Activated Vitamin D for the Prevention and Treatment of Acute Kidney Injury

Phase 2

Completed

Brief Summary: The purpose of this study is to assess the efficacy of calcifediol (25-hydroxyvitamin D) and calcitriol (1,25-dihydroxyvitamin D) in preventing and reducing the severity of acute kidney injury (AKI) in critically ill patients.

Detailed Description: 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 acute kidney injury (AKI). Further, administration of 25D and 1,25D attenuates AKI in animal models. The purpose of this study is to assess if administration of 25D and 1,25D decreases the incidence and severity of AKI in critically ill patients.

Recruitment & Eligibility

Inclusion Criteria

Exclusion Criteria

Serum total calcium > 9.0 mg/dl or phosphate > 6.0 mg/dL within previous 48h
Currently receiving oral calcium supplementation
Ingestion of vitamin D3 >1,000 IU/day or any 25-hydroxyvitamin D or 1,25-dihydroxyvitamin D during the previous 7 days
AKI stage 2 or 3 (based on KDIGO serum creatinine and/or urine output criteria)
History of transplantation or receiving chronic (>7days) of immunosuppressive medications (not including glucocorticoid steroids at a dose less than or equivalent to prednisone 20 mg/day)
Neutropenia in the previous 48h
Active primary parathyroid disease, active granulomatous disease, or symptomatic nephrolithiasis in the previous 3 months
Receiving cytochrome P450 inhibitors
Chronic Kidney Disease stage V or End Stage Renal Disease
Hemoglobin < 7 g/dL
GI malabsorption
Prisoner
Pregnancy or breast feeding

Arm && Interventions

Group	Intervention	Description
Placebo	Placebos	Equal volume of medium chain triglyceride (MCT) oil orally daily x 5 days
Calcifediol	Calcifediol	Calcifediol 400mcg orally x 1, followed by 200mcg orally daily x 4
Calcitriol	Calcitriol	Calcitriol 4mcg orally daily x 5 days

Primary Outcome Measures

Name	Time	Method
Death Within 7 Days	7 days	All-cause mortality within 7 days following randomization
Number of Participants Who Received Renal Replacement Therapy Within 7 Days	7 days	Number of participants who received renal replacement therapy within 7 days following randomization
Relative Average Change in Serum Creatinine From Day 0 to Days 1-7	7 days	Average percentage change in serum creatinine assessed on days 1-7 as compared to day 0

Secondary Outcome Measures

Name	Time	Method
Number of Participants With New or Worsening Stage of AKI, Defined by KDIGO Guidelines	7 days	Any of the following: 1) an increase in serum creatinine ≥50% compared to the immediate pre-randomization value; 2) new or progressive stage of oliguria; or 3) receipt of renal replacement therapy. Oliguria stages 1, 2, and 3 are defined as urine output (UOP) \<0.5 ml/kg/h for 6-12h, \<0.5 ml/kg/h for \>12h, and \<0.3 ml/kg/h for ≥24h or anuria for ≥12h, respectively.
28-day Mortality	28 days	All-cause mortality assessed during the 28 days following randomization
ICU- and Hospital-free Days	28 days	28 minus the number of days in the ICU or hospital, with 0 assigned to patients who die before 28 days
Peak Serum Creatinine (mg/dl)	7 days	Highest serum creatinine value on days 1 to 7