Urinary vitamin D binding protein levels in children with idiopathic nephrotic syndrome: a biomarker differentiating steroid sensitive from steroid resistant nephrotic syndrome

Chaudhary, Anup K.; Mishra, Om P.; Khandhadiya, Ketki; Mishra, Surendra P.; Mishra, Akash; Singh, Ashok; Dua, Priyanka

doi:10.1590/2175-8239-JBN-2025-0094en

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Original Article • Braz. J. Nephrol. 48 (1) • Jan-Mar 2026 • https://doi.org/10.1590/2175-8239-JBN-2025-0094en linkcopy

Urinary vitamin D binding protein levels in children with idiopathic nephrotic syndrome: a biomarker differentiating steroid sensitive from steroid resistant nephrotic syndrome

Authorship SCIMAGO INSTITUTIONS RANKINGS

Abstract

Introduction: The primary objective of this study was to assess urinary vitamin D binding protein (uVDBP) levels in idiopathic nephrotic syndrome. Secondary objectives were to evaluate the ability of uVDBP to differentiate between steroid resistant nephrotic syndrome (SRNS) and steroid sensitive nephrotic syndrome (SSNS), and between minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS) of SRNS.

Methods: Sixty-three cases of idiopathic nephrotic syndrome were included; 23 were first episode nephrotic syndrome (FENS), 24 were relapsing nephrotic syndrome (RNS), and 16 were steroid resistant. Eleven subjects were used as controls and 17 cases were under remission. ELISA kit was used to assay uVDBP.

Results: Median uVDBP levels were increased across FENS, RNS, SRNS groups as compared to controls (P < 0.001). Median uVDBP was significantly higher in SRNS (32.2 ng/mL) than in SSNS (4.0 ng/mL, P < 0.001). Similarly, the median level was also significantly higher in FSGS (56.6 ng/mL) than in MCD (20.8 ng/mL, P = 0.005). The uVDBP was significantly lower during remission (1.2 ng/mL) than in the active (5.1 ng/mL) phase of the disease (P < 0.001). At the 12-ng/mL cut-off value, uVDBP had higher sensitivity, specificity, and area under the curve (100%, 97.9% and 0.983, respectively) for distinguishing steroid-resistant from steroid-sensitive patients. Significant positive correlation was found between uVDBP and urine protein/creatinine ratio (r = 0.441, P < 0.001) and negative correlation between uVDBP and serum albumin (r = −0.303, P = 0.019).

Conclusion: uVDBP level is related to disease activity and can distinguish not only steroid-resistant from steroid-sensitive, but also FSGS from MCD histological subtypes of steroid-resistant NS.

Keywords:
Childhood Idiopathic Nephrotic Syndrome; Corticosteroid Sensitive Nephrotic Syndrome; Steroid-Resistant Nephrotic Syndrome; Urinary Vitamin D Binding Protein

Parameters	Controls n = 11	FENS n = 23	RNS n = 24	SRNS n = 16	P
Age (years)	4 (2,5)	4 (2,7)	3.5 (2,7)	4.5 (3,6.7)	0.701a
Gender Male Female	5 (45.5%) 6 (54.5%)	15 (65.2%) 8 (34.8%)	16 (66.7%) 8 (33.3%)	7 (43.8%) 9 (56.2%)	0.356b
Body mass index (kg/m²)	15.2 ± 2.1	16.5 ± 2.9	16.8 ± 2.4	17.0 ± 3.2	0.338c
Systolic blood pressure (mmHg)	96.5 ± 5.9	100.7 ± 6.5	98.0 ± 7.7	99.6 ± 7.2	0.369c
Diastolic blood pressure (mmHg)	59.0 ± 10.4	62.2 ± 6.5	58.9 ± 7.6	63.5 ± 10.1	0.272c
eGFRcr (mL/1.73m²/min)	100.8 ± 23.7	96.3 ± 28.1	99.9 ± 33.8	99.4 ± 29.9	0.967c
Serum albumin (g/dL)	4.1 ± 0.3	2.3 ± 0.5	2.2 ± 0.6	2.0 ± 0.6	<0.001c
Serum cholesterol l(mg/dL)	139.9 ± 8.2	371.5 ± 106.4	398.4 ± 146.7	414.5 ± 139.6	<0.001c
Blood urea (mg/dl)	24 (19,31)	25 (22,32)	35.5 (21.7,50.2)	29.5 (15.7,47.2)	0.182a
Serum creatinine (mg/dL)	0.5 ± 0.08	0.6 ± 0.17	0.6 ± 0.18	0.6 ± 0.11	0.541c
Serum sodium (mEq/L)	136.7 ± 2.8	136 ± 4.1	136.7 ± 3.4	136.7 ± 2.9	0.905c
Serum potassium (mEq/L)	4.4 ± 0.4	4.2 ± 0.5	4.4 ± 0.4	4.6 ± 0.8	0.298c
Serum calcium (mg/dL)	8.6 ± 0.5	8.5 ± 0.8	8.6 ± 0.7	8.3 ± 0.6	0.670c
Serum phosphate (mg/dL)	4.9 ± 0.3	4.6 ± 0.7	4.9 ± 0.8	5.0 ± 0.7	0.409c
Alkaline phosphatase (U/L)	207.9 ± 58.0	199.1 ± 82.3	191.5 ± 65.3	190.8 ± 38.0	0.892c
Serum vitamin 25 (OH) D (ng/mL)	23.2 ± 11.7	5.6 ± 1.1	6.1 ± 1.3	5.2 ± 1.0	<0.001c
Urine protein/creatinine ratio (mg/mg)	0.2 (0.2,0.3)	4.9d (4.0,8.8)	8.0d (5.3,16.8)	9.9d (6.0,18.5)	<0.001a
Urinary vitamin D binding protein (ng/mL)	1.1 (0.6,1.6)	3.1d (2.4,3.7)	5.7d (4.0,7.9)	32.2d (20.4,55.7)	<0.001a
Urinary vitamin D binding protein/ creatinine (ng/mg)	1.4 (0.9,2)	5.7d (3.5,8.1)	10.3d (4.2,19.0)	85.8d (45,141)	<0.001a

Parameters	Controls n =1 1	SSNS n = 47	SRNS n = 16	P value
Serum calcium (mg/dL)	8.6 ± 0.50	8.6 ± 0.79	8.3 ± 0.68	0.511a
Serum phosphate (mg/dL)	4.9 ± 0.34	4.8 ± 0.79	5.0 ± 0.71	0.532a
Alkaline phosphatase (u/L)	207 ± 58.0	195.3 ± 73.4	190.8 ± 38.0	0.792a
Serum 25 (OH) D (ng/mL)	23.2 ± 11.7	5.8 ± 1.2	5.2 ± 1.0	<0.001a
Urine protein creatinine ratio (mg/mg)	0.20 (0.20,0.30)	6.9c (4.2,11.6)	9.9c (6.0,18.5)	<0.001b
Urinary vitamin D binding protein (ng/mL)	1.07 (0.61,1.6)	4.0c (3.0,6.6)	32.2c (20.4,55.7)	<0.001b
Urinary vitamin D binding protein/ creatinine (ng/mg)	1.47 (0.97,2.0)	6.6c (4.1,14.0)	85.8c (45.0,141.9)	<0.001b

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[1] Abbreviations – n: number of subjects; eGFRcr: Estimated glomerular filtration rate creatinine; FENS: First episode nephrotic syndrome; RNS: Relapsing nephrotic syndrome; SRNS: Steroid resistant nephrotic syndrome.

[T1FN1] Notes – a: Kruskal Wallis test

[T1FN2] b: Chi-square test

[T1FN3] c: Analysis of variance

[T1FN4] d: Mann-Whitney U test.