Preventing AKI

Everyone wants to do it, but how?.

With no definitive cure, but growing evidence that acute kidney injury (AKI) is often preventable, the pressure is on hospitalists to take measures to reduce their patients' vulnerability to this common complication.

AKI impacts nearly 10% of hospitalized patients, according to a 2009 study in the Journal of the American Society of Nephrology. And almost a third (30.5%) of AKI episodes could likely be prevented, according to a recent retrospective analysis of charts from patients with AKI. In that study, the authors concluded that 51 of 167 episodes could have been prevented if various steps had been taken, such as avoiding combinations of nephrotoxic drugs and maintaining sufficient fluid levels.

Photo by Thinkstock
Photo by Thinkstock

The study, published in September in the American Journal of Medicine, is among several published in the past year attempting to provide doctors with some guidance in terms of better flagging and protecting vulnerable patients.

Still, AKI remains a frustrating complication for hospital physicians, with no proven treatment or intervention strategies, said Morgan Grams, MD, PhD, a researcher, nephrologist, and assistant professor of medicine and epidemiology at the Johns Hopkins University School of Medicine in Baltimore.

Even the data on prevention are fairly dispiriting, according to the experts. “AKI prevention trials have been for the most part disappointing,” said Andrew Fenves, MD, FACP, a nephrologist at Massachusetts General Hospital in Boston.

But there are steps that hospital physicians can at least try to avoid the condition's emergence and limit its renal severity, added Dr. Fenves, the co-author of a review article titled “Before You Call Renal: Acute Kidney Injury for Hospitalists,” published in the June Journal of Hospital Medicine.

“Hospitalists in fact can do a lot of good things early in terms of the potential prevention of AKI, the early recognition of AKI, and the early adjustment of medications and dosing,” Dr. Fenves said. “Even those 3 things are important and potentially might avoid the need for us [nephrologists] to ever get involved.”

Protecting the kidneys

In the American Journal of Medicine analysis, one-third of the preventable AKI episodes were traced to a lack of sufficient fluids before administration of a contrast-dose agent. (An agent or event was determined to be responsible if the serum creatinine level had increased by ≥0.3 mg/dL within 48 hours of the exposure and there were no alternative explanations.)

Some of the other causes included the use of nephrotoxic drugs or inappropriate medication dosing, said study author Murray Levin, MD, FACP, professor emeritus of medicine at Northwestern University Feinberg School of Medicine in Chicago.

It's particularly vital to administer prophylactic fluids to anyone who might be susceptible to contrast-induced kidney injury, including someone who has diabetes, marginal kidney function, or chronic kidney disease or is already taking a drug with nephrotoxic effects, he added.

Doctors should be vigilant about preventing hypotension, particularly in elderly patients, by moving quickly to replace fluids lost due to vomiting or diarrhea, Dr. Levin said. As for what fluid, recent findings from the SPLIT (0.9% Saline vs Plasma-Lyte 148 for Intensive Care Unit Fluid Therapy) trial, published online Oct. 7 in the Journal of the American Medical Association, didn't find any difference between the administration of saline and buffered crystalloid in terms of the development of AKI.

A blood pressure drop of more than 20% shouldn't be allowed to persist for longer than 15 to 30 minutes, including in the operating room, Dr. Levin said. Orders should be set up for the nurses to notify the doctor immediately if the blood pressure falls below a designated level.

If a hospitalist treating a patient after surgery notices an unexplained increase in creatinine level in the first day or two, Dr. Levin recommended checking the anesthesia record to see if a prolonged period of hypotension had occurred or if the patient had been started on any new medications that might have kidney effects.

Recent research has tried to identify patient risk factors that predict AKI. Dr. Grams recently published a meta-analysis looking at estimated glomerular filtration rate (eGFR) and albuminuria, as well as demographic indicators, and their relationships to AKI.

While certain categories of patients, such as those who are older or male or African-American, are considered to be at greater risk, the study, published in the American Journal of Kidney Diseases in October, found that the patient's kidney function remains the most consistently strong factor. “Reduced GFR and higher albuminuria are strong and consistent risk factors regardless of age, race, and sex,” she said.

Uncertainty remains

Ongoing research, though, continues to find gaps in what's understood about the onset of AKI and therefore how to prevent it. One study looking at AKI and mortality following percutaneous coronary intervention (PCI) found that nearly one-third of in-hospital deaths following the procedure could be attributed to AKI, and preventing just 9 AKI cases would potentially avert 1 death.

But researchers also concluded that using a high-contrast agent was “only a minor contributor to the overall burden of AKI” in that population, according to the findings, published in June in Circulation: Cardiovascular Interventions.

The study used a regional registry to match patients who developed AKI with others who had experienced a similar acuity of illness. Researchers determined that the mortality risk from AKI was highest in patients with cardiogenic shock or cardiac arrest and in those who presented with ST-segment elevation myocardial infarction. However, mortality risk “was also clinically relevant in patients with a more stable presentation,” they wrote.

A PCI risk calculator can be used to assess a patient's vulnerability to kidney damage as well as other complications, said Hitinder Gurm, MBBS, an author on the study and associate chief of the division of cardiovascular medicine at the University of Michigan Health System in Ann Arbor. (Such a calculator is available online. ) Ensuring that the patient is well hydrated with intravenous fluids before the cardiovascular procedure also is crucial, Dr. Gurm said.

As an additional buffer, Dr. Gurm said that his cardiology group typically doesn't ask PCI patients to fast the night before, allowing them to drink fluids up to 2 hours before the procedure. In fact, they encourage patients to consume slightly more than normal in an effort to limit kidney exposure. “One way to reduce the concentration of contrast is to make sure you have high urine flow,” he said.

If AKI isn't avoided, one aspect that is particularly discouraging for doctors is that by the time the serum creatinine level rises significantly, the damage has already occurred and no reliable treatment is available. And once AKI develops, so does the risk of lingering and perhaps fatal effects, according to the 2009 Journal of the American Society of Nephrology study. Patients with AKI who lived at least 3 months after hospital discharge still faced a 41% higher risk of death within the first 2 years compared with those hospitalized patients who never developed the condition.

A few urine-based biomarkers currently being studied, such as kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL), might hold earlier warning potential because they rise many hours and potentially a day or two before creatinine levels, according to Dr. Fenves.

“Even gaining 24 to 48 hours is therapeutically advantageous,” he said.

After diagnosis

Once AKI has been identified, hospitalists should screen the patient's current medication list for potential toxicities and adjust dosage of any new medications based on the reduced kidney function. Kidney function readings should be followed closely; Dr. Fenves recommended daily lab work, including urine.

One dilemma is when to get nephrology involved. “They don't want to get called too early, but they don't want to get called too late either,” Dr. Fenves said. Much of the patient's care can be handled by hospitalists, but nephrology needs a heads up if renal replacement therapy is becoming a distinct possibility, he recommended.

A key indication is if the patient's urine output is not increasing and the renal function continues to deteriorate. “The only reason to call renal is if things are not improving and now dialysis is looming,” Dr. Fenves said.

Dr. Levin had a different perspective on specialist consults. “Nephrologists can help with fluid management, medication dosing, avoidance of nephrotoxic drugs, both singly and in combination, and in observing subtle signs of early uremia,” he said.

Even with the help of a neurologist, unfortunately, there's no actual fix for AKI. “Really there is no magic bullet,” said Dr. Fenves. “There is no medically proven therapy.”