GLOBAL GLOMERULAR SCLEROSIS AND GLOMERULAR ARTERIOLAR HYALINOSIS IN INSULIN-DEPENDENT DIABETES

We studied the lesions of global glomerular sclerosis and arteriolar hyalinosis in 43 (29 females) insulin-dependent diabetes mellitus (IDDM) patients whose creatinine clearance (C(Cr)) was greater-than-or-equal-to ml/min/1.73 m2 and whose renal biopsies had at least 20 glomeruli available for study. These patients, ages 17 to 55 years, had IDDM for 7 to 32 (20 +/- 6, XBAR +/- SD) years. C(Cr) ranged from 47 to 139 (91 +/- 25) ml/min/1.73 m2 and urinary albumin excretion (UAE) from 5 to 3386 (median = 127) mg/24 hrs. Eighteen patients were hypertensive. Thus, these patients represented a broad clinical range from normal renal function through overt diabetic nephropathy. The percent of glomeruli which were globally sclerosed was strongly correlated with C(Cr) (r = -0.64, P < 0.0001) and log UAE (r = +0.67, P < 0.001). Hypertension was more common in patients with more than 10% sclerosed glomeruli (chi square = 9.5, P < 0.002). Percent sclerosed glomeruli was highly significantly correlated with the index of severity of the arteriolar hyalinosis lesion (r = +0.66, P < 0.0001) and mesangial volume fraction (r = +0.61, P < 0.0001). We hypothesize that arteriolar hyalinosis could contribute to global glomerular sclerosis through severe compromise of glomerular blood flow. Alternately, global glomerular sclerosis may result from marked mesangial expansion and capillary occlusion. However, in this broad range of patients it appeared that global glomerular sclerosis and mesangial expansion were not infrequently independent diabetic renal lesions which could contribute separately to the ultimate development of overt diabetic nephropathy.