Clinical role of urinary low molecular weight proteins: their diagnostic and prognostic implications

In traditional urinalysis, casts in the urinary sediment are the only specific signs of renal tubular injury. When tubulo-interstitial fibrosis became the most predictive sign of renal outcome, tubular enzymes derived from proximal tubular brush border or lysosomes were used as early markers of nephrotoxicity and other tubular dysfunctions. More recently, the increase in low molecular weight proteins in urine, assumed to be freely filtered, was reported to reflect tubular dysfunction. This can have pre-renal, renal and post-renal causes. Among the pre-renal causes, Bence Jones protein (immunoglobulin light chains), myoglobin and haemoglobin are signs of extra-renal diseases. On the other hand, beta(2)-microglobulin, alpha(1)-microglobulin, retinol binding protein and lysozyme were recommended as tubular markers. Because of its lower pre-renal variability and higher stability in urine during storage in the bladder and urinary vessel, alpha(1)-microglobulin proved to be the most valuable in early detection, renal outcome prediction and easy inclusion in routine analytical programmes. In addition, other markers of intra-renal inflammatory processes may help to mirror histological changes occurring in the kidney. Future guidelines should therefore include low molecular protein as a tubular marker.