Search

Aims The combined prophylactic strategy of sodium bicarbonate plus N-acetylsyteine (NAC) seems to be effective in preventing contrast induced acute kidney injury (CI-AKI) in patients at low-to-medium risk. However, in patients at high and very high risk the rate of CI-AKI is still high. In this subset of patients the anticipated advantages of the RenalGuard(tm) System should be investigated. The RenalGuard(tm) System (PLC Medical Systems, Inc., Franklin, MA, USA) is a real-time measurement and real time matched fluid replacement device designed to accommodate the RenalGuard therapy, which is based on the theory that creating and maintaining a high urine output is beneficial by allowing a quick elimination of contrast media, and, therefore, reducing its toxic effects. Methods and results The REMEDIAL II trial is a randomised, multicentre, investigator-sponsored trial addressing the hypothesis that the RenalGuard System is superior to the prophylaxis with sodium bicarbonate infusion plus NAC in preventing CI-AKI in high and very high risk patients. Consecutive patients with chronic kidney disease (CKD) and at high to very high risk for CI-AKI, referred to our institutions for coronary and/or peripheral procedures, will be randomly assigned to 1) prophylactic administration of sodium bicarbonate plus NAC (control group) and 2) RenalGuard System treatment (RenalGuard group). All enrolled patients must have an estimated glomerular filtration rate ≤ 30 ml/min/1.73 m2 and/or a contrast nephropathy risk score ≥ 11. In all cases iodixanol (an iso-osmolar, non-ionic contrast agent) will be administered. The primary endpoint is an increase of ≥ 0.3 mg/dL in the serum creatinine concentration 48 hours after the procedure. Conclusions The REMEDIAL II trial will give important answers on how to prevent CI-AKI in high and very high risk patients undergoing contrast media exposure.

BACKGROUND: High urine flow rate (UFR) has been suggested as a target for effective prevention of contrast-induced acute kidney injury (CI-AKI). The RenalGuard therapy (saline infusion plus furosemide controlled by the RenalGuard system) facilitates the achievement of this target. METHODS: Four hundred consecutive patients with an estimated glomerular filtration rate ≤30 mL/min per 1.73 m(2) and/or a high predicted risk (according to the Mehran score ≥11 and/or the Gurm score >7%) treated by the RenalGuard therapy were analyzed. The primary end points were (1) the relationship between CI-AKI and UFR during preprocedural, intraprocedural, and postprocedural phases of the RenalGuard therapy and (2) the rate of acute pulmonary edema and impairment in electrolytes balance. RESULTS: Urine flow rate was significantly lower in the patients with CI-AKI in the preprocedural phase (208 ± 117 vs 283 ± 160 mL/h, P < .001) and in the intraprocedural phase (389 ± 198 vs 483 ± 225 mL/h, P = .009). The best threshold for CI-AKI prevention was a mean intraprocedural phase UFR ≥450 mL/h (area under curve 0.62, P = .009, sensitivity 80%, specificity 46%). Performance of percutaneous coronary intervention (hazard ratio [HR] 4.13, 95% CI 1.81-9.10, P < .001), the intraprocedural phase UFR 0.32 mg/kg (HR 5.03, 95% CI 2.33-10.87, P < .001) were independent predictors of CI-AKI. Pulmonary edema occurred in 4 patients (1%). Potassium replacement was required in 16 patients (4%). No patients developed severe hypomagnesemia, hyponatremia, or hypernatremia. CONCLUSIONS: RenalGuard therapy is safe and effective in reaching high UFR. Mean intraprocedural UFR ≥450 mL/h should be the target for optimal CI-AKI prevention.

Background— The role of statins in the prevention of contrast-induced acute kidney injury (CIAKI) is controversial. Methods and Results— First, we investigated the in vivo effects of atorvastatin on CIAKI. Patients with chronic kidney disease enrolled in the Novel Approaches for Preventing or Limiting Events (NAPLES) II trial were randomly assigned to (1) the atorvastatin group (80 mg within 24 hours before contrast media [CM] exposure; n=202) or (2) the control group (n=208). All patients received a high dose of N -acetylcysteine and sodium bicarbonate solution. Second, we investigated the in vitro effects of atorvastatin pretreatment on CM-mediated modifications of intracellular pathways leading to apoptosis or survival in renal tubular cells. CIAKI (ie, an increase >10% of serum cystatin C concentration within 24 hours after CM exposure) occurred in 9 of 202 patients in the atorvastatin group (4.5%) and in 37 of 208 patients in the control group (17.8%) ( P =0.005; odds ratio=0.22; 95% confidence interval, 0.07–0.69). CIAKI rate was lower in the atorvastatin group in both diabetics and nondiabetics and in patients with moderate chronic kidney disease (estimated glomerular filtration rate, 31–60 mL/min per 1.73 m 2 ). In the in vitro model, pretreatment with atorvastatin (1) prevented CM-induced renal cell apoptosis by reducing stress kinases activation and (2) restored the survival signals (mediated by Akt and ERK pathways). Conclusions— A single high loading dose of atorvastatin administered within 24 hours before CM exposure is effective in reducing the rate of CIAKI. This beneficial effect is observed only in patients at low to medium risk.

Background— Neutrophil gelatinase–associated lipocalin (NGAL) is an early marker of acute kidney injury (AKI). Methods and Results— Urine NGAL and serum NGAL (sNGAL) were assessed at 2, 6, 24, and 48 hours after contrast media (CM) exposure in 458 high-risk patients (development set). Optimal thresholds in predicting contrast-induced AKI (serum creatinine [sCr] increase ≥0.3 mg/dL at 48 hours after CM administration) were identified. Major adverse events (MAE; death, dialysis, nonfatal myocardial infarction, sustained kidney injury, and myocardial revascularization) at 1 year were assessed. In the development set, optimal thresholds for contrast-induced AKI occurred at 6 hours for both urine NGAL (≥20 ng/mL; 97% negative predictive value and 27% positive predictive value) and sNGAL (≥179 ng/mL; 93% negative predictive value and 20% positive predictive value). Furthermore, sNGAL ≥179 ng/mL at 6 hours was an independent predictor of 1-year MAE. 1-year MAE occurred in 27/198 patients (13.5%) with sNGAL Conclusions— Urine NGAL Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT01098032.