title: Possible effect of angiotensin-converting enzyme inhibition on glomerular charge selectivity.
abstract: Angiotensin-converting enzyme (ACE) inhibitors are known to reduce urinary albumin excretion (UAE) in diabetic patients. Animal studies have shown that, besides diminishing the glomerular capillary pressure, ACE inhibitors might reduce albuminuria by influencing glomerular charge selectivity through glomerular preservation of heparan sulphate proteoglycan. In humans, an indirect measurement of glomerular charge selectivity can be obtained by calculating the glomerular charge selectivity index (SI), a clearance ratio of IgG/IgG4, two identically sized but differently charged molecules. The aim of the present study was to evaluate the effect of ACE inhibition on charge selectivity by comparing SI in type I (insulin-dependent) diabetic patients with microalbuminuria after 6 years of treatment either with or without captopril. Thirty-five of 45 patients participating in a prospective randomized study evaluating the effect of captopril in preventing the development of diabetic nephropathy were included in the present study, 17 being treated with captopril, 18 left as untreated controls. The selectivity index was calculated after measuring s-IgG, u-IgG, s-IgG4, and u-IgG4. The results demonstrated a higher selectivity index in the captopril-treated group [1.21 (0.51-1.94) median (range)] compared to the control group [0.94 (0.31-1.87)], however, the difference was not statistically significant (p = 0.16). A negative correlation between the selectivity index and UAE was demonstrated in the captopril-treated group (r = -0.77; p = 0.0004), whereas the correlation in the control group did not reach statistical significance (r = -0.3; p = 0.2).(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Steno Diabetes Center, Gentofte, Denmark.
authors.forename: P M
authors.initials: PM
authors.lastname: Hansen
authors.forename: E R
authors.initials: ER
authors.lastname: Mathiesen
authors.forename: A
authors.initials: A
authors.lastname: Kofoed-Enevoldsen
authors.forename: T
authors.initials: T
authors.lastname: Deckert
mesh_terms: D000328:Adult; D000419:Albuminuria; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000818:Animals; D001794:Blood Pressure; D002216:Captopril / Q000627:therapeutic use*; D003922:Diabetes Mellitus, Type 1 / Q000503:physiopathology* / Q000652:urine; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000145:classification / Q000652:urine; D007678:Kidney Glomerulus / Q000187:drug effects / Q000503:physiopathology*; D008297:Male; D011446:Prospective Studies
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D007074:Immunoglobulin G; D002216:Captopril