IMPACT OF PARICALCITROL ON INFLAMMATORY AND ANAEMIA MARKERS IN DIALYSIS PATIENTS
Background: The role of Vitamin D in calcium and phosphate homeostasis is renowned. The effects of vitamin D on bone metabolism have been established for long. We planned to see the effects of vitamin D analogue paricalcitrol as on mineral bone disorder in chronic kidney disease. (CKD MBD) parameters and markers of anaemia and inflammation. Method: This prospective and observational study was done at King Fahd Hospital, Medina, Saudi Arabia for 3 months from Jan to Apr 2017. Two hundred and ten (210) patients fulfilled the eligibility criteria. Paricalcitrol was given at a dose of 0.04 Î¼g/Kg 3 times a week and parathyroid (PTH) was monitored for 3 months and subsequently the dose was titrated to the PTH levels. We looked at the relationship between paricalcitrol and anaemia markers, inflammatory markers, and erythropoietic stimulating agent dose. Results: Two hundred and ten (210) patients were studied, mean age was 50 years, 55% were males; 120 were excluded who had vitamin D level in the normal range, who received vitamin D in the recent past, with phosphate levels >2 and calcium levels >2.55 mmol/L, on calcimimmetics, parathyroidectomy cases, and patients with active infection or malignancy. Parathyroid hormone (PTH) fell significantly -166.4 (95% CI -290, -42.5, p<0.05), Transferrin saturation improved significantly (4.4% 95% CI 1.6, 7.2 p=0.003). CRP fell significantly (p<0.01). However, Hb or ESA requirement did not reach statistical significance. Conclusion: Paricalcitrol treatment is associated with improvement in secondary hyperparathyroidism in haemodialysis population. There is a signal towards improvement in markers of inflammation and anaemia but a larger Randomised Control Trial (RCT) is needed to be done.
Pak J Physiol 2018;14(2):3â€“6
2. Bhan I, Bumett-Bowie SA, Ye J, Tonelli M, Thadhani R. Clinical measures identify vitamin D deficiency in dialysis. Clin J Am Soc Nephrol 2010;5:460â€“7.
3. Roj as-Rivera J, De La Piedra C, Ramos A, Ortiz A, Egido J. The expanding spectrum of biological actions of vitamin D. Nephrol Dial Transplant 2010;25:2850â€“65.
4. Dusso AS, Tokumoto M. Defective renal maintenance of the vitamin D endocrine system impairs vitamin D renoprotection: a downward spiral in kidney disease. Kidney Int 2011;79:715â€“29.
5. Pilz S, Tomaschitz A, Friedl C, Amrein K, Drechsler C, Ritz E, et al. Vitamin D status and mortality in chronic kidney disease. Nephrol Dial Transplant 2011;26:3603â€“9.
6. Guillot X, Semerano L, Saidenberg-Kermanac'h N, Falgarone G, Boissier MC. Vitamin D and inflammation. Joint Bone Spine 2010;77;552â€“7.
7. Hewison M. Vitamin D and the immune system: new perspectives on an old theme. Endocrinol Metab Clin North Am 2010;39:365â€“79.
8. Timms PM, Mannan N, Hitman GA, Noonan K, Mills PG, Syndercombe-Court D, et al. Circulating MMP9, vitamin D and variation in the TIMP-1 response with VDR genotype; mechanisms for inflammatory damage in chronic disorders? QJM 2002;95:787â€“96.
9. Amer M, Qayyum R. Relation between serum 25-Hydoxyvitamin D and C-Reactive protein in asymptomatic adults (from the continuous national health and nutrition examination survey 2001 to 2006). Am J Cardiol 2012:109:226â€“30.
10. Bertoldo F, Pancheri S, Zenari S, Boldini S, Giovanazzi B, Zanatta M, et al. Serum 2S-hydroxyvitamin D levels modulate the acute phase response associated with the first nitorogen-containing bisphosphonate infusion. J Bone Miner Res 2010;25:447â€“54.
11. Scharla SH, Scheidt-Nave C, Leidig G, Woitge H, Wuster C, Seibel MJ, et al. Lower serum 25-hydroxyvitamin D is associated with increased bone resorption markers and lower bone density at the proximal femur in normal females: a population-based study. Exp Clin Endocrinal Diabetes 1996;104;289â€“92.
12. Eda S, Kaufmann J. Roos W, Pohl S. Development of a new microparticle-enhanced turbidimetric assay for C-reactive protein with superior features in analytical sensitivity and dynamic range. J Clin Lab Anal 1998;12:137â€“44.
13. Hackeng WH, Lips P, Netelenbos JC, Lips CJ. Clinical implications of estimation of intact parathyroid hormone (PTH) versus total immunoreactive PTH in normal subjects and hyperparathyroid patients. J Clin Endocrino Metab 1986;63:447â€“53.
14. Adams PC, Reboussin DM, Press RD, Barton JC, Acton RT, Moses GC, et al. Biological variability of transferrin saturation and unsaturated iron-binding capacity. Am J Med 2007;120(11):999.
15. Kandula P, Dobre M, Schold JD, Schreiber MJ Jr, Mchrotra R, Navaneethan SD. Vitamin D supplementation in chronic kidney disease: a systematic review and meta-analysis of observational studies and randomized controlled trials. Clin J Am Soc Nephrol 2011;6(1):50â€“62.
16. Daroux M, Shenouda M, Bacri JL, Lemaitre V, Vanhille P, Bataille P. Vitamin D2 versus vitamin D3 supplementation in hemodialysis patients; a comparative pilot study. J Nephrol 2013;26:152â€“7.
17. Izquierdo MJ, Cavia M, MuÃ±iz P, de Francisco AL, Arias M, Santos J, et al. Paricalcitol reduces oxidative stress and inflammation in haemodialysis patients. BMC Nephrol 2012;13:159.
18. Levin A, Bakris GL, Molitch M, Smulders M, Tian J, Williams LA, et al. Prevalence of abnormal serum vitamin D, PTH, calcium, and phosphorus in patients with chronic kidney disease; results of the study to evaluate early kidney disease. Kidney Int 2007;71;31â€“8.
19. Borrego Utiel FJ, Bravo Soto JA, Merino PÃ©rez MJ, GonzÃ¡lez Carmelo I, LÃ³pez JimÃ©nez V, GarcÃa Ãlvarez T, et al. Effect of paricalcitol on mineral metabolism in kidney transplant patients with secondary hyperparathyroidism Nefrologia 2015;35:363â€“73.
20. Korkor AB. Reduced binding of [3H], 25-dihydroxyvitamin D3 in the parathyroid glands of patients with renal failure. N Engl J Med 1987;316:1573â€“7.
21. VeÄeriÄ‡-Haler Å½, Romozi K, AntoniÄ M, Benedik M, Ponikvar JB, Ponikvar R, et al. Comparison of the pharmacological effects of paricalcitol versus calcitriol on secondary hyperparathyroidism in the dialysis population. Ther Apher Dial 2016;20(3):261â€“6.
22. Kates DM, Sherrard DJ, Andress DL. Evidence that serum phosphate is independently associated with serum PTH in patients with chronic renal failure. Am J Kidney Dis 1997;30:809â€“13.
23. Yamamoto M, Igarashi T, Muramatsu M, Fukagawa M, Motokura T, Ogata E. Hypocalcemia increases and hypercalcemia decreases the steady-state level of parathyroid hormone messenger RNA in the rat. J Clin Invest 1989;83:1053â€“6.
24. Llach F, Massry SG, Singer FR, Kurokawa K, Kaye JH, Coburn JW. Skeletal resistance to endogenous parathyroid hormone in pateints with early renal failure. A possible cause for secondary hyperparathyroidism. J Clin Endocrinol Metab 1975;41:339â€“45.
25. Fukagawa M, Kazama JJ. FGF23: Its role in renal bone disease. Pediatr Nephrol 2006;21:1802â€“6.
26. Kazama JJ, Gejyo F, Shigematsu T, Fukagawa M. Role of circulating fibroblast growth factor 23 in the development of secondary hyperparathyroidism. Ther Apher Dial 2005;9:328â€“30.
27. Kramer H, Bems JS, Choi MJ, Martin K, Rocco MV. 25-Hydroxyvitamin D testing and supplementation in CKD: an NKF-KDOQI controversies report, Am J Kidney Dis 2014;64:499â€“509.
28. Matias PJ, Jorge C, Ferreira C, Borges M, Aires I, Amaral T, et al. Cholecalciferol supplementation in hemodialysis patients: effects on mineral metabolism, inflammation, and cardiac dimension parameters. Clin J Am Soc Nephrol 2010;5:905â€“11.
29. Mora JR, Iwata M, von Andrian UH. Vitamin effects on the immune system; vitamins A and D take centre stage. Nat Rev Immunol 2008;8:685â€“98.
30. Cantorna MT, Zhu Y, Froicu M, Wittke A. Vitamin D status, 1,25-dihydroxyvitamin D3, and the immune system. Am J Clin Nutr 2004;80(6 Suppl):1717â€“20.
31. Matilainen JM, Husso T, Toropainen S, Seuter S, Turunen MP, Gynther P, et al. Primary effect of 1Î±, 25(OH)2D3 on IL-10 expression in monocytes is short-term downregulation. Biochem Biophys Acta 2010;1803:1276â€“86.
32. Adorini L, Penna G, Fibbi B, Maggi M. Vitamin D receptor agonists target static, dynamic, and inflammatory components of benign prostatic hyperplasia. Ann N Y Acad Sci 2010; 1193:146â€“52.
33. Han T, Rong G, Quan D, Shu Y, Liang Z, She N, et al. Meta-analysis: the efficacy and safety of paricalcitol for the treatment of secondary hyperparathyroidism and proteinuria in chronic kidney disease. Biomed Res Int 2013;2013:320560.
34. Asemi Z, Samimi M, Tabassi Z, Shakeri H, Esmaillzadeh A. Vitamin D supplementation affects serum high-sensitivity C-reactive protein, insulin resistance, and biomarkers of oxidative stress in pregnant women. J Nutr 2013;143:1432â€“8.
35. Blanco-Rojo R, Pdrez-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;695â€“703.
36. Norman AW. Minireview: vitamin D receptor: new assignments for an already busy receptor. Endocrinol 2006;147;5542â€“8.
37. Goicoechea M, Vazquez MI, Ruiz MA, Gomez-Campdera F, Perez-Garcia R, Valderrabano F. Intravenous calcitriol improves anaemia and reduces the need for erythropoietin in haemodialysis patients. Nephron 1998;78:23â€“7.
38. Kumar VA, Kujubu DA, Sim JJ, Rasgon SA, Yang PS. Vitamin D supplementation and recombinant human erythropoietin utilization in vitamin D-deficient hemodialysis patients. J Nephrol 2011;24:98â€“105.
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