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Publication year
2016Source
American Journal of Pathology, 186, 4, (2016), pp. 794-804ISSN
Publication type
Article / Letter to editor
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Organization
Nephrology
Physiology
Pathology
Journal title
American Journal of Pathology
Volume
vol. 186
Issue
iss. 4
Page start
p. 794
Page end
p. 804
Subject
Radboudumc 11: Renal disorders RIHS: Radboud Institute for Health Sciences; Radboudumc 11: Renal disorders RIMLS: Radboud Institute for Molecular Life SciencesAbstract
Vitamin D plays an important role in renal (patho)physiology. Patients with glomerular diseases have an injured renal filtration barrier, leading to proteinuria and reduced renal function. An impaired renal function also leads to 1,25-vitamin D3 deficiency as a result of reduced renal 1alpha-hydroxylase activity. Vitamin D treatment to reduce proteinuria remains controversial, although there is an inverse correlation between vitamin D levels and proteinuria. Herein, we showed that 1,25-vitamin D3-deficient 25-hydroxy-vitamin-D3-1alpha-hydroxylase knockout mice and 1,25-vitamin D3-deficient rats develop podocyte injury and renal dysfunction. Glomerular injury was characterized by proteinuria and partial podocyte foot process effacement. Expression of nephrin, podocin, desmin, and transient receptor potential channel C6 in the podocyte was significantly altered in 1,25-vitamin D3-deficient animals. Supplementation with 1,25-vitamin D3 or 1,25-vitamin D2 prevented podocyte effacement or reversed glomerular and tubulointerstitial damage in 1,25-vitamin D3-deficient animals, thereby preserving and restoring renal function, respectively. The effect of 1,25-vitamin D3 deficiency and 1,25-vitamin D3 and 1,25-vitamin D2 repletion on proteinuria could not be explained by hypocalcemia, changes in parathyroid hormone, or fibroblast growth factor 23. This study demonstrates that 1,25-vitamin D3 deficiency directly leads to renal injury in rodents. Translated to human subjects, this would underline the need for early vitamin D supplementation in patients with glomerular disease and chronic renal insufficiency, which might inhibit or potentially reverse renal injury.
This item appears in the following Collection(s)
- Academic publications [238441]
- Electronic publications [122544]
- Faculty of Medical Sciences [90373]
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