Abstract
The effect of erythropoiesis-stimulating agent (ESA) on dialysis initiation in advanced chronic kidney disease (CKD) patients is not clear. We retrospectively analyzed the outcome of dialysis initiation in a stage 5 CKD cohort with ESA reimbursement limited to the maximal standardized monthly ESA dose equivalent to epoetin beta 20,000 U by the National Health Insurance program. Totally 423 patients were followed up for a median of 1.37 year. A time-dependent Cox regression model, adjusted for monthly levels of estimated glomerular filtration rate (eGFR) and hemoglobin, was constructed to investigate the association between ESA and outcome. The standardized monthly ESA dose in ESA users was 16,000 ± 3,900 U of epoetin beta. Annual changes of hemoglobin were −0.29 ± 2.19 and −0.99 ± 2.46 g/dL in ESA users and ESA non-users, respectively (P = 0.038). However, annual eGFR decline rates were not different between ESA users and non-users. After adjustment, ESA use was associated with deferred dialysis initiation (hazard ratio 0.63, 95% confidence interval 0.42–0.93, P = 0.021). The protective effect remained when the monthly ESA doses were incorporated. Our data showed that restricted use of ESA was safe and associated with deferred dialysis initiation in stage 5 CKD patients.
Highlights
The results of clinical trials on the renoprotective effect of erythropoiesis-stimulating agent (ESA) are less encouraging
Bahlmann FH and colleagues showed that the administration of low-dose darbepoetin, as low as not to affect the Hb level, improved survival and renal function in rats undergoing 5/6 nephrectomy[7]
Menne J and colleagues demonstrated that the protective effects of continuous erythropoietin receptor activator (CERA) in diabetic nephropathy were lost when the dose was increased to an extent of elevating Hct level[8]
Summary
The results of clinical trials on the renoprotective effect of ESA are less encouraging. ESA treatment significantly increased the Hb levels in all studies, much higher doses were adopted in studies failing to show benefits of ESA16,17. The use of ESAs, the mean ESA dose, and the mean Hb level in pre-dialytic CKD patients in America all decreased after 200724,25. The effect of restricted ESA use on renal outcome in the contemporary era has not been well studied. NHI program restricts the use of ESA in CKD patients with serum creatinine level of more than 6 mg/dL and hematocrit (Hct) level of less than 28%. We aimed to study the association between ESA use and dialysis initiation in a time-dependent Cox regression model in a cohort of stage 5 CKD patients[30]
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