In patients with advanced chronic kidney disease (stage IV or V), does the continued use of renin-angiotensin system inhibitors have a worsening effect on renal function?
Although some experts have recommended the discontinuation of RAS inhibitors in patients with advanced chronic kidney disease (GFR < 30 mL/min/1.73 m2), this study supports their continuation with no evidence of harm and a possible reduction in the need for renal replacement therapy.
Plan de l'etude:
Randomized controlled trial (nonblinded)
Renin–angiotensin system (RAS) inhibitors include angiotensin receptor blockers (ARBs) and angiotensin-converting enzyme inhibitors (ACEIs). Although their use in mild to moderate (stage I–III) chronic kidney disease slows progression of disease, their use in patients with advanced chronic kidney disease is not known. These UK investigators identified adults with stage IV or V chronic kidney disease (glomerular filtration rate [GFR] < 30 mL/min/1.73 m2), who were not on dialysis, with a decrease of 2 mL/min/1.73 m2 per year in GFR over the past 2 years, and at least 6 months of use of an ACEI or ARB prior to enrollment. At baseline, the 411 patients had a median serum creatinine level of 3.4 mg/dL (300 umol/L), median estimated GFR of 18 mL/min/1.73 m2, 45% were 65 years or older, and 36% had either type 2 or type 1 diabetes mellitus. The patients were randomized to either continue or discontinue the ACEI 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 3 years, the eGFR was numerically higher in the group that continued to use RAS inhibitors (13.3 vs 12.6 mL/min/1.73 m2), but this difference was not statistically significant. Regarding patient-oriented outcomes, 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 - 1.65). This is an example of a clinically significant difference (number needed to treat = 17) that was not statistically significant, likely due to 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.
Notice of correction: please note that the following Daily POEM from 17th November contained an error in reporting the primary outcome and thus underwent significant correction.
Mark H. Ebell, MD, MS
University of Georgia