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Kidney Week

Abstract: PO2522

Activated Vitamin D for the Prevention of AKI in Critically Ill Patients

Session Information

Category: Acute Kidney Injury

  • 102 AKI: Clinical, Outcomes, and Trials

Authors

  • Leaf, David E., Brigham and Women's Hospital, Boston, Massachusetts, United States
  • Waikar, Sushrut S., Boston University Medical Campus, Boston, Massachusetts, United States
Background

Decreased circulating levels of active vitamin D metabolites, including 25-hydroxyvitamin D (25D) and 1,25-dihydroxyvitamin D (1,25D), are common in critically ill patients, and lower levels are independently associated with a higher risk of AKI. Administration of 25D and 1,25D attenuates AKI in animal models. Randomized trials of vitamin D in critically ill patients have focused on inactive precursors (e.g., cholecalciferol), which may not be efficiently converted into 25D and 1,25D in this setting.

Methods

We conducted an NIH-funded, 3-arm, double-blind, randomized clinical trial using high doses of 25D and 1,25D in 150 critically ill patients at high risk of AKI. Patients were randomly assigned in a 1:1:1 ratio to receive 25D (oral calcifediol, 400µg on day 1 and 200µg on days 2-5), 1,25D (oral calcitriol, 4ug daily for 5 days), or placebo. The primary outcome was a composite global rank endpoint of death, dialysis, or relative average increase in serum creatinine within 7 days.

Results

Among the 150 patients enrolled, the median age was 65 years (IQR, 52-72), 61% were male, 83% were intubated, and 57% were receiving vasopressors at randomization. The median time from ICU admission to randomization was 1 day (IQR, 1-2). Median levels of 25D and 1,25D at randomization were 17 ng/ml (IQR, 10-26) and 27 pg/ml (IQR, 18-39), and increased to 57 ng/ml (IQR, 53-67) and 91 pg/ml (IQR, 66-122) in the 25D and 1,25D groups, respectively. Neither the primary nor secondary endpoints differed between groups (Table). Longitudinal plasma and urinary KIM-1 levels were also similar between groups. No safety concerns were identified.

Conclusion

Administration of activated vitamin D metabolites did not improve renal outcomes among critically ill patients.

Outcomes
 25D
(n=51)
1,25D
(n=50)
Placebo
(n=49)
P-value (25D vs. Placebo)P-value (1,25D vs. Placebo)
Primary Composite Endpoint   0.85*0.58*
Death - no. (%)4 (7.8)9 (18.0)6 (12.2)0.460.42
RRT - no. %)1 (2.0)1 (2.0)4 (8.2)0.150.16
Relative Average Increase in SCr (%) – median [IQR]-2.3 [-20.7, 18.3]-7.1 [-18.1, 12.3]-7.4 [-21.5, 10.4]0.440.29
Secondary Endpoints     
Stage 2 or 3 AKI - no. (%)18 (35.3)21 (42.0)14 (28.6)0.470.16
RRT or death - no. (%)5 (9.8)10 (20.0)10 (20.4)0.140.96
Peak SCr, mg/dl - median [IQR]1.2 [0.8, 1.5]1.3 [0.8, 1.9]1.2 [0.9, 1.8]0.440.86
28-day mortality - no. (%)10 (19.6)16 (32.0)10 (20.4)0.920.19

Unless otherwise specified, outcomes above were assessed within 7 days following randomization. *Composite P value based on global rank endpoint.

Funding

  • NIDDK Support