Many use the term “uremia” as a synonym for azotemia, although uremia is a syndrome and should be defined in clinical terms. A BUN level of approximately 100 mg/100 ml is usually considered to separate the general category of acute reversible prerenal azotemias from the more prolonged acute episodes and chronic uremias. In general, this is an accurate distinction, but there is a small but important minority of cases that do not follow this rule. Thus, some uremics seem to stabilize at a lower BUN level until their terminal episode, whereas a few persons with acute transient azotemia may have a BUN level close to 100 mg/100 ml (36 mmol/L) and, rarely, more than 125 mg/100 ml (45 mmol/L), which rapidly falls to normal levels after treatment of the primary systemic condition. It must be admitted that easily correctable prerenal azotemia with an appreciably elevated BUN level is almost always superimposed on previous subclinical renal damage or function loss. Although the previous damage may not have been severe enough to cause symptoms, the functional reserve of these kidneys has been eliminated by aging changes, pyelonephritis, or similar conditions. The same is usually true for azotemia of mild levels (30-50 mg/100 ml [11-18 mmol/L]) occurring with dehydration, high protein intake, cardiac failure, and other important but not life-threatening situations. After the BUN level has returned to normal levels, a creatinine clearance determination will allow adequate evaluation of the patient’s renal status.

The onset of oliguria always raises the question of possible renal failure. For a long time oliguria was considered a constant clinical sign of acute renal failure (also called acute tubular necrosis); however, it is now recognized that 30%-50% of patients with acute renal failure do not have oliguria (literature range, 20%-88%). Normal adult urine volume is 500-1,600 ml/24 hours (upper limit depends on fluid intake); a volume less than 400 ml/24 hours is considered to represent oliguria if all urine produced has actually been collected. Incomplete collection or leakage around a catheter may give a false impression of oliguria. Occasionally a patient develops oliguria and progressive azotemia, and it becomes necessary to differentiate between prerenal azotemia, which is correctable by improving that patient’s circulation, and acute renal tubular necrosis. This problem most frequently occurs after a hypotensive episode or after surgery.

The differential diagnosis of azotemia includes prerenal azotemia, acute renal failure (acute tubular necrosis), and chronic renal failure. Two tests, filtered fraction of sodium and the free water clearance, under certain conditions, are usually capable of differentiating prerenal azotemia from renal failure. In general, if the serum creatinine level as well as the BUN level is elevated, this is more suggestive of renal failure than prerenal azotemia. However, this assumes that the BUN elevation is discovered very early after onset. Under most conditions the differentiation between prerenal azotemia and acute tubular necrosis by means of the serum creatinine level is not sufficiently reliable. A number of other tests have been proposed for the same purpose (Chapter 37). These tests have been found useful by some investigators but not useful in a sufficient number of cases by others. Part of the difference of opinion is based on the test criteria each investigator uses to differentiate prerenal azotemia from acute tubular necrosis. In general, when the test criteria are structured simply to provide best statistical separation for all cases of prerenal azotemia and acute tubular necrosis, there is considerable overlap between the two groups. When the criteria are deliberately structured to separate out either the cases of prerenal azotemia or those of acute tubular necrosis and the diagnosis is made only on the remaining cases, the test becomes insufficiently sensitive. A good example is the test using urine excretion of sodium. If one uses the urine sodium cutoff point of less than 15 mEq/L (mmol/L), the test has excellent reliability in ruling out acute tubular necrosis. However, one investigator found that 67% of patients with acute tubular necrosis and 63% of patients with prerenal azotemia had urine sodium values between 15 and 40 mEq/L (mmol/L). Therefore, if one wishes to use less than 15 mEq/L (mmol/L) as a diagnostic limit to avoid the overlap, one excludes 63% of this investigator’s prerenal azotemia cases, and the test becomes poorly sensitive for prerenal azotemia, despite excellent specificity created by ruling out nearly all cases of acute tubular necrosis.

Part of the problem is the fact that acute tubular necrosis may be oliguric or nonoliguric. Some test criteria that enable good separation of prerenal azotemia and oliguric acute tubular necrosis are not as good in distinguishing prerenal azotemia from nonoliguric acute tubular necrosis. If the test cutoff points are restructured to include both oliguric and nonoliguric acute tubular necrosis, the overall accuracy of the test may suffer.

In occasional cases, initial tests indicate that some renal function still remains, but the patient then develops acute tubular necrosis due to progression of the underlying disease or superimposition of some other factor.

Urinalysis may provide useful information in patients with acute tubular necrosis. Red blood cell (RBC) or hemoglobin casts suggest glomerulonephritis, subacute bacterial endocarditis, transfusion reaction, and collagen disease. Uric acid crystals may provide a clue to uric acid nephropathy. Strongly positive urine chemical tests for hemoglobin without significant microscopic RBC raises the possibility of myoglobin.

Differentiation of acute tubular necrosis and chronic renal failure is extremely difficult without clinical evidence of acute onset. If the patient does not have an elevated serum creatinine level when first investigated, or if the creatinine level is only mildly elevated and there is no anemia or other evidence of uremia, the evidence is more in favor of acute tubular necrosis than chronic renal failure. Even more difficulty exists when a patient develops acute tubular necrosis and the question is raised as to whether the patient’s renal function is likely to recover. Radioisotope studies with a scintillation camera may be helpful. Bilateral poor uptake, poor cortex-pelvis transit, and decreased blood flow suggest chronic diffuse renal disease. Good cortex uptake, poor cortex-pelvis transit, and good blood flow are more indicative of acute tubular necrosis or prerenal azotemia. Isotope techniques can demonstrate postrenal obstruction and frequently can visualize the kidneys when the IVP cannot.

In a patient with uremia (chronic azotemia), there is no good way to determine prognosis by laboratory tests. The degree of azotemia does not correlate well with the clinical course in uremia except in a very general way.

Other diagnostic tests

Addis count. This procedure is used in suspected subclinical cases of chronic glomerulonephritis to demonstrate 12-hour abnormally increased rates of RBCs and cast excretion too small to exceed the normal range in ordinary random specimen microscopic examinations. If the random urine specimen already shows hematuria or pyuria, and if contamination can be ruled out by catheter or clean catch collection technique, the Addis count cannot do anything more than show the same abnormality. Addis counts are very rarely necessary with a good history and adequate workup.

Renal biopsy. This procedure is now widely used. It may be the only way to find which disease is present, but it should be reserved for patients whose treatment depends on exact diagnosis. The general category of most renal disease entities can be inferred using routine methods. Because of the random sample nature of renal biopsies, ordinary light microscopy more often than not shows only nonspecific changes reflecting the result rather than the etiology of the disease process, and frequently renal biopsies are requested only for academic rather than for practical diagnostic or therapeutic reasons. In children, electron microscopy and immunofluorescent techniques are more useful than light microscopy.