The definition and staging recommendations are a combination of the RIFLE (Risk, Injury, Failure, Loss, and End-stage renal disease) and AKIN (Acute Kidney Injury Network) criteria for the condition.
“The whole issue of definition is controversial, recognizing that using serum creatinine as the marker does not tell you what GFR is,” said Paul Palevsky, MD, Chair of the NKF Spring Clinical Meetings session on KDOQI's response to the guideline. Dr. Palevsky is Professor of Medicine at the University of Pittsburgh School of Medicine and Chief of the Renal Section at the VA Pittsburgh Healthcare System.
“When RIFLE was developed, it was developed as an interim consensus definition, and I have a concern that it is now becoming the standard. There are many imperfections associated with it, so while not rejecting definitions, there are lots of caveats that need to be considered.”
Use of Diuretics, NAC
Diuretics were also considered in the guideline. The work group recommended that these agents not be used to treat acute kidney injury, except in the management of volume overload, or to prevent AKI, as there is no evidence that they reduce the incidence or severity of the condition (Recommendations 3.4.1 and 3.4.2).
“I think that most nephrologists would agree with this,” Dr. Khwaja said. “It is probably a sensible suggestion.”
The assessment of N-acetylcysteine (NAC), though, is not so clear-cut (Recommendation 4.4.3). The work group suggested using oral NAC, together with intravenous isotonic crystalloids, in patients at increased risk of contrast-induced acute kidney injury (CI-AKI).
“For contrast-induced AKI, there is still enough uncertainty and possibility of effect that we left open the potential for that indication,” Dr. Kellum said. “It's a drug that's possibly effective, cheap, and safe.”
Many, but not all, studies have shown NAC to have a protective effect on CI-AKI when it is administered before the onset of renal insult, the guideline noted.
In one such study, the rate of the composite endpoint of death, acute renal failure requiring temporary renal replacement therapy, or the need for mechanical ventilation was 7% with standard-dose NAC and 5% with double-dose NAC, versus 18% with placebo (Marenzi G et al: N Engl J Med 2006;354:2773–2782).
Other studies have found contradictory results, however, and there is no evidence that NAC influences mortality or need for renal replacement therapy in at-risk patients who have received contrast media.
“There are data that support NAC, and there are data that don't support it,” Dr. Singh said. “The committee came out in favor for use in CI-AKI, and that is an opinion, and when you have opinions, you have controversy. I tend to use NAC as an agent in contrast nephropathy.”
In the conference session on KDOQI's response to the guideline, Dr. Palevsky mentioned the Acetylcysteine for the Prevention of Contrast-Induced Nephropathy Trial (ACT), a large randomized, controlled trial conducted at 46 centers in Brazil that showed no benefit of NAC on contrast-induced nephropathy.
“While the ACT study was a large study, one of the things to consider is that it involved a population that would be considered relatively low risk, with only less than 16% having baseline serum creatinine greater than 1.5,” he said.
“The work group thought that the ACT trial is not the definitive negative trial and does not completely invalidate the use of NAC.”
The Trouble with Guidelines
As is customary for clinical practice guidelines, the recommendations in the AKI guideline were graded. The strength of recommendation was described as Level 1 (we recommend), Level 2 (we suggest), or Not Graded. The quality of the supporting evidence was assigned a letter grade of A (high), B (moderate), C (low), or D (very low).
Just 14.8% of the recommendations were given the highest grade of 1A, while 63.9% were Level 2 suggestions, Dr. Khwaja noted.
“There is a rather wooly statement saying that all patients who have AKI should be managed as if they are at risk of CKD,” he said. “For many patients, that will be true. Many people appear to recover from AKI, and we don't know if it is cost-effective to follow the people up lifelong. There is an absence of any outcome data, so recommending that this happens is a bold statement.”
Dr. Singh's philosophy is to take a narrow approach to guidelines, he said.
“Guidelines tend to generate dogma, and guidelines change practice in ways of which subsequently obtaining evidence becomes more challenging.
“If, for example, a guideline says that you should use drug ‘x’ over drug ‘y’ or drug ‘x’ over nothing, it makes the performance of subsequent trials more challenging because the guideline is now saying that's what standard of care needs to be.
“I think guidelines should largely center around areas where evidence is settled or nearly settled rather than going in the direction of covering clinical evidence where either there is no evidence or weak evidence.”
Overall, the KDIGO guideline represents a constructive literature assessment, Dr. Khwaja said.
“In a way, the guideline tells us what we don't know in eloquent detail. It is a great review of the literature. I think some believe that this is what should be done—just offer recommendations when the evidence is good, and when it is not good, just say we don't know the best way forward.”© 2012 Lippincott Williams & Wilkins, Inc.