Glomerular size-selective dysfunction in NIDDM is not ameliorated by ACE inhibition or by calcium channel blockade

Background. In patients with insulin-dependent diabetes mellitus (IDDM) and overt nephropathy glomerular barrier size-selectivity progressively deteri orates with time and is effectively improved by angiotensin converting enzy me (ACE) inhibition. Whether similar glomerular functional changes develop in proteinuric patients with non-insulin-dependent diabetes mellitus (NIDDM ), and whether antihypertensive agents can favorably affect glomerular filt ration of macromolecules in these patients, has not been documented yet. Methods. We investigated renal hemodynamics and fractional clearance of neu tral dextrans of graded sizes, in nine proteinuric patients with NIDDM and renal biopsy findings of typical diabetic glomerulopathy. Six healthy volun teers served as controls. We also investigated the effects of an ACE inhibi tor and of a calcium channel blocker, both given in doses targeted to achie ve a comparable level of systemic blood pressure control, on glomerular hem odynamics and sieving function. Theoretical analysis of glomerular macromol ecule transport was adopted to evaluate intrinsic glomerular membrane perme ability properties. Results. Fractional clearance of large macromolecules (42 to 66 Angstrom in radius) was significantly higher in diabetic patients than in controls, an d the distribution of membrane pore radii was calculated to be shifted towa rds larger pore sizes in diabetics (mean radius increased from 55 to 60 Ang strom). Despite effective blood pressure control, neither antihypertensive affected glomerular hemodynamics to any significant extent. Fractional clea rance of dextrans, as well as of albumin and IgG, and total urinary protein s were not modified by either treatments. Conclusions. These data indicate that patients with NIDDM and overt nephrop athy develop abnormalities in size-selective function of the glomerular bar rier and, at variance to IDDM, such changes were not ameliorated either by ACE inhibition or calcium channel blockade.