Accumulation of glycated albumin in end-stage renal failure: evidence for the principle of "physiological microalbuminuria".

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.