Renal hemodynamics and segmental tubular reabsorption in early type 1 diabetes

Renal hemodynamics and segmental tubular reabsorption in early type 1 diabetes. To investigate mechanisms underlying GFR control in diabetes mellitus, renal hemodynamics and segmental tubular handling of sodium, using lithium clearance, were assessed in 41 insulin-dependent diabetics (IDD) treated by insulin for 11 ± 8 days, and in 19 normal controls. Average GFR and effective renal plasma flow (ERPF) were slightly but not significantly higher (136 ± 22 vs. 123 ± 16ml/min · 1.73m2) in IDD than in normal subjects. GFR and ERPF were positively and strongly correlated in controls (r = 0.61, P < 0.001) and in diabetics (r = 0.72, P < 0.0001) indicating the marked flow dependency of GFR in both populations. After adjustment for ERPF, GFR was significantly higher in diabetics, suggesting a role of increased glomerular capillary pressure and ultrafiltration coefficient in the subset of “hyperfiltering” patients. Both fractional (FPRNa) and absolute (APRNa) proximal sodium reabsorption were significantly higher in IDD and significantly correlated with GFR. The ensuing decrease in sodium distal delivery could deactivate the tubuloglomerular feedback response and thus favor sustained vasodilation and high GFR in some diabetics. The renal effects of acute administration of drugs acting predominantly at either the pre- or the postglomerular resistance using nicardipine (N = 16) or captopril (N = 25) were further evaluated in IDD. The renal response to captopril or nicardipine was different in IDD. Whereas both drugs induced a marked decrease in renal vascular resistance, GFR was slightly decreased by captopril and was unchanged after nicardipine; these results are similar to those observed in normotensive non-diabetic subjects. Despite a mild decrease after captopril, FPRNa did not return to normal control values and no natriuretic effect was demonstrated in IDD, in contrast to normotensive subjects. In IDD nicardipine induced marked natriuresis by decreasing both the proximal and distal reabsorption rate of sodium, possibly due to a direct tubular effect, a response which was similar to that of non-diabetics. These results suggest that the increased FRPin observed in diabetics is not related to angiotensin formation or hemodynamic changes but rather may represent an independent mechanism possibly supported through sodium-glucose cotransport