Early low-dose erythropoiesis-stimulating agent therapy and progression of moderate chronic kidney disease: a randomized, placebo-controlled trial

Background. It is unknown whether early intervention with low-dose erythropoiesis-stimulating agents (ESAs) in non-anaemic patients delays progression of chronic kidney disease (CKD). Methods. In a single-blind, 24-month trial, adults with estimated glomerular filtration rate (eGFR) 30-59mL/min/1.73m(2) and either Type 2 diabetes mellitus or previous kidney transplantation were randomized to low-dose continuous erythropoiesis receptor activator (CERA; monthly dose 30-75 mu g; n = 115) or placebo (n = 120). The primary endpoint was the annual change in eGFR (abbreviated Modification of Diet in Renal Disease formula). Results. Mean (standard deviation) eGFR was 40.7 (9.8) mL/ min/1.73m(2) versus 39.8 (9.2) mL/min/1.73m(2) at baseline for CERA and placebo, respectively, and 39.0 (11.6) g/dL versus 39.7 (10.6) g/dL at the final visit. The median (interquartile range) annual reduction in eGFR was 0.5 (-2.2, 3.8) mL/min/1.73m(2) with CERA versus 0.4 (-2.0, 3.2) mL/min/1.73m(2) with placebo (P = 0.657). No significant difference in the annual change in eGFR was observed between treatment groups in the subpopulations with Type 2 diabetes or kidney transplant. Adverse events with a suspected relation to study drug occurred in 22.0% and 16.2% of patients randomized to CERA or placebo, respectively, and adverse events led to study drug discontinuation in 11.0% and 8.5% of patients. Conclusions. Patients with moderate CKD and Type 2 diabetes or previous kidney transplantation showed stable renal function that was unaffected by administration of low-dose ESA. In addition, there was no clinically meaningful effect of 2-year low-dose ESA treatment on albuminuria, an important surrogate marker of kidney injury.