Antihypertensives May Delay Kidney Disease Progression

Larry Hand

December 16, 2013

Individuals with an advanced stage of chronic kidney disease (CKD) and stable hypertension may have a lower risk of advancing to long-term dialysis or dying if they are treated with angiotensin-related antihypertensive medicines, according to a study published online December 16 in JAMA Internal Medicine.

Ta-Wei Hsu, MD, from the Division of Nephrology, National Yang-Ming University Hospital, Ilan City, Taiwan, and colleagues conducted a prospective cohort study involving 28,497 predialysis patients with advanced CKD, hypertension, and anemia. Between January 1, 2000, and June 30, 2009, 20,152 of the patients (70.7%) required long-term dialysis and 5696 (20.0%) died before progressing to end-stage renal disease (ESRD) that requires dialysis.

The researchers found that use of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) had a 6% lower risk for long-term dialysis (hazard ratio [HR] 0.94; 95% confidence interval [CI], 0.91 - 0.97) and a 6% lower risk in the composite outcome of long-term dialysis or death (HR, 0.94; 95% CI, 0.92 - 0.97) compared with patients who did not use ACEIs or ARBs. Of the ACEI/ARB users, 53.4% were women, 57.7% had diabetes mellitus, and the mean age was 64.7 years.

Benefit Persisted

The renal benefit of ACEIs and ARBs, in monotherapy or concomitant, remained similar except for patients with cancer or those who had not visited a nephrologist after multivariate regression modeling, with adjustments including age, sex, comorbidities, nephrologist visits, geographic location, and other medication use.

"Compared with ACEI/ARB users, nonusers were older, had fewer comorbidities, were less likely to visit nephrologists in the preceding 3 years, and had greater use of other antihypertensives, including α-blockers and dihydropyridine calcium channel blockers," the researchers write.

In further sensitivity analyses to test their findings, the researchers found similar results, "indicating that our findings in this study are robust."

The researchers did find that ACEI/ARB users had a higher hyperkalemia-associated hospitalization rate, but the risk for predialysis mortality caused by hyperkalemia, or elevated serum potassium levels, did not significantly increase.

The researchers estimate that ACEI/ARB use could prevent the need for dialysis in 5.5% of patients with advanced CKD every year.

Physicians may be reluctant to prescribe ACEIs or ARBs out of concern that they might increase serum creatinine levels in patients, based on previous research, the researchers note, but they conclude that withholding ACEI/ARB therapy may actually speed up progression to ESRD.

"[O]ur findings expand the existing knowledge in the field and provide clinicians with new information about the effectiveness and safety of ACEI/ARB use when CKD progresses to pre-ESRD.... Our study does not support concomitant use of ACEI and ARB in predialysis stage 5 CKD. In these patients and those whose course of treatment involves an ACEI/ARB, physicians should also increase their alertness to prevent hyperkalemia."

Enhanced Generalizability

In an invited commentary, Meyeon Park, MD, and Chi-yuan Hsu, MD, from the Division of Nephrology, University of California, San Francisco, point out some strengths and weaknesses of the study. They write that a strength is the inclusion of a large proportion of patients with diabetes, who were not included in previous studies, which "enhances generalizability."

The lack of some important clinical characteristics such as actual levels of renal function, which were inferred on the basis of prescriptions of erythropoiesis-stimulating agents, is a weakness of the study.

The commentators conclude, however, that, "Overall, the study by Hsu and colleagues makes an important contribution to the literature. These observational data are consistent with randomized clinical trial data among patients with stages 4 to 5 CKD, and also with randomized clinical trial data that [renin-angiotensin-aldosterone system] blockade retards the loss of residual renal function even among patients undergoing dialysis."

This research was supported by the National Science Council, the Taipei Veterans General Hospital, the National Health Research Institutes, and the National Yang-Ming University. The authors and commentators have disclosed no relevant financial relationships.

JAMA Intern Med. Published online December 16, 2013. Article abstract, Commentary extract

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