Research
Original Investigation
Renoprotective Effect of Renin-Angiotensin-Aldosterone System Blockade in Patients With Predialysis Advanced Chronic Kidney Disease, Hypertension, and Anemia Ta-Wei Hsu, MD; Jia-Sin Liu, MS; Szu-Chun Hung, MD; Ko-Lin Kuo, MD; Yu-Kang Chang, PhD; Yu-Chi Chen, PhD; Chih-Cheng Hsu, MD, DrPH; Der-Cherng Tarng, MD, PhD Invited Commentary page 355 IMPORTANCE The benefit of using a renin-angiotensin-aldosterone system blocker such as an
angiotensin-converting enzyme inhibitor (ACEI) or an angiotensin II receptor blocker (ARB) for patients with advanced chronic kidney disease (CKD) remains undetermined. OBJECTIVE To assess the effectiveness and safety of ACEI/ARB use for advanced predialysis CKD in patients with hypertension and anemia.
Supplemental content at jamainternalmedicine.com CME Quiz at jamanetworkcme.com and CME Questions page 488
DESIGN Prospective cohort study. SETTING Taiwan. PARTICIPANTS From January 1, 2000, through June 30, 2009, we selected 28 497 hypertensive adult patients with CKD. Serum creatinine levels were greater than 6 mg/dL, hematocrit levels were less than 28%, and patients were treated with erythropoiesisstimulating agents. INTERVENTIONS Users (n = 14 117) and nonusers (n = 14 380) of ACEIs/ARBs. MAIN OUTCOMES AND MEASURES We used Cox proportional hazards regression models to estimate hazard ratios (HRs) for commencement of long-term dialysis and all-cause mortality for ACRI/ARB users vs nonusers. RESULTS In a median follow-up of 7 months, 20 152 patients (70.7%) required long-term dialysis and 5696 (20.0%) died before progression to end-stage renal disease requiring dialysis. Use of ACEIs/ARBs was associated with a lower risk for long-term dialysis (HR, 0.94 [95% CI, 0.91-0.97]) and the composite outcome of long-term dialysis or death (0.94 [0.92-0.97]). The renal benefit of ACEI/ARB use was consistent across most patient subgroups, as was that of ACEI or ARB monotherapy. Compared with nonusers, the ACEI/ARB users had a higher hyperkalemia-associated hospitalization rate, but the risk of predialysis mortality caused by hyperkalemia was not significantly increased (HR, 1.03 [95% CI, 0.92-1.16]; P = .30). CONCLUSIONS AND RELEVANCE Patients with stable hypertension and advanced CKD who receive therapy with ACEIs/ARBs exhibit an association with lower risk for long-term dialysis or death by 6%. This benefit does not increase the risk of all-cause mortality.
JAMA Intern Med. 2014;174(3):347-354. doi:10.1001/jamainternmed.2013.12700 Published online December 16, 2013.
Author Affiliations: Author affiliations are listed at the end of this article. Corresponding Authors: Chih-Cheng Hsu, MD, DrPH, Division of Geriatrics and Gerontology, Institute of Population Health Sciences, National Health Research Institutes, No. 35, Keyan Road, Zhunan Town, Miaoli County, Taiwan 35053 ([email protected] .tw); and Der-Cherng Tarng, MD, PhD, Institutes of Physiology and Clinical Medicine, National Yang-Ming University, 201, Section 2, Shih-Pai Road, Taipei, Taiwan 11217 ([email protected]).
347
Copyright 2014 American Medical Association. All rights reserved.
Downloaded From: http://archinte.jamanetwork.com/ by a New York University User on 06/01/2015
Research Original Investigation
Renin-Angiotensin System Blockade in CKD
I
nhibition of the renin-angiotensin-aldosterone system with an angiotensin-converting enzyme inhibitor (ACEI) or an angiotensin II receptor blocker (ARB) delays the progression of chronic kidney disease (CKD) in patients with and without diabetes mellitus, particularly those with mild to moderate renal insufficiency as reflected by a serum creatinine level of 1.5 to 3.0 mg/dL (to convert to micromoles per liter, multiply by 88.4).1-4 Two randomized clinical trials in China5,6 and a post hoc analysis of the Ramipril Efficacy in Nephropathy trial7 further demonstrated that the use of ACEIs or ARBs is beneficial in patients with stage 4 CKD, defined by a glomerular filtration rate (GFR) of 15 to 29 mL/min/1.73 m2 and a serum creatinine level of approximately 3.0 to 5.0 mg/dL, who do not have diabetes mellitus. However, data focusing on the use of ACEIs and/or ARBs in patients with serum creatinine levels of greater than 5.0 mg/dL or a GFR of less than 15 mL/min/1.73 m2 are limited. Because most prospective, large-scale clinical trials of ACEI/ARB use excluded individuals with stage 5 CKD who were not undergoing dialysis (predialysis CKD), whether ACEI/ARB therapy should be used continuously in patients with advanced CKD remains unclear. The prevalence and incidence of end-stage renal disease (ESRD) are extremely high in Taiwan compared with other countries.8 The timing for initiation of dialysis in Taiwan is late (characteristically starting at an estimated GFR
Original Investigation
Renoprotective Effect of Renin-Angiotensin-Aldosterone System Blockade in Patients With Predialysis Advanced Chronic Kidney Disease, Hypertension, and Anemia Ta-Wei Hsu, MD; Jia-Sin Liu, MS; Szu-Chun Hung, MD; Ko-Lin Kuo, MD; Yu-Kang Chang, PhD; Yu-Chi Chen, PhD; Chih-Cheng Hsu, MD, DrPH; Der-Cherng Tarng, MD, PhD Invited Commentary page 355 IMPORTANCE The benefit of using a renin-angiotensin-aldosterone system blocker such as an
angiotensin-converting enzyme inhibitor (ACEI) or an angiotensin II receptor blocker (ARB) for patients with advanced chronic kidney disease (CKD) remains undetermined. OBJECTIVE To assess the effectiveness and safety of ACEI/ARB use for advanced predialysis CKD in patients with hypertension and anemia.
Supplemental content at jamainternalmedicine.com CME Quiz at jamanetworkcme.com and CME Questions page 488
DESIGN Prospective cohort study. SETTING Taiwan. PARTICIPANTS From January 1, 2000, through June 30, 2009, we selected 28 497 hypertensive adult patients with CKD. Serum creatinine levels were greater than 6 mg/dL, hematocrit levels were less than 28%, and patients were treated with erythropoiesisstimulating agents. INTERVENTIONS Users (n = 14 117) and nonusers (n = 14 380) of ACEIs/ARBs. MAIN OUTCOMES AND MEASURES We used Cox proportional hazards regression models to estimate hazard ratios (HRs) for commencement of long-term dialysis and all-cause mortality for ACRI/ARB users vs nonusers. RESULTS In a median follow-up of 7 months, 20 152 patients (70.7%) required long-term dialysis and 5696 (20.0%) died before progression to end-stage renal disease requiring dialysis. Use of ACEIs/ARBs was associated with a lower risk for long-term dialysis (HR, 0.94 [95% CI, 0.91-0.97]) and the composite outcome of long-term dialysis or death (0.94 [0.92-0.97]). The renal benefit of ACEI/ARB use was consistent across most patient subgroups, as was that of ACEI or ARB monotherapy. Compared with nonusers, the ACEI/ARB users had a higher hyperkalemia-associated hospitalization rate, but the risk of predialysis mortality caused by hyperkalemia was not significantly increased (HR, 1.03 [95% CI, 0.92-1.16]; P = .30). CONCLUSIONS AND RELEVANCE Patients with stable hypertension and advanced CKD who receive therapy with ACEIs/ARBs exhibit an association with lower risk for long-term dialysis or death by 6%. This benefit does not increase the risk of all-cause mortality.
JAMA Intern Med. 2014;174(3):347-354. doi:10.1001/jamainternmed.2013.12700 Published online December 16, 2013.
Author Affiliations: Author affiliations are listed at the end of this article. Corresponding Authors: Chih-Cheng Hsu, MD, DrPH, Division of Geriatrics and Gerontology, Institute of Population Health Sciences, National Health Research Institutes, No. 35, Keyan Road, Zhunan Town, Miaoli County, Taiwan 35053 ([email protected] .tw); and Der-Cherng Tarng, MD, PhD, Institutes of Physiology and Clinical Medicine, National Yang-Ming University, 201, Section 2, Shih-Pai Road, Taipei, Taiwan 11217 ([email protected]).
347
Copyright 2014 American Medical Association. All rights reserved.
Downloaded From: http://archinte.jamanetwork.com/ by a New York University User on 06/01/2015
Research Original Investigation
Renin-Angiotensin System Blockade in CKD
I
nhibition of the renin-angiotensin-aldosterone system with an angiotensin-converting enzyme inhibitor (ACEI) or an angiotensin II receptor blocker (ARB) delays the progression of chronic kidney disease (CKD) in patients with and without diabetes mellitus, particularly those with mild to moderate renal insufficiency as reflected by a serum creatinine level of 1.5 to 3.0 mg/dL (to convert to micromoles per liter, multiply by 88.4).1-4 Two randomized clinical trials in China5,6 and a post hoc analysis of the Ramipril Efficacy in Nephropathy trial7 further demonstrated that the use of ACEIs or ARBs is beneficial in patients with stage 4 CKD, defined by a glomerular filtration rate (GFR) of 15 to 29 mL/min/1.73 m2 and a serum creatinine level of approximately 3.0 to 5.0 mg/dL, who do not have diabetes mellitus. However, data focusing on the use of ACEIs and/or ARBs in patients with serum creatinine levels of greater than 5.0 mg/dL or a GFR of less than 15 mL/min/1.73 m2 are limited. Because most prospective, large-scale clinical trials of ACEI/ARB use excluded individuals with stage 5 CKD who were not undergoing dialysis (predialysis CKD), whether ACEI/ARB therapy should be used continuously in patients with advanced CKD remains unclear. The prevalence and incidence of end-stage renal disease (ESRD) are extremely high in Taiwan compared with other countries.8 The timing for initiation of dialysis in Taiwan is late (characteristically starting at an estimated GFR
