Association between responsiveness to methoxy polyethylene glycol-epoetin beta and renal survival in patients with non-dialysis-dependent chronic kidney disease: A pooled analysis of individual patient-level data from clinical trials.
OBJECTIVE
The association between responsiveness to continuous erythropoietin-receptor activator (CERA) and renal survival in patients with non-dialysis-dependent chronic kidney disease (NDD-CKD) is uncertain.


METHODS
We performed a pooled analysis of individual patient-level data drawn from five clinical trials involving CERA administration. Based on the responsiveness to CERA, patients were classified into poor- or good-response groups. Primary endpoints were defined as the initiation of dialysis or a 30% decrease in the estimated glomerular filtration rate (eGFR) from baseline. We set the landmark time point at 12 weeks after the start of CERA, from which we evaluated the time to the first renal event. The cumulative renal survival rates were calculated for each group using the Kaplan-Meier method. The adjusted hazard ratio was calculated using a stratified Cox regression model.


RESULTS
Of 408 patients, 226 were analyzed. Haemoglobin levels and eGFRs were significantly lower in the poor-response group (n = 113) than in the good-response group (n = 113). Renal events occurred in 36.3% of the poor-response group and in 23.0% of the good-response group. The intergroup difference in renal survival rates was significant (log-rank test, P = 0.03) and the adjusted hazard ratio was 1.71 (95% confidence interval, 1.03-2.83), indicating an unfavorable outcome in the poor-response group.


CONCLUSIONS
Hyporesponsiveness to CERA was associated with poor renal survival, consistent with the results of the conventional erythropoiesis-stimulating agent (ESA). It is recommended that a randomized controlled trial on CERA use be performed in patients with NDD-CKD with ESA-hyporesponsive anaemia.
Department of Integrated Therapy for Chronic Kidney Disease, Kyushu University, Fukuoka, Japan.|Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Kazuhiko
K
Tsuruya
Biostatistics Department, Central Coordinating Unit, Clinical Research Support Center, The University of Tokyo Hospital, Tokyo, Japan.
Yukari
Y
Uemura
Nephrology & Dialysis Center, Japanese Red Cross, Fukuoka Hospital, Fukuoka, Japan.
Hideki
H
Hirakata
Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Takanari
T
Kitazono
Course of Safety Management in Health Care Sciences, Graduate School of Health Care Sciences, Jikei Institute, Osaka, Japan.
Yoshiharu
Y
Tsubakihara
Shinraku-en Hospital, Social Welfare Corporation, Niigata City Social Services Association, Niigata, Japan.
Masashi
M
Suzuki
Department of Integrated Science and Engineering for Sustainable Society, Chuo University, Tokyo, Japan.
Yasuo
Y
Ohashi
D000368:Aged; D000740:Anemia / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D015415:Biomarkers / Q000097:blood; D002986:Clinical Trials as Topic; D004921:Erythropoietin / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006397:Hematinics / Q000009:adverse effects / Q000627:therapeutic use*; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D053208:Kaplan-Meier Estimate; D007668:Kidney / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000009:adverse effects / Q000627:therapeutic use*; D016016:Proportional Hazards Models; D006435:Renal Dialysis; D051436:Renal Insufficiency, Chronic / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D012189:Retrospective Studies; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome
D015415:Biomarkers; D006397:Hematinics; D006454:Hemoglobins; C508420:continuous erythropoietin receptor activator; D004921:Erythropoietin; D011092:Polyethylene Glycols
ESA hyporesponsiveness; anaemia; continuous erythropoietin receptor activator; landmark analysis; pooled analysis; renal survival