The document discusses the implications of vitamin D deficiency in children with nephrotic syndrome, highlighting its multi-factorial causes and systemic effects such as hypocalcemia and cardiovascular disease. It notes that while vitamin D levels improve significantly with supplementation during treatment, full normalization is rare, suggesting a need for routine monitoring and individualized approaches for management. Additionally, it covers the importance of combining vitamin D with other nutrients to mitigate potential bone loss from steroid therapy and the role of various vitamins in regulating health outcomes in these patients.

1. Nephrotic syndrom and
vitamins
Ahmad Ali
Nikibakhsh Pediatric
Nephrologist
Urmia University of
Medical Sciences

2. Abnormal vitamin D metabolism in
idiopathic NS is multi-factorial
 losses of both vitamin D binding protein and 25(OH)D in the
urine
 The urinary losses of vitamin D binding protein may be
secondary to proteinuria.
 Deficiency in 25(OH)D may lead to hypocalcemia,
hyperparathyroidism, and diminished bone mineral
density/content.
 Vitamin D deficiency has also been associated with multiple
systemic effects including elevated blood pressure ,metabolic
syndrome, cardiovascular disease ,anemia and impaired
immune system regulation .
 Roos BA. Urinary and plasma vitamin D3 metabolites in the nephrotic syndrome. Metab
Bone Dis Relat Res. 1982;4:7–15.

3. 25(OH)D levels25(OH)D levels
 There has been an increasing amount of data suggesting
that 25(OH)D levels may not completely normalize when
children go into remission
 Data suggest that abnormalities in 25(OH)D levels persist
and occur at a greater frequency than would be expected in
the general population.
 Banerjee S, Basu S, Sengupta J. Vitamin D in nephrotic
syndrome remission: a case–control study. Pediatr Nephrol.
2013;28

4. Study by
Nikibakhsh.Ahmadali,
Mahmoodzadeh.Hashem,Valizade
h.Mohammad
Effect of supplementary
use of Vitamin D on
serum level of vitamin D3
in patients with nephrotic
syndrome receiving
steroid therapy

5. Study by
Nikibakhsh.Ahmadali,
Mahmoodzadeh.Hashem,Valizade
h.Mohammad
 Out of 30 children 60% were male and 40% were female with
mean age of 6.91 + 3.34 years.
 Before intervention 70% of patients had sever deficiency,
26.7% mild to moderate deficiency.
 Mean level of 25(OH) D was 8.277±0.84 ng/ml rising to
14.364±1.14 ng/ml after two months that was statistically
significant (P=0.001).

6. Study by
Nikibakhsh.Ahmadali,
Mahmoodzadeh.Hashem,Valizade
h.Mohammad
Severe deficiency;
 The serum level of 25-hydroxy vitamin-D3 less than 10 ng/ml
Mild to moderate ;
 Patients with the levels between 10 and 20 ng/ml
Insufficient
 those with the levels between 20 and 30 ng/ml
Normal ;
 serum levels of more than 30 ng/ml

7.  Before intervention none of the patients had normal serum level
of 25-(OH)-D and after one month, only one patient gained
normal level which was not statistically significant (P=0.500).
 vitamin D levels at three times (beginning, one month, and two
month after intervention). According to the results of this table, it
can be seen that the mean serum level of vitamin D before
intervention was 8.27 ± 0.84 ng/ml, with increasing to 14.36±
1.14 and finally reaching 27.78 ±2.80 after two month of
treatment.
 After two months of intervention, 12 patients escaped deficiency
but still insufficient followed by 8 people with deficiency and 10
reached normal values which was statistically significant
(P=0.002)

8. Time Baseline After 1month
Treatment
After2Month Treatment P value
Severe Deficiency 21 (70) 5 (16.7) 1 (3.3) 0.001
Mild-Moderate Deficiency 8 (26.7) 21 (70) 7 (23.3)
Insufficient 1 (3.3) 3 (10) 12 (40)
Normal --- 1 (3.3) 10 (33.3)
Total 30 (100) 30 (100) 30 (100)

9. Study by
Nikibakhsh.Ahmadali,
Mahmoodzadeh.Hashem,Valizade
h.Mohammad
We suggest that children may benefit
from routine measurement of their
serum vitamin D levels at the time of
diagnosis and later on fallow-up visits
so an individual strategy for treatment
with vitamin D can be given.

10.  A daily dose of systemic steroids as low as 5 mg per day has
been shown to contribute to osteoporosis in adults .
 This is of concern in pediatric patients following a new
diagnosis of NS where steroid treatment protocols exceed
the dose at which adult osteoporosis risk increases with
repeated exposures to steroids during subsequent relapses
 Leonard MB, Zemel BS. Current concepts in pediatric bone
disease. Pediatr Clin N Am. 2002;49:143–173.

11.  Data suggest that, all children with incident NS had
25(OH)D deficiency at diagnosis and the majority
continued to have a deficiency at 2–4 months.
 Furthermore, supplemental vitamin D decreased the
odds of 25(OH)D deficiency, suggesting the need for
future interventional studies addressing vitamin D
supplementation in incident NS to evaluate optimal
vitamin D dosing and long-term impact in these
children.
 Selewski DT Vitamin D in incident nephrotic syndrome: a
Midwest Pediatric Nephrology Consortium study. Pediatric
Nephrology (Berlin, Germany), 22 Oct 2015, 31(3):465-472

12.  Short-term, high-dose glucocorticoid therapy decreases
the BMC of the lumbar spine in steroid-naïve children
with NS. Vitamin D and calcium co-administration not
only prevents this decline, but also enhances BMC of
the lumbar spine.
 The 1000 IU/day dose is marginally more effective than
400 IU/day and it is likely than an even larger dose is
required.
 Further research is required to assess the efficacy and
safety of vitamin D doses higher than 1000 IU/day.
 S Choudhary, Calcium and vitamin D for
osteoprotection in children with new-onset
nephrotic syndrome treated with steroids Pediatric
Nephrology, 2014,

13.  Vitamin D plus calcium therapy at the current doses(vitamin
D 40 0 IU plus calcium 1 g daily) reduces but does not
completely prevent bone loss, with no additional adverse
effects
 S Choudhary, Calcium and vitamin D for osteoprotection
in children with new-onset nephrotic syndrome treated
with steroids Pediatric Nephrology, 2014

14.  Several studies indicate a relationship between
hypovitaminosis D, survival, vascular calcification and
inflammation.
 In addition to its central role in the regulation of bone mineral
metabolism, vitamin D also contributes to other systems,
including the immune, cardiovascular and endocrine
systems.
 Vitamin D analogs reduces proteinuria, in particular through
suppression of the renin-angiotensin-aldosterone system
(RAAS) and exerts anti-inflammatory and immunomodulatory
effects.
 A Passantino, C Aloisi, V Cernaro, D Santoro New insights
on the role of vitamin D in the progression of renal
damage- Kidney and Blood …, 2013
 …,

15.  Vitamin D deficiency contribute to an inappropriately activated
RAAS, as a mechanism for progression of chronic kidney
disease (CKD) and/or cardiovascular disease.
 Vitamin D may interact with B and T lymphocytes and influence
the phenotype and function of the antigen presenting cells and
dendritic cells, promoting properties that favor the induction of
tolerogenic T regulators rather than T effectory.
 A Passantino, C Aloisi, V Cernaro, D Santoro New insights on
the role of vitamin D in the progression of renal damage-
Kidney and Blood …, 2013

16.  Interstitial fibrosis may be prevented through vitamin D
supplementation.
 It turns out that calcitriol effectively blocks myofibroblast
activation from interstitial fibroblasts, as evidenced by
suppression of TGF-β1-mediated α-SMA expression.
 A Passantino, C Aloisi, V Cernaro, D Santoro New insights
on the role of vitamin D in the progression of renal
damage- Kidney and Blood …, 2013

17.  previous studies confirmed that vitamin D receptors reduced
proteinuria, lessened the degree of glomerular sclerosis, and
exerted protective effects against kidney diseases by
inhibiting the renin angiotensin system, and having an anti-
inflammatory and anti-fibrotic effect.
 Supplementation with 1,25-vitamin D3or1,25-vitamin
D2prevented podocyte effacement or reversed glomerular
and tubulointerstitial damage in1,25-vitamin D3edeficient
animals, thereby preserving and restoring renal function,
respectively.
 Ramon Sonneveld 1,25-Vitamin D3 Deficiency Induces
Albuminuria Am J Pathol 2016 Apr;

18. vitamin B6
 Patients with the nephrotic syndrome have multiple risk factors for
thrombosis.
 Some reports indicate that they frequently have low circulating levels of
vitamin B6, which associate with a heightened risk for venous and
arterial thrombosis.
 GM Podda, F Lussana, G Moroni ,Abnormalities of homocysteine
and B vitamins in the nephrotic syndrome
 - Thrombosis research, 2007
 .

19. α-tocopherol and vitamin C,
 The combination of vitamins C and E had beneficial effects in endothelial-dependent
vasodilation and arterial stiffness.
 Thus, combination of α-tocopherol and vitamin C can be used in the clinical
management of pediatric idiopathic nephrotic syndrome.
 significant reduction in first-morning urine pro- tein:creatinine ratios in 10 of the 11
children with FSGS (the mean protein:creatinine ratio decreased from 9.7 to 4.1 .
 O Mellyana, R Widajat, N Sekarwana Combined supplementation
with α-tocopherol and vitamin C improves the blood pressure
of pediatric idiopathic nephrotic syndrome patients
 - Clinical Nutrition Experimental, 2019


21. Thanks