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Can renal fibrosis be reversed?

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Abstract

New therapeutic approaches are needed to address the current epidemic of chronic kidney disease. Beyond delaying the inevitable onset of end-stage kidney disease the ultimate dream of clinical therapy is disease regression. Degradation of the interstitial matrix proteins is potentially feasible, especially before the interstitial “scar” becomes highly organized. Currently the specific matrix-degrading proteases that perform this function in vivo have not been clearly identified although several candidates have been suggested. Reversing renal fibrosis will also mandate removal of interstitial myofibroblasts that are the major source of the fibrosis-associated interstitial matrix proteins. However, the greater therapeutic challenge pertains to the current inability to regenerate intact functional nephrons in a site where they have been destroyed. In chronic tubulointerstitial damage that typifies all progressive kidney diseases, it is not interstitial matrix accumulation per se that leads to renal functional decline but rather its destructive effects on neighboring cells. In particular, loss of peritubular capillaries and tubules are the morphological features that underlie declining renal function. Recent advances in several basic scientific fields of investigation such as matrix biology, developmental biology, angiogenesis, and stem cell biology have identified new candidate therapeutic targets. A powerful new molecular tool-box is at our disposal that can be used to begin to translate recent discoveries into the clinical research arena with the goal of reversing renal fibrosis in a functionally meaningful way.

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Acknowledgements

The author acknowledges research support from the National Institutes of Health grants DK54500 and DK44757. Laura Finn, M.D. kindly provided the photomicrographs in Fig. 2.

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  1. Division of Nephrology, University of Washington and Children’s Hospital and Regional Medical Center, 4800 Sand Point Way NE, Seattle, WA, 98105, USA

    Allison A. Eddy

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Correspondence to Allison A. Eddy.

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Eddy, A.A. Can renal fibrosis be reversed?. Pediatr Nephrol 20, 1369–1375 (2005). https://doi.org/10.1007/s00467-005-1995-5

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