American Journal of Kidney Diseases
Volume 52, Issue 3 , Pages 464-474 , September 2008

Effect of Pentoxifylline in Addition to Losartan on Proteinuria and GFR in CKD: A 12-Month Randomized Trial

Received 31 December 2007 ,Accepted 1 May 2008.

References 

  1. Jones CA, McQuillan GM, Kusek JW, et al. Serum creatinine levels in the US population: Third National Health and Nutrition Examination Survey. Am J Kidney Dis. 1998;32:992–999
  2. Lewis EJ, Hunsicker LG, Bain RP, Rohde RD Collaborative Study Group. The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy. N Engl J Med. 1993;329:1456–1462
  3. Lewis EJ, Hunsicker LG, Clarke WR, et al. 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
  4. Brenner BM, Cooper ME, de Zeeuw D, et al. Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med. 2001;345:861–869
  5. Zeisberg M, Hanai J, Sugimoto H, et al. BMP-7 counteracts TGF-beta1-induced epithelial-to-mesenchymal transition and reverses chronic renal injury. Nat Med. 2003;9:964–968
  6. Anders HJ, Vielhauer V, Schlondorff D. Chemokines and chemokine receptors are involved in the resolution or progression of renal disease. Kidney Int. 2003;63:401–415
  7. Kagami S, Border WA, Miller DE, Noble NA. Angiotensin II stimulates extracellular matrix protein synthesis through induction of transforming growth factor-beta expression in rat glomerular mesangial cells. J Clin Invest. 1994;93:2431–2437
  8. Ostendorf T, Rong S, Boor P, et al. Antagonism of PDGF-D by human antibody CR002 prevents renal scarring in experimental glomerulonephritis. J Am Soc Nephrol. 2006;17:1054–1062
  9. Amann B, Tinzmann R, Angelkort B. ACE inhibitors improve diabetic nephropathy through suppression of renal MCP-1. Diabetes Care. 2003;26:2421–2425
  10. Wada T, Furuichi K, Sakai N, et al. Gene therapy via blockade of monocyte chemoattractant protein-1 for renal fibrosis. J Am Soc Nephrol. 2004;15:940–948
  11. Navarro JF, 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
  12. Chen YM, Lin SL, Chiang WC, Wu KD, Tsai TJ. Pentoxifylline ameliorates proteinuria through suppression of renal monocyte chemoattractant protein-1 in patients with proteinuric primary glomerular diseases. Kidney Int. 2006;69:1410–1415
  13. Hostetter TH. The next treatments of chronic kidney disease: If we find them, can we test them?. J Am Soc Nephrol. 2002;13:3024–3026
  14. Mogensen CE, Neldam S, Tikkanen I, et al. Randomised controlled trial of dual blockade of renin-angiotensin system in patients with hypertension, microalbuminuria, and non-insulin dependent diabetes: The Candesartan And Lisinopril Microalbuminuria (CALM) Study. BMJ. 2000;321:1440–1444
  15. Nakao N, Yoshimura A, Morita H, Takada M, Kayano T, Ideura T. Combination treatment of angiotensin-II receptor blocker and angiotensin-converting-enzyme inhibitor in non-diabetic renal disease (COOPERATE): A randomised controlled trial. Lancet. 2003;361:117–124
  16. Rossing K, Schjoedt KJ, Smidt UM, Boomsma F, Parving HH. Beneficial effects of adding spironolactone to recommended antihypertensive treatment in diabetic nephropathy: A randomized, double-masked, crossover study. Diabetes Care. 2005;28:2106–2112
  17. Bianchi S, Bigazzi R, Campese VM. Long-term effects of spironolactone on proteinuria and kidney function in patients with chronic kidney disease. Kidney Int. 2006;70:2116–2123
  18. Remuzzi G, Zoja C, Gagliardini E, Corna D, Abbate M, Benigni A. Combining an antiproteinuric approach with mycophenolate mofetil fully suppresses progressive nephropathy of experimental animals. J Am Soc Nephrol. 1999;10:1542–1549
  19. Benigni A, Zoja C, Corna D, et al. Add-on anti-TGF-beta antibody to ACE inhibitor arrests progressive diabetic nephropathy in the rat. J Am Soc Nephrol. 2003;14:1816–1824
  20. Benigni A, Zoja C, Campana M, et al. Beneficial effect of TGF beta antagonism in treating diabetic nephropathy depends on when treatment is started. Nephron Exp Nephrol. 2006;104:e158–e168
  21. Chen YM, Chien CT, Hu-Tsai MI, et al. Pentoxifylline attenuates experimental mesangial proliferative glomerulonephritis. Kidney Int. 1999;56:932–943
  22. Lin SL, Chen YM, Chien CT, Chiang WC, Tsai CC, Tsai TJ. Pentoxifylline attenuated the renal disease progression in rats with remnant kidney. J Am Soc Nephrol. 2002;13:2916–2929
  23. Lin SL, Chen RH, Chen YM, Chiang WC, Tsai TJ, Hsieh BS. Pentoxifylline inhibits platelet-derived growth factor-stimulated cyclin D1 expression in mesangial cells by blocking Akt membrane translocation. Mol Pharmacol. 2003;64:811–822
  24. Chen YM, Chiang WC, Lin SL, Wu KD, Tsai TJ, Hsieh BS. Dual regulation of tumor necrosis factor-alpha-induced CCL2/monocyte chemoattractant protein-1 expression in vascular smooth muscle cells by nuclear factor-kappaB and activator protein-1: Modulation by type III phosphodiesterase inhibition. J Pharmacol Exp Ther. 2004;309:978–986
  25. Chen YM, Ng YY, Lin SL, Chiang WC, Lan HY, Tsai TJ. Pentoxifylline suppresses renal tumor necrosis factor-alpha and ameliorates experimental crescentic glomerulonephritis in rats. Nephrol Dial Transplant. 2004;19:1106–1115
  26. Lin SL, Chen RH, Chen YM, et al. Pentoxifylline attenuates tubulointerstitial fibrosis by blocking Smad3/4-activated transcription and profibrogenic effects of connective tissue growth factor. J Am Soc Nephrol. 2005;16:2702–2713
  27. Ducloux D, Bresson-Vautrin C, Chalopin J. Use of pentoxifylline in membranous nephropathy. Lancet. 2001;357:1672–1673
  28. Galindo-Rodriguez G, Bustamante R, Esquivel-Nava G, et al. Pentoxifylline in the treatment of refractory nephrotic syndrome secondary to lupus nephritis. J Rheumatol. 2003;30:2382–2384
  29. Navarro JF, 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
  30. National Kidney Foundation. K/DOQI Clinical Practice Guidelines for Chronic Kidney Disease (Evaluation, classification, and stratification). Am J Kidney Dis. 2002;39(suppl 1):S17–S31
  31. Levey AS, Bosch JP, Lewis JB, et al. A more accurate method to estimate glomerular filtration rate from serum creatinine: A new prediction equation. Ann Intern Med. 1999;130:461–470
  32. Paap CM, Simpson KS, Horton MW, Schaefer KL, Lassman HB, Sack MR. Multiple-dose pharmacokinetics of pentoxifylline and its metabolites during renal insufficiency. Ann Pharmacother. 1996;30:724–729
  33. Ruggenenti P, Gaspari F, Perna A, Remuzzi G. Cross sectional longitudinal study of spot morning urine protein:creatinine ratio, 24 hour urine protein excretion rate, glomerular filtration rate, and end stage renal failure in chronic renal disease in patients without diabetes. BMJ. 1998;316:504–509
  34. Remuzzi G, Schieppati A, Ruggenenti P. Clinical practice (Nephropathy in patients with type 2 diabetes). N Engl J Med. 2002;346:1145–1151
  35. Levey AS. Clinical practice (Nondiabetic kidney disease). N Engl J Med. 2002;347:1505–1511
  36. Bullo B, Zdrojewski Z, Rutkowski B. Mycophenolate mofetil (MMF) therapeutic approach in patients with chronic glomerulonephritis. Kidney Int. 2003;64:1139
  37. Ibsen H, Olsen MH, Wachtell K, et al. Does albuminuria predict cardiovascular outcomes on treatment with losartan versus atenolol in patients with diabetes, hypertension, and left ventricular hypertrophy? (The LIFE Study). Diabetes Care. 2006;29:595–600
  38. Schjoedt KJ, Andersen S, Rossing P, Tarnow L, Parving HH. Aldosterone escape during blockade of the renin-angiotensin-aldosterone system in diabetic nephropathy is associated with enhanced decline in glomerular filtration rate. Diabetologia. 2004;47:1936–1939
  39. Gaedeke J, Peters H, Noble NA, Border WA. Angiotensin II, TGF-beta and renal fibrosis. Contrib Nephrol. 2001;135:153–160

 Originally published online as doi:10.1053/j.ajkd.2008.05.012 on July 10, 2008.

 Trial registration: www.clinicialtrials.gov; study number: NCT00155246.

PII: S0272-6386(08)00889-5

doi: 10.1053/j.ajkd.2008.05.012

American Journal of Kidney Diseases
Volume 52, Issue 3 , Pages 464-474 , September 2008