American Journal of Kidney Diseases
Volume 53, Issue 4 , Pages 606-616 , April 2009

Effect of Pentoxifylline on GFR Decline in CKD: A Pilot, Double-Blind, Randomized, Placebo-Controlled Trial

  • Robert M. Perkins, MD

      Affiliations

    • Nephrology Service, Madigan Army Medical Center, Fort Lewis, WA
    • Corresponding Author InformationAddress correspondence to Robert M. Perkins, MD, Nephrology Service, Madigan Army Medical Center, Fort Lewis, WA 98431
  • ,
  • Matthew C. Aboudara, MD

      Affiliations

    • Nephrology Service, Walter Reed Army Medical Center, Washington, DC
  • ,
  • Alice L. Uy, MD

      Affiliations

    • Nephrology Service, Madigan Army Medical Center, Fort Lewis, WA
  • ,
  • Stephen W. Olson, MD

      Affiliations

    • Nephrology Service, Walter Reed Army Medical Center, Washington, DC
  • ,
  • Howard M. Cushner, MD

      Affiliations

    • Nephrology Service, Madigan Army Medical Center, Fort Lewis, WA
  • ,
  • Christina M. Yuan, MD

      Affiliations

    • Nephrology Service, Walter Reed Army Medical Center, Washington, DC

Received 27 July 2008 ,Accepted 12 November 2008.

References 

  1. Coresh J, Selvin E, Stevens LA, et al. Prevalence of chronic kidney disease in the United States. JAMA. 2007;298:2038–2047
  2. John R, Webb M, Young A, Stevens PE. Unreferred chronic kidney disease: A longitudinal study. Am J Kidney Dis. 2004;43:823–835
  3. McClellan W, Flaanders W. Risk factors for progressive chronic kidney disease. J Am Soc Nephrol. 2003;14(suppl 2):S65–S70
  4. Lewis E, Hunsicker L, Bain R, Rohde R Collaborative Study Group. The effect of angiotensin converting enzyme inhibition on diabetic nephropathy. N Engl J Med. 1993;329:1456–1462
  5. Lewis EJ, Hunsicker LG, Clarke WR, et al. Collaborative Study Group Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. N Engl J Med. 2001;345:851–860
  6. Brenner BM, Cooper ME, De Zeeuw D, et al. RENAAL Study Investigators Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med. 2001;345:861–869
  7. Maschio G, Alberti D, Janin G, et al. Angiotensin Converting Enzyme Inhibition in Progressive Renal Insufficiency Study Group Effect of the angiotensin converting enzyme benazepril on the progression of chronic renal insufficiency. N Engl J Med. 1996;334:939–945
  8. The GISEN Group. Randomised placebo-controlled trial of effect of ramipril on decline in glomerular filtration rate and risk of terminal renal failure in proteinuric, non-diabetic nephropathy. Lancet. 1997;349:1857–1863
  9. Chen Y, Wu K, Tsai T, Hsieh B. Pentoxifylline inhibits PDGF-induced proliferation of and TGF-β-stimulated collagen synthesis by vascular smooth muscle cells. J Mol Cell Cardiol. 1999;31:773–783
  10. Rao K, Currie M, McCachren S, Cohen H. Pentoxifylline and other methyl xanthines inhibit interleukin-2 receptor expression in human lymphocytes. Cell Immunol. 1991;135:314–325
  11. Strutz F, Heeg M, Kochsiek T, Siemers G, Zeisberg M, Muller G. Effects of pentoxifylline, pentifylline and gamma-interferon on proliferation, differentiation, and matrix synthesis of human renal fibroblasts. Nephrol Dial Transplant. 2000;15:1535–1546
  12. Hecht M, Muller M, Lohmann-Matthes M, Emmendorffer A. In vitro and in vivo effects of pentoxifylline on macrophages and lymphocytes derived from autoimmune MRL-lpr/lpr mice. J Leukoc Biol. 1995;57:242–249
  13. Segal R, Dayan M, Zinger H, Mozes E. Suppression of experimental systemic lupus erythematosus (SLE) in mice via TNF inhibition by an anti-TNF-alpha monoclonal antibody and by pentoxifylline. Lupus. 2001;10:23–30
  14. Lin S, Chen Y, Chien C, Chiaang W, Tsai C, Tsai T. Pentoxifylline attenuated renal disease progression in rats with remnant kidney. J Am Soc Nephrol. 2002;13:2916–2929
  15. Navarro J, Mora C, Rivero A, et al. Urinary protein excretion and serum tumor necrosis factor in diabetic patients with advanced renal failure: Effects of pentoxifylline administration. Am J Kidney Dis. 1999;33:458–463
  16. Solerte S, Fioravanti M, Bozzetti A, et al. Pentoxifylline, albumin excretion rate, and proteinuria in type I and type II diabetic patients with microproteinuria (Results of a short-term randomized study). Acta Diabetol Lat. 1986;23:171–177
  17. Rodriguez-Moran M, Gonzalez-Gonzalez G, Bermudez-Barba M, et al. Effects of pentoxifylline on the urinary protein excretion profile of type 2 diabetic patients with microproteinuria: A double-blind, placebo-controlled randomized trial. Clin Nephrol. 2006;66:3–10
  18. Aminorroaya A, Janghorbani M, Rezvanian H, Aminian T, Gharavi M, Amini M. Comparison of the effect of pentoxifylline and captopril on proteinuria in patients with type 2 diabetes mellitus. Nephron Clin Pract. 2005;99:c73–c77
  19. Rodriguez-Moran M, Guerrero-Romero F. Pentoxifylline is as effective as captopril in the reduction of microalbuminuria in non-hypertensive type 2 diabetic patients—A randomized, equivalent trial. Clin Nephrol. 2005;64:91–97
  20. Chen Y, Lin S, Chiang W, Wu K, Tsai T. Pentoxifylline ameliorates proteinuria through suppression of renal monocyte chemoattractant protein-1 in patients with proteinuric primary glomerular diseases. Kidney Int. 2006;69:1410–1415
  21. Navarro J, Mora C, Muros M, Macia M, Garcia J. Effects of pentoxifylline administration on urinary N-acetyl-B-glucosaminidase excretion in type 2 diabetic patients: A short-term, prospective, randomized study. Am J Kidney Dis. 2003;42:264–270
  22. Levey A, Greene T, Kusek T, Beck G. A simplified equation to predict glomerular filtration rate from serum creatinine. J Am Soc Nephrol. 2000;11:155A;(abstr)
  23. Maroni BJ, Steinman TI, Mitch WE. A method for estimating nitrogen intake of patients with chronic renal failure. Kidney Int. 1985;27:58–65
  24. Peterson JC, Adler S, Burkhart J, et al. Blood pressure control, proteinuria, and the progression of renal disease: the modification of diet in renal disease study. Ann Intern Med. 1995;123:754–762
  25. Navarro J, Mora C, Muros M, Garcia J. Additive antiproteinuric effect of pentoxifylline in patients with type 2 diabetes under angiotensin II receptor blockade: A short term, randomized, controlled trial. J Am Soc Nephrol. 2005;16:2119–2126
  26. Harmankaya O, Seber S, Yilmaz M. Combination of pentoxifylline with angiotensin converting enzyme inhibitors produces an additional reduction in microalbuminuria in hypertensive type 2 diabetic patients. Ren Fail. 2003;25:465–470
  27. McCormick BB, Sydor A, Akbari A, Fergusson D, Doucette S, Knoll G. The effect of pentoxifylline on proteinuria in diabetic kidney disease: A meta-analysis. Am J Kidney Dis. 2008;52:454–463
  28. Diskin C, Stokes J, Dansby L, Radcliff L, Carter T. Will the addition of pentoxifylline reduce proteinuria in patients with diabetic glomerulosclerosis refractory to maximal doses of both and angiotensin-converting enzyme inhibitor and an angiotensin receptor blocker?. J Nephrol. 2007;20:410–416
  29. Lin SL, Chen YM, Chaing WC, Wu KW, Tsai TJ. Effect of pentoxifylline in addition to losartan on proteinuria and GFR in CKD: A 12-month randomized trial. Am J Kidney Dis. 2008;52:464–474
  30. Cho ME, Smith DC, Branton MH, Penzak SR, Kopp JB. Pirfenidone slows renal clearance function decline in patients with focal segmental glomerulosclerosis. Clin J Am Soc Nephrol. 2007;2:906–913

 Trial registration: www.clinicaltrials.gov; study number: NCT00285298.

 Originally published online as doi:10.1053/j.ajkd.2008.11.026 on February 13, 2009.

PII: S0272-6386(08)01761-7

doi: 10.1053/j.ajkd.2008.11.026

American Journal of Kidney Diseases
Volume 53, Issue 4 , Pages 606-616 , April 2009