Clinical and Morphometrical Interrelationships in Patients with Overt Nephropathy Induced by Non-Insulin-Dependent Diabetes mellitus

Abstract

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 GBM. In addition, V-MM/glom, the width of the GBM 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 GBM 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.

Hepatocyte Growth Factor Gene Therapy Slows Down the Progression of Diabetic Nephropathy in <i>db/db</i> Mice

“…The cell number in each glomerulus (n = 50) was calculated using preparations stained with hematoxylin and eosin. Glomerular sclerotic index was calculated as the percent of the PAS-positive area in the glomerular area in preparations stained with PAS [27] .…”

Histological predictors for renal prognosis in diabetic nephropathy in diabetes mellitus type 2 patients with overt proteinuria

“…Several studies have shown cross-sectional relationships between histological and clinical findings in diabetes type 1 or type 2 patients with nephropathy. [1][2][3][4][5] Studies by serial biopsies have also shown a relationship between changes in histological findings and the clinical course in these patients. [6][7][8][9] Although some longitudinal studies have demonstrated an association between the severity of global histological change and renal prognosis, 10,11 the specific morphological features predicting renal prognosis have only been described in a limited number of studies.…”

Diabetic Kidney Disease: A Syndrome Rather Than a Single Disease

“…These changes include increased glomerular filtration rate (GFR) and albuminuria after physical exercise, which may be more prevalent in cases of poor diabetes control. The changes determined by kidney biopsy, which were initially reported by Osterby and co-workers and later confirmed by other groups, include thickening of the glomerular basement membrane and mesangial expansion; the latter is considered to be the hallmark of early diabetic nephropathy [65][66][67][68][69][70]. Albeit of great pathophysiological interest, these findings are of limited clinical use for the following reasons (as also stated in the original report):…”