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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 Jan; 31(1):59-67.HR

Abstract

Although dual blockade of the renin-angiotensin-aldosterone system (RAAS) with the combination of an angiotensin-converting enzyme inhibitor (ACE-I) and angiotensin II receptor blocker (ARB) is generally well-established as a treatment for nephropathy, this treatment is not fully effective in some patients. Based on the recent evidence implicating aldosterone in renal disease progression, this study was conducted to examine the efficacy of blockade with three different mechanisms by adding an aldosterone blocker in patients who do not respond adequately to the dual blockade. A 1-year randomized, open-label, multicenter, prospective controlled study was conducted, in which 32 non-diabetic nephropathy patients with proteinuria exceeding 0.5 g/day were enrolled after more than 12 weeks of ACE-I (5 mg enalapril) and ARB (50 mg losartan) combination treatment. These patients were allocated into two groups of 16 patients each: a triple blockade group in which 25 mg of spironolactone daily was added to the ACE-I and ARB combination treatment, and a control group in which 1 mg of trichlormethiazide or 20 mg of furosemide was added to the combination treatment instead of spironolactone depending upon the creatinine level. After 1 year of treatment, the urinary protein level decreased by 58% (p<0.05) with the triple blockade but was unchanged in the controls. Furthermore, urinary type IV collagen level decreased by 40% (p<0.05) with the triple blockade but was unchanged in the controls. The decreases in urinary protein and urinary type IV collagen were not accompanied by a decrease in blood pressure. Mean serum creatinine, potassium and blood pressure did not change significantly by either treatment. In conclusion, triple blockade of the RAAS 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.

Authors+Show Affiliations

Department of Kidney Disease and Hypertension, Osaka General Medical Center, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Multicenter Study
Randomized Controlled Trial

Language

eng

PubMed ID

18360019

Citation

Furumatsu, Yoshiyuki, 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." Hypertension Research : Official Journal of the Japanese Society of Hypertension, vol. 31, no. 1, 2008, pp. 59-67.
Furumatsu Y, Nagasawa Y, Tomida K, 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(1):59-67.
Furumatsu, Y., Nagasawa, Y., Tomida, K., Mikami, S., Kaneko, T., Okada, N., Tsubakihara, Y., Imai, E., & Shoji, T. (2008). 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. Hypertension Research : Official Journal of the Japanese Society of Hypertension, 31(1), 59-67. https://doi.org/10.1291/hypres.31.59
Furumatsu Y, 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(1):59-67. PubMed PMID: 18360019.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Furumatsu,Yoshiyuki, AU - Nagasawa,Yasuyuki, AU - Tomida,Kodo, AU - Mikami,Satoshi, AU - Kaneko,Tetsuya, AU - Okada,Noriyuki, AU - Tsubakihara,Yoshiharu, AU - Imai,Enyu, AU - Shoji,Tatsuya, PY - 2008/3/25/pubmed PY - 2008/4/16/medline PY - 2008/3/25/entrez SP - 59 EP - 67 JF - Hypertension research : official journal of the Japanese Society of Hypertension JO - Hypertens Res VL - 31 IS - 1 N2 - Although dual blockade of the renin-angiotensin-aldosterone system (RAAS) with the combination of an angiotensin-converting enzyme inhibitor (ACE-I) and angiotensin II receptor blocker (ARB) is generally well-established as a treatment for nephropathy, this treatment is not fully effective in some patients. Based on the recent evidence implicating aldosterone in renal disease progression, this study was conducted to examine the efficacy of blockade with three different mechanisms by adding an aldosterone blocker in patients who do not respond adequately to the dual blockade. A 1-year randomized, open-label, multicenter, prospective controlled study was conducted, in which 32 non-diabetic nephropathy patients with proteinuria exceeding 0.5 g/day were enrolled after more than 12 weeks of ACE-I (5 mg enalapril) and ARB (50 mg losartan) combination treatment. These patients were allocated into two groups of 16 patients each: a triple blockade group in which 25 mg of spironolactone daily was added to the ACE-I and ARB combination treatment, and a control group in which 1 mg of trichlormethiazide or 20 mg of furosemide was added to the combination treatment instead of spironolactone depending upon the creatinine level. After 1 year of treatment, the urinary protein level decreased by 58% (p<0.05) with the triple blockade but was unchanged in the controls. Furthermore, urinary type IV collagen level decreased by 40% (p<0.05) with the triple blockade but was unchanged in the controls. The decreases in urinary protein and urinary type IV collagen were not accompanied by a decrease in blood pressure. Mean serum creatinine, potassium and blood pressure did not change significantly by either treatment. In conclusion, triple blockade of the RAAS 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. SN - 0916-9636 UR - https://www.unboundmedicine.com/medline/citation/18360019/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_ L2 - https://medlineplus.gov/kidneydiseases.html DB - PRIME DP - Unbound Medicine ER -