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J Am Soc Nephrol 13:2916-2929, 2002
© 2002 American Society of Nephrology

Pentoxifylline Attenuated the Renal Disease Progression in Rats with Remnant Kidney

Shuei-Liong Lin*,§,||, Yung-Ming Chen*,§, Chiang-Ting Chien{dagger},||, Wen-Chih Chiang*,||, Chien-Chen Tsai{ddagger},¶ and Tun-Jun Tsai*,§

*Department of Internal Medicine, {dagger}Medical Research, and {ddagger}Pathology, National Taiwan University Hospital, Taipei, Taiwan; §Department of Medicine, ¶Pathology, and ||Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.

Correspondence to Dr. Tun-Jun Tsai, Department of Internal Medicine, National Taiwan University Hospital, No. 7, Chung-Shan South Road, Taipei, Taiwan. Phone: 886-2-23123456 ext. 3953; Fax: 886-2-23222955;E-mail: paul{at}ha.mc.ntu.edu.tw

ABSTRACT. Previous studies have reported that pentoxifylline, a phosphodiesterase inhibitor, attenuates experimental mesangial proliferative glomerulonephritis. This study hypothesized that pentoxifylline could also attenuate the renal disease progression in rats with remnant kidney. After 5/6 subtotal nephrectomy, rats developed progressively elevated proteinuria and plasma creatinine, glomerulosclerosis, interstitial inflammation, and fibrosis, all of which were attenuated by 40 to 60% by pentoxifylline. However, the elevated BP was not changed by pentoxifylline. Pentoxifylline reduced the upregulation of monocyte chemoattractant protein-1 gene by 60% in the cortex of remnant kidney, as well as in a dose-dependent manner in the albumin- or angiotensin II-stimulated proximal tubular cells. It also reduced the upregulation of mitogenic and profibrogenic genes by 50%, including platelet-derived growth factor, fibroblast growth factor-2, transforming growth factor-{beta}1, connective tissue growth factor, and types I and III collagen in the cortex of remnant kidney. Furthermore, pentoxifylline was found to decrease the numbers of interstitial myofibroblasts by 60% in the cortex of remnant kidney and suppress the proliferation of cultured interstitial fibroblasts. It also reduced the angiotensin II-induced or transforming growth factor-{beta}1-induced expression of connective tissue growth factor gene in cultured fibroblasts and mesangial cells. Combining pentoxifylline with an angiotensin-converting enzyme inhibitor, cilazapril, almost completely attenuated the renal disease progression in rats with remnant kidney. In conclusion, pentoxifylline alone can attenuate the chronic renal disease progression. Its combination with cilazapril has the potential to prevent the renal disease progression almost completely.




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