Hepcidin and Vitamin D Levels: Mutual Effects in Anemia of Chronic Kidney Disease

Year 2021, , 110 - 114, 29.05.2021

Berna Ustuner , Sibel Bek , Necmi Eren , Serkan Bakirdogen , Betul Kalender

https://doi.org/10.30934/kusbed.661316

Abstract

Objective: Hepcidin is a peptide with anti-microbial properties that is largely synthesized in the liver and has important roles in iron homeostasis, with serum levels elevated in chronic inflammatory conditions, including chronic kidney disease (CKD). Our aim was to discuss on the role of vitamin D in regulation of hepcidin and anemia of CKD.
Methods: The study group included 103 patients with CKD and 59 healthy individuals. The serum concentration of hepcidin was measured using ELISA, and the association to the following factors was evaluated: age, sex, body mass index, renal functions (estimated glomerular filtration rate, eGFR), drug history, serum biochemistry, complete blood count, iron and total iron binding capacity, ferritin, vitamin D, high sensitive C-reactive protein, C-reactive protein, and the erythrocyte sedimentation rate.
Results: The mean age of the CKD group was 58.63 ± 11.8 years (with 16, 26, 27, 19, and 15 patients; respectively in each chronic kidney disease stage, from I through V and nine on haemodialysis, six on peritoneal dialysis). The mean hepcidin concentration was higher in the chronic kidney disease (30.3±24.7 ng/ml) than control (17.8 ± 8.4ng/ml) group (p<0.05). There was a positive association between hepcidin and CRP, ESR and the following serum factors (urea, creatinine, ferritin, phosphate, pH, parathyroid hormone and alkaline phosphatase), with a negative association with eGFR, haemoglobin, haematocrit, calcium, magnesium, 25-OH vitamin D and bicarbonate levels.
Conclusion: Hepcidin levels were found negatively correlated with 25-OH vitamin D levels which was related with the inflammatory effects of vitamin D and hepcidin.

Keywords

Anemia, chronic kidney disease, hepcidin

Hepcidin ve Vitamin D: Kronik Böbrek Hastalığı Anemisinde Karşılıklı Etkileşim

Abstract

Amaç: Hepsidin, kronik böbrek hastalığı (KBH) dahil olmak üzere kronik inflamatuar hastalarda serum seviyesi artan büyük oranda karaciğerde sentezlenen bir peptiddir. Amacımız, hepsidin ve KBH anemisinin düzenlenmesinde D vitamininin rolünü tartışmaktır.
Yöntem: Çalışma grubuna 103 KBH'li hasta ve 59 sağlıklı birey dahil edildi. Hepsidinin serum konsantrasyonu ELISA kullanılarak ölçüldü ve aşağıdaki faktörlerle ilişki değerlendirildi: yaş, cinsiyet, vücut kitle indeksi, böbrek fonksiyonları (tahmini glomerüler filtrasyon hızı, eGFR), ilaç geçmişi, serum biyokimyası, tam kan sayımı, demir ve toplam demir bağlama kapasitesi, ferritin, D vitamini, yüksek duyarlı C-reaktif protein, C-reaktif protein ve eritrosit sedimantasyon hızı (ESR).
Bulgular: KBH grubunun ortalama yaşı 58,63 ± 11,8 yıldı ve sırasıyla 16, 26, 27, 19 ve 15 hasta; her bir kronik böbrek hastalığı evresinde, I'den V'ye ve dokuz hemodiyalizde, altı periton diyalizinde hasta tespit edildi. KBH’da ortalama hepsidin konsantrasyonu (30,3 ± 24.7 ng / ml), kontrol (17,8 ± 8,4 ng / ml) grubundan daha yüksek bulundu (p <0,05). Hepsidin ve CRP, ESR, üre, kreatinin, ferritin, fosfat, pH, paratiroid hormonu ve alkalin fosfataz arasında pozitif; eGFR, hemoglobin, hematokrit, kalsiyum, magnezyum, 25 -OH D vitamini ve bikarbonat seviyeleri ile negatif korelasyon gösterilmiştir.
Sonuç: Hepsidin ve D vitamini arasinda, inlamatuar etkilerine baglantili negatif korelasyon gösterilmiştir.

Keywords

Anemi, kronik böbrek hastalığı, hepcidin

References

• Pigeon C, Ilyin G, Courselaud B et al. A newmouseliver-specific gene, encoding a protein homologous to human antimicrobial peptide hepcidin, is overexpressed during iron overload. J BiolChem 2001;276: 7811 – 7819. doi:10.1074/jbc.m008923200
• Means RT. Hepcidin and Cytokines in Anaemia. Hematology, 2004; 9, 357–362. doi:10.1080/10245330400018540
• Smith, E.M.; Alvarez, J.A.; Kearns, M.D.; Hao, L.; Sloan, J.H.; Konrad, R.J.; Ziegler, T.R.; Zughaier, S.M.; Tangpricha, V. High-dose vitamin D3 reduces circulating hepcidin concentrations: A pilot, randomized, double-blind, placebo-controlled trial in healthy adults. Clin. Nutr. 2017, 36, 980–985 doi:10.1016/j.clnu.2016.06.015
• Alon, D.B.; Chaimovitz, C.; Dvilansky, A.; Lugassy, G.; Douvdevani, A.; Shany, S.; Nathan, I. Novel role of 1,25(OH)(2)D(3) in induction of erythroid progenitor cell proliferation. Exp. Hematol. doi: 10.1016/s0301-472x(02)00789-0.
• Thomas, C.E.; Guillet, R.; Queenan, R.A.; Cooper, E.M.; Kent, T.R.; Pressman, E.K.; Vermeylen, F.M.; Roberson, M.S.; O’Brien, K.O. Vitamin D status is inversely associated with anemia and serum erythropoietin during pregnancy. Am. J. Clin. Nutr. 2015, 102, 1088–1095. doi: 10.3945/ajcn.115.116756.
• Nikooyeh, B.; Neyestani, T.R. Poor vitamin D status increases the risk of anemia in school children: National Food and Nutrition Surveillance. Nutrition 2018, 47, 69–74. doi: 10.1016/j.nut.2017.09.008.
• Bacchetta, J.; Zaritsky, J.J.; Sea, J.L.; Chun, R.F.; Lisse, T.S.; Zavala, K.; Nayak, A.; Wesseling-Perry, K.; Westerman, M.; Hollis, B.W.; et al. Suppression of iron-regulatory hepcidin by vitamin D. J. Am. Soc. Nephrol. 2014, 25, 564–572. doi: 10.1681/ASN.2013040355
• Ashby DR, Gale DP, Busbridge M, Murphy KG, Duncan ND, et al. Plasma hepcidin levels are elevated but responsive to erythropoietin therapy in renal disease. Kidney Int 2009; 75: 976–81. doi: 10.1038/ki.2009.21.
• Maruyama Y, Yokoyama K, Yamamoto H, Nakayama M, Hosoya T. Do serum hepcidin-25 levels correlate with oxidative stress in patients with chronic kidney disease not receiving dialysis? Clin Nephrol. 2012;78:281-286. doi: 10.5414/CN107424
• Hamada Y, Kono TN, Moriguchi Y et al. Alteration of mRNA expression of molecules related to iron metabolism in adenine-induced renal failure rats: a possible mechanism of iron deficiency in chronic kidney disease patients on treatment .Nephrol Dial Transplant2008;23: 1886 – 1891. doi: 10.1093/ndt/gfm900
• Turgut, F., Kanbay, M., Altay, M., Uz, E., Bavbek, N. et al. Pro‐Hepcidin Levels in Peritoneal Dialysis and Hemodialysis Patients. Dial. Transplant. 2009, 38: 203-209. https://doi.org/10.1002/dat.20297
• Bacchetta J, Zaritsky JJ, Sea JL, Chun RF, Lisse TS, Zavala K, et al. Suppression of Iron-Regulatory Hepcidin by Vitamin D.J AmSocNephrol. 2014; 25: 564–572. doi: 10.1681/ASN.2013040355
• Zughaier SM, Alvarez JA, Sloan JH, Konrad RJ, Tangpricha V. The role of vitamin D in regulating the iron-hepcidin-ferroportin axis in monocytes. J ClinTranslEndocrinol. 2014; 1: 19-25. doi: 10.1016/j.jcte.2014.01.003
• Madar AA, Stene LC, Meyer HE, Brekke M, Knutsen KV. Effect of vitamin D3 supplementation on iron status: a randomized, double-blind, placebo-controlled trial among ethnic minorities living in Norway.Nutr J. 2016;15-74. doi: 10.1186/s12937-016-0192-7
• Sim JJ, Lac PT, Liu IL, Meguerditchian SO, Kumar VA, Kujubu DA et al. Vitamin D deficiency and anemia: a cross-sectional study. AnnHematol. 2010; 89:447–452. doi: 10.1007/s00277-009-0850-3
• McGillivray G, Skull SA, Davie G, Kofoed SE, Frydenberg A, Rice J et al. High prevalence of asymptomatic vitamin D and iron deficiency in East African immigrant children and adolescents living in a temperate climate. ArchDis Child. 2007; 92:1088–1093. doi: 10.1136/adc.2006.112813
• Blanco-Rojo R, Perez-Granados AM, Toxqui L, Zazo P, de la Piedra C, Vaquero MP. Relationship between vitamin D deficiency, bone remodelling and iron status in iron-deficient young women consuming an iron-fortified food. Eur J Nutr. 2013; 52:695–703. doi: 10.1007/s00394-012-0375-8
• Donate-Correa J, Dominguez-Pimentel V, Mendez-Perez ML, Muros-de-Fuentes M, Mora-Fernandez C, Martin-Nunez E, et al. Selective vitamin D receptor activation as anti-inflammatory target in chronic kidney disease. Mediators of Inflammation, 2014;670475. doi: 10.1155/2014/670475
• Todd S. Perlstein, ReenaPande, Nancy Berliner and Gary J. Vanasse. Prevalence of 25-hydroxyvitamin D deficiency in subgroups of elderly persons with anemia: association with anemia of inflammation. Blood 2011; 117: 2800-2806. doi: 10.1182/blood-2010-09-309708
• Saab G, Young DO, Gincherman Y, Giles K, Norwood K, Coyne DW. Prevalence of vitamin D deficiency and the safety and effectiveness of monthly ergocalciferol in hemodialysis patients. NephronClinPract 2007; 105:132–138. doi: 10.1159/000098645
• Aucella F, Scalzulli RP, Gatta G, Vigilante M, Carella AM, Stallone C (2003) Calcitriol increases burst-forming unit-erythroid proliferation in chronic renal failure, a synergistic effect with r- HuEpo. NephronClinPract 2003; 95:121-127. doi: 10.1159/000074837.
• Ishizaki N, Kotani M, Funaba M, Matsui T. Hepcidin expression in the liver of rats fed a magnesium-deficient diet. Brit J Nut. 2011;106:1169-1172. doi: 10.1017/S0007114511001553
• Uehata T, Tomosugi N, Shoji T, Sakaguchi Y, Suzuki A, Kaneko T, et al. Serum hepcidin-25 levels and anemia in non-dialysis chronic kidney disease patients: a cross-sectional study. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. 2012 ;27:1076-1083. doi: 10.1093/ndt/gfr431
• Maisetta G, Petruzzelli R, Brancatisano FL, Esin S, Vitali A, Campa M, et al. Antimicrobial activity of human hepcidin 20 and 25 against clinically relevant bacterial strains: effect of copper and acidic pH. Peptides 2010;31:1995-2002. doi: 10.1016/j.peptides.2010.08.007
• Cunningham J, Rodrı´guez M, Messa P. Magnesium in chronic kidney disease Stages 3 and 4 and in dialysis patients. ClinKidney J 2012; 5: 39–51. doi: 10.1093/ndtplus/sfr166