# Investigating the effect of dysregulated vitamin D metabolism on kidney development following preterm birth

> **NIH NIH R01** · UNIVERSITY OF VIRGINIA · 2024 · $727,889

## Abstract

PROJECT SUMMARY/ABSTRACT
Vitamin D deficiency is common in neonates born preterm and implicated the pathogenesis disease in several
organs, such as the lung and retina. In the kidney, vitamin D supplementation clearly prevents the loss of a
podocytes in animals with glomerular disease. The podocyte is a terminally differentiated cell vital to the integrity
of the glomerular filtration barrier, and podocyte loss leads to chronic kidney disease (CKD). Preterm birth is
associated with both increased podocyte loss and CKD. Despite the kidney being a major source for the active
form of vitamin D, little is known about either the effect of perinatal vitamin D deficiency on the developing kidney
or its association with long term kidney disease. The goal of this proposal is to understand the vitamin D pathway
in preterm neonates and the role of vitamin D in podocyte health in a preterm model. This goal is motivated by
our exciting observations of dysregulation of several components of vitamin D metabolism in a mouse model of
preterm birth. Preterm birth altered the expression of genes involved in vitamin D metabolism in the kidney
suggesting a local reduction of active form vitamin D (1,25 vitamin D) as well as decreased Nphs1 expression.
Nphs1 promotes podocyte differentiation, and its expression is regulated by vitamin D. The changes in gene
expression in the preterm kidneys support a novel mechanism for the lower podocyte number and CKD seen in
preterm neonates. We hypothesize that dysregulation of vitamin D metabolism (↓Cyp27b1, ↑Cyp24a1) in the
preterm kidney causes a local deficiency of 1,25 vitamin D, resulting in reduced Nphs1 expression, impaired
podocyte differentiation, deceased podocyte density and albuminuria. Potential therapeutic options to overcome
the vitamin D dysregulation in preterm neonates could include 1,25 vitamin D supplementation or maternal 25
vitamin D administration. To test our hypothesis, we propose two independent Aims investigating neonate and
maternal vitamin D dysregulation. In Aim 1, we will fully characterize vitamin D pathway by measuring systemic
and local (kidney) vitamin D metabolites along with a key regulators of vitamin D metabolism. To determine the
independent effect of activated vitamin D pathway on the podocyte, we will treat preterm mice just after birth with
active vitamin D or vitamin D antagonists. Our primary outcome will be albuminuria and secondary outcomes will
include podocyte density, urinary podocyte loss and glomerular number. We will assess the molecular
mechanisms by testing transcriptional changes at both single-cell and whole kidney resolution. In Aim 2, we will
determine the contribution of maternal vitamin D status on the kidney health of the offspring born preterm. We
will modify the vitamin D status of the dam with a vitamin D deficient diet or provide a high dose of 25 vitamin D
to the mother just before birth of the preterm pups to determine the effect on albuminuria in the offspring. ...

## Key facts

- **NIH application ID:** 10883022
- **Project number:** 1R01DK136989-01A1
- **Recipient organization:** UNIVERSITY OF VIRGINIA
- **Principal Investigator:** Jennifer R Charlton
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $727,889
- **Award type:** 1
- **Project period:** 2024-04-01 → 2028-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10883022

## Citation

> US National Institutes of Health, RePORTER application 10883022, Investigating the effect of dysregulated vitamin D metabolism on kidney development following preterm birth (1R01DK136989-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10883022. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*