D-serine nephrotoxicity. The nature of proteinuria, glucosuria, and aminoaciduria in acute tubular necrosis.

Administration of D-serine to rats induced acute necrosis of the proximal straight tubules, proteinuria, glucosuria, and aminoaciduria. Proteinuria and glucosuria developed at the onset of tubular necrosis and disappeared when the tubules were completely relined by new epithelium. Our findings suggest (1) that abnormal loss of protein and glucose in urine is due to diffusion of these substances from interstitium to tubular fluid across the denuded permeable basement membranes of the necrotic tubules, and (2) that tubular cells normally are a barrier to diffusion of certain solutes betweeen interstitial and tubular fluids. Amino-aciduria preceded the onset of tubular necrosis and increased excretion of some amino acids persisted after tubular repair. Thus, D-serine-induced aminoaciduria may be due to impaired reabsorption of amino acids by the injured proximal straight tubules, as well as by backward diffusion of amino acids from the interstitium.