Abstract: PO2522
Activated Vitamin D for the Prevention of AKI in Critically Ill Patients
Session Information
- Late-Breaking Clinical Trials Posters
November 04, 2021 | Location: On-Demand, Virtual Only
Abstract Time: 10:00 AM - 12:00 PM
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) | 0.46 | 0.42 |
| RRT - no. %) | 1 (2.0) | 1 (2.0) | 4 (8.2) | 0.15 | 0.16 |
| 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] | 0.44 | 0.29 |
| Secondary Endpoints | |||||
| Stage 2 or 3 AKI - no. (%) | 18 (35.3) | 21 (42.0) | 14 (28.6) | 0.47 | 0.16 |
| RRT or death - no. (%) | 5 (9.8) | 10 (20.0) | 10 (20.4) | 0.14 | 0.96 |
| Peak SCr, mg/dl - median [IQR] | 1.2 [0.8, 1.5] | 1.3 [0.8, 1.9] | 1.2 [0.9, 1.8] | 0.44 | 0.86 |
| 28-day mortality - no. (%) | 10 (19.6) | 16 (32.0) | 10 (20.4) | 0.92 | 0.19 |
Unless otherwise specified, outcomes above were assessed within 7 days following randomization. *Composite P value based on global rank endpoint.
Funding
- NIDDK Support