NEW ORLEANS– Preventing acute kidney injury and its progression in hospitalized patients deserves to be a high priority – and now there is finally proof that it’s doable, Harold M. Szerlip, MD, declared at the annual meeting of the American College of Physicians.

The PrevAKI study, a recent randomized controlled clinical trial conducted by German investigators, has demonstrated that the use of renal biomarkers to identify patients at high risk for acute kidney injury (AKI) after major cardiac surgery and providing them with a range of internationally recommended supportive measures known as the KDIGO (Kidney Disease: Improving Global Outcomes) care bundle reduced the occurrence of moderate-to-severe AKI by 34% (Intensive Care Med. 2017 Nov;43[11]:1551-61).

This finding has generated great excitement within the worlds of nephrology, surgery, and intensive care medicine. Inpatient AKI is a huge yet underappreciated problem which costs the U.S. healthcare system $9 billion annually. The incidence of AKI jumped 6-fold during 2001-2011. AKI occurs in 10%-15% of hospitalized patients, doubles hospital costs, and carries a 25% mortality rate, explained Dr. Szerlip, director of nephrology at Baylor University Medical Center, Dallas.

The enthusiasm that greeted the PrevAKI trial findings is reflected in an editorial entitled, “AKI: the Myth of Inevitability is Finally Shattered,” by John A. Kellum, MD, professor of critical care medicine and director of the Center for Critical Care Nephrology at the University of Pittsburgh. Dr. Kellum noted that the renal biomarker-based approach to implementation of the KDIGO care bundle resulted in an attractively low number needed to treat (NNT) of only 6, whereas without biomarker-based enrichment of the target population, the NNT would have been more than 33.

“Now that evidence demonstrates that AKI can be prevented, it is our duty to find more ways to do it,” Dr. Kellum declared in the editorial (Nat Rev Nephrol. 2017 Mar;13[3]:140-1).

Indeed, another way to do it was recently demonstrated in the SALT-ED trial, in which 13,347 noncritically ill hospitalized patients requiring intravenous fluid administration were randomized to conventional saline or balanced crystalloids. The incidence of AKI and other major adverse kidney events was 4.7% in the balanced crystalloids group, for a significant 18% risk reduction relative to the 5.6% rate with saline (N Engl J Med. 2018 Mar 1;378[9]:819-28).

While that absolute 0.9% risk reduction might initially not sound like much, with 35 million people per year getting IV saline while in the hospital, it translates into 315,000 fewer major adverse kidney events as a result of a simple switch to balanced crystalloids, Dr. Szerlip observed.

The PrevAKI findings validate the concept of AKI ‘golden hours’ during which time potentially reversible early kidney injury detectable via renal biomarkers is occurring prior to the abrupt decline in kidney function measured by change in serum creatinine. “The problem with using change in creatinine to define AKI is the delay in diagnosis, which makes AKI more difficult to treat,” he explained.

The renal biomarkers utilized in PrevAKI were insulin-like growth factor binding protein-7 (IGFBP7) and tissue inhibitor of metalloproteinase-2 (TIMP-2), as incorporated in the commercially available urinary NephroCheck test, which was administered to study participants 4 hours after cardiopulmonary bypass. A test result of 0.3 or more identified a group at high risk for AKI for randomization to the KDIGO bundle or usual care. The KDIGO bundle consists of discontinuation of nephrotoxic agents when feasible, early optimization of fluid status, and maintenance of perfusion pressure.

Patients known to be at increased risk for in-hospital AKI include the elderly, those with diabetes, patients with heart failure or other conditions prone to volume contraction or overload, those undergoing major surgery, individuals with chronic kidney disease, and patients with sepsis.

Dr. Szerlip singled out as particularly nephrotoxic several drugs widely used in hospitalized patients, including the combination of vancomycin plus piperacillin-tazobactam, which in a recent metaanalysis was found to have a number needed to harm of 11 in terms of AKI in comparison to vancomycin monotherapy or vancomycin in combination with cefepime or carbapenem (Crit Care Med. 2018 Jan;46[1]:12-20). He was also critical of the American Society of Anesthesiologists practice parameter recommending that in-hospital pain management plans for surgical patients include continuous regimens of NSAIDs or COX-2 inhibitors as a means of combating the ongoing opioid epidemic.

“These are highly toxic drugs to the kidney and we shouldn’t be using them,” Dr. Szerlip said.

He reported receiving research grants from LaJolla, Bayer, Akebia, and BioPorto, serving on a speakers’ bureau for Astute Medical, and acting as a consultant to Zs Pharma, Amarin, and LaJolla.

bjancin@mdedge.com

Avoiding in-hospital acute kidney injury is a new imperative