Clinical and morphometrical interrelationships in patients with overt nephropathy induced by non-insulin-dependent diabetes mellitus - A light- and electron-microscopy study

To clarify the relationships between clinical and renal structural findings in non-insulin-dependent diabetes mellitus (NIDDM), we studied 19 renal biopsy specimens from patients with overt diabetic nephropathy induced by NIDDM. By a conventional biopsy examination using light, immunofluorescent and electron microscopy, we excluded patients with any non-diabetic renal diseases which may have caused urinary abnormalities. Using standard stereological methods, the glomerular filtration surface area per nephron (S-Filt/neph), mesangial volume per glomerulus (V-Mes/glom), mesangial matrix volume per glomerulus (V-MM/glom) and the width of the glomerular basement membrane (GBM) were measured in nonoccluded glomeruli. The hyaline change in the arteriole was analyzed semiquantitatively using light microscopy as an index of arteriolar hyalinosis. Light-microscopic findings demonstrated minimal lesions in 4 cases, focal and/or segmental sclerotic lesions in 4 cases, and diffuse mesangial expansion in 11 cases (with and without nodular lesions in 9 and 2 cases, respectively). Mean glomerular volume of an open glomerulus in diabetic patients was 1.6 times the reference value obtained from nondiabetic patients with mild proteinuria and/or hematuria and normal renal function. Clinical parameters, including the duration of diabetes, urinary protein excretion and creatinine clearance were all related to S-Filt/neph, V-Mes/glom, V-MM/glom and the width of the GEM. In addition, V-MM/glom, the width of the GEM and the index of arteriolar hyalinosis were closely interrelated. Based on these findings, diabetic renal changes, including an increase in the mesangial matrix, thickening of the GEM and arteriolar hyalinosis, appeared to progress in parallel, and may reflect various clinical manifestations in patients with overt diabetic nephropathy induced by NIDDM without nondiabetic renal lesions.