Farzaneh Futuhi
1 
, Zahra Sahraei
2 , Behzad Azimi
3* 1 Department of Adult Nephrology, School of Medicine, Loghman Hakim Hospital, Shahid, Beheshti University of Medical Sciences, Tehran, Iran
2 Department of Clinical Pharmacy, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran
3 Department of General and Vascular Surgery, School of Medicine, Imam Hossein Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Abstract
Chronic kidney disease (CKD) is commonly accompanied by vitamin D deficiency, largely due to impaired renal conversion of 25-hydroxyvitamin D [25(OH)D] to its biologically active form, 1,25-dihydroxyvitamin D [1,25(OH)₂D]. In addition to its classical role in calcium–phosphate homeostasis and bone metabolism, vitamin D exerts multiple extra-skeletal effects, including modulation of renal function, cardiovascular health, and endocrine pathways, primarily through activation of the vitamin D receptor (VDR) and suppression of the renin–angiotensin–aldosterone system (RAAS). This narrative review synthesizes current evidence on the impact of vitamin D supplementation encompassing nutritional forms (cholecalciferol and ergocalciferol) and active or analog forms (calcitriol, paricalcitol, and calcifediol) on proteinuria, CKD progression, and cardiovascular outcomes. A targeted literature search was conducted across PubMed, Web of Science, Scopus, DOAJ, and Google Scholar. Evidence from multiple randomized trials and meta-analyses indicates that active vitamin D analogues, particularly paricalcitol, are associated with consistent reductions in proteinuria among patients with CKD. Nutritional vitamin D, especially cholecalciferol, has also demonstrated potential antiproteinuric effects in selected populations. Observational data consistently show that vitamin D deficiency is independently associated with accelerated decline in estimated glomerular filtration rate (eGFR) and increased risk of progression to end-stage renal disease (ESRD); however, interventional studies have not conclusively demonstrated that vitamin D supplementation slows CKD progression. Similarly, while observational studies link low vitamin D levels with increased cardiovascular morbidity and higher mortality, randomized trials have not consistently shown significant improvements in major cardiovascular outcomes. Overall, vitamin D supplementation, particularly active analogues, appears beneficial for proteinuria reduction. Still, its effects on renal disease progression and cardiovascular endpoints remain uncertain, underscoring the need for larger clinical trial studies.
Implication for health policy/practice/research/medical education:
Vitamin D deficiency is common in chronic kidney disease (CKD) due to impaired renal activation. It contributes to adverse renal and cardiovascular outcomes through mechanisms involving vitamin D receptor (VDR) signaling and suppression of the renin–angiotensin–aldosterone system. Evidence that active vitamin D analogues, particularly paricalcitol, consistently reduce proteinuria, while nutritional vitamin D (especially cholecalciferol) may also provide antiproteinuric benefits in selected populations. Studies show that vitamin D deficiency is independently correlated to more decrease in estimated glomerular filtration rate (eGFR) and increased risk of end-stage renal disease (ESRD); however, interventional trials have not conclusively demonstrated that supplementation slows CKD progression. Similarly, although low vitamin D levels are consistently linked to higher cardiovascular morbidity and mortality, randomized evidence has not confirmed significant improvements in major cardiovascular outcomes, highlighting the need for large, well-designed trials with clinically meaningful endpoints.
Please cite this paper as: Futuhi F, Sahraei Z, Azimi B. Vitamin D supplementation in chronic kidney disease; effects on proteinuria, disease progression, and cardiovascular outcomes. J Nephropharmacol. 2026;15(2):e12882. DOI: 10.34172/npj.12882.