Although most patients undergoing complex cardiac or vascular interventions tolerate contrast, some will develop contrast-induced acute kidney injury—which is associated with increased mortality. In this commentary, Philippe Garot and Andrew Roy review the aims and objectives of the ongoing STRENGTH (Study to evaluate the use of RenalGuard to protect patients at high risk of acute kidney injury) trial.
The use of iodinated contrast is common for most types of catheterisation procedures and although contrast is well tolerated in most patients, some may develop contrast-induced acute kidney injury. Acute kidney injury causes adverse systemic inflammatory effects, is associated with increased mortality, morbidity, hospital stays and costs, and may progress into chronic kidney disease. When it leads to end-stage renal failure that requires dialysis, two-year survival may be as low as 18.8%. Although the pathogenesis of the complication is complex, direct contrast media exposure causes cytotoxic and oxidative damage to renal tubular cells—resulting in hypoxia and vasoconstriction.
Strategies aimed at reducing acute kidney injury have traditionally focused on either prevention strategies for patients at risk (such as older patients, those with diabetes, those with chronic kidney disease, or patients who require high contrast volume) or pharmacological prevention using isotonic saline, sodium bicarbonate, or N-acetylcysteine. To date, no other pharmacological therapies have been shown in randomised trials to be superior to intravenous/oral hydration strategies at reducing the risk of acute kidney injury. Mechanistic studies have, however, suggested that increasing urine output to above 150mL/hour using loop diuretics could reduce the risk of the complication, as long as volume replacement and renal perfusion is maintained; thus, avoiding medullary ischaemia. This can be achieved with the use of frusemide-induced high urine output states in combination with the RenalGuard system (RenalGuard Solutions), which has been designed to deliver sterile replacement solution to a patient in an amount matched to the volume of urine produced by the patient. Therefore, the aim is to prevent hypovolaemia or fluid overload when a high urinary output is desired for at-risk patients receiving iodinated contrast and thus prevent acute kidney injury. Two recent studies—REMEDIAL (Renal insufficiency after contrast media administration) II and AKIGUARD (Acute kidney injury guarding device)—have shown promising results for RenalGuard. For example, AKIGUARD found that the system reduced the rate of a combined endpoint of acute kidney injury, reduced length of stay, and decreased rate of major adverse cardiac and cerebrovascular events (MACCE) at one year compared with standard therapy: 7% vs. 32%, respectively (p<0.001).
STRENTH is an ongoing randomised comparison of RenalGuard vs. conventional management in patients with chronic kidney disease undergoing complex percutaneous cardiac and vascular interventions, such as percutaneous coronary interventions (PCI), transcatheter aortic valve implantation (TAVI), and percutaneous closure of the left atrial appendage.
It is managed and monitored by European Cardiovascular Research Center (CERC) and the primary endpoint is to demonstrate superiority of RenalGuard over standard hydration for preventing moderate-to-severe acute kidney injury, which is defined as an increase in serum creatinine ≥0.3mg/dL and/or an increase of 25% of the basal value at day three or requirement for dialysis within five days after the procedure. Secondary endpoints include MACCE rates and sustained serum creatinine rises at 12 months. For patients to be included in the trial, they must have moderate-to-severe chronic kidney disease—defined as an estimated Glomerular Filtration Rate (eGFR) range from 15mL/min/m2 to 40mL/min/m2. Patients will not be included in the trial if they have had other diagnostic procedures requiring iodinated contrast within five days, require emergency procedures or primary PCI, have cardiogenic shock or hypoxaemia (SaO2 ≤90%), have been hospitalised within the last month for renal replacement therapy of any kind, or are anuric or intolerant of frusemide.
The recruitment target is 300 patients for the study, with a 12-month follow-up period, and is being carried out in six centres in Europe (Germany and France).
Philippe Garot and Andrew Roy are both at the Department of Cardiology, Institut Cardiovasculaire Paris Sud, Massy, France
The STENGTH study is sponsored by RenalGuard Solutions.