KIDNEY-FUNCTION AFTER WITHDRAWAL OF LONG-TERM ANTIHYPERTENSIVE TREATMENT IN DIABETIC NEPHROPATHY

Initiation of antihypertensive treatment in hypertensive non-insulin-d ependent diabetic (NIDDM) patients with diabetic nephropathy induces a faster initial (0 to 6 months) and slower subsequent (6 months-end) d ecline in GFR [Delta GFR (ml . min(-1) . 1.73 m(-2) . month(-1)) appro ximately 1.5 vs. 0.4]. Whether this initial phenomenon is reversible ( hemodynamic) or irreversible (structural damage) after prolonged antih ypertensive treatment is not known. To elucidate these mechanisms we i nvestigated 40 hypertensive NIDDM patients (age 61 +/- 7 years, mean /- SD), known duration of diabetes 14 years (2 to 33 years) [median (r ange)] with diabetic nephropathy receiving antihypertensive treatment (angiotensin converting enzyme inhibition, N = 30) for 5 years (1 to 2 0 years). The following variables were measured the last day on antihy pertensive treatment and one month after withdrawal of treatment: GFR (Cr-51-EDTA), 24-hour arterial blood pressure (24 hr MABP, Takeda TM24 20) and albuminuria (ELISA); the mean 24-hour MABP rose from 102 +/- 1 1 to 111 +/- 10 (P < 0.0001) and albuminuria [geometric mean (antilog SEM)] increased from 634 (1.3) to 1159 (1.2) (P < 0.0001), while GFR ( mean +/- SD) remained unchanged (69 +/- 25 to 70 +/- 26 ml . min(-1) . 1.73 m(-2), P = 0.21), after withdrawal of antihypertensive treatment . A significant correlation between the relative change in the 24 hour MABP measurement and the relative change in GFR (r = 0.44, P < 0.01) was found. In conclusion, our results suggest that the faster initial decline in GFR after initiating antihypertensive treatment in hyperten sive NIDDM patients with diabetic nephropathy is due to a irreversible effect, and should be accounted for when evaluating the beneficial ef fect of antihypertensive treatment on the progression of diabetic neph ropathy in these patients.