For AKI patients, “their renal function is changing every day, and so therefore their drug clearance may be changing every day,” says Bruce Mueller, PharmD, a professor at Clinical Pharmacy Department at the University of Michigan School of Pharmacy. He discussed how renal impairment can affect drug dosing with interviewer Chris Madjerich, PharmD, Clinical Product Specialist at Wolters Kluwer Health, in the webinar “Strategies to provide optimal dosing support for CKD patients,” co-presented by Wolters Kluwer Health with National Cheng Kung University Hospital (NCKUH) and Taiwan Pharmacy Association.
“Kidney disease is something that not everybody talks about. If you have kidney disease, it’s quite possible you don’t know it,” Mueller asserts in the webinar, citing the following statistics:
- As many as one out of seven people has CKD.
- Just over 22% of hospitalized patients will develop an AKI of some sort while hospitalized.
Once patients who develop AKI are admitted to the intensive care unit, the majority of their drugs are going to require a dosing adjustment, Mueller explains.
How do you balance drug benefits with kidney disease risk?
Mueller notes that many times, when dealing with a patient who suffers from CKD or AKI, the curative benefits of a first-line drug treatment for any given condition or comorbidity have to be weighed against the drug’s risk of nephrotoxicity, or being toxic to the kidney.
“The problem is that some of it is our own fault as clinicians because so many of the drugs we give are toxic to the kidneys,” he says.
To illustrate his point, he discussed an internal review his team performed at the University of Michigan Hospital, which revealed that about 22% of all medication orders in the adult intensive care units and nearly 40% of orders in the pediatric ICUs were potentially nephrotoxic. “We’re doing something to these patients that’s injuring their kidneys. But at the same point, we have to give these medications that are nephrotoxic because maybe we don’t have a choice,” he reasons.
Monitoring renal dosing in critical care situations
It is up to clinicians to carefully monitor kidney toxicity and determine an appropriate adjusted dose in order to deliver the needed drug even if it is nephrotoxic, Mueller explains. “It’s something for us to watch every day, particularly in the critical care environment, because we often can’t avoid these medications. Many of our patients are predisposed to developing kidney disease.” Those include patients with:
- Diabetes
- Obesity
- Abnormal liver function
- Pre-existing kidney disease
- Kidney replacement therapy
How does dialysis impact drug dosing?
“Dialysis has changed a lot over the years,” Mueller says, explain that today’s highly efficient dialysis membranes clear drugs better than in the past. Use of continuous therapies in the ICU mean that old hemodialysis dosing recommendations no longer apply. Treatment durations affect drug treatment strategies. “We’re learning a lot about how fast kidney function can change.”
When it comes to treating ICU patients, Mueller notes that there are two extremes to account for:
- Augmented renal clearance, which he describes as an “almost superhuman” glomerular filtration rate (GFR) potentially requiring higher doses than the standard prescribed for somebody with normal renal function.
- Renal insufficiency, requiring clinicians calculate a patient’s current GFR and adjust doses to account for those considerations.
Different types of kidney replacement therapy, including SLED (slow, low efficiency dialysis) or PIRRT (periodic intermittent renal replacement therapies) can also vastly change dosing protocols, Mueller notes. “We are changing the way we use these dialysis technologies, but we haven’t done more pharmacokinetic trials to find out the correct way to dose our medications” when using these new dialysis scenarios, he says. This creates enormous pressure for clinicians as “underdosing is not acceptable … and overdosing obviously isn’t either with a higher rate of adverse effects if we do it wrong.”
Tools to help determine dose adjustments for renal disease
In a perfect world, Mueller muses in the webinar, clinicians would be able to continually measure every patient’s drug serum concentration in order to determine if drug treatment is effectively therapeutic, and if not, how to most appropriately adjust dosing for renal considerations.
While the world is not perfect, in healthcare today, there is a better understanding of the pharmacokinetics and pharmacodynamics that help determine how to manage medications for those with altered renal function, Mueller acknowledges.
He has worked alongside the content development team at UpToDate® Lexidrug™ (formerly Lexicomp®) and UpToDate® to build out renal dosing reference information to help inform decision-making for clinicians in critical care situations who need to consider dosing adjustments for patients with impaired or augmented renal functions. Mueller and his team approached the content development process by starting with the foundation of drug recommendations for normal renal function, he explains, and then evaluated contemporary pharmacokinetic and pharmacodynamic literature. They reviewed the latest best practices to determine recommendations for a variety of patient scenarios including multiple plans for renal replacement therapies. Those recommendations continue to be updated on an ongoing basis.
“We really started fresh,” says Mueller, noting that his content development team didn’t refer to the old recommendations when reviewing the most current literature to develop new ones. “We put together recommendations that would apply to every available kidney replacement therapy that we see used in the inpatient and outpatient setting. And so, I can say that the recommendations are really ‘up-to-date.’”
Because various dialysis rates and other standards of practice may be “in the ballpark” but not consistent from hospital to hospital, Mueller says, it is important for clinicians to have access to reliable references on renal adjusted dosing to help support their decision-making. “We put out recommendations that we felt would apply to just about anybody, anywhere,” no matter how an institution is using their kidney replacement therapies. “By using the UpToDate format, we can provide all our recommendations in one place.”
