Mechanisms of tubulo-interstitial injury in progressive renal diseases.
A vast amount of evidence, based upon human renal biopsy material, indicates that the presence of tubular atrophy and interstitial fibrosis is a better indicator of outcome of renal function than is the extent of glomerular sclerosis. The pathophysiological basis for this surprising fact has not been adequately addressed. In this review we point out that the systemic hypertension which accompanies most forms of chronic renal disease could impact adversely upon the vasodilated interstitial vascular compartment which, together with a component of primary capillary injury related to the disease process, could cause progressive obliteration of particular capillaries. This would initiate a process of chronic tubular ischaemia ultimately leading to tubular atrophy. Since tubular cells have been shown to produce an array of cytokines and growth factors which modulate fibroblast proliferation, extracellular matrix production and chemo-attracts for infiltrating cells, it is further proposed that it is the tubular injury which initiates the deleterious cascade of events. Tubular injury may be aggravated by the filtration of potentially 'noxious' molecules through the diseased glomerulus and by infiltrating cells. As the vascular bed into which glomerular blood flow empties is progressively obliterated, glomerular function declines and renal failure advances in relation to the degree of tubulo-interstitial fibrosis.
Fine
L G
LG
Department of Medicine, University College London Medical School, Rayne Institute.
Ong
A C
AC
Norman
J T
JT
D001284:Atrophy; D005347:Fibroblasts / Q000473:pathology; D006801:Humans; D007511:Ischemia / Q000473:pathology / Q000503:physiopathology; D007674:Kidney Diseases / Q000209:etiology / Q000473:pathology* / Q000503:physiopathology; D007684:Kidney Tubules / Q000098:blood supply / Q000293:injuries* / Q000503:physiopathology; D008833:Microcirculation / Q000473:pathology / Q000503:physiopathology; D008954:Models, Biological