Renal fibrosis: insights into pathogenesis and treatment.
The progression of chronic renal failure is characterised histologically by glomerulosclerosis, tubulointerstitial fibrosis and vascular sclerosis. Recent research has identified common mechanisms underlying these fibrotic processes. In particular, the scarring process within the glomeruli and the tubulointerstitium involves the infiltration by inflammatory cells including monocytes, the activation of intrinsic renal cells as well as interactions between infiltrating and resident cells. These interactions depend, to a large extent, on the release by these cells of chemokines, cytokines and growth factors. These factors are in turn involved in the induction of cellular proliferation within the kidney and the stimulation of the synthesis and deposition of extracellular collagenous matrix. Fibrosis is believed to result from excessive synthesis of extracellular matrix and a concommitant decrease in its breakdown. This fibrotic process resulting in end stage renal insufficiency bears strong similarities to that taking place within cirrhotic livers or fibrotic lungs. The new insights in our understanding of renal fibrosis have opened the way to new interventions aimed at its prevention. This may ultimately slow the progression of chronic renal insufficiency and decrease the number of patients requiring dialysis replacement therapy.
el Nahas
A M
AM
Sheffield Kidney Institute, Northern General Hospital Trust, U.K.
Muchaneta-Kubara
E C
EC
Essawy
M
M
Soylemezoglu
O
O
D000818:Animals; D005355:Fibrosis; D005923:Glomerulosclerosis, Focal Segmental / Q000209:etiology / Q000473:pathology / Q000628:therapy; D006801:Humans; D007668:Kidney / Q000473:pathology*; D007676:Kidney Failure, Chronic / Q000209:etiology / Q000473:pathology / Q000628:therapy; D009395:Nephritis, Interstitial / Q000209:etiology / Q000473:pathology / Q000628:therapy