Abstract
Purpose
The goal of this systematic review is to evaluate the efficacy and safety of paricalcitol versus active non-selective vitamin D receptor activators (VDRAs) for secondary hyperparathyroidism (SHPT) management in chronic kidney disease (CKD) patients.
Methods
PubMed, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), clinicaltrials.gov (inception to September 2015), and ASN Web site were searched for relevant studies. A meta-analysis of randomized controlled trials (RCTs) and quasi-RCTs that assessed the effects and adverse events of paricalcitol and active non-selective VDRA in adult CKD patients with SHPT was performed using Review Manager 5.2.
Results
A total of 10 trials involving 734 patients were identified for this review. The quality of included trials was limited, and very few trials reported all-cause mortality or cardiovascular calcification without any differences between two groups. Compared with active non-selective VDRAs, paricalcitol showed no significant difference in both PTH reduction (MD −7.78, 95 % CI −28.59–13.03, P = 0.46) and the proportion of patients who achieved the target reduction of PTH (OR 1.27, 95 % CI 0.87–1.85, P = 0.22). In addition, no statistical differences were found in terms of serum calcium, episodes of hypercalcemia, serum phosphorus, calcium × phosphorus products, and bone metabolism index.
Conclusions
Current evidence is insufficient, showing paricalcitol is superior to active non-selective VDRAs in lowering PTH or reducing the burden of mineral loading. Further trials are required to prove the tissue-selective effect of paricalcitol and to overcome the limitation of current research.
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References
Llach F, Velasquez Forero F (2001) Secondary hyperparathyroidism in chronic renal failure: pathogenic and clinical aspects. Am J Kidney Dis 38(5 Suppl 5):S20–S33
Saito H, Kusano K, Kinosaki M et al (2003) Human fibroblast growth factor-23 mutants suppress Na1-dependent phosphate co-transport activity and 1alpha, 25-dihydroxyvitamin D3 production. J Biol Chem 278:2206–2211
Krajisnik T, Björklund P, Marsell R et al (2007) Fibroblast growth factor-23 regulates parathyroid hormone and 1alpha-hydroxylase expression in cultured bovine parathyroid cells. Endocrinology 195(1):125–131
Shimada T, Hasegawa H, Yamazaki Y et al (2004) FGF-23 is a potent regulator of vitamin D metabolism and phosphate homeostasis. Bone Miner Res 19(3):429–435
Rix M, Andreassen H, Eskildsen P et al (1999) Bone mineral density and biochemical markers of bone turnover in patients with predialysis chronic renal failure. Kidney Int 56:1084–1093
Jadoul M, Albert JM, Akiba T et al (2006) Incidence and risk factors for hip or other bone fractures among hemodialysis patients in the Dialysis Outcomes and Practice Patterns Study. Kidney Int 70:1358–1366
Slinin Y, Foley RN, Collins AJ (2005) Calcium, phosphorus, parathyroid hormone, and cardiovascular disease in hemodialysis patients: the USRDS Waves 1, 3, and 4 study. J Am Soc Nephrol 16:1788–1793
Tentori F, Blayney MJ, Albert JM et al (2008) Mortality risk for dialysis patients with different levels of serum calcium, phosphorus, and PTH: the Dialysis Outcomes and Practice Patterns Study (DOPPS). Am J Kidney Dis 52:519–530
National Kidney Foundation (2009) Chapter 4.1: treatment of CKD-MBD targeted at lowering high serum phosphorus and maintaining serum calcium. Kidney Int 76(2):S50–S99
Coyne DW, Andress DL, Amdahl MJ et al (2013) Effects of paricalcitol on calcium and phosphate metabolism and markers of bone health in patients with diabetic nephropathy: results of the VITAL study. Nephrol Dial Transplant 28:2260–2268
Andress DL, Norris KC, Coburn JW et al (1989) Intravenous calcitriol in the treatment of refractory osteitis fibrosa of chronic renal failure. N Engl J Med 321:274–279
Slatopolsky E, Finch J, Ritter C, Takahashi F (1998) Effects of 19-nor-1,25(OH)2D2, a new analogue of calcitriol, on secondary hyperparathyroidism in uremic rats. Am J Kidney Dis 32(4 Suppl 2):S40–S47
Finch JL, Brown AJ, Slatopolsky E (1999) Differential effects of 1,25-dihydroxy-vitamin D3 and 19-nor-1,25-dihydroxy-vitamin D2 on calcium and phosphorus resorption in bone. J Am Soc Nephrol 10:980–985
Block GA, Klassen PS, Lazarus JM et al (2004) Mineral metabolism, mortality, and morbidity in maintenance hemodialysis. J Am Soc Nephrol 15:2208–2218
Coyne D, Acharya M, Qiu P et al (2006) Paricalcitol capsule for the treatment of secondary hyperparathyroidism in stages 3 and 4 CKD. Am J Kidney Dis 47:263–276
Martin KJ, Gonzalez EA, Gellens M et al (1998) 19-Nor-1-alpha-25-dihydroxyvitamin D2 (paricalcitol) safely and effectively reduces the levels of intact parathyroid hormone in patients on hemodialysis. J Am Soc Nephrol 9:1427–1432
Teng M, Wolf M, Lowrie E et al (2003) Survival of patients undergoing hemodialysis with paricalcitol or calcitriol therapy. N Engl J Med 349:446–456
Han T, Rong G, Quan D et al (2013) Meta-analysis: the efficacy and safety of paricalcitol for the treatment of secondary hyperparathyroidism and proteinuria in chronic kidney disease. Biomed Res Int 2013:320560
Cheng J, Zhang W, Zhang X et al (2012) Efficacy and safety of paricalcitol therapy for chronic kidney disease: a meta-analysis. Clin J Am Soc Nephrol 7:391–400
Abdul Gafor AH, Saidin R, Loo CY et al (2009) Intravenous calcitriol versus paricalcitol in haemodialysis patients with severe secondary hyperparathyroidism. Nephrology 14:488–492
Sprague SM, Llach F, Amdahl M et al (2003) Paricalcitol versus calcitriol in the treatment of secondary hyperparathyroidism. Kidney Int 63:1483–1490
Ong LM, Narayanan P, Goh HK et al (2013) Randomized controlled trial to compare the efficacy and safety of oral paricalcitol with oral calcitriol in dialysis patients with secondary hyperparathyroidism. Nephrology 18:194–200
Coyne DW, Goldberg S, Faber M et al (2014) A randomized multicenter trial of paricalcitol versus calcitriol for secondary hyperparathyroidism in stages 3–4 CKD. Clin J Am Soc Nephrol 9:1620–1626
Palmer SC, McGregor DO, Craig JC et al (2009) Vitamin D compounds for people with chronic kidney disease requiring dialysis. Cochrane Database Syst Rev 7(4):CD008175. doi:10.1002/14651858.CD008175
Higgins JPT, Green S (2008) Cochrane handbook for systematic reviews of interventions version 5.0.0. The Cochrane Collaboration 2008: Editors. http://www.cochrane-handbook.org
Riccio E, Sabbatini M, Bruzzese D et al (2015) Effect of paricalcitol vs calcitriol on hemoglobin levels in chronic kidney disease patients: a randomized trial. PLoS ONE 10:e0118174
Yonova D, Vazelov E, Tcakova A et al (2014) Paricalcitol therapy and the inflammatory markers in peritoneal dialysis patients. Int J Artif Organs 37:607
Trillini M, Cortinovis M, Ruggenenti P et al (2015) Paricalcitol for secondary hyperparathyroidism in renal transplantation. J Am Soc Nephrol 26(5):1205–1214
Sezer S, Tutal E, Bal Z et al (2012) Treatment of secondary hyperparathyroidism in maintenance hemodialysis patients: a randomised clinical trial comparing paricalcitol, calcitriol and sinacalcet. Nephrol Dial Transplant 27:ii509–ii510
Kharlamov AN, Perrish AN, Gabiskii Ia L et al (2012) Vitamin D in the treatment of cardiorenal syndrome in patients with chronic nephropathy. Kardiologiia 52:33–44
Rosas SE, Yang W, Litt H (2013) A phase IV, randomized, blinded single-center study of the effects of calcitriol and paricalcitol on vascular calcification in chronic kidney disease stages 3 and 4-vitamin D and coronary calcification study (VCOR). J Am Soc Nephrol 24:894A
Nikodimopoulou M, Liakos S, Kapoulas S et al (2012) Alfacalcidol and paricalcitol have similar effects on left ventricular hypertrophy. Nephrol Dial Transplant 27:ii242
Jamaluddin EJ, Gafor AH, Yean LC et al (2014) Oral paricalcitol versus oral calcitriol in continuous ambulatory peritoneal dialysis patients with secondary hyperparathyroidism. Clin Exp Nephrol 18:507–514
Hansen D (2012) A randomised clinical study of alfacalcidol and paricalcitol. Dan Med J 59:B4400
Lund RJ, Andress DL, Amdahl M et al (2010) Differential effects of paricalcitol and calcitriol on intestinal calcium absorption in hemodialysis patients. Am J Nephrol 31:165–170
Finch JL, Brown AJ, Slatopolsky E et al (1999) Differential effects of 1,25-dihydroxy-vitamin D3 and 19-nor-1,25-dihydroxy-vitamin D2 on calcium and phosphorus resorption in bone. J Am Soc Nephrol 10(5):980–985
Streja E, Wang HY, Lau WL et al (2014) Mortality of combined serum phosphorus and parathyroid hormone concentrations and their changes over time in hemodialysis patients. Bone 61:201–207
Mittman N, Desiraju B, Meyer KB et al (2010) Treatment of secondary hyperparathyroidism in ESRD: a 2-year, single-center crossover study. Kidney Int. doi:10.1038/ki.2010.191
van Ballegooijen AJ, Reinders I, Visser M et al (2013) Serum parathyroid hormone in relation to all-cause and cardiovascular mortality: the Hoorn study. J Clin Endocrinol Metab 98(4):E638–E645. doi:10.1210/jc.2012-4007
Shoji T, Marubayashi S, Shigematsu T et al (2014) Use of vitamin D receptor activator, incident cardiovascular disease and death in a cohort of hemodialysis patients. Ther Apher Dial. doi:10.1111/1744-9987
Bond TC, Wilson S, Moran J et al (2015) Mortality rates do not differ among patients prescribed various vitamin D agents. Perit Dial Int 35:62–69
Zheng Z, Shi H, Jia J et al (2013) Vitamin D supplementation and mortality risk in chronic kidney disease: a meta-analysis of 20 observational studies. BMC Nephrol 14(1):199. doi:10.1186/1471-2369-14-199
Li XH, Feng L, Yang ZH et al (2015) The effect of active vitamin D on cardiovascular outcomes in predialysis chronic kidney diseases: a systematic review and meta-analysis. Nephrology. doi:10.1111/nep.12505
Thadhani R, Appelbaum E, Pritchett Y et al (2012) Vitamin D therapy and cardiac structure and function in patients with chronic kidney disease: the PRIMO randomized controlled trial. JAMA 307(7):674–684
Wang AY, Fang F, Chan J et al (2014) Effect of paricalcitol on left ventricular mass and function in CKD–the OPERA trial. J Am Soc Nephrol 25(1):175–186
Negri AL, Brandenburg VM (2014) Calcitriol resistance in hemodialysis patients with secondary hyperparathyroidism. Int Urol Nephrol 46(6):1145–1151
Tonbul HZ, Solak Y, Atalay H et al (2012) Efficacy and tolerability of intravenous paricalcitol in calcitriol-resistant hemodialysis patients with secondary hyperparathyroidism: 12-month prospective study. Ren Fail 34:297–303
Llach F, Yudd M et al (2001) Paricalcitol in dialysis patients with calcitriol-resistant secondary hyperparathyroidism. Am J Kidney Dis 38(5 Suppl 5):S45–S50
Ogawa T, Ishida H, Akamatsu M et al (2010) Progression of aortic arch calcification and all-cause and cardiovascular mortality in chronic hemodialysis patients. Int Urol Nephrol 42(1):187–194
Ketteler M, Westenfeld R, Schlieper G et al (2005) Pathogenesis of vascular calcification in dialysis patients. Clin Exp Nephrol 9(4):265–270
Sardiwal S, Magnusson P, Goldsmith DJ, Lamb EJ (2013) Bone Alkaline Phosphatase in CKD–mineral bone disorder. Am J Kidney Dis 62:810–822
Gutiérrez OM, Mannstadt M, Isakova T et al (2008) Fibroblast growth factor-23 and mortality among patients undergoing hemodialysis. N Engl J Med 359:584–592
Isakova T, Xie H, Yang W et al (2011) Fibroblast growth factor 23 and risks of mortality and end-stage renal disease in patients with chronic kidney disease. JAMA 305(23):2432–2439
Kendrick J, Cheung AK, Kaufman JS et al (2011) FGF-23 associates with death, cardiovascular events, and initiation of chronic dialysis. J Am Soc Nephrol 22(10):1913–1922
Julian BA, Quarles LD, Niemann KM et al (1992) Musculoskeletal complications after renal transplantation: pathogenesis and treatment. Am J Kidney Dis 19:99–120
Gonzalez E, Rojas-Rivera J, Polanco N et al (2013) Effects of oral paricalcitol on secondary hyperparathyroidism and proteinuria of kidney transplant patients. Transplantation 95:e49–e52
Amer H, Griffin MD, Stegall MD et al (2013) Oral paricalcitol reduces the prevalence of posttransplant hyperparathyroidism: results of an open label randomized trial. Am J Transplant 13:1576–1585
Acknowledgments
The authors would like to acknowledge Professor Guanjian Liu in Evidence-Based Medicine Center of China for his assistance in the design, literature searching, analysis, and interpretation of this study.
Author’s contribution
TXH contributed to the concept, design, data collection, analysis, interpretation, and manuscript preparation of this study. CPP contributed to the concept, data collection, interpretation and manuscript preparation of this study. JL contributed to the concept, data collection and analysis of this study. QW contributed to the concept, design, analysis and interpretation of this study. LZ contributed to the concept, design, data collection, analysis, interpretation, and manuscript preparation of this study. All authors have read and approved the final manuscript.
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Panpan Cai and Xiaohong Tang have contributed equally to this work.
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Cai, P., Tang, X., Qin, W. et al. Comparison between paricalcitol and active non-selective vitamin D receptor activator for secondary hyperparathyroidism in chronic kidney disease: a systematic review and meta-analysis of randomized controlled trials. Int Urol Nephrol 48, 571–584 (2016). https://doi.org/10.1007/s11255-015-1195-6
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DOI: https://doi.org/10.1007/s11255-015-1195-6