혈액투석을 받는 말기신부전 환자중에서 에리트로포에틴에 치료반응이 불량한 환자들의 임상적 특징 = Clinical Characteristics of Poor Responders to Erythropoietin among ESRD Patients Undergoing Hemodialysis

다국어 초록 (Multilingual Abstract)

Background:The main pathogenic factor causing anemia in chronic renal failure is the erythropoietin deficiency. However, there are some patients showing poor responses to erythropoietin administration. The purposes of this study were to analyze the clinical parameters of poor responders to erythropoietin among ESRD patients undergoing hemodialysis, and to clarify the major potential factors accounting for poor responses to erythropoietin therapy.
Methods:Eighty-one patients with end-stage renal failure undergoing hemodialysis were included in this study. Poor responders to erythropoietin, defined as patients requiring erythropoietin doses more than 200 U/kg/week subcutaneously to correct anemia, were identified. The hematocrit, erythropoietin dose, erythropoietin resistance index (ERI), and other clinical parameters in 77 patients requiring erythropoietin administration were evaluated and analyzed.
Results:Poor responses to erythropoietin were found in 16 patients (20.8%) among 77 patients requiring erythropoietin administration. Serum iron, total iron binding capacity (TIBC), transferrin saturation (TSAT), and albumin concentration were significantly decreased (p<0.05), and increased CRP (≥0.5 mg/dL) was more frequent in poor responders (p<0.01). The independent factor affecting on ERI was TIBC (R=0.44, p<0.01). However, there were no significant difference between poor and good responders in age, gender, duration of dialysis, underlying renal disease, use of ACE inhibitor, dose of dialysis (Kt/V), serum parathyroid hormone, and aluminum concentration.
Conclusion:TIBC seems to be a predicting factor accounting for poor response to erythropoietin among ESRD patients undergoing hemodialysis.

국문 초록 (Abstract)

목 적:만성신부전에 동반되는 빈혈의 주요 원인은 신장에서 생성되는 적혈구생성인자 (erythropoietin)의 결핍이다. 그러나 일부 만성신부전 환자 중에서 적혈구생성인자 투여에도 불구하고 빈혈이 개선되지 않거나 비교적 고용량을 투여하여야 반응하는 경우가 있다. 이러한 적혈구생성인자에 불충분한 반응의 원인으로 여러 요인들이 거론되고 있으나 아직 이론이 있는 부분이 있다. 따라서 본 연구의 목적은 혈액투석 치료를 받고 있는 말기신부전 환자에서 적혈구생성인자에 치료반응이 불량한 환자들의 임상소견을 분석하여 불량한 반응을 보이는데 관여하는 주요 요인들을 규명하는 것이다.
방 법:현재 말기신부전으로 혈액투석을 정기적으로 받고 있는 환자 81명 (연령은 52.0±11.7세, 남녀비는 41:40, 투석기간은 37.3±36.5개월, 원인신질환은 당뇨병성신증이 33%) 중에서 적혈구생성인자에 치료반응이 불량한 환자 (빈혈을 교정하기 위해서 피하 적혈구생성인자를 200 U/kg/week 이상 필요로 하는 환자)들을 분류하고 대상환자 81명 중 적혈구생성인자 투여를 필요로 하는 환자 77명을 대상으로 헤마토크리트, 적혈구생성인자 투여량, 적혈구생성인자 저항지수 및 각종 임상적 지표들을 분석하였다.
결 과:적혈구생성인자에 치료반응이 불량한 환자는 20.8% (16/77)이었고, 혈청 철분, 총철분결합능, transferrin saturation (이하 TSAT로 약기함) 및 알부민 등이 통계적으로 의미있게 감소하였으며, C-반응성단백 증가 (≥0.5 mg/dL)가 관찰되는 경우가 의미있게 많았다 (p< 0.05). 이들 가운데 혈청 총철분결합능은 적혈구생성인자 저항지수를 독립적으로 예견할 수 있었다 (R=0.44, p<0.01). 그러나 투석기간, 원인신질환, angiotensin converting enzyme (이하 ACE로 약기함) 억제제 사용 여부, 투석량 (Kt/V), 혈중 부갑상선호르몬 및 알루미늄 농도 등은 의미있는 차이가 없었다.

참고문헌 (Reference)

1 "혈액투석 환자에서 erythropoietin 저항성에 영향을 미치는 인자-혈액투석 환자에서 EPO 저항성-" 58 : 510-515, 2000

2 "The role of inflammation in the aneamia of end-stage renal disease" 16 : 36-40, 2001

3 "The predictive parameters of erythropoietin hyporesponsiveness in patients on continuous ambulatory peritoneal dialysis" 16 : 110-117, 2001

4 "The intensity of hemodialysis and the response to erythropoietin in patients with end-stage renal disease" 334 : 420-425, 1996

5 "Role of secondary hyperparathyroidism in erythropoietin resistance of chronic renal failure patients" 17 : 28-31, 2002

6 "Purification of human erythropoietin" 252 : 5558-5564, 1977

7 "Pure red-cell aplasia and antierythropoietin antibodies in patients treated with recombinant erythropoietin" 346 : 469-475, 2002

8 "Predictors of erythropoietin responsiveness in chronic hemodialysis patients" 47 : 82-85, 2001

9 "Poor response to erythropoietin:practical guidelines on investigation and management" 10 : 607-614, 1995

10 "NKF-DOQI Clinical Practice Guidelines for the Treatment of Anemia of Chronic Renal Failure" 30 : 192-240, 1997

11 "Isolation and characterization of genomic and cDNA clones of human erythropoietin" 313 : 806-810, 1985

12 "Is it time for a paradigm shift? Is erythropoietin deficiency still the main cause of renal anaemia?" 17 : 2-7, 2002

13 "Hyporesponsiveness to recombinant human erythropoietin" 16 : 25-28, 2001

14 "High C-reactive protein is a strong predictor of resistance to erythropoietin in hemodialysis patients" 29 : 565-568, 1997

15 "Gender modulates responsiveness to recombinant erythropoietin" 38 : 518-522, 2001

16 "European Best Practice Guidelines for the Management of Anaemia in Patients with Chronic Renal Failure" 14 : 1-50, 1999

17 "Erythropoietin resistance : the role of inflammation and pro-inflammatory cytokines" 17 : 39-43, 2002

18 "Effect of serum parathyroid hormone and bone marrow fibrosis on the response to erythropoietin in uremia" 328 : 171-175, 1993

19 "Effect of human erythropoietin derived from recombinant DNA on the anemia of patients maintained by chronic hemodialysis" 2 : 1175-1178, 1986

20 "Effect of aluminum overload on the bone marrow response to recombinant human erythropoietin" 76 : 315-323, 1989

21 "Determinants of album in concentration in hemodialysis patients" 29 : 658-668, 1997

22 "Correction of the anemia of end-stage renal disease with recombinant human erythropoietin:results of a combined phase I and II clinical trial" 316 : 73-78, 1987

23 "Angiotensin-converting enzyme inhibitors and higher erythropoietin requirement in chronic haemodialysis patients" 10 : 2107-2109, 1995

24 "Anemia in hemodialysis patients:variables affecting this outcome predictor" 8 : 1921-1929, 1997

25 "Androgens potentiate the effects of erythropoietin in the treatment of anemia of end-stage renal disease" 17 : 29-33, 1991

26 "Adequacy of dialysis reduces the doses of recombinant erythropoietin independently from the use of biocompatible membranes in haemodialysis patients" 16 : 111-114, 2001

27 "Acute-phase response predicts erythropoietin resistance in hemodialysis and peritoneal dialysis patients" 33 : 63-72, 1999

28 "ACE inhibitors do not induce recombinant human erythropoietin resistance in hemodialysis patients" 35 : 1076-1082, 2000