title: Responsiveness to erythropoiesis-stimulating agents and renal survival in patients with chronic kidney disease.
abstract: BACKGROUND
  Renal anemia of chronic kidney disease (CKD) is generally treated by erythropoiesis-stimulating agents (ESAs). However, there are individual differences in patients' responsiveness to ESA, which may affect the prognosis of CKD.
  
  
  METHODS
  The effect of ESAs on hemoglobin was followed in 297 CKD patients with renal anemia. Three types of ESA, epoetin alfa or beta, darbepoetin alfa, and epoetin beta pegol, were used in this study and dose of ESA was converted to that of epoetin using a dose conversion ratio (epoetin:darbepoetin alfa:epoetin beta pegol = 200:1:0.93). After initial 12-week administration of ESAs, the patients were divided into three groups: poor, intermediate, and good responders based on ΔHb/week/epoetin dose as an index. Hemoglobin values were followed for 144 weeks.
  
  
  RESULTS
  Initial patient characteristics--including age, body mass index, hemoglobin, estimated glomerular filtration rate, transferrin saturation, ferritin, albumin, calcium, parathyroid hormone, C-reactive protein, and urine protein--were similar in the three responder groups, except phosphate in the poor responder group was significantly higher than in the other two groups. The period from ESA use to renal death (RD) was significantly shortest in the poor responder group, and the number of RD patients was fewer in the good responder group. Multivariate Cox regression revealed that low final ΔHb(ΔHb from ESA use to just before dialysis)/week/epoetin dose, and low Hb after 12-week ESA use were significant factors related to responsiveness to ESA, suggesting that hyporesponsiveness to ESA was a risk factor for RD. Cox regression also found that hyperphosphatemia and diabetic nephropathy were risks for RD as well.
  
  
  CONCLUSIONS
  The study results suggest that hyporesponsiveness to ESA after the first 12-week administration as well as after 12 weeks is a risk for RD in pre-dialysis CKD patients. Furthermore, hyperphosphatemia and diabetic nephropathy are risk factors for RD.
authors.affiliation: Department of Nephrology, Shuuwa General Hospital, 1200 Yahara-Shinden, Kasukabe, Saitama, 344-0035, Japan, kuwaharam@shuuwa-gh.or.jp.
authors.forename: Michio
authors.initials: M
authors.lastname: Kuwahara
authors.forename: Shintaro
authors.initials: S
authors.lastname: Mandai
authors.forename: Yuri
authors.initials: Y
authors.lastname: Kasagi
authors.forename: Keita
authors.initials: K
authors.lastname: Kusaka
authors.forename: Tomomi
authors.initials: T
authors.lastname: Tanaka
authors.forename: Satomi
authors.initials: S
authors.lastname: Shikuma
authors.forename: Wataru
authors.initials: W
authors.lastname: Akita
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000740:Anemia / Q000209:etiology / Q000517:prevention & control*; D005260:Female; D006397:Hematinics / Q000494:pharmacology / Q000627:therapeutic use*; D006454:Hemoglobins / Q000378:metabolism*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood / Q000517:prevention & control*; D008297:Male; D008875:Middle Aged; D051436:Renal Insufficiency, Chronic / Q000097:blood / Q000150:complications*
chemical_list: D006397:Hematinics; D006454:Hemoglobins