Role of the Microvascular Endothelium in Progressive Renal... : Journal of the American Society of Nephrology (original) (raw)

REVIEW

Kang, Duk-Hee*|; Kanellis, John*; Hugo, Christian†; Truong, Luan*; Anderson, Sharon‡; Kerjaschki, Dontscho§; Schreiner, George F.¶; Johnson, Richard J.*

*Baylor College of Medicine, Houston, Texas; †University of Nurnberg, Nurnberg, Germany; ‡Division of Nephrology, Oregon Health Sciences University and Portland Veterans Administration Medical Center, Portland, Oregon; §Department of Clinical Pathology, University of Vienna, Vienna, Austria; ¶Scios Inc, Sunnyvale, California; and |Division of Nephrology, Ewha Women’s University College of Medicine, Ewha Medical Research Center, Seoul, Korea.

Correspondence to: Dr. Duk-Hee Kang, Division of Nephrology, Ewha Women’s University College of Medicine, 70 Chongno-ku, Chongo 6-ka, Seoul110-126, Korea. Phone: 82-2-760-5120; Fax: 82-2-3673-1591; E-mail [email protected]

Accepted November 27, 2001

Received August 28, 2001

Abstract

ABSTRACT. The role of the vascular endothelium in progressive renal disease is not well understood. This review presents evidence that progressive renal disease is characterized by a progressive loss of the microvasculature. The loss of the microvasculature correlates directly with the development of glomerular and tubulointerstitial scarring. The mechanism is mediated in part by a reduction in the endothelial proliferative response, and this impairment in capillary repair is mediated by alteration in the local expression of both angiogenic (vascular endothelial growth factor) and antiangiogenic (thrombospondin 1) factors in the kidney. The alteration in balance of angiogenic growth factors is mediated by both macrophage-associated cytokines (interleukin-1β) and vasoactive mediators. Finally, there is intriguing evidence that stimulation of angiogenesis and/or capillary repair may stabilize renal function and slow progression and that this benefit occurs independently of effects on BP or proteinuria. Therefore, angiogenic agents may represent a novel therapeutic approach for slowing the progression of renal disease.