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The spatial relationship between renal perfusion and nephronal structure was determined in 51 nephrotic patients consisting of 11 patients with steroid sensitive, minimal change (MC) nephrosis, 12 patients with steroid resistant, mesangial proliferative (MesP) nephrosis and without tubulointerstitial fibrosis (TIF), 11 patients with steroid resistant, MesP nephrosis and with low grade TIF and 17 patients with focal segmental glomerulosclerosis (FSGS). The intrarenal hemodynamic study revealed a unique correlation between renal perfusion and nephronal structure. A normal or slight reduction in peritubular capillary flow observed in MC or mild MesP nephrosis correlates with an intact tubulointerstitial structure. A moderate reduction in peritubular capillary flow observed in steroid resistant, MesP nephrosis induces a low incidence of TIF. A severe reduction in peritubular capillary flow denotes a higher incidence of TIF as that observed in nephrosis with FSGS. Thus, it is of notion that the reduction in renal perfusion precedes the development of tubulo-interstitial fibrosis and thereby supports the concept of renal perfusion as a crucial determinant of nephronal structure.

A glomerular endothelial funciton with its hemodynamic impact is proposed to determine disease progression. In the clinical settings associated with an intact endothelial function, such as minimal-change steroid-sensitive nephrosis, the early phase of diabetes mellitus and the early stage of an experimental model of renal ablation in animals, it was observed that adequate renal perfusion correlates with the intact structure and function of the nephron with no evidence of disease progression. In contrast, the clinical settings associated with endothelial dysfunction, such as chronic glomerulonephropathy, the late stage of diabetes mellitus and a renal ablation model in animals, are usually associated with a reduction in renal perfusion. The magnitude of renal hypoperfusion observed in all forms of chronic glomerulonephropathies is proportional to the degree of clinical severity. A progressive pattern of renal hypoperfusion is uniquely observed when disease severity progresses. In this context, a new therapeutic maneuver aiming to improve renal perfusion is proposed for treating glomerulonephropathy with disease progression and preventing it from developing to end-stage renal disease.

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