Comparison of the efficacy of triple blockade, double blockade and single blockade of RAAS in non diabetic chronic kidney disease
DOI:
https://doi.org/10.18203/2349-3933.ijam20183124Keywords:
CKD, Double blockade, Hyperkalemia, RAAS, Single blockade, Triple blockadeAbstract
Background: Although dual blockade of the renin-angiotensin-aldosterone system with the combination of an angiotensin-converting enzyme inhibitor and angiotensin II receptor blocker is generally well established as a treatment for nephropathy, this treatment is not fully effective in some patients.
Methods: A prospective observational study was done on 600 chronic kidney disease patients during July 2012 to August 2014 to compare the efficacy of triple blockade, double blockade and single blockade of renin-angiotensin-aldosterone system in non diabetic chronic kidney disease.
Results: At the end of the study, 24 hours urinary protein excretion rate of group I and group III were compared by using student t-test and p value (0.0268) was found significant. Similarly, on comparing group II and group III, p value (0.0160) was again found significant.
Conclusions: Triple blockade of the renin-angiotensin-aldosterone system was effective for the treatment of proteinuria in patients with non-diabetic nephropathy whose increased urinary protein had not responded sufficiently to a dual blockade.
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References
Russo D, Pisani A, Balletta MM, De Nicola L, Savino FA, Andreucci M, et al. Additive antiproteinuric effect of converting enzyme inhibitor and losartan in normotensive patients with IgA nephropathy. Am J Kidney Dis. 1999;33:851-6.
Russo D, Minutolo R, Pisani A, Esposito R, Signoriello G, Andreucci M, et al. Coadministration of losartan and enalapril exerts additive antiproteinuric effect in IgA nephropathy. Am J Kidney Dis. 2001;38:18-25.
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;361:117-24.
4. Okubo S, Niimura F, Nishimura H, Takemoto F, Fogo A, Matsusaka T, et al. Angiotensin-independent mechanism for aldosterone synthesis during chronic extracellular fluid volume depletion. J Clin Invest. 1997;99:855-60.
Epstein M. Aldosterone as a mediator of progressive renal disease: pathogenetic and clinical implications. Am J Kidney Dis. 2001;37:677-88.
Borghi C, Boschi S, Ambrosioni E, Melandri G, Branzi A, Magnani B. Evidence of a partial escape of renin-angiotensin- aldosterone blockade in patients with acute myocardial infarction treated with ACE inhibitors. J Clin Pharmacol. 1993;33:40-5.
Pitt B. “Escape” of aldosterone production in patients with left ventricular dysfunction treated with an angiotensin converting enzyme inhibitor: implications for therapy. Cardiovasc Drugs Ther. 1995;9:145-9.
Sato A, Saruta T. Aldosterone escape during angiotensinconverting enzyme inhibitor therapy in essential hypertensive patients with left ventricular hypertrophy. J Int Med Res. 2001;29:13-21.
Naruse M, Tanabe A, Sato A, Takagi S, Tsuchiya K, Imaki T, et al. Aldosterone breakthrough during angiotensin II receptor antagonist therapy in stroke-prone spontaneously hypertensive rats. Hypertension. 2002;40:28-33.
Robert V, Heymes C, Silvestre JS, Sabri A, Swynghedauw B, Delcayre C. Angiotensin AT1 receptor subtype as a cardiac target of aldosterone: role in aldosterone-salt-induced fibrosis. Hypertension. 1999;33:981-6.
Harada E, Yoshimura M, Yasue H, Nakagawa O, Nakagawa M, Harada M, et al. Aldosterone induces angiotensin-converting-enzyme gene expression in cultured neonatal rat cardiocytes. Circulation. 2001;104:137-9.
Sugiyama T, Yoshimoto T, Tsuchiya K, Gochou N, Hirono Y, Tateno T, et al. Aldosterone induces angiotensin converting enzyme gene expression via a JAK2-dependent pathway in rat endothelial cells. Endocrinology. 2005;146:3900-06.
Fisher ND, Hollenberg NK. Renin inhibition: what are the therapeutic opportunities? J Am Soc Nephrol. 2005;16:592-9.
Burnier M, Brunner HR. Angiotensin II receptor antagonists. Lancet. 2000;355:637-45.
Rousseau MF, Gurné O, Duprez D, Van Mieghem W, Robert A, Ahn S, et al. Beneficial neurohormonal profile of spironolactone in severe congestive heart failure: results from the RALES neurohormonal substudy. J Am Coll Cardiol. 2002;40:1596-601.
van de Wal RM, Plokker HW, Lok DJ, Boomsma F, van der Horst FA, van Veldhuisen DJ, et al. Determinants of increased angiotensin II levels in severe chronic heart failure patients despite ACE inhibition. Int J Cardiol. 2006;106:367-72.
Bomback AS, Klemmer PJ. The incidence and implications of aldosterone breakthrough. Nat Clin Pract Nephrol. 2007;3:486-92.
Brenner BM, Cooper ME, de Zeeuw D, Keane WF, Mitch WE, Parving HH, et al. Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med. 2001;345:861-9.
Kunz R, Friedrich C, Wolbers M, Mann JF. Meta-analysis: effect of monotherapy and combination therapy with inhibitors of the renin angiotensin system on proteinuria in renal disease. Ann Intern Med. 2008;148:30-48.
Lewis EJ, Hunsicker LG, Bain RP, Rohde RD. The effect of angiotensin-converting enzyme inhibition on diabetic nephropathy. The collaborative study group. N Engl J Med. 1993;329:1456-62.
Jafar TH, Schmid CH, Landa M, Giatras I, Toto R, Remuzzi G, et al. Angiotensin-converting enzyme inhibitors and progression of nondiabetic renal disease. A meta-analysis of patient-level data. Ann Intern Med. 2001;135:73-87.
Schjoedt KJ, Rossing K, Juhl TR, Boomsma F, Tarnow L, Rossing P, et al. Beneficial impact of spironolactone on nephrotic range albuminuria in diabetic nephropathy. Kidney Int. 2006;70:536-42.
Rachmani R, Slavachevsky I, Amit M, Levi Z, Kedar Y, Berla M, et al. The effect of spironolactone, cilazapril and their combination on albuminuria in patients with hypertension and diabetic nephropathy is independent of blood pressure reduction: a randomized controlled study. Diabet Med. 2004;21:471-5.
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;28:2106-12.
Schjoedt KJ, Rossing K, Juhl TR, Boomsma F, Rossing P, Tarnow L, et al. Beneficial impact of spironolactone in diabetic nephropathy. Kidney Int. 2005;68:2829-36.
van den Meiracker AH, Baggen RG, Pauli S, Lindemans A, Vulto AG, Poldermans D, et al. Spironolactone in type 2 diabetic nephropathy: effects on proteinuria, blood pressure and renal function. J Hypertens. 2006;24:2285-92.
Chrysostomou A, Pedagogos E, MacGregor L, Becker GJ. Double-blind, placebo-controlled study on the effect of the aldosterone receptor antagonist spironolactone in patients who have persistent proteinuria and are on long-term angiotensin-converting enzyme inhibitor therapy, with or without an angiotensin II receptor blocker. Clin J Am Soc Nephrol. 2006;1:256-62.
Epstein M, Williams GH, Weinberger M, Lewin A, Krause S, Mukherjee R, et al. Selective aldosterone blockade with eplerenone reduces albuminuria in patients with type 2 diabetes. Clin J Am Soc Nephrol. 2006;1:940-51.
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;70:2116-23.
Tylicki L, Rutkowski P, Renke M, Larczynski W, Aleksandrowicz E, Lysiak‑Szydlowska W, et al. Triple pharmacological blockade of the renin‑angiotensin-aldosterone system in nondiabetic CKD: an open-label crossover randomized controlled trial. Am J Kidney Dis. 2008;52:486-93.
Furumatsu Y, Nagasawa Y, Tomida K, Mikami S, Kaneko T, Okada N, et al. Effect of renin-angiotensin-aldosterone system triple blockade on non-diabetic renal disease: addition of an aldosterone blocker, spironolactone, to combination treatment with an angiotensin-converting enzyme inhibitor and angiotensin II receptor blocker. Hypertens Res. 2008;31:59-67.
Pitt B, Remme W, Zannad F, Neaton J, Martinez F, Roniker B, et al. Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med. 2003;348:1309-21.
Bomback AS, Kshirsagar AV, Amamoo MA, Klemmer PJ. Change in proteinuria after adding aldosterone blockers to ACE inhibitors or angiotensin receptor blockers in CKD: a systematic review. Am J Kidney Dis. 2008;51:199-211.