MAASTRICHT, THE NETHERLANDS — A randomized trial raises doubts about guideline recommendations to give certain patients with chronic kidney disease intravenous saline hydration to prevent contrast-induced nephropathy when they have procedures such as computed tomography and coronary interventions that use iodinated contrast material.
Specifically, in this single-center, randomized noninferiority trial, high-risk patients who did not receive prophylactic hydration had a similar low incidence of contrast-induced nephropathy as patients who received this standard-of-care preventive therapy—and they incurred lower healthcare costs (largely because of a shorter hospital stay) and avoided hydration-related complications. The results were published online February 20, 2017 in the Lancet.
"The mechanism by which iodinated contrast material may induce contrast-induced nephropathy is unclear, as is the mechanism by which prophylactic hydration may protect renal function," Dr Estelle C Nijssen (Maastricht University Medical Centre, the Netherlands) told heartwire from Medscape. Although international guidelines recommend the prophylactic strategy, this is based on expert consensus opinion, and until now, the option of not giving prophylaxis had not been compared with standard prophylactic hydration in a prospective, randomized trial.
The A Maastricht Contrast-Induced Nephropathy Guideline (AMACING) trial showed that "assuming optimum contrast media administration, prophylactic intravenous hydration might not be necessary in patients with an [estimated glomerular filtration rate] eGFR higher than 29 mL/min/1.73 m²," the researchers report.
Moreover, "the substantial healthcare costs, patient burden, and logistical complications of this prophylaxis might henceforth be avoided while maintaining patient safety," they suggest.
However, in an accompanying editorial, Dr Peter A McCullough (Baylor University Medical Center, Dallas, TX) and colleagues raised questions about the statistical margins for noninferiority in the trial, to which Nijssen replied in an email to heartwire.
Forgoing prophylaxis is "somewhat provocative," she agrees, but she also questions "whether it is ethical to continue giving a treatment that is unproven, carries risks," and is costly.
Prospective, Randomized, Phase 3 Noninferiority Trial
The AMACING trial hypothesized that withholding prophylaxis would be noninferior to the standard-of-care administration of normal saline in patients at high risk of contrast-induced nephropathy.
Researchers randomized 660 adults with an eGFR of 30 to 59 mL/min/1.73 m² who visited their center from June 2014 to July 2016 for an elective procedure that required the use of iodated contrast material, such as a CT scan, coronary angiography, PCI, or percutaneous transluminal angioplasty.
Patients were a mean age of 72 years and 62% were men. In addition to having moderately reduced kidney function, other risk factors for acute kidney injury were cardiovascular disease (75% of patients), prescribed NSAIDs (49%), prescribed diuretics (46%), age >75 years (44%), diabetes (32%), and anemia (25%).
Researchers measured serum creatinine immediately before and 2 to 6 days and 26 to 35 days after exposure to the contrast agent. Patients in each group had an average baseline serum creatinine of 119 μmol/L.
Contrast-induced nephropathy—defined as an increase in serum creatinine from a baseline of more than 25% or 44 μmol/L within 2 to 6 days of exposure to contrast agent—occurred in 2.7% of patients who received prophylactic hydration vs 2.6% of patients who did not.
In patients who received standard-of-care intravascular volume expansion, 4% developed symptomatic heart failure, 0.3% developed hyponatremia, and 1.2% developed arrhythmia, but none of the other patients developed these complications.
About half of patients who received prophylactic hydration (54%) required an overnight hospital stay of 1 to more than 2 nights, whereas only 23% of patients who did not receive the preventive treatment were hospitalized.
None of the patients died or needed dialysis within 35 days of contrast exposure.
All procedures used minimum volume prewarmed, low-osmolar, monomer, nonionic contrast material, which might explain why the rate of contrast-induced nephropathy in the study was at the low end of the rate reported in the scientific literature (0 to >50%), the researchers speculate.
"The results suggest that standardized, safe, and effective use of iodinated contrast material is possible across procedure types, even in high-risk patients," Nijssen and colleagues report.
Withholding Prophylaxis "Might Be Considered"
In the AMACING trial, McCullough and colleagues questioned the assumption "that the contrast-induced acute kidney injury rate in the normal saline group would be 2.4% and the rate in the no saline prophylaxis group could be as high as 4.5% with a relative risk or hazard ratio of less than 1.88 to meet noninferiority."
The assumption of a 2.4% incidence of contrast-induced nephropathy with usual prophylaxis is based on the rate reported in a recent Dutch study, Nijssen explained. They deemed that a maximum difference of 2.1% in contrast-induced nephropathy between the two groups, in favor of the hydrated group was acceptable, because serum creatinine elevation usually resolves within 2 weeks with no lasting effects, and it has not been shown that prophylaxis reduces the risk of long-term effects.
The editorialists also feel that it is too soon for a noninferiority trial, because there is no widely accepted, proven prophylactic hydration strategy. "In our view this field is not ready for noninferiority trials until we have a reference standard intervention that is agreed upon as proven and thus can be positioned as the control group and be compared with novel treatment or strategy," they write.
"Attention should be shifted to large collaborative efforts that are patient-centered, rely on methods of precision medicine, and use the approved methods that allow us to better ascertain the outcome," McCullough and colleagues conclude.
However, in the meantime, the recommended prophylactic procedure is costly and puts large number of patients at risk of complications, Nijssen countered.
High-risk patients need to be admitted to the hospital for 8 to 24 hours for the periprocedural prophylactic treatment, and the number of patients with possible complications from prophylactic hydration is "substantial," given that an estimated 6 to 12 million patients with chronic kidney disease undergo procedures with intravascular iodinated contrast administration every year worldwide.
Thus, "based on these findings and assuming optimal contrast media administration, withholding prophylaxis for high-risk patients with eGFR higher than 29 mL/min/1.73 m² might be considered without compromising patient safety," Nijssen and colleagues conclude.
The study was funded by the Weijerhorst Foundation.The authors report no relevant financial relationships.
Heartwire from Medscape © 2017
Cite this article: Trial Questions Hydration to Avoid Contrast-Induced Nephropathy - Medscape - Mar 02, 2017.