Initiation of erythropoiesis-stimulating agents and outcomes: a nationwide observational cohort study in anaemic chronic kidney disease patients.
BACKGROUND
In 2012, new clinical guidelines were introduced for use of erythropoiesis-stimulating agents (ESA) in chronic kidney disease (CKD) patients, recommending lower haemoglobin (Hb) target levels and thresholds for ESA initiation. These changes resulted in lower blood levels in these patients. However, there is limited evidence on just when ESA should be initiated and the safety of a low Hb initiation policy.


METHODS
In this observational inception cohort study, Swedish, nephology-referred, ESA-naïve CKD patients (n = 6348) were enrolled when their Hb dropped below 12.0 g/L, and they were followed for mortality and cardiovascular events. Four different ESA treatments were evaluated applying dynamic marginal structural models: (i) begin ESA immediately, (ii) begin ESA when Hb <11.0 g/dL, (iii) begin ESA when Hb <10.0 g/dL and (iv) never begin ESA in comparison with 'current practice' [the observed (factual) survival of the entire study cohort]. The adjusted 3-year survival following ESA begun over a range of Hb (from <9.0 to 12.0 g/dL) was evaluated, after adjustment for covariates at baseline and during follow-up.


RESULTS
Overall, 36% were treated with ESA. Mortality during follow-up was 33.4% of the ESA-treated and 27.9% of the non-treated subjects. The adjusted 3-year survival associated with ESA initiation improved for subjects with initial Hb <9.0 to 11 g/dL and then decreased again for those with Hb above 11.5 g/dL. Initiating ESA at Hb <11.0 g/dL and <10.0 g/dL was associated with improved survival compared with 'current practice' [hazard ratio (HR) 0.83; 95% confidence interval (CI) 0.79-0.89 and 0.90; 95% CI 0.86-0.94, respectively] and did not increase the risk of a cardiovascular event (HR 0.93; 95% CI 0.87-1.00).


CONCLUSIONS
In non-dialysis patients with CKD, ESA initiation at Hb < 10.0-11.0 g/dL is associated with improved survival in patients otherwise treated according to guidelines.
CLINTEC Renal Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
Marie
M
Evans
CLINTEC Renal Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.|Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.
Juan-Jesus
JJ
Carrero
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.|Department of Statistics and Quantitative Methods, University of Milano-Bicocca, Milan, Italy.
Rino
R
Bellocco
CLINTEC Renal Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
Peter
P
Barany
CLINTEC Renal Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
Abdul R
AR
Qureshi
CLINTEC Renal Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
Astrid
A
Seeberger
Division of Nephrology, Department of Clinical Sciences, Karolinska Institutet, Danderyd Hospital, Stockholm, Sweden.
Stefan H
SH
Jacobson
CLINTEC Renal Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
Britta
B
Hylander-Rössner
University Di Tella and CONICET, Buenos Aires, Argentina.
Andrea
A
Rotnitzky
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Arvid
A
Sjölander
D000368:Aged; D000740:Anemia / Q000188:drug therapy* / Q000401:mortality; D015331:Cohort Studies; D004920:Erythropoiesis; D005260:Female; D006397:Hematinics / Q000627:therapeutic use*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D051436:Renal Insufficiency, Chronic / Q000401:mortality / Q000503:physiopathology*; D016896:Treatment Outcome
D006397:Hematinics
anaemia; chronic kidney disease; epidemiology; erythropoiesis-stimulating agents; mortality