The urine dipstick, performed as a part of the routine urinalysis, is the method that most frequently identifies the presence of proteinuria, specifically albuminuria. However, since the dipstick measurement will vary depending on whether the urine sample is concentrated or dilute, a 24-hour urine collection is the only reliable way to quantify proteinuria. The presence of nephrotic syndrome (> 3.5 g/24 h of protein) has significant medical implications. Thus, any individual with persistent proteinuria by dipstick should complete a 24-hour urinary protein determination. A finding of over 150 mg/24 h of protein is the criterion for proteinuria.

Proteinuria is not a disease but a clinical marker signifying that an underlying renal abnormality exists. When caused by a renal or systemic disease, proteinuria is accompanied by other clinical abnormalities—elevated BUN and serum creatinine levels, abnormal urinary sediment, elevated blood pressure measurements, or evidence of systemic illness (eg, fever, rash, vasculitis). Severe proteinuria, generally in the nephrotic range (> 3.5 g/24 h) is usually associated with glomerulonephritis. Lesser amounts of proteinuria, though not excluding glomerulonephritis, usually signify tubulointerstitial nephritis. "Benign" proteinuria includes functional, idiopathic transient, orthostatic, and intermittent proteinuria.

Functional proteinuria occurs in association with conditions such as high fever, strenuous exercise, and congestive heart failure. Up to 10% of patients admitted for acute medical illnesses have transient proteinuria. The proteinuria is glomerular in origin, caused by renal hemodynamic alterations that increase the glomerular filtration of plasma proteins, and clears with resolution of the precipitating event.

Idiopathic transient proteinuria is a benign physiologic phenomenon in children and young adults that comes and goes. Intermittent proteinuria is a condition in which proteinuria is found in half of all urine specimens tested in an individual over a number of years. Most renal biopsies are normal and the condition appears to be benign, especially in young people.

Orthostatic proteinuria is a benign condition that does not require further diagnostic evaluation and usually remits spontaneously. It is confirmed by collecting the 24-hour urine in two 12-hour samples. The first 12-hour specimen is collected during the day, when the patient is active and upright; the second is collected overnight while the patient is resting and supine. Significant proteinuria (150 mg/dL) when the patient is upright (first 12 hours) and under 75 mg/dL during the 12 hours when sleeping and supine establishes the diagnosis.

The glomerular filtration rate (GFR) is used as a clinical assessment of renal function. The creatinine clearance (Ccr) is the clinical measurement that most closely approximates GFR. The BUN and serum creatinine (Scr) often but not always correlate with the GFR.

Amino acids from endogenous (muscle) and exogenous (dietary) protein generate NH3, which is converted in the liver to urea and measured in the blood as urea nitrogen. Urea is filtered by the glomerulus, and approximately 50% is reabsorbed by the tubules. However, the percentage absorbed varies inversely with urine flow rates, so that in volume-depleted states (prerenal azotemia), the BUN is elevated out of proportion to the fall in GFR. BUN can be affected by other factors as well, thus making it an unreliable index of GFR.

Creatinine is produced by the nonenzymatic dehydration of muscle creatine. Because the daily production of creatinine is relatively constant, its clearance is a relatively reliable index of GFR.

The measurement of creatinine clearance requires the completion of a 24-hour urine collection. Complete urine collections for males should have total creatinine concentrations of 15–25 mg/kg body weight/24 h and for females 10–20 mg/kg body weight/24 h.

The Ccr declines by 1 mL/min/y over the age of 40 as part of the aging process. In individuals with GFRs of 20 mL/min/1.73 m2 or less, the Ccr may overestimate the GFR, since a small portion of the urinary creatinine is due to the secretion of creatinine by the renal tubules.