GLOMERULAR HANDLING OF CIRCULATING GLYCATED ALBUMIN IN THE NORMAL MOUSE KIDNEY

In the present study, we have evaluated the glomerular handling of cir culating glycated albumin in the normal mouse kidney by quantitative i mmunocytochemistry. Bovine serum albumin (BSA) was glycated in vitro a nd dinitrophenylated. Glycated and nonglycated probes were introduced into the circulation of anesthetized mice and traced by postembedding immunogold cytochemistry after 10 and 30 min of circulation. Endogenou s albumin, as well. as dinitrophenylated native BSA (DNP-BSA) and glyc ated albumins (DNP-gBSA), were localized within the capillary lumen, g lomerular and peritubular basement membranes, and the mesangial matrix . Morphometric evaluation of the labeling over the glomerular basement membrane (GEM) revealed a peak of labeling in the endothelial side fo r either endogenous albumin or DNP-BSA. In contrast, the labeling dist ribution for DNP-gBSA showed a shift toward the epithelial side, sugge sting a further penetration of the glycated probe into the GEM. When c oinjected with gBSA, DNP-BSA was found to display a labeling distribut ion similar to that displayed by DNP-gBSA. These results indicate that the glycated tracer penetrates the normal glomerular wall deeper than the nonglycated one. Moreover, glycated albumin increases the infiltr ation of the nonglycated tracer through the normal glomerular wall. Ci rculating glycated serum proteins thus appear to play an important rol e in the onset of the glomerular dysfunction and proteinuria, which ta ke place in long-term hyperglycemic states.