Objective To investigate the influencing factors for erythropoietin responsiveness in hemodialysis patients. Methods Patients with regular hemodialysis in the Hemodialysis Purification Center, the Second Xiangya Hospital of Central South University from January 1st, 2021 to July 31st, 2021 were recruited. Their clinical data were collected. According to the quartile and third quartile of erythropoietin resistance index (ERI), patients were divided into groups for comparison. The influencing factors for erythropoietin responsiveness were analyzed by logistic regression. Patients were further divided into groups according to body mass index (BMI), and the parameters were compared between the groups. ROC curve was used to evaluate the parameters for the predictive performance of ERI. Results BMI and hemoglobin were higher (t=2.896 and 4.246, respectively; P=0.004 and＜0.001, respectively), while interleukin-6 (IL-6) and weekly doses of erythropoiesis-stimulating agents were lower (Z=-2.738 and -8.820, respectively; P=0.006 and ＜0.001, respectively) in the lower ERI group, as compare with those in the higher ERI group. Logistic regression showed that BMI (OR=0.844, 95% CI: 0.740～0.963, P=0.012) and IL-6 (OR=1.119, 95% CI:1.031～1.215, P=0.007) were the independent risk factors for erythropoietin responsiveness in maintenance hemodialysis patients. The working characteristic curve showed that BMI had the greatest guiding and assistant effects on prediction of ERI. Overweight patients had lower ERI and erythropoiesis-stimulating agent doses (K=15.015 and 16.937, respectively; P=0.001 and ＜0.001, respectively), as compared with those in the low and the normal BMI groups. Conclusions BMI and IL-6 are the independent risk factors for erythropoietin responsiveness in maintenance hemodialysis patients. BMI may have guiding and assistant roles in the diagnosis and prediction of ERI.
[1]Zhou Q G, Jiang J P, Wu S J, et al.Current pattern of Chinese dialysis units: a cohort study in a representative sample of units[J].Chin Med J (Engl), 2012, 125(19):3434-3439
[2]Li Y, Shi H, Wang W M, et al.Prevalence,awareness,and treatment of anemia in Chinese patients with nondialysis chronic kidney disease: First multicenter,cross-sectional study[J].Medicine (Baltimore), 2016, 95(24):e3872--
[3]中国医师协会肾脏内科医师分会肾性贫血指南工作组.中国肾性贫血诊治临床实践指南[J].中华医学杂志, 2021, 101(20):1463-1502
[4]Smrzova J, Balla J, Barany P.Inflammation and resistance to erythropoiesis-stimulating agents--what do we know and what needs to be clarified?[J].Nephrol Dial Transplant, 2005, 20(Suppl 8):i2-i7
[5]KDOQI .KDOQI Clinical Practice Guideline and Clinical Practice Recommendations for anemia in chronic kidney disease[J].Am J Kidney Dis, 2007, 50(3):471-530
[6]Kilpatrick R D, Critchlow C W, Fishbane S, et al.Greater epoetin alfa responsiveness is associated with improved survival in hemodialysis patients[J].Clin J Am Soc Nephrol, 2008, 3(4):1077-1083
[7]Regidor D L, Kopple J D, Kovesdy C P, et al.Associations between changes in hemoglobin and administered erythropoiesis-stimulating agent and survival in hemodialysis patients[J].J Am Soc Nephrol, 2006, 17(4):1181-1191
[8]Zhang Y, Thamer M, Stefanik K, et al.Epoetin requirements predict mortality in hemodialysis patients[J].Am J Kidney Dis, 2004, 44(5):866-876
[9]Pfeffer M A, Burdmann E A, Chen C Y, et al.A trial of darbepoetin alfa in type 2 diabetes and chronic kidney disease[J].N Engl J Med, 2009, 361(21):2019-2032
[10]Singh A K, Szczech L, Tang K L, et al.Correction of anemia with epoetin alfa in chronic kidney disease[J].N Engl J Med, 2006, 355(20):2085-2098
[11]Minutolo R, Conte G, Cianciaruso B, et al.Hyporesponsiveness to erythropoiesis-stimulating agents and renal survival in non-dialysis CKD patients[J].Nephrol Dial Transplant, 2012, 27(7):2880-2886
[12]Fukuma S, Yamaguchi T, Hashimoto S, et al.Erythropoiesis-stimulating agent responsiveness and mortality in hemodialysis patients: results from a cohort study from the dialysis registry in Japan[J].Am J Kidney Dis, 2012, 59(1):108-116
[13]Eriguchi R, Taniguchi M, Ninomiya T, et al.Hyporesponsiveness to erythropoiesis-stimulating agent as a prognostic factor in Japanese hemodialysis patients: the Q-Cohort study[J].J Nephrol, 2015, 28(2):217-225
[14]KDOQI.KDOQI Clinical Practice Guidelines and Clinical Practice Recommendations for Anemia in Chronic Kidney Disease[J].Am J Kidney Dis, 2006, 47(5 Suppl 3):S11-S145
[15]El-Kannishy G M, Megahed A F, Tawfik M M, et al.Obesity may be erythropoietin dose-saving in hemodialysis patients[J].Kidney Res Clin Pract, 2018, 37(2):148-156
[16]Do S M, Ribeiro S, Rocha-Pereira P, et al.Body mass index and resistance to recombinant human erythropoietin therapy in maintenance hemodialysis patients[J].Ren Fail, 2013, 35(10):1392-1398
[17]Salahudeen A K.Obesity and survival on dialysis[J].Am J Kidney Dis, 2003, 41(5):925-932
[18]Fleischmann E, Teal N, Dudley J, et al.Influence of excess weight on mortality and hospital stay in 1346 hemodialysis patients[J].Kidney Int, 1999, 55(4):1560-1567
[19]Obradovic M, Sudar-Milovanovic E, Soskic S, et al.Leptin and Obesity: Role and Clinical Implication[J].Front Endocrinol (Lausanne), 2021, 12(-):585887--
[20]Vega A, Ruiz C, Abad S, et al.Body composition affects the response to erythropoiesis-stimulating agents in patients with chronic kidney disease in dialysis[J].Ren Fail, 2014, 36(7):1073-1077
[21]Kotanko P, Thijssen S, Levin N W.Association between erythropoietin responsiveness and body composition in dialysis patients[J].Blood Purif, 2008, 26(1):82-89
[22]Honda H, Kimata N, Wakai K, et al.Associations among epoetin therapy,inflammation,nutritional status,and mortality in patients on hemodialysis[J].J Ren Nutr, 2014, 24(5):322-329
[23]Lowrie E G.Acute-phase inflammatory process contributes to malnutrition,anemia,and possibly other abnormalities in dialysis patients[J].Am J Kidney Dis, 1998, 32(6 Suppl 4):S105-S112
[24]Akchurin O, Patino E, Dalal V, et al.Interleukin-6 Contributes to the Development of Anemia in Juvenile CKD[J].Kidney Int Rep, 2019, 4(3):470-483
[25]Rattanasompattikul M, Molnar M Z, Zaritsky J J, et al.Association of malnutrition-inflammation complex and responsiveness to erythropoiesis-stimulating agents in long-term hemodialysis patients[J].Nephrol Dial Transplant, 2013, 28(7):1936-1945
[26]Weiss G, Goodnough L T.Anemia of chronic disease[J].N Engl J Med, 2005, 352(10):1011-1023
[27]Valenti L, Messa P, Pelusi S, et al.Hepcidin levels in chronic hemodialysis patients: a critical evaluation[J].Clin Chem Lab Med, 2014, 52(5):613-619
[28]Romao J J, Haiashi A R, Elias R M, et al.Positive acute-phase inflammatory markers in different stages of chronic kidney disease[J].Am J Nephrol, 2006, 26(1):59-66
[29]Barany P.Inflammation,serum C-reactive protein,and erythropoietin resistance[J].Nephrol Dial Transplant, 2001, 16(2):224-227
[30]Nemeth E, Valore E V, Territo M, et al.Hepcidin,a putative mediator of anemia of inflammation,is a type II acute-phase protein[J].Blood, 2003, 101(7):2461-2463
[31]Pergola P E, Devalaraja M, Fishbane S, et al.Ziltivekimab for Treatment of Anemia of Inflammation in Patients on Hemodialysis: Results from a Phase 12 Multicenter,Randomized,Double-Blind,Placebo-Controlled Trial[J].J Am Soc Nephrol, 2021, 32(1):211-222
