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Abstract: TH-PO1070

Rapidly Increased Pattern of Erythropoiesis‐Stimulating Agent (ESA) Resistance Is a Predictor of Poor Renal Prognosis in Predialysis CKD Patients: BRIGHTEN Study Subanalysis

Session Information

Category: CKD (Non-Dialysis)

  • 2302 CKD (Non-Dialysis): Clinical, Outcomes, and Trials


  • Kawamoto, Shinya, Dokkyo Ika Daigaku Nikko Iryo Center, Nikko, Japan
  • Masaki, Takao, BRIGHTEN Study, Tokyo, Japan
  • Maruyama, Shoichi, BRIGHTEN Study, Tokyo, Japan
  • Yamakawa, Akane, BRIGHTEN Study, Tokyo, Japan
  • Kagimura, Tatsuo, BRIGHTEN Study, Tokyo, Japan
  • Narita, Ichiei, BRIGHTEN Study, Tokyo, Japan

As CKD progresses, Hb level becomes sluggish in pre-dialysis CKD patients even though the dosage of ESA increases. We investigated whether renal prognosis can be predicted from transition pattern in ESA resistance as a sub-analysis of the BRIGHTEN study.


The ESA Resistance Index (ERI) was defined as Darbepoietin (DA) dosage/Hb. After the start of DA administration, ERI measured over time and renal events (dialysis initiation/ kidney transplantation) were investigated . The onset relationships were analyzed with Joint latent class models for longitudinal and time-to event data. The Kaplan-Meier method was used to estimate renal survival curves for each ERI transitional pattern. The patient background was compared.


During an average observation period of 3.5 years in 1625 patients, renal events in 517 dialysis initiation and 18 kidney transplantation were analyzed. ERI transition pattern were divide into 3 classes: ERI unchanged Class A (1237 patients, Hb 9.9g/dL, Cr 2.6mg/dL), moderately increased ClassB (274 patients, Hb 9.6g/dL, Cr 3.6mg/dL), and rapidly increased Class C (114 patients, Hb 9.4g/dL, Cr 3.8mg/dL). Class C showed significant poor renal survival curve in 3 groups, and Class B showed intermediate(P<0.0001). The median renal survival time was 1.09 years in Class B, and 0.61 years in Class C. Between Class B and C, though there was no significant difference in Cr levels at the start of DA, Class C showed significant higher ERI throughout all observation period, higher rate of hypertension and ischemic heart disease.


(Discussion) In HD patients, several studies showed that the ESA resistance is an independent predictor of mortality. On the other hand, in pre dialysis CKD patients, a few reports showed the relationship between ESA resistance and mortality, cardio-renal outcome. The BRIGHTEN study of 1724 Japanese was the largest study and found that reduced initial responsiveness to DA was a risk factor for cardio-renal outcomes. In this sub-analysis, even if the initial response is good, rapidly increased ESA resistance during the course of CKD indicates poor renal prognosis.
(Conclusion) Rapidly increased pattern of ESA resistance is a predictor of poor renal prognosis in pre-dialysis CKD.


  • Clinical Revenue Support