ANGIOTENSIN-CONVERTING ENZYME GENE POLYMORPHISM AND ACE-INHIBITION INDIABETIC NEPHROPATHY

The antiproteinuric effect of angiotensin converting enzyme (ACE) inhi bition in insulin-dependent diabetes mellitus (IDDM) patients with dia betic nephropathy varies considerably. Therefore, we tested the potent ial role of an insertion (I)/deletion (D) polymorphism of the ACE gene on this early antiproteinuric responsiveness in an observational foll ow-up study. Sixty (II, N = 13; ID, N = 26 and DD, N = 21) young hyper tensive IDDM patients suffering from diabetic nephropathy were investi gated during three months before and for the initial six month period during ACE inhibition [captopril 44 SD 22) mg/24 hr, no differences in drug dose between groups]. Blood pressure (MABP) and albuminuria (ELI SA) were measured three (1 to 6) times before and three (1 to 13) time s during ACE inhibition. At baseline the groups (II/ID/DD) had compara ble (1) mean arterial blood pressure (MABP mm Hg) of 113 +/- 10/108 +/ - 9/114 +/- 8, (2) albuminuria (geometric mean with 95% CI) 1394 (747 to 2608)/1176 (844 to 1797) and 1261 (827 to 2017) mg/24 hr, and (3) s erum creatinine (geometric mean with 95% CI), 80 (68 to 93)/85 (76 to 97)/103 (85 to 119) mu mol/liter, respectively. Angiotensin converting enzyme inhibition induced a significant reduction in MABP, albuminuri a and kidney function in ail three groups (II/ID/DD; P < 0.05): (1) MA BP (mean +/- SD) 12 +/- 7/5 +/- 7/5 +/- 7/8 +/- 9 mm Hg (ANOVA, P = 0. 02); (2) albuminuria [mean (95%CI)] 61 (34 to 77)/22 (3 to 37)/31 (13 to 46) %, (ANOVA, P < 0.01); and (3) increasing serum creatinine [mean (95%CI)] 8 (4 to 12)/9 (3 to 16)/8 (0 to 16) % (ANOVA, NS), respectiv ely. Adjusting for differences in reduction in MABP did not change the association between decrease in albuminuria and ACE/ID genotypes (P < 0.01). A multiple linear regression analysis revealed that the ACE/ID polymorphism, albuminuria and MABP at baseline independently influenc ed the decline in albuminuria after initiation of ACE inhibition (R-2 = 0.21, P < 0.01). A significant association between changes in MABP a nd albuminuria was demonstrated (R-2 = 0.16, P < 0.01). Our data show that hypertensive albuminuric IDDM patients with the II genotype are p articularly susceptible to commonly advocated renoprotective treatment .