Effect of a low protein diet on the relationship of nonenzymatic glycation to altered renal structure and function in diabetes mellitus

Abstract

Renal functional parameters including creatinine clearance, urinary albumin excretion, basement membrane thickening, and levels of nonenzymatic glycation of glomerular basement membrane were studied in streptozotocin-induced diabetic rats and age-matched controls subjected to low protein diet. In addition, these parameters were also assessed in diabetic and streptozotocin injected nondiabetic animals fed a 24% protein diet, which served as “positive controls.” While diabetic animals from both diet groups had similar elevated glycated hemoglobin levels and increased levels of nonenzymatic glycation of glomerular basement membrane, these were significantly elevated as compared to insulin treated diabetic (euglycemic), age-matched controls on an 8% protein diet, and streptozotocin injected nondiabetic animals from both diet groups. However, urinary albumin excretion and creatinine clearance levels were significantly elevated only in the 24% protein diet fed diabetics over values seen in the various groups of animals on 8% and controls on 24% protein diet. In contrast, there were no statistical differences among diabetic, euglycemic and control (8% and 24% protein) animals with respect to creatinine clearance, urinary albumin excretion, and glomerular basement membrane thickness. Taken together these data cast some doubt on the role of nonenzymatic glycation in the development of diabetic nephropathy. Moreover, hyperglycemia per se causes a compensatory increase in kidney size irrespective of protein intake; a low protein diet, however, inhibits the hyperfiltration commonly seen in early diabetic nephropathy. The authors, thus, hypothesize that a low protein diet, by preventing compensatory increase in blood flow to surviving nephrons, in some fashion protects these functional units from subsequent damage and possibly delays the onset of renal failure.