Skip to main content
SpringerLink
Log in

Free vitamin D levels in steroid-sensitive nephrotic syndrome and healthy controls

  • Original Article
  • Published:
Pediatric Nephrology Aims and scope Submit manuscript

Abstract

Introduction

Body stores of vitamin D are measured as “total” serum 25-hydroxy vitamin D (25(OH)D). Its largest component is protein bound and lost in urine in nephrotic syndrome (NS). Our study investigates whether “free” 25(OH)D levels are a better guide to bone health and need for vitamin D supplementation in patients with steroid-sensitive NS (SSNS).

Methods

A cross-sectional study was performed in children with SSNS and healthy controls. Blood was tested for albumin, creatinine, calcium, phosphate, ALP, total and free (by direct ELISA) 25(OH)D, iPTH, and urine for protein–creatinine ratio.

Results

Seventy-nine NS patients (48 in relapse, 31 in remission) and 60 healthy controls were included. The levels of total 25(OH)D were significantly different (lowest in NS relapse and highest in controls) (p < 0.001). Corrected calcium and phosphate levels were normal, and there were no differences in free 25(OH)D, ALP, or iPTH levels between groups. Only total and not free 25(OH)D correlated significantly and negatively with urinary protein creatinine ratios (rs = − 0.42 vs. 0.04). Free 25(OH)D values of 3.75 and 2.85 pg/ml corresponded to total 25(OH)D levels of 20 and 12 ng/ml, respectively, in healthy controls.

Conclusion

These results confirm that total 25(OH)D levels are low in NS and related to degree of proteinuria. However levels of free 25(OH)D, ALP, and iPTH did not change in relapse or remission in comparison with healthy controls. Our results suggest that in proteinuric renal diseases, free 25(OH)D rather than total 25(OH)D levels should be used to diagnose vitamin D deficiency and guide therapy.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Christakos S, Li S, De La Cruz J, Bikle DD (2019) New developments in our understanding of vitamin metabolism, action and treatment. Metabolism 98:112–120

    Article  CAS  Google Scholar 

  2. Bouillon R, Marcocci C, Carmeliet G, Bikle D, White JH, Dawson-Hughes B, Lips P, Munns CF, Lazaretti-Castro M, Giustina A, Bilezikian J (2019) Skeletal and extraskeletal actions of vitamin D: current evidence and outstanding questions. Endocr Rev 40:1109–1151

    Article  Google Scholar 

  3. Holick MF (2007) Vitamin D deficiency. N Engl J Med 357:266–281

    Article  CAS  Google Scholar 

  4. Rathi N, Rathi A (2011) Vitamin D and child health in the 21st century. Indian Pediatr 48:619–625

    Article  Google Scholar 

  5. Munns CF, Shaw N, Kiely M, Specker BL, Thacher TD, Ozono K, Michigami T, Tiosano D, Mughal MZ, Mäkitie O, Ramos-Abad L, Ward L, DiMeglio LA, Atapattu N, Cassinelli H, Braegger C, Pettifor JM, Seth A, Idris HW, Bhatia V, Fu J, Goldberg G, Sävendahl L, Khadgawat R, Pludowski P, Maddock J, Hyppönen E, Oduwole A, Frew E, Aguiar M, Tulchinsky T, Butler G, Högler W (2016) Global consensus recommendations on prevention and management of nutritional rickets. J Clin Endocrinol Metab 101:394–415

    Article  CAS  Google Scholar 

  6. From Indian Academy of Pediatrics ‘Guideline for Vitamin D and Calcium in Children’ Committee, Khadilkar A, Khadilkar V, Chinnappa J, Rathi N, Khadgawat R, Balasubramanian S, Parekh B, Jog P (2017) Prevention and treatment of vitamin D and calcium deficiency in children and adolescents: Indian Academy of Pediatrics (IAP) guidelines. Indian Pediatr 54:567–573

    Article  Google Scholar 

  7. Bischoff-Ferrari HA, Giovannucci E, Willett WC, Dietrich T, Dawson-Hughes B (2006) Estimation of optimal serum concentrations of 25-hydroxyvitamin D for multiple health outcomes. Am J Clin Nutr 84:18–28

    Article  CAS  Google Scholar 

  8. Herrmann M, Farrell CL, Pusceddu I, Fabregat-Cabello N, Cavalier E (2017) Assessment of vitamin D status - a changing landscape. Clin Chem Lab Med 55:3–26

    Article  CAS  Google Scholar 

  9. Kulie T, Groff A, Redmer J, Hounshell J, Schrager S (2009) Vitamin D: an evidence-based review. J Am Board Fam Med 22:698–706

    Article  Google Scholar 

  10. Schwartz JB, Gallagher JC, Jorde R, Berg V, Walsh J, Eastell R, Evans AL, Bowles S, Naylor KE, Jones KS, Schoenmakers I, Holick M, Orwoll E, Nielson C, Kaufmann M, Jones G, Bouillon R, Lai J, Verotta D, Bikle D (2018) Determination of free 25(OH)D concentrations and their relationships to total 25(OH)D in multiple clinical populations. J Clin Endocrinol Metab 103:3278–3288

    Article  Google Scholar 

  11. Bikle DD, Malmstroem S, Schwartz J (2017) Current controversies: are free vitamin metabolite levels a more accurate assessment of vitamin D status than total levels? Endocrinol Metab Clin North Am 46:901–918

    Article  Google Scholar 

  12. 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  Google Scholar 

  13. 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  Google Scholar 

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

    CAS  Google Scholar 

  15. Barragry JM, France MW, Carter ND, Auton JA, Beer M, Boucher BJ, Cohen RD (1977) Vitamin D metabolism in nephrotic syndrome. Lancet 2:629–632

    Article  CAS  Google Scholar 

  16. 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  Google Scholar 

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

    Article  Google Scholar 

  18. Banerjee S, Basu S, Sen A, Sengupta J (2017) The effect of vitamin D and calcium supplementation in pediatric steroid-sensitive nephrotic syndrome. Pediatr Nephrol 32:2063–2070

    Article  Google Scholar 

  19. 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 

  20. 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  Google Scholar 

  21. Risteli J, Winter WE, Kleerekoper M, Risteli L (2015) Chapter 39, disorders of bone and mineral metabolism. In: Burtis CA, Bruns DE (eds) (2015) Tietz fundamentals of clinical chemistry and molecular diagnostics, 7th edn. Elsevier, Amsterdam, p 749

    Google Scholar 

  22. Mendel CM (1989) The free hormone hypothesis: a physiologically based mathematical model. Endocr Rev 10:232–274

    Article  CAS  Google Scholar 

  23. Recant L, Riggs DS (1952) Thyroid function in nephrosis. J Clin Invest 31:789–797

    Article  CAS  Google Scholar 

  24. Refetoff S (2015) Thyroid hormone serum transport proteins. In: Feingold KR, Anawalt B, Boyce A, Chrousos G, Dungan K, Grossman A, Hershman JM, Kaltsas G, Koch C, Kopp P, Korbonits M, McLachlan R, Morley JE, New M, Perreault L, Purnell J, Rebar R, Singer F, Trence DL, Vinik A, Wilson DP (eds) Endotext, MDText.comhttp://www.ncbi.nlm.nih.gov/books/NBK285566/

  25. Siiteri PK, Murai JT, Hammond GL, Nisker JA, Raymoure WJ, Kuhn RW (1982) The serum transport of steroid hormones. Recent Prog Horm Res 38:457–510

    CAS  PubMed  Google Scholar 

  26. Hammond GL (2016) Plasma steroid-binding proteins: primary gatekeepers of steroid hormone action. J Endocrinol 230:R13–R25

    Article  CAS  Google Scholar 

  27. Bikle D, Bouillon R, Thadhani R, Schoenmakers I (2017) Vitamin D metabolites in captivity? Should we measure free or total 25(OH)D to assess vitamin D status? J Steroid Biochem Mol Biol 173:105–116

    Article  CAS  Google Scholar 

  28. Tsuprykov O, Chen X, Hocher CF, Skoblo R, Yin L, Hocher B (2018) Why should we measure free 25(OH) vitamin D? J Steroid Biochem Mol Biol 180:87–104

    Article  CAS  Google Scholar 

  29. Heureux N (2017) Vitamin D testing-where are we and what is on the horizon? Adv Clin Chem 78:59–101

    Article  CAS  Google Scholar 

  30. Herrmann M, Farrell CL, Pusceddu I, Fabregat-Cabello N, Cavalier E (2017) Assessment of vitamin D status - a changing landscape. Clin Chem Lab Med 55:3–26

    Article  CAS  Google Scholar 

  31. Schwartz JB, Lai J, Lizaola B, Kane L, Markova S, Weyland P, Terrault NA, Stotland N, Bikle D (2014) A comparison of measured and calculated free 25(OH) vitamin D levels in clinical populations. J Clin Endocrinol Metab 99:1631–1637

    Article  CAS  Google Scholar 

  32. Malmstroem S, Rejnmark L, Imboden JB, Shoback DM, Bikle DD (2017) Current assays to determine free 25-hydroxyvitamin D in serum. J AOAC Int 100:1323–1327

    Article  CAS  Google Scholar 

  33. ALopez-Molina M, Santillan C, Murillo M, Valls A, Bosch L, Bel J, Granada ML (2018) Measured free 25-hydroxyvitamin D in healthy children and relationship to total 25-hydroxyvitamin D, calculated free 25-hydroxyvitamin D and vitamin D binding protein. Clin Biochem 61:23–27

    Article  Google Scholar 

  34. Arneson WL, Arneson DL (2013) Current methods for routine clinical laboratory testing of vitamin D levels. Lab Medicine 44:e38–e42

    Article  Google Scholar 

  35. Emmen JM, Wielders JP, Boer AK, van den Ouweland JM, Vader HL (2012) The new Roche vitamin D total assay: fit for its purpose? Clin Chem Lab Med 50:1969–1972

    Article  CAS  Google Scholar 

  36. DEQAS Review 2016/2017: http://www.deqas.org/downloads/DEQAS%20Review%20October%202017.pdf

  37. 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 

  38. Freundlich M, Jofe M, Goodman WG, Salusky IB (2004) Bone histology in steroid-treated children with non-azotemic nephrotic syndrome. Pediatr Nephrol 19:400–407

    Article  Google Scholar 

  39. 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  Google Scholar 

  40. 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  Google Scholar 

  41. 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  Google Scholar 

  42. Gopal-Kothandapani JS, Evans LF, Walsh JS, Gossiel F, Rigby AS, Eastell R, Bishop NJ (2019) Effect of vitamin D supplementation on free and total vitamin D: a comparison of Asians and Caucasians. Clin Endocrinol (Oxf) 90:222–231

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pediatric Nephrology, Institute of Child Health, Kolkata, India

    Sushmita Banerjee, Shakil Akhtar, Rajiv Sinha & Jayati Sengupta

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

    Surupa Basu

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

    Ananda Sen

Authors
  1. Sushmita Banerjee
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Surupa Basu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Shakil Akhtar
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Rajiv Sinha
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ananda Sen
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jayati Sengupta
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sushmita Banerjee.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Banerjee, S., Basu, S., Akhtar, S. et al. Free vitamin D levels in steroid-sensitive nephrotic syndrome and healthy controls. Pediatr Nephrol 35, 447–454 (2020). https://doi.org/10.1007/s00467-019-04433-1

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00467-019-04433-1

Keywords

Search

Navigation