title: Early low-dose erythropoiesis-stimulating agent therapy and progression of moderate chronic kidney disease: a randomized, placebo-controlled trial.
abstract: It is unknown whether early intervention with low-dose erythropoiesis-stimulating agents (ESAs) in non-anaemic patients delays progression of chronic kidney disease (CKD).
  
  
  
  In a single-blind, 24-month trial, adults with estimated glomerular filtration rate (eGFR) 30–59 mL/min/1.73 m2 and either Type 2 diabetes mellitus or previous kidney transplantation were randomized to low-dose continuous erythropoiesis receptor activator (CERA; monthly dose 30–75 µg; n = 115) or placebo (n = 120). The primary endpoint was the annual change in eGFR (abbreviated Modification of Diet in Renal Disease formula).
  
  
  
  Mean (standard deviation) eGFR was 40.7 (9.8) mL/min/1.73 m2 versus 39.8 (9.2) mL/min/1.73 m2 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/1.73 m2 with CERA versus 0.4 (−2.0, 3.2) mL/min/1.73 m2 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.
  
  
  
  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.
authors.affiliation: Department of Internal Medicine IV, Saarland University Medical Centre, Kirrbergerstrasse, Homburg/Saar, Germany.
authors.forename: Danilo
authors.initials: D
authors.lastname: Fliser
authors.affiliation: MVZ Davita Rhein-Ruhr, Düsseldorf, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Dellanna
authors.affiliation: Centre of Nephrology, Mettmann, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Koch
authors.affiliation: Roche Pharma AG Germany, Grenzach-Wyhlen, Germany.
authors.forename: Alfons
authors.initials: A
authors.lastname: Wiggenhauser
mesh_terms: D000740:Anemia / Q000188:drug therapy* / Q000209:etiology; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy*; D018450:Disease Progression; D004920:Erythropoiesis / Q000187:drug effects; D004921:Erythropoietin / Q000627:therapeutic use*; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006397:Hematinics / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D051436:Renal Insufficiency, Chronic / Q000150:complications / Q000188:drug therapy*; D016037:Single-Blind Method
chemical_list: D006397:Hematinics; D004921:Erythropoietin
keywords: CERA, chronic kidney disease, ESA, GFR, progression