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The effect of vitamin D and calcium supplementation in pediatric steroid-sensitive nephrotic syndrome

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Abstract

Background

Low serum levels of total 25-hydroxycholecalciferol (25(OH)D) occur in nephrotic syndrome (NS). We aimed to assess the effects of vitamin D3 and calcium supplementation on 25(OH)D levels, bone mineralization, and NS relapse rate in children with steroid-sensitive NS.

Methods

A randomized controlled trial (RCT) was performed in children with steroid-sensitive NS. The treatment group received vitamin D3 (60,000 IU orally, weekly for 4 weeks) and calcium supplements (500 to 1,000 mg/day for 3 months) after achieving NS remission. Blood samples for bone biochemistry were taken during relapse (T0), after 6 weeks (T1) and 6 months (T2) of randomization, whereas a lumbar DXA scan was performed at T0 and T2. Renal ultrasound was performed after study completion in the treatment group and in all patients with hypercalciuria.

Results

Of the 48 initial recruits, 43 patients completed the study. Post-intervention, 25(OH)D levels showed significant improvements in the treatment group compared with controls at T1 (p < 0.001) and T2 (p < 0.001). However, this was not associated with differences in bone mineral content (BMC) (p = 0.44) or bone mineral density (BMD) (p = 0.64) between the groups. Additionally, there was no reduction in relapse number in treated patients (p = 0.54). Documented hypercalciuria occurred in 52% of patients in the treatment group, but was not associated with nephrocalcinosis.

Conclusions

Although supplementation with calcium and vitamin D improved 25(OH)D levels significantly, there was no effect on BMC, BMD or relapse rate over a 6-month follow-up. Occurrence of hypercalciuria mandates caution and appropriate monitoring if using such therapy. Appropriate dosage of vitamin D3 remains uncertain and studies examining biologically active vitamin D may provide answers.

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References

  1. Bak M, Serdaroglu E, Guclu R (2006) Prophylactic calcium and vitamin D treatments in steroid-treated children with nephrotic syndrome. Pediatr Nephrol 21:350–354

    Article  PubMed  Google Scholar 

  2. Koşan C, Ayar G, Orbak Z (2012) Effects of steroid treatment on bone mineral metabolism in children with glucocorticoid-sensitive nephrotic syndrome. West Indian Med J 61:627–630

    PubMed  Google Scholar 

  3. El-Mashad GM, El-Hawy MA, El-Hefnawy SM, Mohamed SM (2017) Bone mineral density in children with idiopathic nephrotic syndrome. J Pediatr 93:142–147

    Article  Google Scholar 

  4. Gulati S, Godbole M, Singh U, Gulati K, Srivastava A (2003) Are children with idiopathic nephrotic syndrome at risk for metabolic bone disease. Am J Kidney Dis 41:1163–1169

    Article  PubMed  Google Scholar 

  5. Lettgen B, Jeken C, Reiners C (1994) Influence of steroid medication on bone mineral density in children with nephrotic syndrome. Pediatr Nephrol 8:667–670

    Article  CAS  PubMed  Google Scholar 

  6. Ribeiro D, Zawadynski S, Pittet LF, Chevalley T, Girardin E, Parvex P (2015) Effect of glucocorticoids on growth and bone mineral density in children with nephrotic syndrome. Eur J Pediatr 174:911–917

    Article  CAS  PubMed  Google Scholar 

  7. Grymonprez A, Proesmans W, Van Dyck M, Jans I, Goos G, Bouillon R (1995) Vitamin D metabolites in childhood nephrotic syndrome. Pediatr Nephrol 9:278–281

    Article  CAS  PubMed  Google Scholar 

  8. Bennett MR, Pordal A, Haffner C, Pleasant L, Ma Q, Devarajan P (2016) Urinary vitamin D - binding protein as a biomarker of steroid-resistant nephrotic syndrome. Biomark Insights 11:1–6

    Article  PubMed  PubMed Central  Google Scholar 

  9. Banerjee S, Basu S, Sengupta J (2013) Vitamin D in nephrotic syndrome remission: a case-control study. Pediatr Nephrol 28:1983–1989

    Article  PubMed  Google Scholar 

  10. Freundlich M, Bourgoignie JJ, Zilleruelo G, Abitbol C, Canterbury JM, Strauss J (1986) Calcium and vitamin D metabolism in children with nephrotic syndrome. J Pediatr 108:383–387

    Article  CAS  PubMed  Google Scholar 

  11. Huang JP, Bai KM, Wang BL (1992) Vitamin D and calcium metabolism in children with nephrotic syndrome of normal renal function. Chin Med J 105:828–832

    CAS  PubMed  Google Scholar 

  12. Weng FL, Shults J, Herskovitz RM, Zemel BS, Leonard MB (2005) Vitamin D insufficiency in steroid-sensitive nephrotic syndrome in remission. Pediatr Nephrol 20:56–63

    Article  PubMed  Google Scholar 

  13. Biyikli NK, Emre S, Sirin A, Bilge I (2004) Biochemical bone markers in nephrotic children. Pediatr Nephrol 19:869–873

    Article  PubMed  Google Scholar 

  14. Gulati S, Sharma RK, Gulati K, Singh U, Srivastava A (2005) Longitudinal follow-up of bone mineral density in children with nephrotic syndrome and the role of calcium and vitamin D supplements. Nephrol Dial Transplant 20:1598–1603

    Article  CAS  PubMed  Google Scholar 

  15. Chen Y, Wan JX, Jiang DW, Fu BB, Cui J, Li GF, Chen CM (2015) Efficacy of calcitriol in treating glucocorticoid induced osteoporosis in patients with nephrotic syndrome: an open-label, randomized controlled study. Clin Nephrol 84:262–269

    Article  CAS  PubMed  Google Scholar 

  16. Bucak IH, Ozturk AB, Almis H, Cevik MÖ, Tekin M, Konca Ç, Turgut M, Bulbul M (2016) Is there a relationship between low vitamin D and rotaviral diarrhea? Pediatr Int 58:270–273

    Article  CAS  PubMed  Google Scholar 

  17. Facchini L, Venturini E, Galli L, de Martino M, Chiappini E (2015) Vitamin D and tuberculosis: a review on a hot topic. J Chemother 27:128–138

    Article  CAS  PubMed  Google Scholar 

  18. Larkin A, Lassetter J (2014) Vitamin D deficiency and acute lower respiratory infections in children younger than 5 years: identification and treatment. J Pediatr Health Care 28:572–582; quiz 583–584

    Article  PubMed  Google Scholar 

  19. Science M, Maguire JL, Russell ML, Smieja M, Walter SD, Loeb M (2013) Low serum 25-hydroxyvitamin D level and risk of upper respiratory tract infection in children and adolescents. Clin Infect Dis 57:392–397

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Bozzetto S, Carraro S, Giordano G, Boner A, Baraldi E (2012) Asthma, allergy and respiratory infections: the vitamin D hypothesis. Allergy 67:10–17

    Article  CAS  PubMed  Google Scholar 

  21. Christakos S, Dhawan P, Verstuyf A, Verlinden L, Carmeliet G (2016) Vitamin D: metabolism, molecular mechanism of action, and pleiotropic effects. Physiol Rev 96:365–408

    Article  CAS  PubMed  Google Scholar 

  22. Pereira Wde F, Brito-Melo GE, Guimarães FT, Carvalho TG, Mateo EC, Simões e Silva AC (2014) The role of the immune system in idiopathic nephrotic syndrome: a review of clinical and experimental studies. Inflamm Res 63:1–12

    Article  PubMed  Google Scholar 

  23. Indian Pediatric Nephrology Group, Indian Academy of Pediatrics, Bagga A, Ali U, Banerjee S, Kanitkar M, Phadke KD, Senguttuvan P, Sethi S, Shah M (2008) Management of steroid sensitive nephrotic syndrome: revised guidelines. Indian Pediatr 45:203–214

    Google Scholar 

  24. Choudhary S, Agarwal I, Seshadri MS (2014) Calcium and vitamin D for osteoprotection in children with new-onset nephrotic syndrome treated with steroids: a prospective, randomized, controlled, interventional study. Pediatr Nephrol 29:1025–1032

    Article  PubMed  Google Scholar 

  25. Buehring B, Viswanathan R, Binkley N, Busse W (2013) Glucocorticoid-induced osteoporosis: an update on effects and management. J Allergy Clin Immunol 132:1019–1030

    Article  CAS  PubMed  Google Scholar 

  26. Leonard MB (2007) Glucocorticoid-induced osteoporosis in children: impact of the underlying disease. Pediatrics 119 [Suppl 2]:S166–S174

    Article  PubMed  Google Scholar 

  27. Mishra OP, Meena SK, Singh SK, Prasad R, Mishra RN (2009) Bone mineral density in children with steroid-sensitive nephrotic syndrome. Indian J Pediatr 76:1237–1239

    Article  CAS  PubMed  Google Scholar 

  28. Esbjörner E, Arvidsson B, Jones IL, Palmér M (2001) Bone mineral content and collagen metabolites in children receiving steroid treatment for nephrotic syndrome. Acta Paediatr 90:1127–1130

    Article  PubMed  Google Scholar 

  29. Moon RJ, Gilbert RD, Page A, Murphy L, Taylor P, Cooper C, Dennison EM, Davies JH (2014) Children with nephrotic syndrome have greater bone area but similar volumetric bone mineral density to healthy controls. Bone 58:108–113

    Article  CAS  PubMed  Google Scholar 

  30. Leonard MB, Feldman HI, Shults J, Zemel BS, Foster BJ, Stallings VA (2004) Long-term, high-dose glucocorticoids and bone mineral content in childhood glucocorticoid-sensitive nephrotic syndrome. N Engl J Med 351:868–875

    Article  CAS  PubMed  Google Scholar 

  31. Polito C, La Manna A, Todisco N, Cimmaruta E, Sessa G, Pirozzi M (1995) Bone mineral content in nephrotic children on long-term, alternate-day prednisone therapy. Clin Pediatr (Phila) 34:234–236

    Article  CAS  Google Scholar 

  32. Phan V, Blydt-Hansen T, Feber J, Alos N, Arora S, Atkinson S, Bell L, Clarson C, Couch R, Cummings EA, Filler G, Grant RM, Grimmer J, Hebert D, Lentle B, Ma J, Matzinger M, Midgley J, Pinsk M, Rodd C, Shenouda N, Stein R, Stephure D, Taback S, Williams K, Rauch F, Siminoski K, Ward LM, Canadian STOPP Consortium (2014) Skeletal findings in the first 12 months following initiation of glucocorticoid therapy for pediatric nephrotic syndrome. Osteoporos Int 25:627–637

    Article  CAS  PubMed  Google Scholar 

  33. Hahn D, Hodson EM, Willis NS, Craig JC (2015) Corticosteroid therapy for nephrotic syndrome in children. Cochrane Database Syst Rev 3:CD001533

    Google Scholar 

  34. Lombel RM, Gipson DS, Hodson EM (2013) Kidney disease: improving global outcomes. Treatment of steroid-sensitive nephrotic syndrome: new guidelines from KDIGO. Pediatr Nephrol 28:415–426

    Article  PubMed  Google Scholar 

  35. Pańczyk-Tomaszewska M, Adamczuk D, Kisiel A, Skrzypczyk P, Przedlacki J, Górska E, Stelmaszczyk-Emmel A, Demkow U, Roszkowska-Blaim M (2015) Markers of bone metabolism in children with nephrotic syndrome treated with corticosteroids. Adv Exp Med Biol 840:21–28

    Article  PubMed  Google Scholar 

  36. Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, Murad MH, Weaver CM (2011) Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 96:1911–1930

    Article  CAS  PubMed  Google Scholar 

  37. Malihi Z, Wu Z, Stewart AW, Lawes CM, Scragg R (2016) Hypercalcemia, hypercalciuria, and kidney stones in long-term studies of vitamin D supplementation: a systematic review and meta-analysis. Am J Clin Nutr 104:1039–1051

    Article  CAS  PubMed  Google Scholar 

  38. Vogiatzi MG, Jacobson-Dickman E, MD DB, Drugs and Therapeutics Committee of The Pediatric Endocrine Society (2014) Vitamin D supplementation and risk of toxicity in pediatrics: a review of current literature. J Clin Endocrinol Metab 99:1132–1141

    Article  CAS  PubMed  Google Scholar 

  39. Aggarwal A, Yadav AK, Ramachandran R, Kumar V, Kumar V, Sachdeva N, Khandelwal N, Jha V (2016) Bioavailable vitamin D levels are reduced and correlate with bone mineral density and markers of mineral metabolism in adults with nephrotic syndrome. Nephrology (Carlton) 21:483–489

    Article  CAS  Google Scholar 

  40. Yao P, Sun L, Lu L, Ding H, Chen X, Tang L, Xu X, Liu G, Hu Y, Ma Y, Wang F, Jin Q, Zheng H, Yin H, Zeng R, Chen Y, Hu FB, Li H, Lin X (2017) Effects of genetic and non-genetic factors on Total and bioavailable 25(OH)D responses to vitamin D supplementation. J Clin Endocrinol Metab 102:100–110

    PubMed  Google Scholar 

  41. Powe CE, Evans MK, Wenger J, Zonderman AB, Berg AH, Nalls M, Tamez H, Zhang D, Bhan I, Karumanchi SA, Powe NR, Thadhani R (2013) Vitamin D-binding protein and vitamin D status of black Americans and white Americans. N Engl J Med 69:1991–2000

    Article  Google Scholar 

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Acknowledgements

We sincerely thank Dr Ravi Thadani, Chief of Nephrology, Massachusetts General Hospital, for reviewing the manuscript and Dr Subrata Das, H.O.D., Department of Radiology, Calcutta Medical Research Institute, for advice and supervision of the DXA scans.

Author information

Authors and Affiliations

  1. Department of Paediatric Nephrology, Institute of Child Health and Calcutta Medical Research Institute, Kolkata, India

    Sushmita Banerjee

  2. Department of Biochemistry, Institute of Child Health, Kolkata, India

    Surupa Basu

  3. Department of Family Medicine and Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA

    Ananda Sen

  4. Department of Paediatric Nephrology, Institute of Child Health, Kolkata, India

    Jayati Sengupta

Authors
  1. Sushmita Banerjee
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  2. Surupa Basu
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  3. Ananda Sen
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  4. Jayati Sengupta
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Contributions

Sushmita Banerjee and Jayati Sengupta reviewed and recruited patients, and Surupa Basu supervised biochemical assays. All three were involved in the study design and in manuscript writing. Ananda Sen reviewed and edited the manuscript and guided the statistical analysis.

Corresponding author

Correspondence to Sushmita Banerjee.

Ethics declarations

The study design was approved by the institutional ethics committees of the Institute of Child Health and Calcutta Medical Research Institute, and adhered to the Declaration of Helsinki. Informed consent was obtained from parents before recruitment.

Conflicts of interest

None of the authors involved have any conflicts of interest to declare.

Funding

The study was supported by an internal Institute of Child Health Nephrology Fund.

Additional information

Study design: randomized controlled open label intervention trial

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Banerjee, S., Basu, S., Sen, A. et al. The effect of vitamin D and calcium supplementation in pediatric steroid-sensitive nephrotic syndrome. Pediatr Nephrol 32, 2063–2070 (2017). https://doi.org/10.1007/s00467-017-3716-2

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  • DOI: https://doi.org/10.1007/s00467-017-3716-2

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