Vitamin D supplementation and mortality risk in chronic kidney disease: a meta-analysis of 20 observational studies

BMC Nephrology

Shan Lin¹  Dong Li¹  Junya Jia¹  Huilan Shi²  Zhenfeng Zheng¹ 

[1] Nephrology Department, General Hospital of Tianjin Medical University, No.I54 Anshan Road, Heping District, Tianjin 300052, China;Radiology Department, General Hospital of Tianjin Medical University, No.I54 Anshan Road, Heping District, Tianjin 300052, China

关键词: Chronic kidney disease;    Paricalcitol;    Calcitriol;    Mortality;    Vitamin D;   

Others  :  1082840
DOI  :  10.1186/1471-2369-14-199

 received in 2013-05-12, accepted in 2013-09-04,  发布年份 2013

【 摘 要 】

Background

Vitamin D insufficiency correlates with mortality risk among patients with chronic kidney disease (CKD). The survival benefits of active vitamin D treatment have been assessed in patients with CKD not requiring dialysis and in patients with end stage renal disease (ESRD) requiring dialysis.

Methods

MEDLINE, Embase, the Cochrance Library, and article reference lists were searched for relevant observational trials. The quality of the studies was evaluated using the Newcastle-Ottawa Scale (NOS) checklist. Pooled effects were calculated as hazard ratios (HR) using random-effects models.

Results

Twenty studies (11 prospective cohorts, 6 historical cohorts and 3 retrospective cohorts) were included in the meta-analysis., Participants receiving vitamin D had lower mortality compared to those with no treatment (adjusted case mixed baseline model: HR, 0.74; 95% confidence interval [95% CI], 0.67-0.82; P <0.001; time-dependent Cox model: HR, 0.71; 95% CI, 0.57-0.89; P <0.001). Participants that received calcitriol (HR, 0.63; 95% CI, 0.50-0.79; P <0.001) and paricalcitol (HR, 0.43 95% CI, 0.29-0.63; P <0.001) had a lower cardiovascular mortality. Patients receiving paricalcitol had a survival advantage over those that received calcitriol (HR, 0.95; 95% CI, 0.91-0.99; P <0.001).

Conclusions

Vitamin D treatment was associated with decreased risk of all-cause and cardiovascular mortality in patients with CKD not requiring dialysis and patients with end stage renal disease (ESRD) requiring dialysis. There was a slight difference in survival depending on the type of vitamin D analogue. Well-designed randomized controlled trials are necessary to assess the survival benefits of vitamin D.

【 授权许可】

   
2013 Zheng et al.; licensee BioMed Central Ltd.

【 参考文献 】

• [1]Moe S, Drueke T, Cunningham J, Goodman W, Martin K, Olgaard K, Ott S, Sprague S, Lameire N, Eknoyan G, et al.: Definition, evaluation, and classification of renal osteodystrophy: a position statement from Kidney Disease: Improving Global Outcomes (KDIGO). Kidney Int 2006, 69:1945-1953.
• [2]Goodman WG, Goldin J, Kuizon BD, Yoon C, Gales B, Sider D, Wang Y, Chung J, Emerick A, Greaser L, et al.: Coronary-artery calcification in young adults with end-stage renal disease who are undergoing dialysis. N Engl J Med 2000, 342:1478-1483.
• [3]Qunibi WY, Nolan CA, Ayus JC: Cardiovascular calcification in patients with end-stage renal disease: a century-old phenomenon. Kidney Int 2002, 62(Suppl):73-80.
• [4]Block GA, Klassen PS, Lazarus JM, Ofsthun N, Lowrie EG, Chertow GM: Mineral metabolism, mortality, and morbidity in maintenance hemodialysis. J Am Soc Nephrol 2004, 15:2208-2218.
• [5]De Boer I, Ioannou GN, Kestenbaum B, Brunzell JD, Weiss NS: 25(OH)D levels and albuminuria in the Third National Health and Nutrition Examination Survey (NHANES III). Am J Kidney Dis 2007, 50:69-77.
• [6]Forman JP, Giovannucci E, Holmes MD, Bischoff-Ferrari HA, Tworoger SS, Willett WC, Curhan GC: Plasma 25(OH)D levels and risk of incident hypertension. Hypertension 2007, 49:1063-1069.
• [7]Pittas AG, Dawson-Hughes B, Li T, Van Dam RM, Willett WC, Manson JE, Hu FB: Vitamin D and calcium intake in relation to type 2 diabetes in women. Diabetes Care 2006, 29:650-656.
• [8]Tentori F, Blayney MJ, Albert JM, Gillespie BW, Kerr PG, Bommer J, Young EW, Akizawa T, Akiba T, Pisoni RL, et al.: 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 2008, 52:519-530.
• [9]Kovesdy CP, Ahmadzadeh S, Anderson JE, Kalantar-Zadeh K: Secondary hyperparathyroidism is associated with higher mortality in men with moderate to severe chronic kidney disease. Kidney Int 2008, 73:1296-1302.
• [10]Artaza JN, Mehrotra R, Norris KC: Vitamin D and cardiovascular system. Clin J Am Soc Nephrol 2009, 4:1515-1522.
• [11]Wang L, Manson JE, Song Y, Sesso HD: Systematic review: Vitamin D and calcium supplementation in prevention of cardiovascular events. Ann Intern Med 2010, 152:315-323.
• [12]Pittas AG, Chung M, Trikalinos T, Brendel M, Patel K, Lichtenstein AH, Lau J, Balk EM: Systematic review: Vitamin D and cardiometabolic outcomes. Ann Intern Med 2010, 152:307-314.
• [13]Kandula P, Dobre M, Schold JD, Schreiber MJ, Mehrotra R, Navaneethan SD: Vitamin D supplementaion in chronic kidney disease: A systematic review and meta-analysis of observational studies and randomized controlled trials. Clin J Am Soc Nephrol 2011, 6:50-62.
• [14]Dickersin K, Scherer R, Lefebvre C: Identifying relevant studies for systematic reviews. BMJ 1994, 309(6964):1286-1291.
• [15]Lefebvre C, McDonald S: Development of sensitive search strategy for reports of randomized controlled trials in EMBASE. In Fourth International Cochrane Colloquium: Oct 20–24 1996; Adelaide. Adelaide (Australia): The Australian Cochrane Centre; 1996.
• [16]Stroup DF, Berlin JA, Morton SC, Olkin I, Williamson GD, Rennie D, Moher D, Becker BJ, Sipe TA, Thacker SB: Meta-analysis Of Observational Studies in Epidemiology (MOOSE) Group. Meta-analysis of observational studies in epidemiology. JAMA 2000, 283(15):2008-2012.
• [17]Wells GA, Shea B, O'Connell D, Peterson J, Welch V, Losos M, Tugwell P: The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomized studies in meta-analysis. Ottawa, Canada: Department of Epidemiology and Community Medicine, University of Ottawa; 2010. http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp webcite
• [18]von Elm E, Altman DG, Egger M, Pocock SJ, Gøtzsche PC, Vandenbroucke JP: STROBE Initiative: Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. BMJ 2007, 335(7624):806-808.
• [19]Higgins JPT, Thompson SG: Quantifying heterogeneity in a meta-analysis. Stat Med 2002, 21(11):1539-1558.
• [20]Huedo-Medina TB, Sánchez-Meca J, Marín-Martínez F, Botella J: Assessing heterogeneity in meta-analysis: Q statistic or I2 index? Psychol Methods 2006, 11(2):193-206.
• [21]Higgins JP, Thompson SG, Deeks JJ, Altman DG: Measuring inconsistency in meta-analysis. BMJ 2003, 327(7417):557-560.
• [22]Begg CB, Mazumdar M: Operating characteristics of a rank correlation test for publiction bias. Biometrics 1994, 50(4):1088-1101.
• [23]Egger M, Davey SG, Schneider M, Minder C: Bias in meta-analysis detected by a simple graphical test. BMJ 1997, 315(7109):629-634.
• [24]Peters JL, Sutton AJ, Jones DR, Abrams KR, Rushton L: Contour-enhanced meta-analysis funnel plots help distinguish publication bias from other causes of asymmetry. J Clin Epidemiol 2008, 61(10):991-996.
• [25]Teng M, Wolf M, Lowrie E, Ofsthun N, Lazarus JM, Thadhani R: Survival of patients undergoing hemodialysis with paricalcitol or calcitriol therapy. N Engl J Med 2003, 349(5):446-456.
• [26]Shoji T, Shinohara K, Kimoto E, Emoto M, Tahara H, Koyama H, Inaba M, Fukumoto S, Ishimura E, Miki T, et al.: Lower risk for cardiovascular mortality in oral 1alpha-hydroxy vitamin D3 users in a haemodialysis population. Nephrol Dial Transplant 2004, 19(1):179-184.
• [27]Teng M, Wolf M, Ofsthun MN, Lazarus JM, Hernán MA, Camargo CA Jr, Thadhani R: Activated injectable vitamin D and hemodialysis survival: a historical cohort study. J Am Soc Nephrol 2005, 16(4):1115-1125.
• [28]Melamed ML, Eustace JA, Plantinga L, Jaar BG, Fink NE, Coresh J, Klag MJ, Powe NR: Changes in serum calcium, phosphate, and PTH and the risk of death in incident dialysis patients: a longitudinal study. Kidney Int 2006, 70(2):351-357.
• [29]Kalantar-Zadeh K, Kuwae N, Regidor DL, Kovesdy CP, Kilpatrick RD, Shinaberger CS, McAllister CJ, Budoff MJ, Salusky IB, Kopple JD: Survival predictability of time-varying indicators of bone disease in maintenance hemodialysis patients. Kidney Int 2006, 70(4):771-780.
• [30]Tentori F, Hunt WC, Stidley CA, Rohrscheib MR, Bedrick EJ, Meyer KB, Johnson HK, Zager PG, Medical Directors of Dialysis Clinic Inc: Mortality risk among hemodialysis patients receiving different vitamin D analogs. Kidney Int 2006, 70(10):1858-1865.
• [31]Kovesdy CP, Ahmadzadeh S, Anderson JE, Kalantar-Zadeh K: Association of activated vitamin D treatment and mortality in chronic kidney disease. Arch Intern Med 2008, 168(4):397-403.
• [32]Naves-Díaz M, Alvarez-Hernández D, Passlick-Deetjen J, Guinsburg A, Marelli C, Rodriguez-Puyol D, Cannata-Andía JB: Oral active vitamin D is associated with improved survival in hemodialysis patients. Kidney Int 2008, 74(8):1070-1078.
• [33]Shinaberger CS, Kopple JD, Kovesdy CP, McAllister CJ, van Wyck D, Greenland S, Kalantar-Zadeh K: Ratio of paricalcitol dosage to serum parathyroid hormone level and survival in maintenance hemodialysis patients. Clin J Am Soc Nephrol 2008, 3(6):1769-1776.
• [34]Shoben AB, Rudser KD, de Boer IH, Young B, Kestenbaum B: Association of oral calcitriol with improved survival in nondialyzed CKD. J Am Soc Nephrol 2008, 19(8):1613-1619.
• [35]Wolf M, Betancourt J, Chang Y, Shah A, Teng M, Tamez H, Gutierrez O, Camargo CA Jr, Melamed M, Norris K, et al.: Impact of activated vitamin D and race on survival among hemodialysis patients. J Am Soc Nephrol 2008, 19(7):1379-1388.
• [36]Tentori F, Albert JM, Young EW, Blayney MJ, Robinson BM, Pisoni RL, Akiba T, Greenwood RN, Kimata N, Levin NW, et al.: The survival advantage for haemodialysis patients taking vitamin D is questioned: findings from the Dialysis Outcomes and Practice Patterns Study. Nephrol Dial Transplant 2009, 24(3):963-972.
• [37]St Peter WL, Li S, Liu J, Gilbertson DT, Arneson TJ, Collins AJ: Effects of monthly dose and regular dosing of intravenous active vitamin D use on mortality among patients undergoing hemodialysis. Pharmacotherapy 2009, 29(2):154-164.
• [38]Chang HC, Chen CL, Chiu TL, Chen SI, Yen AM, Chen TH: Effectiveness of recombinant human erythropoietin, vitamin D3 and iron therapy on long-term survival of patients with end-stage renal disease receiving haemodialysis: analysis of 702 patients after 10-year follow-up. Public Health Nutr 2009, 12(12):2410-2415.
• [39]Konta T, Hoshikawa M, Takasaki S, Ichikawa K, Mashima Y, Takahashi T, Abiko H, Masakane I, Matsunaga T, Suzuki M, et al.: Patient survival and the combination of vitamin D and phosphorus binder in dialysis. Dialysis and Transplantation 2010, 39(10):427-431.
• [40]Sugiura S, Inaguma D, Kitagawa A, Murata M, Kamimura Y, Sendo S, Hamaguchi K, Nagaya H, Tatematsu M, Kurata K, et al.: Administration of alfacalcidol for patients with predialysis chronic kidney disease may reduce cardiovascular disease events. Clin Exp Nephrol 2010, 14(1):43-50.
• [41]Jean G, Lataillade D, Genet L, Legrand E, Kuentz F, Moreau-Gaudry X, Fouque D: ARNOS Study Investigators: Impact of hypovitaminosis D and alfacalcidol therapy on survival of hemodialysis patients: results from the French ARNOS study. Nephron Clin Pract 2011, 118(2):c204-c210.
• [42]Brancaccio D, Cozzolino M, Cannella G, Messa P, Bonomini M, Cancarini G, Caruso MR, Cascone C, Costanzo AM, di Luzio PU, et al.: Secondary hyperparathyroidism in chronic dialysis patients: results of the Italian FARO survey on treatment and mortality. Blood Purif 2011, 32(2):124-132.
• [43]Dierkes J, Kropf S, Machlitt P, Domroese U, Neumann K, Westphal S, Luley C, Heinz J: Vitamin D supplementation and mortality in patients with end-stage renal disease. Ann Nutr Metab 2011, 58(Suppl 3):326.
• [44]Ogawa M, Ogawa T, Inoue T, Otsuka K, Nitta K: Effect of alfacalcidol therapy on the survival of chronic hemodialysis patients. Ther Apher Dial 2012, 16(3):248-253.
• [45]Rammos G, Tseke P, Ziakka S: Vitamin D, the renin-angiotensin system, and insulin resistance. Int Urol Nephrol 2008, 40:419-426.
• [46]Chiu KC, Chu A, Go VL, Saad MF: Hypovitaminosis D is associated with insulin resistance and beta cell dysfunction. Am J Clin Nutr 2004, 79:820-825.
• [47]Carthy EP, Yamashita W, Hsu A, Ooi BS: 1,25-Dihydroxyvitamin D3 and rat vascular smooth muscle cell growth. Hypertension 1989, 13:954-959.
• [48]Levin A, Li YC: Vitamin D and its analogues: do they protect against cardiovascular disease in patients with kidney disease? Kidney Int 2005, 68:1973-1981.
• [49]Gysemans CA, Cardozo AK, Callewaert H, Giulietti A, Hulshagen L, Bouillon R, Eizirik DL, Mathieu C: 1,25-Dihydroxyvitamin D3 modulates expression of chemokines and cytokines in pancreatic islets: implications for prevention of diabetes in nonobese diabetic mice. Endocrinology 2005, 146:1956-1964.
• [50]Ohsawa M, Koyama T, Yamamoto K, Hirosawa S, Kamei S, Kamiyama R: 1,25-dihydroxyvitamin D(3) and its potent synthetic analogs downregulate tissue factor and upregulate thrombomodulin expression in monocytic cells, counteracting the effects of tumor necrosis factor and oxidized LDL. Circulation 2000, 102:2867-2872.
• [51]Simpson RU, Hershey SH, Nibbelink KA: Characterization of heart size and blood pressure in the vitamin D receptor knockout mouse. J Steroid Biochem Mol Biol 2007, 103:521-524.
• [52]Young EW, Albert JM, Satayathum S, Goodkin DA, Pisoni RL, Akiba T, Akizawa T, Kurokawa K, Bommer J, Piera L, et al.: Predictors and consequences of altered mineral metabolism: the Dialysis Outcomes and Practice Patterns Study. Kidney Int 2005, 67:1179-1187.
• [53]Robins JM, Hernan MA, Brumback B: Marginal structural models and causal inference in epidemiology. Epidemiology 2000, 11:550-560.
• [54]Robins JM: Correction for non-compliance in equivalence trials. Stat Med 1998, 17:269-302.
• [55]Cole SR, Hernan MA, Robins JM, Anastos K, Chmiel J, Detels R, Ervin C, Feldman J, Greenblatt R, Kingsley L, et al.: Effect of highly active antiretroviral therapy on time to acquired immunodeficiency syndrome or death using marginal structural models. Am J Epidemiol 2003, 158:687-694.
• [56]Cardus A, Panizo S, Parisi E, Fernandez E, Valdivielso JM: Differential effects of vitamin D analogs on vascular calcifiction. J Bone Miner Res 2007, 22:860-866.
• [57]Mizobuchi M, Finch JL, Martin DR, Slatopolsky E: Differential effects if vitamin D receptor activators on vascular calcification in uremic rats. Kidney Int 2007, 72:709-715.