A Diagnostic approach to Proteinuria

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Mechanisms of Proteinuria

Normal barriers to protein filtration begin in the glomerulus, which consists of unique capillaries that are permeable to fluid and small solutes but effective barriers to plasma proteins. The adjacent basement membrane and visceral epithelial cells are covered with negatively charged heparan sulfate proteoglycans.

Proteins cross to the tubular fluid in inverse proportion to their size and negative charge.

Proteins with a molecular weight of less than 20,000 pass easily across the glomerular capillary wall. Conversely, albumin, with a molecular weight of 65,000 Daltons and a negative charge, is restricted under normal conditions. The smaller proteins are largely reabsorbed at the proximal tubule, and only small amounts are excreted. The patho-physiologic mechanisms of proteinuria can be classified as glomerular, tubular or overflow. Glomerular disease is the most common cause of pathologic proteinuria. Several glomerular abnormalities alter the permeability of the glomerular basement membrane, resulting in urinary loss of albumin and immunoglobulins. Glomerular malfunction can cause large protein losses; urinary excretion of more than 2 g per 24 hours is usually a result of glomerular disease

Tubular proteinuria occurs when tubulointerstitial disease prevents the proximal tubule from reabsorbing low-molecular-weight proteins (part of the normal glomerular ultrafiltrate). When a patient has tubular disease, usually less than 2 g of protein is excreted in 24 hours. Tubular diseases include hypertensive nephrosclerosis and tubulo-interstitial nephropathy caused by nonsteroidal anti-inflammatory drugs.

In overflow proteinuria, low-molecular-weight proteins overwhelm the ability of the proximal tubules to reabsorb filtered proteins. Most often, this is a result of the immunoglobulin overproduction that occurs in multiple myeloma. The resultant light-chain immunoglobulin fragments (Bence Jones proteins) produce a monoclonal spike in the urine electrophoretic pattern.

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