New form of urinary albumin in early diabetes.

A report in this issue by Osicka and Comper (1) points out the complexity of the urinary excretion of albumin in mild diabetes mellitus and raises a challenge to clinical chemists for the early detection of renal damage. The authors demonstrate a hitherto unrecognized form of albumin that is not detected by customary immunoassays of urine. For background, let us look first at the current understanding of the excretion of albumin by healthy kidneys. The two kidneys together treat ∼650 mL of plasma every minute. This means that, in the course of a day, ∼37 000 g of serum albumin pass through the glomeruli, of which ∼1.3 g leak through the glomerular walls (2). This is ∼0.004% of the presented albumin, an amazing efficiency for any filtration system. It is equally amazing that only ∼15 mg, ∼1%, of the 1.3 g of leaked albumin appears in the urine daily as determined by RIA. The remainder is not saved as albumin, but is degraded to fragments by the renal proximal tubules. (In perspective, this renal degradation, 1.3 g, is ∼10% of the daily albumin turnover of 14 g.) The albumin is taken up into endosomes of the proximal tubular cells. These endosomes then merge with lysosomes, where lysosomal enzymes, cathepsins B and D, and particularly the cysteine proteases (3) cleave the …