Significance of Postglomerular Capillaries in the Pathogenesis of Chronic Renal Failure

Abstract

Correlations between the relative volume of the intertubular capillaries in the renal cortex and the serum creatinine concentration in primary glomerulopathies, renal vasculopathies, and chronic interstitial nephritides are reported. In the mesangioproliferative glomerulonephritides, there are significant negative correlations between the number and area of the intertubular capillaries in the cortex and the serum creatinine concentration. In diabetic glomerulosclerosis, renal glomerular amyloidosis, decompensated benign nephrosclerosis, secondary malignant nephrosclerosis, and chronic interstitial nephritis, there is a significant negative correlation between the relative area of the intertubular capillaries and the serum creatinine concentration. Thus, in these diseases, there is progressive narrowing/ obliteration of the postglomerular capillaries which leads to a progressive decrease in glomerular filtration rate and thus to a rise in serum creatinine concentration.

Mechanisms of Tubulointerstitial Injury in the Kidney: Final Common Pathways to End-stage Renal Failure

“…Histological studies of human kidneys confirmed that peritubular capillary loss is correlated with interstitial fibrosis and tubular atrophy (58,59). The significance of peritubular capillary damage, with subsequent tissue hypoxia and ischemia, has been emphasized by recent findings in animal models.…”

Cobalt promotes angiogenesis via hypoxia-inducible factor and protects tubulointerstitium in the remnant kidney model

“…32 Furthermore, the experimental adminis- . Control cells and HIF2a clones (#3 and #7) were seeded at 1.0 Â 10 5 per six-well plate and cultured in either normoxia or hypoxia for up to 72 h. There was no difference in growth among these clones in the monolayer culture system.…”

“…Given the observations that the degree of tubulointerstitial injury correlates with renal insufficiency 54 and that the damage in this compartment is correlated with loss of peritubular capillaries, 32 angiogenesis through activation of HIF is a promising therapeutic target against progressive, hypoxic renal diseases. In this sense, modalities that activate HIF, including methods to inhibit prolyl-hydroxylase activities, 55,56 should be eagerly pursued.…”

Suppression of glomerulosclerosis by adenovirus-mediated IL-10 expression in the kidney

“…These glomerular changes are followed by tubulointerstitial fibrosis, which progresses into eventual renal failure. [21][22][23] Cytokines such as IL-1, tumor necrosis factor-a (TNFa) and substances derived from platelets have a role in augmenting neutrophil-mediated glomerular damages. 24 Through the release of inflammatory cytokines, macrophages may also stimulate mesangial cells to proliferate and synthesize ECM proteins.…”