Chronic kidney disease is characterized by the decline in renal excretory, homeostatic and endocrine functions. In most instances, the primary event is glomerular injury. With ongoing progression and glomerular extracapillary proliferation, tubulointerstitial damage occurs with consequent nephron loss and development of fibrotic lesions, finally resulting in terminal renal failure. Renal tubulointerstitial damage is the final common pathway in all forms of renal disease leading to CKD. Recent research has focused on how glomerular injury spreads to the tubulointerstitium. Presently, four possible mechanisms are being discussed: (1) obstruction of the urinary pole; (2) proteinuria-induced overload of the proximal tubule; (3) chronic hypoxia and (4) inflammation induced by a glomerulotubular feedback loop. Fibrosis is hypothesized to account for further deterioration of renal functions. As to the role of fibrosis, conflicting results have been published and new data question the damaging character of fibrosis.
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