Clinical Question

In patients with advanced chronic kidney disease (CKD; stages IV or V), does the continued use of renin-angiotensin system inhibitors have a worsening effect on renal function?

Bottom Line

Although some experts have recommended the discontinuation of renin-angiotensin system inhibitors in patients with advanced CKD (glomerular filtration rate [GFR] of less than 30 mL per minute per 1.73 m²), the study supports their continuation with no evidence of harm and a possible reduction in the need for renal replacement therapy. (Level of Evidence = 1b)

Synopsis

Renin-angiotensin system inhibitors include angiotensin receptor blockers (ARBs) and angiotensin-converting enzyme (ACE) inhibitors. Although their use in mild to moderate CKD (i.e., stages I through III) slows progression of the disease, their use in patients with advanced CKD is not known. The U.K. investigators identified adults with stage IV or V CKD and a decrease in GFR of 2 mL per minute per 1.73 m² per year over the past two years who were not on dialysis and used an ACE inhibitor or ARB for at least six months before enrollment. At baseline, the 411 patients had a median serum creatinine level of 3.4 mg per dL (300.6 μmol per L), a median estimated GFR of 18 mL per minute per 1.73 m², 45% were 65 years or older, and 36% had type 1 or type 2 diabetes mellitus. The patients were randomized to continue or discontinue their ACE inhibitor or ARB. In both groups, other classes of antihypertensives could be used to control blood pressure at the discretion of the treating physician. Analysis was by intention to treat, and the groups were balanced at baseline. After a median follow-up of three years, the estimated GFR was higher in the group that continued to use renin-angiotensin system inhibitors (13.3 vs. 12.6 mL per minute per 1.73 m²), but this difference was not statistically significant. Patients in the continuation group had a strong trend toward a lower rate of requiring renal replacement therapy (56% vs. 62%; hazard ratio = 1.28; 95% CI, 0.99 to 1.65). This is an example of a clinically significant difference (number needed to treat = 17) that was not statistically significant, likely because of inadequate sample size and/or duration of follow-up. Hospitalizations, cardiovascular events, and deaths were similar between groups. Adherence to the assigned treatment was very good and there was no difference between groups in serious adverse events.