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The Role of Vitamin D in Modulating the Innate Immune Response in Children with Vesicoureteral Reflux
Marius-Cosmin Colceriu1,2, Diana Jecan-Toader2,3, Paul Luchian Aldea4
1Discipline of Physiology, Department of Functional Biosciences, "Iuliu Hațieganu" University of Medicine and Pharmacy, 400006 Cluj-Napoca, Romania.
Insights
Vitamin D influences urinary tract infections (UTIs) and reflux nephropathy (RN) by affecting antimicrobial peptide (AMP) expression, particularly LL-37. Low vitamin D levels correlate with increased UTIs and potential RN development in pediatric VUR patients.
Area of Science:
- Pediatric Nephrology
- Immunology
- Nutritional Science
Background:
- Vitamin D plays a role in innate immunity and inflammation via antimicrobial peptide (AMP) expression.
- Urinary tract infections (UTIs) and reflux nephropathy (RN) are significant concerns in pediatric populations.
- Vesicoureteral reflux (VUR) is a key risk factor for recurrent UTIs and RN.
Purpose of the Study:
- To evaluate the role of vitamin D in pediatric patients with VUR.
- To investigate the association between vitamin D status and recurrent UTIs and reflux scarring (RS).
- To explore the relationship between vitamin D and urinary markers of innate immune function (LL-37, NGAL, IL-6).
Main Methods:
- Cross-sectional observational study of 25 pediatric VUR patients.
- Assessment of serum vitamin D levels.
- Correlation analysis with recurrent UTIs, RS, and urinary LL-37, NGAL, and IL-6 levels.
Main Results:
- 12% of patients had vitamin D deficiency and 20% had insufficient levels.
- Low vitamin D levels were associated with more frequent acute pyelonephritis (APNs) and reflux scarring (RS).
- A strong positive correlation was found between vitamin D levels and urinary LL-37 concentration.
Conclusions:
- Vitamin D status appears to influence UTI frequency and the development of reflux scarring (RS) in pediatric VUR patients.
- The primary mechanism involves modulation of LL-37 secretion, impacting innate immunity.
- Findings suggest a potential role for vitamin D in the pathophysiology of reflux nephropathy (RN).
Abstract:
Background: Vitamin D, through its role in antimicrobial peptide (AMP) expression, may influence innate immunity and inflammation in urinary tract infections (UTIs). This study evaluated its role in patients with vesicoureteral reflux (VUR) and its contribution to the pathophysiology of reflux nephropathy (RN). Methods: We conducted a cross-sectional observational study of 25 pediatric patients with VUR, representing a subgroup analysis of a larger cohort examined in a previous study. We determined patients' vitamin D status, correlated it with recurrent UTIs and RS, and explored its relationship with urinary LL-37, NGAL, and IL-6 levels as markers of innate immune function. Results: Serum vitamin D levels ranged from 10.7 to 123.2 ng/mL (mean 39.5 ng/mL); 12% had deficiency and 20% had insufficient levels. Low vitamin D levels were detected in patients with more than five acute pyelonephritis (APNs), with a mean value classified as insufficient (27.3 ng/mL). Patients with RS had a lower mean vitamin D level compared to those without (30.51 ng/mL vs. 41.23 ng/mL), though the difference was not statistically significant (p = 0.39). No significant associations were found between vitamin D and urinary IL-6 or NGAL levels. A strong positive correlation was observed between vitamin D and urinary LL-37/creatinine (r = 0.78, r2 = 0.61). Conclusions: Vitamin D appears to influence the frequency of UTIs and the development of RS, primarily by modulating LL-37 secretion, suggesting a possible role in the pathophysiology of RN.
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