Atorvastatin Ameliorates Tubulointerstitial Fibrosis and Protects Renal Function in Chronic Partial Ureteral Obstruction Cases

No AccessJournal of UrologySection on Urology American Academy of Pediatrics1 Oct 2009Atorvastatin Ameliorates Tubulointerstitial Fibrosis and Protects Renal Function in Chronic Partial Ureteral Obstruction Cases John P. Fitzgerald, Shyan-Yih Chou, Israel Franco, Unni M. Mooppan, Hong Kim, Rajiv Saini, and Frederick A. Gulmi John P. FitzgeraldJohn P. Fitzgerald More articles by this author , Shyan-Yih ChouShyan-Yih Chou More articles by this author , Israel FrancoIsrael Franco More articles by this author , Unni M. MooppanUnni M. Mooppan More articles by this author , Hong KimHong Kim More articles by this author , Rajiv SainiRajiv Saini More articles by this author , and Frederick A. GulmiFrederick A. Gulmi More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2009.04.086AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: Tubulointerstitial fibrosis, the histological feature of chronic obstructive nephropathy, is delineated in complete unilateral ureteral obstruction models. Histological changes during chronic partial ureteral obstruction are not well studied. We describe changes in a rat model of partial ureteral obstruction. We examined the effects of atorvastatin on histological alterations, fibrosis and function in this model. Materials and Methods: All rats underwent right nephrectomy. To create partial ureteral obstruction the left ureter was incorporated into the psoas muscle, which was split and reapproximated. Excretory urogram, histology, Western blot of α-smooth muscle actin and renal clearance were examined in rats with sham, 14-day or 30-day partial ureteral obstruction. Obstructed rats received a regular or a diet supplemented with 50 mg/kg body weight atorvastatin per day. Results: At 14 days of partial ureteral obstruction pyelogram showed hydronephrosis, which was more pronounced on obstruction day 30. Histological studies on obstruction days 14 and 30 revealed tubulointerstitial fibrosis in the medulla and cortex. Atorvastatin significantly decreased tubulointerstitial fibrosis seen in α-smooth muscle actin expression. On obstruction day 14 or 30 the glomerular filtration rate in rats on a regular diet was significantly lower than in sham PUO rats or rats on atorvastatin. Conclusions: This model of partial ureteral obstruction enables chronic studies of morphological and histological changes of the obstructed kidney. It showed progressive fibrosis and decreased filtration function. Atorvastatin ameliorated fibrosis and helped preserve kidney filtration function. References 1 : Obstructive nephropathy and renal fibrosis. Am J Physiol Renal Physiol2002; 283: F861. Google Scholar 2 : Experimental fetal vesicoureteral reflux induces renal tubular and glomerular damage and is associated with persistent bladder instability. J Urol1999; 162: 1090. Link, Google Scholar 3 : Molecular and cellular pathophysiology of obstructive nephropathy. Pediatr Nephrol1999; 13: 612. Google Scholar 4 : Obstructive nephropathy: insights from genetically engineered animals. Kidney Int2005; 68: 925. Google Scholar 5 : Contributions of angiotensin II and tumor necrosis factor-alpha to the development of renal fibrosis. Am J Physiol Renal Physiol2001; 280: F777. Google Scholar 6 : Role of angiotensin II in the tubulointerstitial fibrosis of obstructive nephropathy. Am J Kidney Dis1995; 26: 141. Google Scholar 7 : Statins and renal function. Angiology2002; 53: 493. Google Scholar 8 : Potential nontraditional applications of statins. Ann Pharmacother2003; 37: 1063. Google Scholar 9 : Isoprenoids as mediators of the biological effects of statins. J Clin Invest2002; 110: 285. Google Scholar 10 : Ibuprofen combined with antibiotics suppresses renal scarring due to ascending pyelonephritis in rats. J Urol1999; 162: 1396. Link, Google Scholar 11 : Suppression of renal inflammation with vitamins A and E in ascending pyelonephritis in rats. J Urol1999; 161: 1681. Link, Google Scholar 12 : Atorvastatin ameliorates renal tissue damage in unilateral ureteral obstruction. J Urol2004; 172: 2456. Link, Google Scholar 13 : Fluvastatin suppresses oxidative stress and fibrosis in the interstitium of mouse kidneys with unilateral ureteral obstruction. Kidney Int2001; 59: 2095. Google Scholar 14 : Role of TNFR1 and TNFR2 receptors in tubulointerstitial fibrosis of obstructive nephropathy. Am J Physiol1999; 277: F766. Google Scholar 15 : An operation to produce experimental reversible hydronephrosis in dogs. J Urol1962; 88: 337. Link, Google Scholar 16 : Pathophysiology of unilateral ureteral obstruction: studies from Charlottesville to New York. J Urol2004; 172: 2563. Link, Google Scholar 17 : Aristolochic acids induce chronic renal failure with interstitial fibrosis in salt-depleted rats. J Am Soc Nephrol2002; 13: 431. Google Scholar 18 : Reduced angiotensinogen expression attenuates renal interstitial fibrosis in obstructive nephropathy in mice. J Clin Invest1999; 103: 39. Google Scholar 19 : The role of growth factors, cytokines, and vasoactive compounds in obstructive nephropathy. Semin Nephrol1998; 18: 622. Google Scholar 20 : Regulation of the mevalonate pathway. Nature1990; 343: 425. Google Scholar 21 : Pleiotropic effects of 3-hydroxy-3-methylglutaryl coenzyme a reductase inhibitors. Arterioscler Thromb Vasc Biol2001; 21: 1712. Google Scholar 22 : Statins do more than just lower cholesterol. Lancet1996; 348: 1079. Google Scholar 23 : Lipid-lowering activity of atorvastatin and lovastatin in rodent species: triglyceride-lowering in rats correlates with efficacy in LDL animal models. Atherosclerosis1995; 117: 237. Google Scholar 24 : Tubulointerstitial changes as a major determinant in the progression of renal damage. Am J Kidney Dis1992; 20: 1. Google Scholar Department of Urology, Brookdale University Hospital and Medical Center, Brooklyn and Division of Pediatric Urology, New York Medical College, Valhalla, New York© 2009 by American Urological AssociationFiguresReferencesRelatedDetails Volume 182Issue 4SOctober 2009Page: 1860-1868 Advertisement Copyright & Permissions© 2009 by American Urological AssociationKeywordsfibrosisnephrectomyatorvastatinkidneyureteral obstructionMetricsAuthor Information John P. Fitzgerald More articles by this author Shyan-Yih Chou More articles by this author Israel Franco More articles by this author Unni M. Mooppan More articles by this author Hong Kim More articles by this author Rajiv Saini More articles by this author Frederick A. Gulmi More articles by this author Expand All Advertisement PDF downloadLoading ...