Exploring the Relationship Between Mitochondrial Health and Hemodynamic Instability Related to Renal Replacement Therapy in Critically Ill Patients
Trial Snapshot
- Phase
- Not Applicable
- Status
- Recruiting
- Enrollment
- 60
- Locations
- 1
- Primary Endpoint
- Change in mean arterial pressure (MAP)
Study Overview
Brief Summary
Renal replacement therapy is a life-saving treatment for patients who have sudden and severe kidney failure. However, some of these patients blood pressure who receive this treatment could become unstable, thus resulting in more injuries to their kidneys and may limit the ability of kidney recovery. In order to mitigate the instability in blood pressure, the mitochondrial functions should be studied. Mitochondria are organelles within our bodies' cells that serve as the main source of energy for cell function. Kidney cells have many of these organelles and when they are damaged, it could contribute to kidney disease. At this time, it is not known whether boosting mitochondria health and function in humans could reduce the harm of instability in blood pressure.
This research study is being done to try to explore the impact of HIRRT on mitochondria health and kidney recovery by assessing critically ill patients with AKI who are undergoing SLED treatment in ICU at The Ottawa Hospital.
Detailed Description
BACKGROUND:
Acute kidney injury (AKI) that requires renal replacement therapy (RRT) affects 2% of all hospitalized patients and 15% of those admitted to ICU. Non-recovery of kidney function and consequent long-term dialysis-dependence, has a profoundly negative impact on patients' health and quality of life.
While RRT is life-saving treatment for severe AKI, hemodynamic instability related to RRT (HIRRT) occurs frequently during all forms of RRT used in ICU. For slow low-efficiency dialysis (SLED), the RRT modality used for hemodynamically unstable patients at The Ottawa Hospital, HIRRT occurs during up to 86% of treatments. HIRRT may cause repetetive ischemia-reperfusion injury (IRI) to patients' already injured kidneys and may limit kidney recovery.
At the cellular level, after IRI, there is pronounced loss and dysfunction of mitochondria. Mitochondria are the organelles that serve as the primary source of energy to maintain cellular function. Their depletion and dysfunction results in the evolution of AKI to fibrosis and limits recovery of kidney function. The health of mitochondria depends greatly on a metabolite called nicotinamide adenine dinucleotide (NAD+). Animal studies and a recent phase 1 trial suggest that boosting NAD+ is a promising strategy to attenuate cardiac and kidney IRI. One potential NAD+ booster, nicotinamide riboside (NR), a NAD+ precursor, has an excellent safety profile after having undergone testing in multiple human trials for other indications.
Our group's recent systematic review found that few studies have assessed interventions to mitigate HIRRT in critically ill patients and that none targeted or assessed mitochondrial function. Whether boosting mitochondrial function is a truly a promising strategy for mitigating the harms of HIRRT depends on several unknowns. It remains to be determined if baseline levels of NAD+ and NAD+-related biomarkers (NRBs) in patients starting RRT are diminished and if these levels are affected by HIRRT.
Study Design
- Study Type
- Observational
- Observational Model
- Cohort
- Time Perspective
- Prospective
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •>/=18 years;
- •Diagnosis of stage 3 AKI per Kidney Disease Improving Global Outcomes (KDIGO) AKI guidelines;
- •Starting SLED as first RRT received during current hospitalization.
Exclusion Criteria
- •Prior kidney transplant;
- •Prior nephrectomy;
- •Any RRT in the previous year;
- •Baseline estimated glomerular filtration rate (eGFR) <15ml/min/1.73m2.
Outcomes
Primary Outcomes
Change in mean arterial pressure (MAP)
Time Frame: 24 months
Decline in MAP \>=20 mmHg from the start of SLED or initiation of/increased dose of vasopressors required during SLED, occurring once or more during the SLED session.
Secondary Outcomes
- Frequency of HIRRT(24 months)
Investigators
Edward Clark
Clinical investigator
Ottawa Hospital Research Institute