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Original Investigation |

Renoprotective Effect of Renin-Angiotensin-Aldosterone System Blockade in Patients With Predialysis Advanced Chronic Kidney Disease, Hypertension, and Anemia

Ta-Wei Hsu, MD1; Jia-Sin Liu, MS2; Szu-Chun Hung, MD3; Ko-Lin Kuo, MD3; Yu-Kang Chang, PhD2; Yu-Chi Chen, PhD4; Chih-Cheng Hsu, MD, DrPH2,5; Der-Cherng Tarng, MD, PhD6,7
[+] Author Affiliations
1Division of Nephrology, Department of Internal Medicine, National Yang-Ming University Hospital, Ilan City, Taiwan
2Division of Geriatrics and Gerontology, Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Taiwan
3Division of Nephrology, Buddhist Tzu Chi Hospital Taipei Branch, New Taipei, Taiwan
4Department and Institute of Nursing, School of Nursing, National Yang-Ming University, Taipei, Taiwan
5Department of Health Services Administration, China Medical University and Hospital, Taichung, Taiwan
6Division of Nephrology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
7Institutes of Physiology and Clinical Medicine, National Yang-Ming University, Taipei, Taiwan
JAMA Intern Med. 2014;174(3):347-354. doi:10.1001/jamainternmed.2013.12700.
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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.

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 erythropoiesis-stimulating 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.

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Figure 1.
Flowchart of Patient Selection

CKD indicates chronic kidney disease; ESA, erythropoiesis-stimulating agent.aIncludes angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, α-blockers, β-blockers, calcium channel blockers, and diuretics.

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Figure 2.
Cumulative Hazards of Study Outcomes Among Patients With Predialysis Stage 5 Chronic Kidney Disease

A, Long-term dialysis. B, Composite outcome of long-term dialysis or death. We used the Nelson-Aalen method12 to calculate the cumulative hazards of both outcomes in users and nonusers of angiotensin-converting enzyme inhibitors (ACEIs) and/or angiotensin II receptor blockers (ARBs). A multivariate analysis was adjusted for all variables listed in Table 1. P < .001, users vs nonusers.

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Figure 3.
Adjusted Hazard Ratios (HRs) of Study Outcomes Among Patients With Predialysis Stage 5 Chronic Kidney Disease

Outcomes include long-term dialysis and the composite outcome of long-term dialysis or death associated with use of angiotensin-converting enzyme inhibitors (ACEIs) and/or angiotensin II receptor blockers (ARBs). Each factor was adjusted for all other factors listed in Table 1. CCB indicates calcium channel blocker; CHD, coronary heart disease.

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