Navigating nephrotoxic waters: A comprehensive overview of contrast-induced acute kidney injury prevention.

Contrast-induced acute kidney injury (CI-AKI) is the third leading cause of acute kidney injury deriving from the intravascular administration of contrast media in diagnostic and therapeutic procedures and leading to longer in-hospital stay and increased short and long-term mortality. Its pathophysiology, although not well-established, revolves around medullary hypoxia paired with the direct toxicity of the substance to the kidney. Critically ill patients, as well as those with pre-existing renal disease and cardiovascular comorbidities, are more susceptible to CI-AKI. Despite the continuous research in the field of CI-AKI prevention, clinical practice is based mostly on periprocedural hydration. In this review, all the investigated methods of prevention are presented, with an emphasis on the latest evidence regarding the potential of RenalGuard and contrast removal systems for CI-AKI prevention in high-risk individuals.

Effect of periprocedural furosemide-induced diuresis with matched isotonic intravenous hydration in patients with chronic kidney disease undergoing transcatheter aortic valve implantation.

BACKGROUND: Acute kidney injury (AKI) after transcatheter aortic valve implantation (TAVI) is a serious complication which is associated with increased mortality. The RenalGuard system was developed to reduce the risk of AKI after contrast media exposition by furosemide-induced diuresis with matched isotonic intravenous hydration. The aim of this study was to examine the effect of the RenalGuard system on the occurrence of AKI after TAVI in patients with chronic kidney disease. METHODS: The present study is a single-center randomized trial including patients with severe aortic valve stenosis undergoing TAVI. Overall, a total of 100 patients treated by TAVI between January 2017 and August 2018 were randomly assigned to a periprocedural treatment with the RenalGuard system or standard treatment by pre- and postprocedural intravenous hydration. Primary endpoint was the occurrence of AKI after TAVI, and secondary endpoints were assessed according to valve academic research consortium 2 criteria. RESULTS: Overall, the prevalence of AKI was 18.4% (n = 18). The majority of these patients developed mild AKI according to stage 1. Comparing RenalGuard to standard therapy, no significant differences were observed in the occurrence of AKI (RenalGuard: 21.3%; control group: 15.7%; p = 0.651). In addition, there were no differences between the groups with regard to 30-day and 12-month mortality and procedure-associated complication rates. CONCLUSION: In this randomized trial, we did not detect a reduction in AKI after TAVI by using the RenalGuard system. A substantial number of patients with chronic kidney disease developed AKI after TAVI, whereas the majority presented with mild AKI according to stage 1 (ClinicalTrials.gov number NCT04537325).

Forced Diuresis with Matched Isotonic Intravenous Hydration Prevents Renal Contrast Media Accumulation.

The accumulation of contrast media in the kidneys might lead to contrast-induced acute kidney injury. In this prospective, controlled observational study, we aimed to evaluate whether forced diuresis with matched isotonic intravenous hydration prevents the accumulation of contrast media in the kidneys of patients undergoing cardiac interventional procedures. We compared the intensity of contrast media accumulation as observed in nephrograms following these procedures, with and without peri-procedural controlled renal flushing. The study group consisted of 25 patients with impaired renal function treated with the RenalGuard system. The two control groups included 25 patients with normal kidney function and 8 patients with impaired renal function undergoing similar procedures with routine pre-procedural hydration, but without controlled renal flushing. Renal contrast media accumulation at the end of each procedure was scored by blinded cardiologists. The renal contrast accumulation score (CAS) in the study group was significantly lower, with a median score of 0 (IQR (0-0)) compared with 1.5 (IQR (1-2)) in the normal renal function control group and 1 (IQR (0.38-1.62)) in the impaired renal function control group (p < 0.001 and 0.003, respectively). In a multivariate analysis of CAS, RenalGuard treatment was independently associated with lower CAS compared to both control groups. In conclusion, RenalGuard use prevents renal contrast accumulation in patients with impaired renal function undergoing cardiac procedures with intra-arterial contrast media injection.

[Monocentric experience of the RenalGuard® system to limit post-contrast acute kidney injury in patients at high-risk undergoing interventional coronary procedures]. / Expérience monocentrique du système RenalGuard® pour limiter l'insuffisance rénale aiguë post-contraste après une procédure coronaire interventionnelle chez des patients à haut risque.

BACKGROUND: Despite an often favorable risk/benefit ratio, patients with severe chronic kidney disease are sometimes declined for interventional coronary procedures, due to the risk of acute kidney injury post-contrast (AKI-PC). A large preventive supply of intravenous fluid may be problematic in this population. The RenalGuard® system allows hyperhydration by maintaining a stable volemia through an enhanced diuresis. METHODS AND RESULTS: This work reports the evaluation of the RenalGuard® system in 25 consecutive patients with chronic kidney disease (glomerular filtration rate < 40 mL/min/1.73 m²) requiring an interventional coronary procedure (coronary angiography and/or percutaneous coronary intervention) and at high risk of IRA-PC. An increase in serum creatinine ≥ 26.5 µmol/L at 48-72 hours (AKI-PC definition) was observed in 4 patients (16%). The mean glomerular filtration rate was 26 ± 8 mL/min/1.73 m² at 48-72 hours versus 25 ± 8 mL/min/1.73 m² at baseline. No patient presented with an increase in serum creatinine ≥ 1.5 from baseline, stage 2 or 3 AKI, or acute pulmonary edema. No renal replacement therapy was necessary. One death unrelated to AKI-PC occurred during hospital stay. CONCLUSIONS: This single-center observational study suggests that the RenalGuard® system, allowing diuresis-adjusted hyperhydration, is safe and useful for patients at high risk of AKI-PC after an interventional coronary procedure.

Reduction in acute kidney injury post cardiac surgery using balanced forced diuresis: a randomized, controlled trial.

OBJECTIVES: Our goal was to investigate the efficacy of balanced forced diuresis in reducing the rate of acute kidney injury (AKI) in cardiac surgical patients requiring cardiopulmonary bypass (CPB), using the RenalGuard® (RG) system. METHODS: Patients at risk of developing AKI (history of diabetes and/or anaemia; estimated glomerular filtration rate 20-60 ml/min/1.73 m2; anticipated CPB time >120 min; log EuroSCORE > 5) were randomized to the RG system group (n = 110) or managed according to current practice (control = 110). The primary end point was the development of AKI within the first 3 postoperative days as defined by the RIFLE (Risk, Injury, Failure, Loss of kidney function, End-stage renal disease) criteria. RESULTS: There were no significant differences in preoperative and intraoperative characteristics between the 2 groups. Postoperative AKI rates were significantly lower in the RG system group compared to the control group [10% (11/110) vs 20.9% (23/110); P = 0.025]. This effect persisted even after controlling for a number of potential confounders (odds ratio 2.82, 95% confidence interval 1.20-6.60; P = 0.017) when assessed by binary logistic regression analysis. The mean volumes of urine produced during surgery and within the first 24 h postoperatively were significantly higher in the RG system group (P < 0.001). There were no significant differences in the incidence of blood transfusions, atrial fibrillation and infections and in the median duration of intensive care unit stays between the groups. The number needed to treat with the RG system to prevent AKI was 9 patients (95% confidence interval 6.0-19.2). CONCLUSIONS: In patients at risk for AKI who had cardiac surgery with CPB, the RS RG system significantly reduced the incidence of AKI and can be used safely and reproducibly. Larger studies are required to confirm cost benefits. CLINICAL TRIAL REGISTRATION NUMBER: NCT02974946.

Balanced forced-diuresis compared to control as a reno-protective approach in cardiac surgery: secondary outcome of a randomized controlled trial, assessment of neutrophil gelatinase-associated lipocalin levels.

BACKGROUND: Neutrophil gelatinase-associated lipocalin (NGAL) is a recognised biomarker for acute kidney injury (AKI).This study investigated the impact of balanced forced-diuresis using RenalGuard® system (RG), in reducing acute kidney injury (AKI) rates and the associated NGAL levels (6-h post-CPB plasma level) post adult cardiac surgery with cardiopulmonary bypass (CPB). METHODS: Patients included in the study were at high-risk for AKI post cardiac surgery, namely history of diabetes and/or anaemia, e-GFR 20-60 ml/min/1.73 m2, Logistic EuroScore > 5, anticipated CPB time > 120 min. Patients were randomized to either RG (n = 110) or managed as per current practice (control = 110). RIFLE-defined AKI rate (based on serum creatinine level increase) within first 3 days of surgery and 6-h post CPB NGAL levels were the primary and secondary end-points. RESULTS: Pre and intra-operative characteristics between the two groups were similar (p > 0.05) including the pre-op NGAL levels, the oxygen delivery (ecDO2i) and the carbon dioxide production (ecVCO2i) during CPB. Patients in the RG group had a significantly lower post-operative RIFLE-defined AKI rate compared to control (10% (11/110) v/s 20.9% (23/110), p = 0.03). Overall, median 6-h post CPB NGAL levels in patients with AKI were significantly higher than those who did not develop AKI (211 vs 150 ng/ml, p < 0.001). Patients managed by balanced forced-diuresis had lower post-operative NGAL levels (146 vs 178 ng/ml, p = 0.09). Using previously reported NGAL cut-off level for AKI (142 ng/ml), binary logistic regression analysis confirmed a beneficial effect of the RG system, with an increased risk of AKI of 2.2 times in the control group (OR 2.2, 95% CI 1.14-4.27, p = 0.02). CONCLUSIONS: Overall, the 6-h post-CPB plasma NGAL levels were significantly higher in patients who developed AKI. Patients managed with the novel approach of balanced forced-diuresis, provided by the RenalGuard® system, had a lower AKI rate and lower NGAL levels indicating a lesser degree of renal tissue injury. Trial registration ClinicalTrials.gov website, NCT02974946, https://clinicaltrials.gov/ct2/show/NCT02974946 .

RenalGuard system and conventional hydration for preventing contrast-associated acute kidney injury in patients undergoing cardiac interventional procedures: A systematic review and meta-analysis.

BACKGROUND: Contrast-associated acute kidney injury (CA-AKI) can increase the mortality of patients undergoing transcatheter aortic valve replacement (TAVR) or percutaneous coronary intervention (PCI). The purpose of this paper was to compare the efficacy of the RenalGuard System and conventional hydration regimen in preventing CA-AKI in patients with TAVR or PCI. METHODS: We searched PubMed, Embase, Web of Science, and the Cochrane Central Register of Clinical Trials (last updated July 11, 2020) for suitable reports. The primary outcome was the occurrence of CA-AKI. The secondary outcomes were renal replacement therapy (RRT), major cardiovascular events (MACEs), and other adverse complications. RESULTS: The search strategy yielded 270 studies (with data for 2067 participants). In the subgroup of PCI, low incidence of CA-AKI (6.7% vs 15.7%; 95%CI: 0.27 to 0.54; I2 = 8%; P < 0.00001) associate with RenalGuard group (RG) rather than control group (CG). Similarly, in the subgroup of TAVR, a low incidence of CA-AKI (15.6% vs 26.9%; 95%CI: 0.35 to 0.82; I2 = 88%; P = 0.004) relates to RG. However, this result is highly heterogeneous. Compare with conventional hydration, RenalGuard significantly reduce the incidence of pulmonary edema (1.5%vs4.1%; 95%CI: 0.18 to 0.72; I2 = 0%; P = 0.004). CONCLUSIONS: RenalGuard System can lessen the risk of CA-AKI and RRT in patients undergoing PCI. But for patients experiencing TAVR, due to unique hemodynamic effects, the role of RenalGuard remains questionable. RenalGuard is more secure than conventional hydration. Future work should elucidate the feasibility and safety of this prophylactic intervention in cardiac interventional therapy.

RenalGuard system to prevent contrast-induced acute kidney injury in Japanese patients with renal dysfunction; RESPECT KIDNEY study.

Increasing the urine flow rate (UFR) reduces the toxic effect of contrast media. Use of the RenalGuard system enables the achievement of a high UFR by maintaining intravascular volume and prevents the development of contrast-induced acute kidney injury (CI-AKI). However, the efficacy and safety of RenalGuard system have not yet been evaluated in Japan. This multicenter prospective study evaluated the efficacy and safety of the RenalGuard therapy in preventing CI-AKI development in 60 Japanese patients with renal dysfunction [estimated glomerular filtration rate (eGFR) < 45 mL/min/1.73 m2] undergoing catheter procedures. Baseline eGFR and Mehran's CIN (contrast-induced nephropathy) risk score were 35.1 ± 8.5 mL/min/1.73 m2 and 11.7 ± 4.3, respectively. Regardless of this high-risk profile, the incidence of CI-AKI was 8.6% (5/58) compared with the 26.1% incidence estimated by the CIN risk score. Moreover, two-sided 95% (Fisher's) exact confidence interval was 2.9-19.0 and its upper limit (i.e., 19.0) was less than the prespecified threshold incidence of 25.0. Univariate logistic regression analysis demonstrated that the UFR during catheter procedure was one of the most important factor associated with CI-AKI (odds ratio 0.99, confidence interval 0.98-1.00, p = 0.03). In conclusion, RenalGuard therapy may prevent CI-AKI development in Japanese patients with renal dysfunction. Further large-scale prospective multicenter studies are necessary to confirm our findings.

Prevention of post procedural acute kidney injury in the catheterization laboratory in a real-world population.

BACKGROUND: Radiologists and cardiologists have a remarkably different approach to the clinical importance and to the need for prophylactic treatment of contrast-induced acute kidney injury (CI-AKI). OBJECTIVES: To evaluate the efficacy of forced diuresis with matched controlled hydration (FMH) in a real-world, high risk population. METHODS: This is an investigator-driven, single-center, retrospective analysis of prospectively collected data. A total of 150 consecutive patients undergoing coronary angiography, angioplasty or TAVR who were treated with FMH were compared to a matched historical control cohort. RESULTS: In the FMH treated patients, eGFR improved following the procedure from 37ml/min per 1.73m2 at baseline to 39ml/min per 1.73m2 (p<0.001); the net creatinine decreased from 1.85mg/dl to 1.78mg/dl (p<0.001). Among the matched control group, eGFR deteriorated from a baseline value of 36.7ml/min per 1.73m2 to 33.2ml/min per 1.73m2 post procedurally (p<0.001); the net creatinine increased from 1.88mg/dl to 2.14mg/dl (p<0.001). The incidence of post procedural AKI was substantially lower in the FMH treated group (2.7%) compared to the control group (26.7%). By multivariable analysis FMH treatment was independently correlated with reduced incidence of post procedural AKI compared with the control group (OR 0.06, p<0.001). Contrast volume did not correlate with AKI in neither univariate nor multivariate analyses. CONCLUSIONS: In patients undergoing coronary angiography, angioplasty or TAVR, who are considered high risk to develop post procedural AKI, forced diuresis with matched controlled hydration resulted in a significant net creatinine decrease, eGFR increase and a decrease in the incidence of AKI.

Acute Kidney Injury With the RenalGuard System in Patients Undergoing Transcatheter Aortic Valve Replacement: The PROTECT-TAVI Trial (PROphylactic effecT of furosEmide-induCed diuresis with matched isotonic intravenous hydraTion in Transcatheter Aortic Valve Implantation).

OBJECTIVES: The purpose of this study was to investigate the effect of the RenalGuard System (PLC Medical Systems, Milford, Massachusetts) on prevention of acute kidney injury (AKI) in patients undergoing transcatheter aortic valve replacement (TAVR). BACKGROUND: TAVR is associated with varying degrees of post-procedural AKI. The RenalGuard System is a dedicated device designed for contrast-induced AKI prevention. Whether this device is also effective in patients with severe aortic stenosis undergoing TAVR is unexplored. METHODS: The present is an investigator-driven, single-center, prospective, open-label, registry-based randomized study that used the TAVR institutional registry of the Ferrarotto Hospital in Catania, Italy, as the platform for randomization, data collection, and follow-up assessment. A total of 112 consecutive patients undergoing TAVR were randomly assigned to hydration with normal saline solution controlled by the RenalGuard system and furosemide (RenalGuard group) or normal saline solution (control group). The primary endpoint was the incidence of Valve Academic Research Consortium-defined AKI in the first 72 h after the procedure. RESULTS: The AKI rate was lower in the RenalGuard group than in the control group (n = 3 [5.4%] vs. n =14 [25.0%], respectively, p = 0.014). The majority of patients (5.4% vs. 23.2%) developed a mild AKI (stage 1); severe damage (stage 3) occurred only in 1 patient in the control group (0.0% vs. 1.8%). No case of in-hospital renal failure requiring dialysis was reported. No significant differences in terms of mortality, cerebrovascular events, bleeding, and hospitalization for heart failure were noted in both groups at 30 days. CONCLUSIONS: Furosemide-induced diuresis with matched isotonic intravenous hydration using the RenalGuard system is an effective therapeutic tool to reduce the occurrence of AKI in patients undergoing TAVR.

Contrast Medium-Induced Acute Kidney Injury.

Contrast medium-induced acute kidney injury (CI-AKI) is a predominant cause of hospital-acquired renal insufficiency. With an increasing number of contrast medium-enhanced radiological procedures being performed in a rapidly increasing ageing population in the Western world, it is imperative that more attention is given to understand the aetiology of CI-AKI to devise novel diagnostic methods and to formulate effective prophylactic and therapeutic regimens to reduce its incidence and its associated morbidity and mortality. This article presents high-yield information on the above-mentioned aspects of CI-AKI, primarily based on results of randomised controlled trials, meta-analyses, systematic reviews and international consensus guidelines.