Rationale and design of oBservational clinical Research In chronic kidney disease patients with renal anemia: renal proGnosis in patients with Hyporesponsive anemia To Erythropoiesis-stimulating agents, darbepoetiN alfa (BRIGHTEN Trial)

BACKGROUND: Renal anemia is an important complication in non-dialysis chronic kidney disease (CKD) patients as well as in dialysis patients. Although recombinant human erythropoietin has dramatically improved prognosis and quality of life in these patients, there have been issues among non-dialysis CKD patients who exhibit hyporesponsiveness to erythropoiesis-stimulating agent (ESA). The causes and definition of ESA hyporesponsiveness, as well as the incidence of renal and cardiovascular disease (CVD) events in such patients, are yet to be clarified. METHODS: This ongoing trial is a multicenter, prospective, observational study of non-dialysis CKD patients with renal anemia. The primary objective is to survey the current realities of the therapy with ESA in Japan and evaluate the correlation between hyporesponsiveness to darbepoetin alfa and CKD progression. The secondary objective is to investigate relationship between ESA hyporesponsiveness and CVD events based on the clinical situation in Japan, and to explore an ESA response index. RESULTS: The subjects consist of CKD patients with estimated glomerular filtration rate (eGFR) below 60 mL/min/1.73 m(2) who present renal anemia. The target number of registered cases is 2000 patients, based on estimates of incidences of renal and CVD events from past studies. Renal function and CVD events will be observed for 96 weeks after the initiation of darbepoetin alfa administration. Definitions of ESA hyporesponsiveness will also be investigated. CONCLUSION: By clarifying markers and factors involved in ESA hyporesponsiveness and their relationships with renal and CVD events, this ongoing study aims to improve evidence-based therapies for renal anemia in non-dialysis CKD patients.