A novel simplified hydration (SH) protocol is safe, convenient, and non-inferior to standard hydration protocols in preventing contrast-associated acute kidney injury (CA-AKI) in patients with chronic kidney disease (CKD), new trial data report. The study, published online Monday and in the June 26 issue of JACC: Cardiovascular Interventions, noted that patients with CKD undergoing coronary angiography (CAG) are at high risk of CA-AKI and mortality – meaning there is a clinical need to explore safe, convenient and effective strategies for prevention. “At present, the prevention of CA-AKI in patients with high-risk renal insufficiency undergoing CAG is a hot research topic,” said the study authors, led by Yong Liu, MD, PhD, and Ning Tan, MD, PhD, from the Southern Medical University, and the Guangdong Academy of Medical Sciences, both in Guangzhou, China. “According to the European Society of Cardiology (ESC)/European Association for Cardio-Thoracic Surgery (EACTS) guidelines on myocardial revascularization, standard long-term perioperative intravenous saline hydration is the foundation to prevent CAAKI among patients with moderate or severe CKD. However, standard hydration is performed from 12 hours before to 24 hours after the procedure, which influences feasibility and is time-consuming,” they added, noting that additional randomized studies on effective, safe, and convenient strategies to prevent CA-AKI in the high-risk CKD population are needed. Study setup Liu, Tan and colleagues assessed whether a simplified rapid hydration protocol is noninferior to standard hydration for CA-AKI prevention in 1,002 patients with CKD as part of a multicenter, open-label, randomized controlled study across 21 teaching hospitals in China. The team enrolled patients aged 18 or over with CKD who were scheduled for CAG or percutaneous coronary intervention (PCI) with at least one risk factor from: age >75 years, medical history of diabetes or hypertension, congestive heart failure (CHF; New York Heart Association functional class >II or left ventricular ejection fraction ≤35%) or a history of acute pulmonary edema. Patients were randomly divided into a control group of standard long-term hydration (n = 501), – in which patients were hydrated with normal saline 12 hours before and 12 hours after coronary intervention at a rate of 1 mL/kg/h – or the SH group (n = 501) – in which patients were hydrated with normal saline from 1 hour before to 4 hours after coronary intervention at a rate of 3 mL/kg/h – before coronary intervention stratified by the central network. The authors noted that in patients with CHF, the rate of hydration was halved, while the use of diuretic agents was at the clinician’s discretion according to the condition of the patient. The primary endpoint was CA-AKI, which the investigators defined as a ≥25% or 0.5 mg/dL absolute increase in serum creatinine from baseline in the first 48 to 72 hours after PCI or CAG. “The prespecified trial hypothesis was that SH would be noninferior to standard long-term hydration with respect to the risk of CA-AKI among CKD patients undergoing CAG,” said the team, adding that the study was performed according to intention-to-treat as the major analysis. Key findings The team reported that the total hydration duration in the control group was fourfold longer than in the intervention group (25 vs 6 hours, respectively; P < 0.001) – with both pre-procedure hydration duration (13 vs 1 hour; P < 0.001), and post-procedure protocols (12 hours vs 4 hours; P < 0.001) differing significantly. The overall incidence of CA-AKI was 7.3% (67/921), they added, noting incidence rates of 6.2% (29/466) in the SH group vs 8.4% (38/455) in the control group. As such, they reported no statistical differences in the primary endpoint between the SH and control groups (relative risk [RR]: 0.8, 95% confidence interval [CI]: 0.5-1.2; P = 0.216) – adding that the absolute risk difference was 2.1% (95% CI: 5.5% to 1.2%) “Similar results were seen in additional multivariable logistic regression analyses in the intention-to-treat data set and per-protocol data set for the primary endpoint,” said Liu, Tan and colleagues, adding that there were also no significant differences in the secondary endpoints, which included alternative definitions of CA-AKI. Furthermore, the incidence of postprocedural acute heart failure was consistent between the two groups (3.4% vs 3.4%; P > 0.999), they said, adding that no differences were seen in in-hospital mortality (0.4% vs 0.4%; P > 0.999) and the rate of major adverse cardiovascular events (17.4% vs 15.9%; P = 0.594). “During a median follow-up of 1.0 year (IQR [interquartile range]: 1.0-1.0 year), the Kaplan-Meier curves indicated that the cumulative incidences of the 1-year all-cause mortality and major adverse cardiovascular events were similar between the 2 groups,” the authors reported. “The present study showed that the SH protocol was non-inferior to the standard hydration protocol in preventing CA-AKI in CKD patients undergoing CAG. Furthermore, SH did not increase the risk of acute heart failure in these patients,” they concluded. “SH greatly shortened hydration duration compared with standard long-term hydration.” The team noted that further studies are now needed clarify whether the SH protocol has potential benefit in preventing CA-AKI in other high-risk patients such as those with severe coronary lesions or emergent PCI. Time to revisit guidelines? Writing in an accompanying editorial, Hitinder S. Gurm, MBBS, and S. Nabeel Hyder, MD, from the University of Michigan Medical School, Ann Arbor, noted that greater awareness of CA-AKI and select preventive strategies – especially broader uptake of safe contrast dosing thresholds – has reduced renal complications in recent years. “In the absence of clear data favoring any 1 strategy, the 2018 European Society of Cardiology (ESC) and 2021 American College of Cardiology/American Heart Association/Society for Cardiovascular Angiography and Interventions revascularization guidelines advocate for adequate hydration and allow for tailored strategies to reduce risk of CA-AKI,” said Gurm and Hyder, adding that specific hydration guidance “remains largely absent.” “Based on these results, we agree with the investigators that most CKD patients undergoing angiography or PCI may receive simplified rapid hydration regimens without incurring adverse event risks,” they said, noting that simpler regimens are generally easier to implement, and the catheterization laboratory workflow may benefit as well from the simpler regimen. The editorialists wrote that the authors should be commended for filling a gap in the data – adding that the study adds to the growing evidence that “more may not be necessarily better” when it comes to hydration for prevention of CA-AKI. “Given the multiplicity of studies challenging routine hydration, it is perhaps time for society guidelines to revisit hydration recommendations,” they suggested, noting that it is likely that the total dose of hydration needed for CA-AKI risk reduction is smaller than current practice has normalized. “Catheterization labs should continue to avoid dehydration, however, and maintain efforts to remain congruent with contemporary contrast dosing limits. For now, the hydration hypothesis has not dried up, but a thirst for new research on CA-AKI persists,” they said. Sources: Liu Y, Tan N, Huo Y, et al. Simplified Rapid Hydration Prevents Contrast-Associated Acute Kidney Injury Among CKD Patients Undergoing Coronary Angiography. JACC Cardiovasc Interv 2023;16:1503-1513. Gurm HS, Hyder SN. Reducing Risk of Contrast-Associated Acute Kidney Injury: Is the Hydration Hypothesis Drying Up? JACC Cardiovasc Interv 2023;16:1514-1516. Image Credit: Crystal light – stock.adobe.com