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Correlation between erythropoietin resistance and secondary hyperparathyroidism in patients with chronic kidney disease undergoing dialysis

Miroslava Stancheva Benkova-Petrova

Abstract

Chronic kidney disease (CKD) is a global socially significant health problem that affects more than 10% of the world's population today. Anemia is a common complication of CKD and is associated with reduced quality of life, increased morbidity and mortality, and higher treatment costs. Erythropoietin resistance is one of the most potent predictors of risk for cardiovascular events and mortality. The aim of this publication is to review and analyze the results from the scientific database about the relationship between erythropoietin resistance and secondary hyperparathyroidism in patients with chronic kidney disease undergoing dialysis. For the period 1998–2021 a review was made in the scientific databases Scopus, Web of Science, Science Direct, Up to Date by keywords in English: erythropoietin resistance, dialysis, chronic kidney disease, secondary hyperparathyroidism. A total of 3778 publications were found, of which 590 were review articles and 1392 were articles with research results. The results of the analysis of the literature data show that the main cause of erythropoietin resistance is iron deficiency. Even after adequate iron supplementation, other factors are also important: acute or chronic inflammation, malnutrition, secondary hyperparathyroidism, aluminum intoxication, hemolysis, folic acid and vitamin B12 deficiency, myelosuppressive agents, aplastic anemia, use of ACE- inhibitors and angiotensin-receptor blockers, genetic polymorphism, antibodies against erythropoietin. Dialysis adequacy, dialysis modality and biocompatibility of dialysis membranes also play an important role.


Keywords

chronic kidney disease, erythropoietin resistance, secondary hyperparathyroidism, hemodialysis treatment

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References

Al-Hilali N, Al-Humoud H, Ninan VT et al. Does parathyroid hormone affect erythropoietin therapy in dialysis patients? Med Princ Pract 2007; 16: 63–67

Alon D.B, Chaimovitz C.Dvilansky A.et al; Novel role of 1,25(OH)(2)D(3) in induction of erythroid progenitor cell proliferation. Exp Hematol. 2002; 30: 403-409

Astor BC, Coresh J, Heiss G, Pettitt D. Kidney function and anemia as risk factors for coronary heart disease and mortality: the atherosclerosis risk in communities (ARIC) study. Am Hear J. (2006) 151:492–500. doi: 10.1016/j.ahj.2005.03.055

Aucella F. Scalzulli R.P. Gatta G. et al. Calcitriol increases burst-forming unit-erythroid proliferation in chronic renal failure. A synergistic effect with r-HuEpo. Nephron Clin Pract. 2003; 95: c121-c127

Brancaccio D, Cozzolino M, Gallieni M. Hyperparathyroidism and anemia in uremic subjects: a combined therapeutic approach. J Am Soc Nephrol. 2004;15 Suppl. 1:S21–4.

Brunner S, Theiss HD, Murr A et al. Primary hyperparathyroidism is associated with increased circulating bone marrow-derived progenitor cells. Am J Physiol Endocrinol Metab 2007; 293: E1670–E1675.

Carozzi S. Ramello A. Nasini M.G. et al. Ca++ and 1,25(OH)2D3 regulate in vitro and in vivo the response to human recombinant erythropoietin in CAPD patients. Adv Perit Dial. 1990; 6: 312-315

David V, Martin A, Isakova T, et al. Inflammation and functional iron deficiency regulate fibroblast growth factor 23 production. Kidney Int. 2016; 89: 135- 146.

Drechsler, C. et al. Vitamin D deficiency is associated with sudden cardiac death, combined cardiovascular events, and mortality in haemodialysis patients. Eur. Heart J. 31(18), 2253–2261 (2010).

Druek TB, Eckard K. Role of secondary hyperparathyroidism in erythropoietin resistance of chronic renal failure patients. Nephrol Dial Transplant. 2002;17(S5):28–31.

Duarte ME, Carvalho EF, Cruz EA et al. Cytokine accumulation in osteitis fibrosa of renal osteodystrophy. Braz J Med Biol Res 2002; 35: 25–29.

El-Kishawi AM, El-Nahas AM. Renal osteodystrophy: review of the disease and its treatment. Saudi J Kidney Dis Transpl 2006;17:373–82

Fabrice Mac Way 1, Myriam Lessard, Marie-Hélène Lafage-Proust; Pathophysiology of chronic kidney disease-mineral and bone disorder Joint Bone Spine 2012 Dec;79(6):544-9. doi: 10.1016/j.jbspin.2012.09.014. Epub 2012 Nov 21.

Flamme I, Ellinghaus P, Urrego D, Krüger T. FGF23 expression in rodents is directly induced via erythropoietin after inhibition of hypoxia inducible factor proline hydroxylase. PLoS One. 2017; 12:e0186979.

Gal-Moscovici A, Sprague SM. Bone health in chronic kidney diseasedmineral and bone disease. Adv Chronic Kidney Dis 2007;14:27–36

Gaweda AE, Goldsmith LJ, Brier ME, Aronoff GR. Iron, inflammation, dialysis adequacy, nutritional status, and hyperparathyroidism modify erythropoietic response. Clin J Am Soc Nephrol. 2010;5(4):576–81

Glosse P, Fajol A, Hirche F, et al. A high-fat diet stimulates fibroblast growth factor 23 formation in mice through TNFα upregulation. Nutr Diabetes. 2018; 8:36.

Glosse P, Feger M, Mutig K, et al. AMP-activated kinase is a regulator of fibroblast growth factor 23 production. Kidney Int. 2018; 94: 491- 501.

Goicoechea M. Vazquez M.I. Ruiz M.A.et al. Intravenous calcitriol improves anaemia and reduces the need for erythropoietin in haemodialysis patients. Nephron. 1998; 78: 23-27

Gonza´lez EA, Lund RJ, Martin KJ et al. Treatment of a murine model of high-turnover renal osteodystrophy by exogenous BMP-7. Kidney Int 2002; 61: 1322–1331

Gutiérrez OM, Mannstadt M, Isakova T, et al. Fibroblast growth factor 23 and mortality among patients undergoing hemodialysis. N Engl J Med. 2008; 359: 584- 592.

Hanudel MR, Eisenga MF, Rappaport M, et al. Effects of erythropoietin on fibroblast growth factor 23 in mice and humans. Nephrol Dial Transplant. 2019; 34: 2057- 2065.

Hazin MAA Anemia in chronic kidney disease. Rev Assoc Med Bras (1992). 2020 Jan 13; 66Suppl 1(Suppl 1):s55-s58.

Holick MF. Vitamin D and the kidney. Kidney Int 1987; 32: 912–929.

Hruska KA, Teitelbaum SL. Renal osteodystrophy. N Engl J Med 1995;333:166–74.

Hutchison JA. Vascular calcification in dialysis patients. Prilozi 2007;28:215–24 Int Urol Nephrol. 2006; 38: 175-177

Jiayn Duan, Chonjian Wang, Dongwei Liu Prevalence and risk factors of chronic kidney disease and diabetic kidney disease in Chinese rural residents: a cross-sectional survey, Scientific reports; Article number: 10408 (2019)

Joy MS, Karagiannis PC, Peyerl FW. Outcomes of secondary hyperparathyroidism in chronic kidney disease and the direct costs of treatment. J Manag Care Pharm 2007;13: 397–411

Kalantar-Zadeh K, Lee GH, Miller JE, Streja E, Jing J, Robertson JA, et al. Predictors of hyporesponsiveness to erythropoiesis-stimulating agents in hemodialysis patients. Am J Kidney Dis. 2009;53(5):823–34.

Kalantar-Zadeh K, McAllister CJ, Lehn RS, Lee GH, Nissenson AR, Kopple JD. Effect of malnutrition-inflammation complex syndrome on EPO hyporesponsiveness in maintenance hemodialysis patients. Am J Kidney Dis. 2003; 42: 761- 773

KDIGO Anemia Working Group. KDIGO clinical practice guideline for anemia in chronic kidney disease. Kidney Int. (2012) 2:279–335. doi: 10.1038/kisup.2012.38

Keithi-Reddy S.R.Addabbo F. Patel T.V. et al. Association of anemia and erythropoiesis stimulating agents with inflammatory biomarkers in chronic kidney disease. Kidney Int. 2008; 74: 782-790

Kilpatrick RD, Critchlow CW, Fishbane S et al. Greater epoetin alfa responsiveness is associated with improved survival in hemodialysis patients. Clin J Am Soc Nephrol 2008; 3: 1077–1083.

Kiss, Z. et al. Serum 25(OH)-cholecalciferol concentration is associated with hemoglobin level and erythropoietin resistance in patients on maintenance haemodialysis. Nephron. Clin. Pract. 117(4), 373–378 (2010).

Koenig KG, Lindberg JS, Zerwekh JE et al. Free and total 1, 25- dihydroxyvitamin D levels in subjects with renal disease. Kidney Int 1992; 41: 161–165

Komaba H, Fukagawa M. FGF23-parathyroid interaction: implications in chronic kidney disease. Kidney Int. 2010; 77: 292- 298.

Komaba H, Kakuta T, Fukagawa M. Management of secondary hyperparathyroidism: how and why? Clin Exp Nephrol. 2017;21(Suppl S1):37–45. doi:10.1007/s10157-016-1369-2

Kovesdy CP, Trivedi BK, Kalantar-Zadeh K, Anderson JE. Association of anemia with outcomes in men with moderate and severe chronic kidney disease. Kidney Int. (2006) 69:560–4. doi: 10.1038/sj.ki.5000105

Langman CB, Brooks ER. Renal osteodystrophy in children: a systemic disease associated with cardiovascular manifestations. Growth Horm IGF Res 2006; 16: S79–S83

Lefebvre P, Vekeman F, Sarokhan B, Enny C, Provenzano RCP. Relationship between hemoglobin level and quality of life in anemic patients with chronic kidney disease receiving epoetin alfa. Curr Med Res Opin. (2006) 22:1929–37. doi: 10.1185/030079906X132541

Llach F. Secondary hyperparathyroidism in renal failure: the trade-off hypothesis revisited. Am J Kidney Dis 1995;25:663–79.

Mauro Boronat , Ángelo Santana, Elvira Bosch, Dionisio Lorenzo, Marta Riaño, César García-Cantón Relationship between Anemia and Serum Concentrations of Calcium and Phosphorus in Advanced Non-Dialysis-Dependent Chronic Kidney Disease 2017;135(2):97-104. doi: 10.1159/000450892. Epub 2016 Oct 20.

Mehta R, Cai X, Hodakowski A, et al. Fibroblast growth factor 23 and anemia in the chronic renal insufficiency cohort Study. Clin J Am Soc Nephrol. 2017; 12: 1795- 1803.

Mizobuchi M, Ogata H, Koiwa F. Secondary hyperparathyroidism: pathogenesis and latest treatment. Ther Apher Dial. 2018;23(4):309–318. doi:10.1111/1744-9987.12772

Moe S, Drueke T, Cunningham J, et al. Definition, evaluation, and classification of renal osteodystrophy: a position statement from Kidney Disease: Improving Global Outcomes (KDIGO). Kidney Int 2006;69:1945–53.

Moreno F, Gomez JML, Jofre R, Valderrabano F, Gonzalez L, Gorriz JL, et al. Nephrology dialysis transplantation quality of life in dialysis patients. A Spanish multicentre study. NDT. (1996) 11(Suppl 2):125–9. doi: 10.1093/ndt/11.supp2.125

Nam KH, Kim H, An SY, et al. Circulating fibroblast growth Factor-23 levels are associated with an increased risk of anemia development in patients with nondialysis chronic kidney disease. Sci Rep. 2018; 8:7294.

National Kidney Foundation. Kidney disease-dialysis outcome quality initiative: K/DOQI Clinical Practice Guidelines for bone metabolism and disease in chronic kidney disease. Am J Kidney Dis. 2003;42 4 Suppl. 3:S1–202

Nazem A.K. Mako J. The effect of calcitriol on renal anaemia in patients undergoing long-term dialysis. Int Urol Nephrol. 1997; 29: 119-127

Neha M. Patel Orlando M. Gutiérrez Dennis L. Andress Daniel W. Coyne Adeera Levin Myles Wolf Vitamin D deficiency and anemia in early chronic kidney disease 2010, https://doi.org/10.1038/ki.2009.551

Nephron Clin Pract. 2007; 105: c132-c138

Neves P.L. Trivino J. Casaubon F.et al. Elderly patients on chronic hemodialysis with hyperparathyroidism: increase of hemoglobin level after intravenous calcitriol.

Nissenson AR, Wade S, Goodnough T, Knight K, Dubois RW. Economic burden of anemia in an insured population. J Manag Care Pharm. (2005) 11:565–74. doi: 10.18553/jmcp.2005.11.7.565

Noordzij M, Korevaar JC, Boeschoten EW, et al. The Kidney Disease Outcomes Quality Initiative (K/DOQI) guideline for bone metabolism and disease in CKD: association with mortality in dialysis patients. Am J Kidney Dis 2005;46:925–32

Patel, N. M. et al. Vitamin D deficiency and anaemia in early chronic kidney disease. Kidney Int. 77(8), 715–720 (2010).

Portolés J, Gorriz JL, Rubio E, De Alvaro F, García F, Alvarez-Chivas V, et al. The development of anemia is associated to poor prognosis in NKF/KDOQI stage 3 chronic kidney disease. BMC Nephrol. (2013) 14:2. doi: 10.1186/1471-2369-14-2

Rao DS, Shih M, Mohini R. Effect of serum parathyroid hormone and bone marrow fibrosis on the response to erythropoietin in uremia. N Engl J Med. 1993;328(3):171–5

Saab G. Young D.O. Gincherman Y. et al. Prevalence of vitamin D deficiency and the safety and effectiveness of monthly ergocalciferol in hemodialysis patients.

Sezer S, Tutal E, Bilgic A et al. Possible influence of vitamin D receptor gene polymorphisms on recombinant human erythropoietin requirements in dialysis patients. Transplant Proc 2007; 39: 40–44.

Tanaka M, Komaba H, Fukagawa M. Emerging association between parathyroid hormone and anemia in hemodialysis patients. Ther Apher Dial. 2018;22(3):242–245. doi:10.1111/1744-9987.12685

Tomoko Usui, Junhui Zhao, Douglas S. Fuller, Norio Hanafusa, Takeshi Hasegawa, Hiroshi Fujino, Takanobu Nomura, Jarcy Zee, Eric Young, Bruce M. Robinson, Masaomi Nangaku; Association of erythropoietin resistance and fibroblast growth factor 23 in dialysis patients: Results from the Japanese Dialysis Outcomes and Practice Patterns Study; August 2020 https://doi.org/10.1111/nep.13765

Toro L, Barrientos V, León P, et al. Erythropoietin induces bone marrow and plasma fibroblast growth factor 23 during acute kidney injury. Kidney Int. 2018; 93: 1131- 1141.

Tsai MH, Leu JG, Fang YW, Liou HH. High fibroblast growth factor 23 levels associated with low hemoglobin levels in patients with chronic kidney disease stages 3 and 4. Medicine (Baltimore). 2016; 95:e3049.

Turk S.Akbulut M.Yildiz A.et al.Comparative effect of oral pulse and intravenous calcitriol treatment in hemodialysis patients: the effect on serum IL-1 and IL-6 levels and bone mineral density. Nephron. 2002; 90: 188-194

Urakawa, I., Yamazaki, Y., Shimada, T., Iijima, K., Hasegawa, H., Okawa, K., Fujita, T., Fukumoto, S., and Yamashita, T. (2006) Klotho converts canonical FGF receptor into a specific receptor for FGF23. Nature 444, 770–774

Van Vuren AJ, Gaillard CAJM, Eisenga MF, van Wijk R, van Beers EJ. The EPO-FGF23 signaling pathway in Erythroid progenitor cells: opening a new area of research. Front Physiol. 2019; 10: 304.

Wheeler JA, Clinkenbeard EL. Regulation of fibroblast growth factor 23 by iron, EPO, and HIF. Curr Mol Biol Rep. 2019; 5: 8- 17.

Wolf, M. et al. Vitamin D levels and early mortality among incident haemodialysis patients. Kidney Int. 72(8), 1004–1013 (2007).

World Health Organization. Nutritional anaemias: Report of a WHO scientific group. 1968.

ZhangY, ThamerM,StefanikK, KaufmanJ, CotterDJ. Epoetin requirements predict mortality in hemodialysis patients. AmJKidney Dis.2004;44:866-876




DOI: http://dx.doi.org/10.14748/vmf.v0i0.8002

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