As discussed in Chapter 12, proteinuria is not itself a renal function test but almost invariably accompanies serious renal damage. Its severity does not necessarily correlate with the amount of damaged renal parenchyma or the status of any one renal function or group of systems. Its presence and degree may, in association with other findings, aid in the diagnosis of certain syndromes or disease entities whose renal pathologic findings are known. Proteinuria may be secondary to benign or extra-renal etiologies or even to contamination of the specimen.

One question that continually arises is the significance of small degrees of proteinuria. The urine protein reference range lower limit is usually stated in textbooks to be 10 mg/100 ml (0.1 g/L). Generally speaking, values of up to 30 mg/100 ml are within normal range; 30-40 mg/100 ml may or may not be significantly abnormal. It should be noted that reference values in terms of total urinary protein output per 24 hours may be up to 100 mg/24 hours. Values stated in terms of milligrams per 24 hours may not coincide with values expressed in terms of milligrams per 100 ml due to varying quantities of diluent water. One exception to conventional reference values is diabetes mellitus, in which lesser degrees of albuminuria may reflect early renal damage and may suggest need for revised therapy (Chapter 28). It must be stressed that duration of proteinuria is even more important than quantity, especially at low values. As an example, 60 mg/100 ml (0.4 g/L) may be significant if this level persists. This becomes clear by examining the list of possible causes of proteinuria (Chapter 12). Intrinsic renal disease is usually associated with persistent proteinuria, whereas the proteinuria seen with many of the extrarenal types quickly disappears if the primary disease is successfully treated. However, this does not always hold true, and one must remember that a single disease may cause permanent damage to more than one organ. For example, arteriosclerosis or hypertension may reduce or destroy functioning kidney tissue by means of arteriolar nephrosclerosis, although cardiac symptoms due to heart damage may overshadow the renal picture.

A common situation is the patient who has asymptomatic proteinuria alone or in association with a disease in which it is not expected. The first step is to repeat the test after 2 or 3 days (in clinically healthy persons) or when the presenting disease is under control (in hospitalized patients) using an early morning specimen to avoid orthostatic proteinuria. This is important because orthostatic proteinuria is common; several reports indicate that it is the cause in about 20% (range, 15%-70%) of healthy young men with proteinuria on routine urinalysis. If proteinuria persists and orthostatic proteinuria is ruled out, the microscopy report should be analyzed for any diagnostic hints. Care should be taken to prevent contamination of the urine specimen, especially in female patients. The presence and degree of hematuria or pyuria suggest a certain number of diseases. If either is present, there should be a careful search for RBC or white blood cell (WBC) casts. A careful history may elicit information of previous proteinuria or hematuria, suggesting chronic glomerulonephritis, or previous kidney infection or calculi, which favors chronic pyelonephritis. Uremia due to chronic bilateral renal disease often has an associated hypertension. (Of course, hypertension may itself be the primary disease and cause extensive secondary renal damage.) In addition, a low-grade or moderate anemia, either normochromic or slightly hypochromic and without evidence of reticulocytosis or blood loss, is often found with severe chronic diffuse renal disease. The next step is to note any random specific gravities obtained. If one measurement is normal (i.e., >1.020), renal function is probably adequate. If all are lower, one can proceed to a concentration or creatinine clearance test, since low random specific gravities may simply mean high water excretion rather than lack of urine-concentrating ability. If the creatinine clearance rate is mildly or moderately reduced, the patient most likely has only mild or possibly moderate functional loss. If the creatinine clearance rate is markedly abnormal and the BUN level is normal with no hypertension or anemia present, the patient most likely has severe diffuse bilateral renal abnormality but not completely end-stage disease. When the BUN level is elevated but the serum creatinine level is still within reference range, some test or tests, such as the free water clearance, could be done to differentiate prerenal azotemia from early renal failure (acute or chronic). When both the BUN and serum creatinine levels are elevated and there is no anemia or hypertension, the differential diagnosis of prerenal azotemia or renal failure must still be made, but prerenal azotemia becomes less likely. When the BUN and serum creatinine levels are significantly elevated and there is anemia and other evidence of uremia, the prognosis is generally very bad, although some patients with definite uremia may live for years with proper therapy. There are exceptions to the situations just outlined but not too many.