Disorganization process in the development of diabetic nodular glomerulosclerosis.

Abstract

In order to clarify the mode of development of the diabetic nodular glomerulosclerosis, 38 kidney specimens of autopsied and biopsied diabetic cases were studied light and electron microscopically including serial sections. Disorganization process occurred chiefly at the capillary region of glomeruli. Early change of this process was proliferation of intramembranous cells following histolysis in the glomerular loop and it was characterized by transformation of the glomerular loop into enmeshed or reticular structure, that is, disorganization of the glomerular architecture. In the subsequent stage intercellular matrix production and hyalinization accompanied by axial crowding of proliferated intramembranous cells and peripheral recanalization of blood spaces were clarified. And in the later stage axially crowded intramembranous cells decreased in number and the matrix was increased and hyalinized, resulting in the formation of the axial hyaline nodule. The distribution of this process was focal and segmental, lesions of various stages coexisted, and it was suggested that glomerular lesions may spread all over the kidney by recurrence of this process. This process was quite similar to those seen in disorganization process of glomerulonephritis. But another characteristic changes were the presence of foam cells, intra-and intercellular deposition of lipid droplets, and increased matrix formation. diabetic nodular glomerulosclerosis ; disorganization ; recurrence ; lobular glomerulonephritis Diabetic nodular glomerulosclerosis, which was first described by Kimmelstiel and Wilson (1936), is thought to be the most characteristic lesion in diabetic nephropathy.In the recent decades it has been proposed that lytic changes in glomerular loops may play an important role in the morphogenesis of this lesion. Bloodworth (1978) postulated that large Kimmelstiel-Wilson nodules are formed by the organization of the glomerulocapillary microaneurysms caused by disruption of so-called "anchor points". Saito et al. (1988) suggested the concept of "mesangiolysis" as a developmental process of nodular lesions without microaneurysm formation, in which loosening and dissociation of the mesangial matrix

Apoptotic Cell Loss following Cell Proliferation in Renal Glomeruli of Otsuka Long-Evans Tokushima Fatty Rats, a Model of Human Type 2 Diabetes

“…This may indicate specific aspects of this animal distinct from human diabetic nephropathy. However, it is still controversial whether glomerular proliferation occurs in very early stage of human diabetic nephropathy [14,15]. This is probably due to little information because of rare opportunity for examination of such very early stage of human diabetic nephropathy.…”

Accelerated glomerulosclerosis in alloxan-induced diabetic rabbits with anti-glomerular basement membrane nephritis.

“…The results discussed above may help the understanding of the morphogenesis of human diabetic glomerulosclerosis. Shioi and Fujimoto (1989) studied the mode of the development of human diabetic nodular glomerulosclerosis, and suggested that the disturbance of lipid metabolism in the diabetes mellitus might be important in the development of the nodular lesions. Our study also suggests that abnormal fat metabolism in the DM-GN group may in some way be concerned the glomerular changes with an increase of the mesangial matrix, resulting in a formation of nodular lesions.…”

Dyslipoproteinemia and Impairment of Renal Function in Diabetic Kidney Disease: An Analysis of Animal Studies, Observational Studies, and Clinical Trials

“…The histologic features of focal segmental glomerulosclerosis and diabetic nodular glomerulosclerosis, including glomerular accumulation of serum proteins, lipids, and macrophages, resemble the patterns of the lesions seen in atherosclerosis [38,40]. Also, the developing atherosclerotic and glomerulosclerotic lesions seem to share certain pathophysiologic mechanisms, including endothelial cell injury, macrophage infiltration, hyperlipoproteinemia, and hypertension (glomerular hypertension) [41].…”