POSSIBLE EFFECT OF ANGIOTENSIN-CONVERTING ENZYME-INHIBITION AN GLOMERULAR CHARGE SELECTIVITY

Angiotensin-converting enzyme (ACE) inhibitors are known to reduce uri nary albumin excretion (UAE) in diabetic patients. Animal studies have shown that, besides diminishing the glomerular capillary pressure, AC E inhibitors might reduce albuminuria by influencing glomerular charge selectivity through glomerular preservation of heparan sulphate prote oglycan. In humans, an indirect measurement of glomerular charge selec tivity can be obtained by calculating the glomerular charge selectivit y index (SI), a clearance ratio of IgG/IgG(4), two identically sized b ut differently charged molecules. The aim of the present study was to evaluate the effect of ACE inhibition on charge selectivity by compari ng SI in type I (insulin-dependent) diabetic patients with microalbumi nuria after 6 years of treatment either with or without captopril. Thi rty-five of 45 patients participating in a prospective randomized stud y evaluating the effect of captopril in preventing the development of diabetic nephropathy were included in the present study, 17 being trea ted with captopril, 18 left as untreated controls. The selectivity ind ex was calculated after measuring s-IgG, u-IgG, s-IgG(4), and u-IgG(4) . The results demonstrated a higher selectivity index in the captopril -treated group [1.21 (0.51-1.94) median (range)] compared to the contr ol group [0.94 (0.31-1.87)], however, the difference was not statistic ally significant (p = 0.16). A negative correlation between the select ivity index and UAE was demonstrated in the captopril-treated group (r = - 0.77; p = 0.0004), whereas the correlation in the control group d id not reach statistical significance (r = - 0.3; p = 0.2). It is conc luded that, though no statistically significant difference was seen in the selectivity index between captopril-treated and untreated patient s with type I diabetes, a favorable influence of captopril on glomerul ar charge selectivity cannot be totally excluded. A prospective study calculating selectivity index before and during treatment with the ACE inhibitor is needed.