We studied the lesions of global glomerular sclerosis and arteriolar hyalinosis in 43 (29 females) insulin-dependent diabetes mellitus (IDDM) patients whose creatinine clearance (CCr) was ≥45 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, X ± SD) years. CCr 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 CCr (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.
Bibliographical noteFunding Information:
This work was supported by the NIH grants 2P01 AM13083-20 and 2M01 RROO400-22 and the Juvenile Diabetes Foundation. Dr. Harris was a recipient of the 1986—87 Walter E. Matheson Clinical Fellowship from Loma Linda University, allowing him to spend his sabbatical year at the University of Minnesota. RWB was the recipient of a Post- doctoral Fellowship from the Juvenile Diabetes Foundation. We thank the patients for participating in the study and the nursing staff of the Clinical Research Center for their scientific and patient care contribu-tions. The technical contributions of John Basgen and Thomas Groppoli are greatly appreciated. We thank Janice Sugden for the statistical analyses, Marshall Hoff for the biomedical graphics and Cynthia Dawis for manuscript preparation.