Exploring the Relationship Between Mitochondrial Health and Hemodynamic Instability Related to Renal Replacement Therapy in Critically Ill Patients
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Change in mean arterial pressure (MAP)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •>/=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.
排除标准
- •Prior kidney transplant;
- •Prior nephrectomy;
- •Any RRT in the previous year;
- •Baseline estimated glomerular filtration rate (eGFR) <15ml/min/1.73m2.
结局指标
主要结局
Change in mean arterial pressure (MAP)
时间窗: 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.
次要结局
- Frequency of HIRRT(24 months)
研究者
Edward Clark
Clinical investigator
Ottawa Hospital Research Institute