Supplementary Material for: Vitamin D status and treatment in ESKD; links to improved CKD-MBD laboratory parameters in a real-world setting

Introduction: Vitamin D insufficiency is common in patients who receive hemodialysis yet there is no clear guidance regarding surveillance or treatment. We hypothesized that increasing 25(OH)D3 levels is associated with lower phosphate, parathyroid hormone (PTH) and alkaline phosphatase (ALP).

Methods: Baseline 25(OH)D3 level was measured in all patients receiving in-centre hemodialysis in June, 2017. Laboratory parameters were measured every 6 (phosphate, calcium) or 12 weeks (25(OH)D3, PTH, ALP) until February, 2021. In September, 2018 a treatment algorithm of 50,000 IU weekly until sufficient, followed by 50,000 IU monthly was suggested. Generalized linear mixed regression models including linear spline effects, a log link function, and random effects were used to examine the impact of increasing 25(OH)D3 levels on calcium, phosphate, ALP and PTH.

Results: Of 697 participants, 15% and 57% had vitamin D deficiency (25(OH)D3 < 25 nmol/L) and insufficiency (between 25 and 74 nmol/L). Incorporating up to 7272 observations, increasing 25(OH)D3 was associated with significantly decreasing PTH for 25(OH)D3 levels between 25 and 75 nmol/L regardless of vitamin D treatment. In an interaction model, the negative slope between 25(OH)D3 and PTH remained significant beyond 75 nmol/L in the absence of calcitriol. Increasing 25(OH)D3 was associated with significantly decreasing phosphate for 25(OH)D3 levels between 25 and 75nmol/L regardless of vitamin D treatment, and below 25 nmol/L in values of untreated patients. Calcium increased across the spectrum of 25(OH)D3 regardless of vitamin D treatment. 0.2% of 25(OH)D3 levels exceeded 250 nmol/L and 2.1% of calcium levels exceeded the normal range.

Conclusions: Vitamin D treatment in a real-world setting was safe and associated with lower PTH levels. Whether improved biochemical markers translate to a reduction in