Renal sonogram is the most commonly used renal imaging study because of its ease of use and broad application for the following:
- Renal sonogram can determine renal size, which is important when considering renal biopsy. Small kidneys (< 9 cm) may be suggestive of scarring from advanced renal disease, whereas normal or large kidneys with smooth contours may indicate a potentially reversible process.
- It can differentiate cystic lesions from solid lesions.
- It is a test of choice for diagnosing urinary tract obstruction.
- Renal sonogram can detect kidney stones.
- Doppler renal ultrasonography can be used to evaluate renal vascular flow (eg, renal vein thrombosis, renal infarction, renal artery stenosis).
- Intravenous pyelogram
- The risk of contrast nephrotoxicity should be weighed against the benefits of making a diagnosis that will not change management.
- Intravenous pyelogram can provide detailed information concerning calyceal anatomy and the size and shape of the kidney.
- It is extremely useful for detecting renal stones.
- It is the preferred technique in the evaluation and diagnosis of certain structural disorders, such as chronic pyelonephritis, medullary sponge kidney, and papillary necrosis.
- It can provide data on the degree of obstruction.
- Computed tomography (CT) scanning[4] is complementary to ultrasonography, especially when the diagnosis is uncertain. Contrast nephrotoxicity should be weighed against the benefits. CT scanning does the following:
- It can be used to distinguish (in most cases) neoplastic lesions from simple cyst and is the criterion standard for radiologic diagnosis of renal stone disease, including radiolucent stones.
- It can be used to evaluate and stage renal cell carcinoma and to diagnose renal vein thrombosis. It can diagnose polycystic kidney disease with higher sensitivity than ultrasonography, particularly in younger patients.
- Magnetic resonance imaging (MRI) or magnetic resonance angiography (MRA)
- MRI or MRA is used only when CT scanning and ultrasonography are nondiagnostic.
- They are the criterion standard for diagnosis of renal vein thrombosis.
- They are used in the evaluation of renal cell carcinoma and renal artery stenosis or vasculitis.
- Renal arteriography
- The availability of procedures not requiring contrast material (ie, sonography, MRI, MRA) and the risk of contracting contrast nephrotoxicity have reduced use of this test.
- Renal arteriography is used in polyarteritis nodosa and renal artery stenosis to demonstrate multiple aneurysms and/or stenoses.
- Renal venography
- Risk of contrast nephrotoxicity is present.
- Renal venography is the criterion standard for diagnosis of renal vein thrombosis.
- Radionuclide studies
- Technetium dimercaptosuccinic acid (99m Tc DMSA) distributes heavily within the renal parenchyma at first pass and so is best for detecting renal parenchymal scarring.
- Technetium diethylenetriamine pentaacetic acid (99m Tc DTPA) is heavily filtered at first pass and therefore is best for qualitative assessment of renal function (filtration, and excretion). Because it is heavily filtered, it is most sensitive in detecting urine leaks after renal transplant. For the same reason, it is also used concomitantly with Lasix washout scan (see below) for assessing functional obstruction of the collecting system.
- Mercaptoacetyltriglycine (MAG3) scan is evenly distributed at first pass in the kidney and so is best for qualitative assessment of perfusion, filtration, and excretion. It is the preferred test after renal transplantation, to assess the 3 aspects of function. It can be used to detect urine leaks or functional obstruction with Lasix, although99m Tc DTPA scan remains the test of choice for these conditions. Voiding cystourethrogram can be performed with a radionuclide study, to detect vesicoureteral reflux.
- Retrograde or anterograde pyelography
- This test has limited use because of the availability of sonography.
- It may be used in patients with a high index of suspicion for hydronephrosis for whom sonogram results are normal, such as in retroperitoneal fibrosis.
- Lasix washout scan
- The 2 agents used in performing Lasix washout renal scans are99m Tc DTPA and MAG3.
- Usually, the renal scan is performed first. Then, if needed, the Lasix washout is performed after the radionuclide has accumulated in the collecting system. Lasix is used as a part of the renogram to separate nonobstructive hydronephrosis from obstructive hydronephrosis. If there is no obstruction, flow induced by Lasix and containing little or no radionuclide will fill the collecting system, washing out urine that contains radionuclide from the system. However, in the presence of obstruction, the radionuclide is not washed out as quickly.
- The half life or clearance of the radioisotope is plotted on a curve. A half life of less than 10 minutes is considered normal, of greater than 20 minutes is considered obstruction, and of between 10-20 minutes is subject to further interpretation.
- Conditions that can make it difficult to interpret the Lasix washout curve include a megaureter or pelvis that accepts a large bolus of urine and poor renal function. In patients with a megaureter, it can be difficult to determine when the renal pelvis is full, and, in patients with renal disease, Lasix onset of action may be prolonged. To overcome the problem of poor renal function or relative hypovolemia if a patient has been fasting, the patient should be well hydrated with IV fluids prior to the study.
- The test also is operator dependent, as the Lasix should be administered when it is thought that the renal pelvis is full. A full bladder also delays washout of isotope. Therefore, the patient's bladder needs to be catheterized before the study can be performed.
Procedures
- Renal biopsy is indicated when glomerulonephritis, vasculitis, and, occasionally, interstitial nephritis are suspected to establish correct diagnosis and to guide therapy. The following are common indications for renal biopsy:
- Isolated glomerular proteinuria or hematuria
- Nephrotic syndrome
- Acute nephritic syndrome
- Unexplained acute or subacute renal failure
- Percutaneous renal biopsy complications
- Severe bleeding causing hypotension occurs in 1-2% of patients.
- Bleeding requiring transfusion occurs in about 0.1-0.3% of patients. Bleeding complications can be minimized by data obtained from tests for bleeding time, prothrombin time, partial thromboplastin time, and platelet count. NSAIDs should be stopped at least 1 week prior to a scheduled elective biopsy. Patients on Coumadin should be started on heparin at least 3 days prior to renal biopsy. Patients on heparin for other reasons should be stopped for at least 1 day.
- Percutaneous renal biopsy contraindications
- Contraindications include uncorrectable bleeding diathesis, small kidneys, severe hypertension, multiple bilateral cysts or renal tumor, hydronephrosis, active renal or perirenal infection, and uncooperative patient.
- Percutaneous biopsy may be performed in selected patients with a solitary kidney because of the generally low risk of bleeding.
- Open renal biopsy may be performed if a percutaneous attempt either is unsuccessful or contraindicated and if the benefits of diagnosis outweigh the risks.
- When percutaneous biopsy is contraindicated but a diagnosis is necessary, a transvenous transjugular renal core biopsy can be performed.[5] With this approach, bleeding occurs intravascularly, thereby reducing the risk of hematoma.
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