In light of the growing understanding of the toxic effects of glycated albumin 
and of the preferential excretion of this substance, the excretion of glycated 
albumin could be considered a physiologic function of the kidney. Furthermore, 
if the increased load of glycated albumin in diabetic patients results in 
glycated albumin excretion rates in the range of 20 to 200 microg/min, might 
this not be considered "physiologic microalbuminuria"? The hypothesis is 
presented that microalbuminuria composed of glycated albumin is a homeostatic 
renal function. Although some proteins are glycosylated for their normal 
physiologic function, many proteins are glycated nonenzymatically according to 
ambient blood glucose. Albumin is subject to nonenzymatic glycation in all 
humans, but at increased rates in diabetic patients. Glycated albumin induces 
changes in the microvasculature and glomerulus that may lead to endothelial 
dysfunction and diabetic nephropathy, respectively. Renal excretion of glycated 
albumin is enhanced compared with native albumin. To explore this potential 
homeostatic function of the kidney, patients with impaired renal function were 
studied to determine whether glycated albumin accumulates. Plasma levels of 
glycated albumin were determined in diabetic and nondiabetic patients on 
hemodialysis. Hemoglobin A1c was used as an index of the rate of nonenzymatic 
glycation of proteins. Hemoglobin A1c was increased in the diabetic subjects but 
was normal in the nondiabetic group (7.9% +/- 0.5% v 6.2% +/- 0.2%, 
respectively; P < 0.01). On the other hand, the glycated albumin was elevated in 
both groups and was not significantly different between them (1.95% +/- 0.15% in 
the diabetic patients v 1.75% +/- 0.14% in the nondiabetic patients; P = NS). 
The results of this study provide the first clinical evidence supporting the 
hypothesis that the excretion of glycated albumin is a homeostatic renal 
function.