To the Editor The recent study by Hsu et al1 regarding the renoprotective effect of renin-angiotensin-aldosterone system blockade in patients with predialysis advanced chronic kidney disease, hypertension, and anemia is important but we believe that the findings should be interpreted with caution.
According to the way that angiotensin-converting enzyme inhibitor or angiotensin receptor blocker (ACEI/ARB) users were defined, people who had taken and then ceased ACEI/ARB therapy prior to the first erythropoiesis-stimulating agent (ESA) prescription would have been classified as nonusers. For a proportion of these participants, ACEI/ARB therapy may have been stopped for safety reasons, for example, to attempt to delay dialysis treatment.2 Indeed, 25% of those defined as nonusers received a prescription for ACEI/ARB in the 90 days prior to the first ESA prescription, and many “nonusers” had clear indications for ACEI/ARB therapy. This study design could create differential misclassification where those defined as ACEI/ARB users were more likely to have better kidney function or slower decline than those defined as nonusers. A “new user” design including all patients who initiate ACEI/ARB therapy rather than prevalent users may have led to less bias and provided a more balanced comparison.3
Tomlinson L, Smeeth L. Angiotensin-Converting Enzyme Inhibitor or Angiotensin Receptor Blocker Use and Renal OutcomesPrevalent User Designs May Overestimate Benefit. JAMA Intern Med. 2014;174(10):1706. doi:10.1001/jamainternmed.2014.1585