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201 active trials for Acute Kidney Injury

Acute Post-cardiac Surgery Renal Failure: Prevention Through Individualized Intensive Hemodynamic Management

BACKGROUND: The incidence of acute kidney injury (AKI) in patients undergoing cardiac surgery can reach 35% and between 2 and 5% require kidney replacement therapy during the AKI episode. The development of AKI n this context is independently associated with higher long-term mortality (5-10 years). In addition, there is strong evidence that an episode of AKI in the hospital increases the risk of developing chronic kidney disease in the medium-long term. On the other hand, once AKI has been recovered according to creatinine values, there are no established biomarkers to predict patients at risk of progression to chronic kidney disease, which will allow us to increase nephroprotection and surveillance measures in this group of patients. STUDY DESIGN: Open-label randomized unicentric prospective study of patients undergoing valvular replacement heart surgery ± coronary bypass with acute kidney injury (AKI) risk >30% according to the Leicester Cardiosurgery scale. Patients will be randomized 1:1 in two groups: standard hemodynamic management or intensive hemodynamic management based on premorbid mean perfusion pressure (MPP). The interventional period will span from intra-operation until the first 24 hours postoperative. The incidence of AKI will be evaluated according to KDIGO criteria between 48 hours and 7 days after surgery. Patients will be followed for one year. Biomarkers of mitochondrial damage will be analyzed at various points during the follow-up to patients presenting AKI. INTERVENTIONS: A) Group 1/Intensive management: Intra-surgical values of ± 25% basal MAP will be maintained and once in the ICU an algorithm corresponding to group 1 based on cardiac index and ± 25% MPP will be followed for 24 hours. B) Group 2/Standard management: MAP during surgery will be maintained > 60 mmHg according to usual protocol. Once in ICU, during the first 24 hours an algorithm corresponding to group 2 based on cardiac index, MAP and CVP will be followed. Biomarkers of mitochondrial damage will be determined in urine in patients in both groups only in patients developing AKI according to KDIGO guidelines between 48h and 7 days. EXPECTED RESULTS:A 50% reduction in the incidence of AKI in the intervention group compared to the control group is expected. At the same time, markers of mitochondrial damage are expected to be validated in our cohort as biomarkers of AKI progression and to investigate its usefulness as biomarkers of transition to Chronic kidney disease.

Start: October 2019
Chloride Transfer During Continuous Renal Replacement Therapy in the Intensive Care Unit: a Prospective Observational Cohort Study

Acute kidney injury (AKI) is a frequently encountered complication in the intensive care unit (ICU), affecting on average 25 to 35% of patients. It is associated with an increased mortality, proportional to AKI severity. RRT induces important shifts of water and electrolytes. Thus, significant amount of chloride might unintentionally be transferred to patients. Chloride is the main anion of the organism. It is involved in the regulation of numerous physiological processes. Thus, significant and rapid modification of chloride amount contained in the organism (as might be induced by renal replacement therapy) may be responsible for important, and potentially deleterious, consequences to critically ill patients. Studies have shown that the administration of high amounts of chloride rich solutions (such as sodium chloride (NaCl) 0,9%) was associated with the development of hyperchloremic acidosis in a dose-dependent manner. This hyperchloremic acidosis could also be theoretically associated with deleterious physiological effects. However, the true clinical consequences of administration of high amounts of chloride rich solutions remains unclear. Their effect on mortality remains a matter of debate, the results of studies being very conflicting in that respect. Nevertheless, hyperchloremia itself and/or the rise of chloremia in the intensive care unit seems to be associated with increased mortality. Moreover, the impact of those chloride rich solutions on the development of acute kidney injury is also a subject of controversy, data from the literature being here again very conflicting. A recent study already showed that continuous RRT (CRRT) techniques induce a significant transfer of sodium to patients benefiting from those techniques. In that study, the amount of sodium transferred depended mainly on the difference between patient's natremia and sodium concentration in dialysate and/or replacement fluid (usually higher than patient's natremia) used. By analogy, it is likely that an occult transfer of chloride also happens during RRT, given the high chloride concentration of dialysate fluids (in continuous veno-venous dialysis, CVVD) and replacement fluids (in continuous veno-venous hemofiltration, CVVH), or when these 2 modalities are combined (continuous veno-venous hemodiafiltration, CVVHDF). Finally, the investigators suspect, although it remains undemonstrated so far, that the RRT technique (convective vs. diffusive) may influence this transfer, to an unknown extent. Nevertheless, this transfer and its potential determinants have never been studied yet. If chloride overload (and its potential clinical consequences) induced by the administration of solutions such as NaCl 0,9% is being extensively studied, no study has ever focused on chloride transfer that may result from the use of renal replacement therapy. However, as mentioned above, it is very likely that such a chloride transfer to patients happens, and that its magnitude depends on different parameters such as RRT modality, RRT fluids characteristics, or patient's chloremia at the start of RRT. The investigators conduct the present study to describe and compare the intensity of chloride transfer during the first 24 hours of renal replacement therapy by continuous veno-venous hemofiltration (CVVH), continuous veno-venous hemodialysis (CVVD),or continuous veno-venous hemodiafiltration (CVVHDF), and to determine if that transfer is more important with one or the other of those two techniques, in ICU patients affected with severe AKI requiring RRT. Secondary aims are to describe and compare the effects of chloride transfer under 3 RRT modalities (CVVD, CVVH and CVVHDF) on patient's outcome, organ failures, electrolyte and acid-base balance, fluid balance and hemodynamics. Finally, the investigators aim to develop a pharmacokinetic compartment model of chloride transfer during different modalities of RRT.

Start: March 2021
Registry for HF20 for Pediatric CRRT Under Emergency Use Authorization

Historically, innovations for acute kidney injury (AKI) and continuous renal replacement therapy (CRRT) have centered around an adult population. However, research has shown that over 10% of pediatric patients develop severe AKI within the first week in an intensive care unit (ICU). When a pediatric patient requires renal replacement therapy for AKI in the ICU, CRRT is usually the modality of choice. The HF20™ is indicated for supporting patients weighing 8 to 20 kilograms, addressing a critical clinical need for critically ill children who require CRRT. Current US Food and Drug Administration (FDA) approved CRRT filters are designed for patients weighing more than 20 kg or less than 10 kg, leaving a gap in appropriately designed filters for pediatric patients. A previous trial in the US showed that the HF20™ is safe and effective, however the membrane composition of the HF20™ used in that trial is different than what is currently manufacturer and available. Baxter Healthcare Corporation has received an Emergency Use Authorization (EUA) for the currently available HF20™ to be used in the era of the COVID-19 pandemic, however participants do not need to be infected with the SAR-CoV-2 virus in order to be treated. The EUA for the HF20™ allows for treatment for any children weighing between 8 and 20 kilograms in need of CRRT. This registry will collect clinical data related to the safety and efficacy of the HF20™ filter for CRRT in pediatric patients weighing 8 to 20 kilograms at participating institutions, however participation in this registry is not a requirement in order to be treated with the HF20™ filter.

Start: January 2021
Dapagliflozin to Prevent the Incidence of Contrast Induced Nephropathy After Heart Catheterization and Percutaneous Coronary Intervention

Left heart catheterization and percutaneous coronary intervention (PCI) has become a useful tool in interventional cardiology, in which iodinated contrast media is used. Although the use of iodinated contrast media (CM) is considered to be safe in patients with normal renal function, it is risky in patients with known chronic renal insufficiency (CKD) and diabetes mellitus. Contrast induced nephropathy (CIN) remains one of the most leading causes of in hospital acute kidney injury (AKI), affecting morbidity and mortality. There are various mechanisms through which CM develop their nephrotoxic effects, including renal vasoconstriction and medullary hypoxia, tubular cell toxicity and reactive oxygen species formation. Inhibitors of type 2 sodium- glucose co-transporter (SGLT2i) is a relatively recent addition to the array of anti-diabetic agents, becoming part of everyday clinical practice. However, although SGLT2i were first used solely as antidiabetics because of their glycosuric effect, further research demonstrated that these drugs may independently reduce cardiovascular events, especially in patients with heart failure, a benefit that was consistent among diabetic and non-diabetic patients. Moreover, pleiotropic effects have been observed, including a reno-protective action. In addition to the effects mediated by intrarenal hemodynamic changes, SGLT2-i also have direct anti-inflammatory and antifibrotic nephroprotective effects. Indeed, SGLT2-i suppress the production of reactive oxygen species, lessening glomerulosclerosis and tubulo-interstitial fibrosis. These findings suggest that the use of SGLT2i could offer benefit by reducing/ preventing the nephrotoxic effects of contrast media leading to the assumption that the use of these drugs could prevent the incidence nephropathy after cardiac catheterization and percutaneous coronary intervention.

Start: April 2021