DIMINISHED GLOMERULAR CAPILLARY HYDRAULIC CONDUCTIVITY PRECEDES MORPHOLOGICAL-CHANGES IN EXPERIMENTAL DIABETES-MELLITUS IN THE RAT

Glomerular ultrafiltration coefficient, K(f), is diminished in established diabetic nephropathy. To determine whether K(f) is decreased because of a decrease in capillary area, A, and or in hydraulic conductivity, Lp, glomerular K(f) and morphometric parameters were measured, and Lp was calculated in glomeruli of young rats with STZ-induced DM and in control rats. STZ was administered to Fischer 344 rats that weighed 50-75 g; glomeruli were examined after 3 or 5 mo of DM, and their structure and function was compared with that of control rats. The effects of insulin or of an ACEI, enalapril, also were assessed after 3 or 5 mo. Growth of DM rats was markedly impaired, and their ratio of kidney weight to body weight was increased. C(cr) was proportional to rat weight, and the ratio of C(cr) to body weight was not different in DM and control rats. At 3 mo, average volume of glomeruli isolated from DM rats was less than that of glomeruli from control rats. In contrast, glomerular volume after 5 mo was equal in DM and control rats. No increase in GBM thickness or mesangial volume was observed, nor was any decrease seen in GBM area in DM rats at 5 mo. K(f) was lower in DM rats than controls after 3 mo, but not after 5 mo. The Lp of DM and control glomeruli did not differ at 3 mo, but was lower in DM at 5 mo. Insulin therapy improved somatic growth and increased kidney and glomerular size in DM rats; the kidney weight/body weight ratio remained elevated. Insulin therapy was associated with an increase in capillary volume and GBM area and with a decrease in total slit pore length. The ACEI did not change somatic or renal growth but diminished GBM area and total slit pore length. Neither insulin nor ACEI therapy affected the Lp of DM rats. We conclude that diminished Lp occurs in established DM in the rat; it precedes structural glomerular changes and is not corrected by insulin nor an ACEI in the dosage used.