Early Versus Delayed ESA Treatment for Anemia in NDD-CKD

Anemia is a common problem in patients with chronic kidney disease (CKD), and it becomes more prevalent as CKD severity increases. The standard treatment for anemia in CKD is erythropoiesis-stimulating agent (ESA) therapy in combination with iron supplementation.

There is some evidence that earlier treatment with short-acting ESAs may lead to improved renal outcomes. Kouji Kawai and others conducted a retrospective cohort study of patients with nondialysis-dependent CKD (NDD-CKD) to better understand renal and cardiovascular outcomes with early versus delayed treatment with long-acting ESAs in these patients. Their findings were published in Kidney International Reports.

The study used data from two Japanese databases, Medical Data Vision Co. Ltd. (MDV) and Real World Data Co. Ltd. (RWD). Patients who initiated long-acting ESA treatment were divided into two groups: early treatment (hemoglobin levels ≥9.0 g/dL) and delayed treatment (<9.0 g/dL). The primary study outcome was a renal composite (renal replacement therapy, ≥50% reduction in estimated glomerular filtration rate [eGFR], eGFR <6.0 mL/min/1.73 m², and all-cause mortality). Secondary outcomes were a cardiovascular composite (hospitalization due to ischemic heart disease, including myocardial infarction; hospitalization due to stroke and heart failure; and cardiovascular death) and components of the composite outcomes.

After propensity score matching, the researchers evaluated 1472 MDV and 1264 RWD patients. Delayed treatment of anemia was not associated with an increased risk of the renal composite outcome (MDV: hazard ratio [HR], 1.15; 95% CI, 0.99-1.33; and RWD: HR, 1.08; 95% CI, 0.92-1.28).

However, delayed treatment for anemia was associated with higher risks of cardiovascular events and all-cause mortality. This was true for the cardiovascular composite outcome (MDV: HR, 1.47; 95% CI, 1.16-1.84; and RWD: HR, 1.34; 95% CI, 1.09-1.64), heart failure (MDV: HR, 1.50; 95% CI, 1.13-2.00; and RWD: HR, 1.53; 95% CI, 1.20-1.96), and all-cause mortality (MDV: HR, 1.83; 95% CI, 1.32-2.54; and RWD: HR, 1.64; 95% CI, 1.21-2.22).

The authors acknowledged limitations of the study. These include the assignment of diagnoses based on health insurance claims data, which may have resulted in inaccuracies; inability to adjust for some confounding factors; potential bias between the groups due to unmeasured confounding factors and the lack of information on the severity of comorbidities; and possible underestimation of events due to some patients transferring to another facility.

“In conclusion, delayed treatment of anemia in Japanese patients with NDD-CKD was not associated with a risk of renal events,” the authors summarized, “however, it was associated with risks of cardiovascular events and all-cause mortality, highlighting the importance of early intervention before hemoglobin values fall below 9.0 g/dL.”

Source: Kidney International Reports