Top

Pediatric Nephrology

Published in:

01-03-2020 | Nephrotic Syndrome | Original Article

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

Authors: Sushmita Banerjee, Surupa Basu, Shakil Akhtar, Rajiv Sinha, Ananda Sen, Jayati Sengupta

Published in: Pediatric Nephrology | Issue 3/2020

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 (r_s = − 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.

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

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 40:1109–1151CrossRef

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

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

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 101:394–415CrossRef

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 54:567–573CrossRef

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 84:18–28CrossRef

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

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

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 103:3278–3288CrossRef

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 46:901–918CrossRef

12.

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

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 108:383–387CrossRef

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

15.

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

16.

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

17.

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

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 32:2063–2070CrossRef

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

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 28:415–426CrossRef

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

22.

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

23.

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

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 38:457–510PubMed

26.

Hammond GL (2016) Plasma steroid-binding proteins: primary gatekeepers of steroid hormone action. J Endocrinol 230:R13–R25CrossRef

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 173:105–116CrossRef

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 180:87–104CrossRef

29.

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

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 55:3–26CrossRef

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 99:1631–1637CrossRef

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 100:1323–1327CrossRef

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 61:23–27CrossRef

34.

Arneson WL, Arneson DL (2013) Current methods for routine clinical laboratory testing of vitamin D levels. Lab Medicine 44:e38–e42CrossRef

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 50:1969–1972CrossRef

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 61:627–630PubMed

38.

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

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 840:21–28CrossRef

40.

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

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 29:1025–1032CrossRef

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) 90:222–231CrossRef

Title: Free vitamin D levels in steroid-sensitive nephrotic syndrome and healthy controls
Authors: Sushmita Banerjee
Surupa Basu
Shakil Akhtar
Rajiv Sinha
Ananda Sen
Jayati Sengupta
Publication date: 01-03-2020
Publisher: Springer Berlin Heidelberg
Keyword: Nephrotic Syndrome
Published in: Pediatric Nephrology / Issue 3/2020
Print ISSN: 0931-041X
Electronic ISSN: 1432-198X
DOI: https://doi.org/10.1007/s00467-019-04433-1

Keynote webinar | Spotlight on medication adherence

Springer Medicine

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

Abstract

Introduction

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Introduction

Methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 3/2020

A single-center study to evaluate the efficacy of a fetal urine peptide signature predicting postnatal renal outcome in fetuses with posterior urethral valves

Periumbilical swelling, erythema, and discharge in a girl: Answers

Energy and protein requirements for children with CKD stages 2-5 and on dialysis–clinical practice recommendations from the Pediatric Renal Nutrition Taskforce

Sex and age as determinants for high blood pressure in pediatric renal transplant recipients: a longitudinal analysis of the CERTAIN Registry

Diagnostics, treatment, and immune response in BK polyomavirus infection after pediatric kidney transplantation

A cross-sectional study on uric acid levels among Chinese adolescents