Kidney Week

Abstract: FR-PO0503

Effect of High-Dose Cholecalciferol on Mortality in Patients on Dialysis: Results of the SIMPLIFIED Trial

Session Information

• CKM: Clinical - Trials, Epidemiology, and Biomarkers
  October 23, 2026 | Location: Exhibit Hall A, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Cardiovascular-Kidney-Metabolic Health

• 602 Cardiovascular-Kidney-Metabolic Health: Clinical

Authors

• Smith, Rona M., University of Cambridge, Cambridge, England, United Kingdom

Rona M. Smith, MD, MBBS

• Cui, Molly, University of Cambridge, Cambridge, England, United Kingdom

Molly Cui, PhD

• Caskey, Fergus, University of Bristol, Bristol, England, United Kingdom

Fergus Caskey, MD, MBChB

• Chaudhry, Afzal, Epic Systems Corporation, Cambridge, United Kingdom

Afzal Chaudhry, MA, MBBS, PhD

• Cunningham, John, University College London, London, England, United Kingdom

John Cunningham, MD

• Humphrey, Toby, Cambridge University Hospitals NHS Foundation Trust, Cambridge, England, United Kingdom

Toby Humphrey, MBBS, PhD

• Mitra, Sandip, Manchester University NHS Foundation Trust, Manchester, England, United Kingdom

Sandip Mitra, MD, MBBS

• Schoenmakers, Inez, University of East Anglia, Norwich, England, United Kingdom

Inez Schoenmakers, MSc, PhD

• Wagner, Adam P., University of East Anglia, Norwich, England, United Kingdom

Adam P. Wagner, MA, MSc, PhD

• Wheeler, David C., University College London, London, England, United Kingdom

David C. Wheeler, MD

• Wilkinson, Ian, University of Cambridge, Cambridge, England, United Kingdom

Ian Wilkinson, MA

• Wilson, Edward C F, University of Exeter, Exeter, England, United Kingdom

Edward C F Wilson, PhD

• Yahia, Amer, Cambridge University Hospitals NHS Foundation Trust, Cambridge, England, United Kingdom

Amer Yahia, MBBS

• Bond, Simon, University of Cambridge, Cambridge, England, United Kingdom

Simon Bond, PhD

• Hiemstra, Thomas, Cambridge University Hospitals NHS Foundation Trust, Cambridge, England, United Kingdom

Thomas Hiemstra, MD, PhD

Group or Team Name

• On behalf of SIMPLIFIED investigators

Background

Survival for patients on dialysis is poor with 50% alive after 5 years. Vitamin D deficiency is common in patients with end stage kidney disease and a predictor of death from cardiovascular disease, infection and cancer. Trials of vitamin D supplementation in the general population have failed to improve outcomes. However, contemporary CKD treatment guidelines recommend vitamin D₃ (cholecalciferol) replacement. The impact of vitamin D supplementation on outcomes in dialysis patients is unknown.

Methods

The SIMPLIFIED trial randomised adult dialysis patients 1:1 to open-label high-dose oral cholecalciferol (60,000IU every 2 weeks) or standard of care (SOC). Primary endpoint was all-cause mortality. The study employed a pragmatic design and trial outcomes were captured using existing data sources including Office of National Statistics for deaths and Hospital Episode Statistics for secondary endpoints.

Results

3866 patients (1940 cholecalciferol; 1926 SOC) were randomised between March 2017 and July 2025 at 55 UK renal units. Baseline characteristics were balanced between arms (Table 1). Death occurred in 881 cholecalciferol versus 936 SOC participants HR 0.94 (95%CI 0.86-1.04); p=0.22 Figure 1A). Median survival was 5.06 years (4.71-5.34) versus 4.78 years (4.48-5.05) in the cholecalciferol versus SOC groups respectively. There was treatment effect heterogeneity for death by gender (interaction p=0.02) and ethnicity (interaction p=0.01); estimated HRs of 0.88 (0.79–0.99) in males and 0.70 (0.55–0.91) in non-white participants, favouring cholecalciferol (Figure 1B).

Conclusion

Overall high dose cholecalciferol did not reduce mortality but was safe and did offer a survival benefit in male and ethnic minority patients on dialysis over standard of care.

Table1:Baseline demographics

Funding

• Government Support – Non-U.S.