American Journal of Kidney Diseases
Volume 52, Issue 3 , Pages 486-493 , September 2008

Triple Pharmacological Blockade of the Renin-Angiotensin-Aldosterone System in Nondiabetic CKD: An Open-Label Crossover Randomized Controlled Trial

  • Leszek Tylicki, MD, PhD

      Affiliations

    • Department of Nephrology Transplantology and Internal Medicine, Medical University of Gdansk, Gdansk, Poland
    • Corresponding Author InformationAddress correspondence to Leszek Tylicki, MD, PhD, Department of Nephrology, Transplantology and Internal Medicine, Medical University of Gdansk, Dębinki 7 St. Gdańsk 80-211, Poland
    • ,
  • Przemysław Rutkowski, MD, PhD

      Affiliations

    • Department of Nephrology Transplantology and Internal Medicine, Medical University of Gdansk, Gdansk, Poland
    • ,
  • Marcin Renke, MD, PhD

      Affiliations

    • Department of Nephrology Transplantology and Internal Medicine, Medical University of Gdansk, Gdansk, Poland
    • ,
  • Wojciech Larczyński, MD

      Affiliations

    • Department of Nephrology Transplantology and Internal Medicine, Medical University of Gdansk, Gdansk, Poland
    • ,
  • Ewa Aleksandrowicz, PhD

      Affiliations

    • Department of Clinical Nutrition and Laboratory Diagnostic, Medical University of Gdansk, Gdansk, Poland
    • ,
  • Wiesława Lysiak-Szydlowska, MD, PhD

      Affiliations

    • Department of Clinical Nutrition and Laboratory Diagnostic, Medical University of Gdansk, Gdansk, Poland
    • ,
  • Bolesław Rutkowski, MD, PhD

      Affiliations

    • Department of Nephrology Transplantology and Internal Medicine, Medical University of Gdansk, Gdansk, Poland

Received 26 September 2007 ,Accepted 14 February 2008.

References 

  1. Tylicki L, Larczynski W, Rutkowski B. Renal protective effects of the renin-angiotensin-aldosterone system blockade: From evidence-based approach to perspectives. Kidney Blood Press Res. 2005;28:230–242
  2. Remuzzi G, Perico N, Macia M, Ruggenenti P. The role of renin-angiotensin-aldosterone system in the progression of chronic kidney disease. Kidney Int Suppl. 2005;99:S57–S65
  3. Nakao N, Yoshimura A, Morita H, et al. 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
  4. Ruggenenti P, Remuzzi A. Is therapy with combined ACE inhibitor and angiotensin receptor antagonist the new gold standard of treatment for nondiabetc, chronic proteinuric nephropathies?. NephSAP. 2003;2:235–237
  5. Rutkowski P, Tylicki L, Renke M, et al. Low-dose dual blockade of the renin-angiotensin system in patients with primary glomerulonephritis. Am J Kidney Dis. 2004;43:260–268
  6. Tylicki L, Biedunkiewicz B, Chamienia A, et al. Renal allograft protection with angiotensin II type 1 receptor antagonists. Am J Transplant. 2007;7:243–248
  7. Hollenberg NK. Aldosterone in the development and progression of renal injury. Kidney Int. 2004;66:1–9
  8. Iglarz M, Touyz RM, Viel EC, Amiri F, Schiffrin EL. Involvement of oxidative stress in the profibrotic action of aldosterone: Interaction with the renin-angiotension system. Am J Hypertens. 2004;17:597–603
  9. Arima S, Kohagura K, Xu HL, et al. Nongenomic vascular action of aldosterone in the glomerular microcirculation. J Am Soc Nephrol. 2003;14:2255–2263
  10. Lakkis J, Lu W, Weir M. RAAS escape: A real clinical entity that may be important in the progression of cardiovascular and renal disease. Curr Hypertens Rep. 2003;5:408–417
  11. Maroni BJ, Steinman TI, Mitch WE. A method for estimating nitrogen intake of patients with chronic renal failure. Kidney Int. 1985;27:58–65
  12. Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron. 1976;16:31–41
  13. Maruhn D. Rapid calorimetric assay of β-galactosidase and N-acetyl-β-d-glucosaminidase in human urine. Clin Chim Acta. 1976;73:453–461
  14. Bianchi S, Bigazii 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
  15. Chrysostomou A, Becker G. Spironolactone in addition to ACE inhibition to reduce proteinuria in patients with chronic renal disease. N Engl J Med. 2001;345:925–926
  16. Senn S. Cross-over Trials in Clinical Research. Chichester, NY: Wiley; 2002;
  17. Grubbs FE. Procedures for detecting outlying observations. Technometrics. 1969;11:1–21
  18. Schjoedt KJ, Rossing K, Juhl TR, et al. Beneficial impact of spironolactone on nephrotic range albuminuria in diabetic nephropathy. Kidney Int. 2006;70:536–542
  19. 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, cross-over study. Diabetes Care. 2005;28:2106–2112
  20. Nitta K, Uchida K, Nihei H. Spironolactone and angiotensin receptor blocker in nondiabetic renal diseases. Am J Med. 2004;117:444–445
  21. Aranda P, Segura J, Ruilope LM, et al. Long-term renoprotective effects of standard versus high doses of telmisartan in hypertensive nondiabetic nephropathies. Am J Kidney Dis. 2005;46:1074–1079
  22. Minutolo R, Gabbai FB, Borrelli S, et al. Changing the timing of antihypertensive therapy to reduce nocturnal blood pressure in CKD: An 8-week uncontrolled trial. Am J Kidney Dis. 2007;50:908–917
  23. Butter H, Hemmelder M, Navis G, De Jong P, De Zeeuw D. The blunting of the antiproteinuric efficacy of ACE inhibition by high sodium intake can be restored by hydrochlorothiazide. Nephrol Dial Transplant. 1998;13:1682–1685
  24. Kramer AB, van der Meulen EF, Hamming I, van Goor H, Navis G. Effect of combining ACE inhibition with aldosterone blockade on proteinuria and renal damage in experimental nephrosis. Kidney Int. 2007;71:417–424
  25. Abbate M, Zoja C, Rottoli D, et al. Antiproteinuric therapy while preventing the abnormal protein traffic in proximal tubule abrogates protein-and complement-dependent interstitial inflamation in experimental renal disease. J Am Soc Nephrol. 1999;10:804–813
  26. Teppo AM, Tornroth T, Honkanen E, Gronhagen-Riska C. Urinary amino-terminal propeptide of type III procollagen (PIIINP) as a marker of interstitial fibrosis in renal transplant recipients. Transplantation. 2003;75:2113–2119
  27. Bazzi C, Petrini C, Rizza V, et al. Urinary N-acetylglucosaminidase excretion is a marker of tubular cell dysfunction and a predictor of outcome in primary glomerulonephritis. Nephrol Dial Transplant. 2002;17:1890–1896
  28. Holdt-Lehmann B, Lehmann A, Korten G, et al. Diagnostic value of urinary alanine aminopeptidase and N-acetyl-β-d-glucosaminidase in comparison to alfa-1 microglobulin as a marker in evaluating tubular dysfunction in glomerulonephritis patients. Clin Chim Acta. 2000;297:93–102
  29. Sawathiparnich P, Murphey LJ, Kumar S, Vaughan DE, Brown NJ. Effect of combined AT1 receptor and aldosterone receptor antagonism on plasminogen activator inhibitor-1. J Clin Endocrinol Metab. 2003;88:3867–3873
  30. Wrenger E, Muller R, Moesenthin M, et al. Interaction of spironolactone with ACE inhibitors or angiotensin receptor blockers: Analysis of 44 cases. BMJ. 2003;327:147–149

 Originally published online as doi:10.1053/j.ajkd.2008.02.297 on April 17, 2008.

 Trial registration: clinicaltrials.gov, study number: NCT00528385.

PII: S0272-6386(08)00467-8

doi: 10.1053/j.ajkd.2008.02.297

American Journal of Kidney Diseases
Volume 52, Issue 3 , Pages 486-493 , September 2008

Article Tools

* Image Usage & Resolution