Does Evidence Support Renin–Angiotensin System Blockade for Slowing Nephropathy Progression in Elderly Persons?

Authoritative practice guidelines recommend agents that block the renin–angiotensin system (RAS) as first-line therapy for patients with chronic kidney disease (CKD) (1–3). The evidence to support these recommendations comes from more than 2 decades of studies, as well as from several randomized trials demonstrating that angiotensin-converting enzyme inhibitors and angiotensin-receptor blockers slow CKD progression more effectively than other antihypertensive agents (4–6). All of these nephropathy outcome trials define “benefit” as a slowed time to doubling of serum creatinine level, dialysis, or death.

All of the trials favoring use of RAS blockers to slow nephropathy progression have similar study populations. Specifically, they enrolled patients with advanced proteinuric nephropathy (estimated glomerular filtration rate [eGFR] <60 mL/min per 1.73 m²) and proteinuria greater than 500 mg/d (4). Strictly speaking, the conclusion that RAS blockade slows doubling of creatinine level or time to dialysis applies only to patients who fit this definition.

In contrast, studies that directly compared RAS blockers with other blood pressure–lowering agents demonstrated that RAS blockers did not slow nephropathy progression at similar degrees of blood pressure reduction (7, 8). The patients in these studies had lower urinary protein excretion (<300 mg/d) and higher eGFR (>60 mL/min per 1.73 m²) than the patients in the studies that showed that RAS blockade slowed the progression of nephropathy. Meta-analyses of studies that included participants with less advanced nephropathy support the conclusion that RAS blockade is not effective in patients with early-stage nephropathy (9–11).

Age is an important factor to consider when evaluating effects on nephropathy outcomes. The average age at initiation of dialysis in the United States has increased steadily since 1980, with a more than 5-fold increase in persons age 65 to 74 years and a 3-fold increase in persons age 75 or older (12) …