Association between 25(OH) vitamin D and graft survival in renal transplanted children.
Adolescent
Allografts
Biomarkers
/ blood
Child
Child, Preschool
Female
Follow-Up Studies
France
/ epidemiology
Graft Rejection
/ blood
Graft Survival
Humans
Incidence
Infant
Infant, Newborn
Kidney Transplantation
/ adverse effects
Male
Radioimmunoassay
Retrospective Studies
Seasons
Survival Rate
/ trends
Transplant Recipients
Vitamin D
/ analogs & derivatives
Vitamin D Deficiency
/ blood
allograft
pediatric
rejection
transplantation
vitamin D
Journal
Pediatric transplantation
ISSN: 1399-3046
Titre abrégé: Pediatr Transplant
Pays: Denmark
ID NLM: 9802574
Informations de publication
Date de publication:
11 2020
11 2020
Historique:
received:
18
04
2020
revised:
18
06
2020
accepted:
20
06
2020
pubmed:
28
8
2020
medline:
8
10
2021
entrez:
27
8
2020
Statut:
ppublish
Résumé
In children, vitamin D deficiency is common after renal transplantation. Besides promoting bone and muscle development, vitamin D has immunomodulatory effects, which could protect kidney allografts. The purpose of this study was to assess the association between vitamin D status and the occurrence of renal rejection. We studied a retrospective cohort of 123 children, who were transplanted at a single institution between September 2008 and April 2019. Patients did not receive vitamin D supplementation systematically. In addition, factors influencing vitamin D status were analyzed using univariate and multivariate analyses. Median 25-hydroxy-vitamin D (25-OH-D) concentration was close to reference values at the time of transplantation (30 ng/mL (min-max 5-100)), but rapidly decreased within the first 3 months to 19 ng/mL (min-max 3-91) (P < .001). The overall acute rejection rate was 7%. The clinical rejection rate (5% vs 9%), subclinical rejection (12% vs 36%), and borderline changes (21% vs 28%) were not statistically different during the follow-up between the 3-month 25-OH-D < 20 ng/mL and 3-month 25-OH-D > 20 ng/mL groups. There was a correlation between the 25-OH-D levels and PTH concentration at 3 months (r = -.2491, P = .01), but no correlation between the 3-month 25-OH-D and the season of the year (F = 0.19, P = .90; F = 1.34, P = .27, respectively). Multivariate analyses revealed that age and mGFR at 3 months, were independent predictors of mGFR at 12 months. Our data show that vitamin D deficiency can develop rapidly after transplantation; vitamin D levels at 3 months are not associated with lower mGFR or a higher rejection rate at 1 year in children as opposed to adult recipients.
Sections du résumé
BACKGROUND
In children, vitamin D deficiency is common after renal transplantation. Besides promoting bone and muscle development, vitamin D has immunomodulatory effects, which could protect kidney allografts. The purpose of this study was to assess the association between vitamin D status and the occurrence of renal rejection.
METHODS
We studied a retrospective cohort of 123 children, who were transplanted at a single institution between September 2008 and April 2019. Patients did not receive vitamin D supplementation systematically. In addition, factors influencing vitamin D status were analyzed using univariate and multivariate analyses.
RESULTS
Median 25-hydroxy-vitamin D (25-OH-D) concentration was close to reference values at the time of transplantation (30 ng/mL (min-max 5-100)), but rapidly decreased within the first 3 months to 19 ng/mL (min-max 3-91) (P < .001). The overall acute rejection rate was 7%. The clinical rejection rate (5% vs 9%), subclinical rejection (12% vs 36%), and borderline changes (21% vs 28%) were not statistically different during the follow-up between the 3-month 25-OH-D < 20 ng/mL and 3-month 25-OH-D > 20 ng/mL groups. There was a correlation between the 25-OH-D levels and PTH concentration at 3 months (r = -.2491, P = .01), but no correlation between the 3-month 25-OH-D and the season of the year (F = 0.19, P = .90; F = 1.34, P = .27, respectively). Multivariate analyses revealed that age and mGFR at 3 months, were independent predictors of mGFR at 12 months.
CONCLUSION
Our data show that vitamin D deficiency can develop rapidly after transplantation; vitamin D levels at 3 months are not associated with lower mGFR or a higher rejection rate at 1 year in children as opposed to adult recipients.
Substances chimiques
Biomarkers
0
Vitamin D
1406-16-2
25-hydroxyvitamin D
A288AR3C9H
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e13809Informations de copyright
© 2020 Wiley Periodicals LLC.
Références
Harambat J, van Stralen KJ, Kim JJ, Tizard EJ. Epidemiology of chronic kidney disease in children. Pediatr Nephrol. 2012;27:363-373. https://doi.org/10.1007/s00467-011-1939-1
Lassalle M, Monnet E, Ayav C, et al. 2017 Annual Report Digest of the Renal Epidemiology Information Network (REIN) registry. Transpl Int. 2019;32:892-902. https://doi.org/10.1111/tri.13466
Chesnaye N, Bonthuis M, Schaefer F, et al. Demographics of paediatric renal replacement therapy in Europe: a report of the ESPN/ERA-EDTA registry. Pediatr Nephrol. 2014;29:2403-2410. https://doi.org/10.1007/s00467-014-2884-6
McDonald SP, Craig JC. (2009) Long-Term Survival of Children with End-Stage Renal Disease.
Fraser DR. Vitamin D. The Lancet. 1995;345:104-107. https://doi.org/10.1016/S0140-6736(95)90067-5
Mohr SB, Gorham ED, Alcaraz JE, et al. Serum 25-hydroxyvitamin D and prevention of breast cancer: pooled analysis. Anticancer Res. 2011;31:2939-2948.
Feskanich D, Ma J, Fuchs CS, et al. Plasma vitamin D metabolites and risk of colorectal cancer in women. Cancer Epidemiol Prev Biomark. 2004;13:1502-1508.
Pipili C, Oreopoulos DG. Vitamin D status in patients with recurrent kidney stones. Nephron Clin Pract. 2012;122:134-138. https://doi.org/10.1159/000351377
Prietl B, Treiber G, Mader JK, et al. High-dose cholecalciferol supplementation significantly increases peripheral CD4+ Tregs in healthy adults without negatively affecting the frequency of other immune cells. Eur J Nutr. 2014;53:751-759. https://doi.org/10.1007/s00394-013-0579-6
Prietl B, Treiber G, Pieber TR, Amrein K. Vitamin D and immune function. Nutrients. 2013;5:2502-2521. https://doi.org/10.3390/nu5072502
Lisse TS, Hewison M. Vitamin D: a new player in the world of mTOR signaling. Cell Cycle. 2011;10:1888-1889. https://doi.org/10.4161/cc.10.12.15620
Baeke F, Takiishi T, Korf H, et al. Vitamin D: modulator of the immune system. Curr Opin Pharmacol. 2010;10:482-496. https://doi.org/10.1016/j.coph.2010.04.001
Provvedini DM, Tsoukas CD, Deftos LJ, Manolagas SC. 1,25-dihydroxyvitamin D3 receptors in human leukocytes. Science. 1983;221:1181-1183. https://doi.org/10.1126/science.6310748
Hewison M. An update on vitamin D and human immunity. Clin Endocrinol (Oxf). 2012;76:315-325. https://doi.org/10.1111/j.1365-2265.2011.04261.x
Kandula P, Dobre M, Schold JD, et al. 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 CJASN. 2011;6:50-62. https://doi.org/10.2215/CJN.03940510
Zheng Z, Shi H, Jia J, et al. Vitamin D supplementation and mortality risk in chronic kidney disease: a meta-analysis of 20 observational studies. BMC Nephrol. 2013;14:199. https://doi.org/10.1186/1471-2369-14-199
Melamed ML, Astor B, Michos ED, et al. 25-Hydroxyvitamin D levels, race, and the progression of kidney disease. J Am Soc Nephrol. 2009;20:2631-2639. https://doi.org/10.1681/ASN.2009030283
de Boer IH, Katz R, Chonchol M, et al. Serum 25-hydroxyvitamin D and change in estimated glomerular filtration rate. Clin J Am Soc Nephrol CJASN. 2011;6:2141-2149. https://doi.org/10.2215/CJN.02640311
Shroff R, Aitkenhead H, Costa N, et al. Normal 25-hydroxyvitamin D levels are associated with less proteinuria and attenuate renal failure progression in children with CKD. J Am Soc Nephrol. 2016;27:314-322. https://doi.org/10.1681/ASN.2014090947
Tan X, Li Y, Liu Y. Paricalcitol attenuates renal interstitial fibrosis in obstructive nephropathy. J Am Soc Nephrol. 2006;17:3382-3393. https://doi.org/10.1681/ASN.2006050520
Liu Y. Epithelial to mesenchymal transition in renal fibrogenesis: pathologic significance, molecular mechanism, and therapeutic intervention. J Am Soc Nephrol. 2004;15:1-12. https://doi.org/10.1097/01.ASN.0000106015.29070.E7
Tan X, Wen X, Liu Y. Paricalcitol inhibits renal inflammation by promoting vitamin D receptor-mediated sequestration of NF-κB signaling. J Am Soc Nephrol. 2008;19:1741-1752. https://doi.org/10.1681/ASN.2007060666
Hullett DA, Laeseke PF, Malin G, et al. Prevention of chronic allograft nephropathy with vitamin D*. Transpl Int. 2005;18:1175-1186. https://doi.org/10.1111/j.1432-2277.2005.00187.x
Zhang Y, Kong J, Deb DK, et al. Vitamin D receptor attenuates renal fibrosis by suppressing the renin-angiotensin system. J Am Soc Nephrol. 2010;21:966-973. https://doi.org/10.1681/ASN.2009080872
Schwartz GJ, Abraham A, Furth SL, et al. Optimizing duration and sampling times for iohexol plasma disappearance curves to measure glomerular filtration rate in children with chronic kidney disease. Kidney Int. 2010;77:65-71. https://doi.org/10.1038/ki.2009.398
Holick MF, Binkley NC, Bischoff-Ferrari HA, et al. Evaluation, treatment, and prevention of vitamin D deficiency: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2011;96:1911-1930. https://doi.org/10.1210/jc.2011-0385
Shroff R, Wan M, Nagler EV, et al. Clinical practice recommendations for native vitamin D therapy in children with chronic kidney disease Stages 2-5 and on dialysis. Nephrol Dial Transplant. 2017;32:1098-1113. https://doi.org/10.1093/ndt/gfx065
Larkins N, Matsell DG. Tacrolimus therapeutic drug monitoring and pediatric renal transplant graft outcomes. Pediatr Transplant. 2014;18:803-809. https://doi.org/10.1111/petr.12369
Gwinner W, Suppa S, Mengel M, et al. Early calcification of renal allografts detected by protocol biopsies: causes and clinical implications. Am J Transplant. 2005;5:1934-1941. https://doi.org/10.1111/j.1600-6143.2005.00938.x
Sis B, Mengel M, Haas M, et al. Banff ’09 meeting report: antibody mediated graft deterioration and implementation of banff working groups. Am J Transplant. 2010;10:464-471. https://doi.org/10.1111/j.1600-6143.2009.02987.x
Roufosse C, Simmonds N, Clahsen-van Groningen M, et al. A 2018 reference guide to the banff classification of renal allograft pathology. Transplantation. 2018;102:1795-1814. https://doi.org/10.1097/TP.0000000000002366
Pludowski P, Holick MF, Grant WB. Vitamin D supplementation guidelines. J Steroid Biochem Mol Biol. 2017;11.
Kasiske BL, Zeier MG, Chapman JR, et al. KDIGO clinical practice guideline for the care of kidney transplant recipients: a summary. Kidney Int. 2010;77:299-311. https://doi.org/10.1038/ki.2009.377
Tuchman S, Kalkwarf HJ, Zemel BS, et al. Vitamin D deficiency and parathyroid hormone levels following renal transplantation in children. Pediatr Nephrol. 2010;25:2509-2516. https://doi.org/10.1007/s00467-010-1612-0
Wesseling-Perry K, Tsai EW, Ettenger RB, et al. Mineral abnormalities and long-term graft function in pediatric renal transplant recipients: a role for FGF-23? Nephrol Dial Transplant. 2011;26:3779-3784. https://doi.org/10.1093/ndt/gfr126
Alshayeb HM, Josephson MA, Sprague SM. CKD-mineral and bone disorder management in kidney transplant recipients. Am J Kidney Dis. 2013;61:310-325. https://doi.org/10.1053/j.ajkd.2012.07.022
Giannini S, Sella S, Silva-Netto F, et al. Persistent secondary hyperparathyroidism and vertebral fractures in kidney transplantation: Role of calcium-sensing receptor polymorphisms and vitamin D deficiency. J Bone Miner Res. 2010;25:841-848. https://doi.org/10.1359/jbmr.091025
Pihlstrøm H, Dahle DO, Mjøen G, et al. Increased risk of all-cause mortality and renal graft loss in stable renal transplant recipients with hyperparathyroidism. Transplantation. 2015;99:351-359. https://doi.org/10.1097/TP.0000000000000583
Sánchez Fructuoso AI, Maestro ML, Calvo N, et al. Role of fibroblast growth factor 23 (FGF23) in the metabolism of phosphorus and calcium immediately after kidney transplantation. Transplant Proc. 2012;44:2551-2554. https://doi.org/10.1016/j.transproceed.2012.09.070
Haffner D, Leifheit-Nestler M. CKD-MBD post kidney transplantation. Pediatr Nephrol Berl Ger. 2019;. https://doi.org/10.1007/s00467-019-04421-5
Bouquegneau A, Salam S, Delanaye P, et al. Bone disease after kidney transplantation. Clin J Am Soc Nephrol CJASN. 2016;11:1282-1296. https://doi.org/10.2215/CJN.11371015
Bernardor J, Schmitt CP, Oh J, et al. The use of cinacalcet after pediatric renal transplantation: an international CERTAIN Registry analysis. Pediatr Nephrol Berl Ger. 2020;. https://doi.org/10.1007/s00467-020-04558-8
Avioli LV, Birge SJ, Lee SW. Effects of prednisone on vitamin D metabolism in man. J Clin Endocrinol Metab. 1968;28:1341-1346. https://doi.org/10.1210/jcem-28-9-1341
Filipov JJ, Zlatkov BK, Dimitrov EP, Svinarov D. Relationship between vitamin D status and immunosuppressive therapy in kidney transplant recipients. Biotechnol Biotechnol Equip. 2015;29:331-335. https://doi.org/10.1080/13102818.2014.995415
Lee C-T, Ng H-Y, Lien Y-H, et al. Effects of cyclosporine, tacrolimus and rapamycin on renal calcium transport and vitamin D metabolism. Am J Nephrol. 2011;34:87-94. https://doi.org/10.1159/000328874
Grenet O, Bobadilla M, Chibout SD, Steiner S. Evidence for the impairment of the vitamin D activation pathway by cyclosporine A. Biochem Pharmacol. 2000;59:267-272. https://doi.org/10.1016/s0006-2952(99)00321-4
Eyal O, Aharon M, Safadi R, Elhalel M. Serum vitamin D levels in kidney transplant recipients: the importance of an immunosuppression regimen and sun exposure. Isr Med Assoc J. 2013;15:628-633.
Obi Y, Hamano T, Ichimaru N, et al. Vitamin D deficiency predicts decline in kidney allograft function: a prospective cohort study. J Clin Endocrinol Metab. 2014;99:527-535. https://doi.org/10.1210/jc.2013-2421
Bienaimé F, Girard D, Anglicheau D, et al. Vitamin D status and outcomes after renal transplantation. J Am Soc Nephrol. 2013;24:831-841. https://doi.org/10.1681/ASN.2012060614
Chesnaye NC, van Stralen KJ, Bonthuis M, et al. Survival in children requiring chronic renal replacement therapy. Pediatr Nephrol. 2018;33:585-594. https://doi.org/10.1007/s00467-017-3681-9
Winterberg PD, Garro R. Long-term outcomes of kidney transplantation in children. Pediatr Clin. 2019;66:269-280. https://doi.org/10.1016/j.pcl.2018.09.008
Beimler J, Zeier M. Borderline rejection after renal transplantation - to treat or not to treat: Treatment of borderline rejection. Clin Transplant. 2009;23:19-25. https://doi.org/10.1111/j.1399-0012.2009.01105.x
Loupy A, Vernerey D, Tinel C, et al. Subclinical rejection phenotypes at 1 year post-transplant and outcome of kidney allografts. J Am Soc Nephrol. 2015;26:1721-1731. https://doi.org/10.1681/ASN.2014040399
Weaver DJ, Mitsnefes M. Cardiovascular disease in children and adolescents with chronic kidney disease. Semin Nephrol. 2018;38:559-569. https://doi.org/10.1016/j.semnephrol.2018.08.002
Lee DR, Kong JM, Cho KI, Chan L. Impact of vitamin D on proteinuria, insulin resistance, and cardiovascular parameters in kidney transplant recipients. Transplant Proc. 2011;43:3723-3729. https://doi.org/10.1016/j.transproceed.2011.08.081
Miragliotta G, Miragliotta L. Vitamin D and infectious diseases. Endocr Metab Immune Disord - Drug Targets. 2014;14: https://doi.org/10.2174/1871530314666141027102627
Saber A, Fotuhi F, Rostami Z, et al. Vitamin D levels after kidney transplantation and the risk of cytomegalovirus infection. Nephro-Urol Mon. 2015;7: https://doi.org/10.5812/numonthly.29677
Preka E, Wan M, Price KL, et al. Free 25-hydroxyvitamin-D concentrations are lower in children with renal transplant compared with chronic kidney disease. Pediatr Nephrol Berl Ger. 2020;35:1069-1079. https://doi.org/10.1007/s00467-020-04472-z
Carlow DC, Schofield RC, Denburg M. Quantitation of 25-OH-vitamin-D₂ and 25-OH-vitamin-D₃ in urine using LC-MS/MS. Methods Mol Biol. 2016;1378:321-329. https://doi.org/10.1007/978-1-4939-3182-8_33