Low 1,25-dihydroxyvitamin D level is associated with erythropoietin deficiency and endogenous erythropoietin resistance in patients with chronic kidney disease
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Erythropoietin (EPO) deficiency and resistance to endogenous EPO is an important pathophysiological feature in anemia of chronic kidney disease (CKD). Low 1,25 dihydroxyvitamin D [1,25(OH)2D] level is known to contribute to anemia of CKD. We aimed to investigate the associations between serum 1,25(OH)2D and anemia, EPO deficiency, and endogenous EPO resistance in patients with CKD.
This study included 409 patients with CKD [glomerular filtration rate (GFR) < 60 ml/min/1.73 m2] who were not on dialysis therapy. Patients on exogenous EPO therapy and patients with iron deficiencies were excluded. Endogenous EPO resistance was assessed by calculating the ratio of endogenous EPO to hemoglobin (Hb) (endogenous EPO/Hb ratio). The associations of Hb level, endogenous EPO level, and the endogenous EPO/Hb ratio with clinical and laboratory variables were investigated by univariate and multivariate analyses.
In univariate analysis, serum 1,25(OH)2D level was correlated with the Hb level, endogenous EPO level, and the endogenous EPO/Hb ratio. Multiple regression analysis revealed that the serum 1,25(OH)2D level remained significantly associated with the Hb level (β = 0.532, P < 0.001), endogenous EPO level (β = 0.149, P = 0.010), and the endogenous EPO/Hb ratio (β = − 0.187, P = 0.002), even after adjusting for other confounding factors, including the levels of parathyroid hormone and the inflammatory marker C-reactive protein.
The serum 1,25(OH)2D level exhibited significant associations with anemia, EPO deficiency, and endogenous EPO resistance in CKD patients. These associations were independent of secondary hyperparathyroidism and inflammation status.
Keywords1,25 Dihydroxyvitamin D Anemia Chronic kidney disease Erythropoietin
This work was supported by a 2-Year Research Grant of Pusan National University.
Compliance with ethical standards
Conflict of interest
The authors have declared that no conflict of interest exists.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
For retrospective type of this study, formal consent is not required.
- 6.Solomon SD, Uno H, Lewis EF, Eckardt KU, Lin J, Burdmann EA, de Zeeuw D, Ivanovich P, Levey AS, Parfrey P, Remuzzi G, Singh AK, Toto R, Huang F, Rossert J, McMurray JJ, Pfeffer MA, Investigators TtRCEwATT (2010) Erythropoietic response and outcomes in kidney disease and type 2 diabetes. N Engl J Med 363:1146–1155. https://doi.org/10.1056/NEJMoa1005109 CrossRefPubMedGoogle Scholar
- 7.Kilpatrick RD, Critchlow CW, Fishbane S, Besarab A, Stehman-Breen C, Krishnan M, Bradbury BD (2008) Greater epoetin alfa responsiveness is associated with improved survival in hemodialysis patients. Clin J Am Soc Nephrol 3:1077–1083. https://doi.org/10.2215/CJN.04601007 CrossRefPubMedPubMedCentralGoogle Scholar
- 8.Molnar MZ, Tabak AG, Alam A, Czira ME, Rudas A, Ujszaszi A, Beko G, Novak M, Kalantar-Zadeh K, Kovesdy CP, Mucsi I (2011) Serum erythropoietin level and mortality in kidney transplant recipients. Clin J Am Soc Nephrol 6:2879–2886. https://doi.org/10.2215/CJN.05590611 CrossRefPubMedPubMedCentralGoogle Scholar
- 11.Kiss Z, Ambrus C, Almasi C, Berta K, Deak G, Horonyi P, Kiss I, Lakatos P, Marton A, Molnar MZ, Nemeth Z, Szabo A, Mucsi I (2011) Serum 25(OH)-cholecalciferol concentration is associated with hemoglobin level and erythropoietin resistance in patients on maintenance hemodialysis. Nephron Clin Pract 117:c373–378. https://doi.org/10.1159/000321521 CrossRefPubMedGoogle Scholar
- 13.Wagner M, Alam A, Zimmermann J, Rauh K, Koljaja-Batzner A, Raff U, Wanner C, Schramm L (2011) Endogenous erythropoietin and the association with inflammation and mortality in diabetic chronic kidney disease. Clin J Am Soc Nephrol 6:1573–1579. https://doi.org/10.2215/CJN.00380111 CrossRefPubMedGoogle Scholar