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Best Practice Spotlight
Use best practices when estimating renal function
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Adjusting drug dosage for patients with chronic kidney disease is a core function of clinical pharmacy practice, but deciding on best practices in doing so can be complicated.
"Over the last three to four decades there have been a number of methods proposed to estimate renal function," says Gary R. Matzke, PharmD, FCP, FCCP, FASN, DPNAP, professor of pharmacy and pharmaceutics and professor of medicine at the Medical College of Virginia, Virginia Commonwealth University in Richmond, VA.
The Cockcroft-Gault method for creatinine clearance (CrCl) emerged as the primary way to estimate renal function, and it's been accepted as the standard approach for decades, Matzke says.
Pharmacists can make modifications to this method to accommodate its use for morbidly obese patients, as well as for patients who have lost limbs, had traumatic injuries, and are elderly, he says.
During the last 10 years, there was a renaissance of new approaches introduced for estimating renal function, Matzke says.
These include a method introduced by Andrew S. Levey, MD, and colleagues from The Institute for Clinical Research and Health Policy Studies, Tufts Medical Center in Boston, MA.
"Levey and colleagues looked at a unique set of data from over 1,600 patients with chronic kidney disease (CKD), who had measured renal function," Matzke explains. "They looked at the patients' characteristics of age, weight, gender, urea nitrogen concentration, albumin, serum creatinine, and they came up with an equation for estimating the glomerular filtration rate (GFR)."
Levey's method was published in 1999 as the Modification of Diet in Renal Disease (MDRD) study equation.1
"They followed up that six variable equation about two years later with a four variable equation," Matzke says. "That methodology began to receive lots of support as a foundation for staging chronic kidney disease."
The researchers' intent was to identify patients at risk of experiencing progression from mild renal disease to moderate, severe disease and even to the need for dialysis, he notes.
In the decade since this introduction, public health officials and others have focused attention on the need to identify people at risk of CKD and have advocated having hospital laboratories use the four variable method to estimate GFR and report it as a part of their standard practice, he adds.
"In a survey that Tom Dowling, John Murphy, and I conducted last year, we found that 90% of the surveyed pharmacists stated that their hospital now has this as a standard in their hospital lab," Matzke says.
So the use of MDRD evolved from a method with useful public health benefits to a method that some have proposed may be a useful means for adjusting drug dosing regimens, he explains.
The National Kidney Foundation now recommends that hospitals use the MDRD study equation to estimate GFR.
And this change raises questions for hospital pharmacists who need to know the most appropriate way to adjust drug dosage in patients, Matzke says.
"The controversy in drug dosing is that creatinine clearance is not the same as GFR," he says. "And currently, the industry guidance the Food and Drug Administration published in 1997 urged that companies use creatinine clearance as the index of renal function for determining the relationship between drugs pharmacokinetic parameters and renal function."
The key is to find another marker of kidney function that can be used, as well. (See expert guidelines for measuring renal function, right.)
"We're entering an era where there will be an expanded need for assessment of renal function," he says. "There are some good ways, some bad ways, and some really ugly ways which have been proposed."
But even the method that now looks the worst or the most complicated could prove to ultimately be the most useful.
"Right now, everybody in the pharmacy community and everyone who takes care of patients who have CKD or acute kidney injury need to be on their toes so they'll know what they're estimating (CrCl or GFR)," Matzke says. "If the equation to estimate the dose is based on renal function measure or estimate X, Y, or Z, then the clinician needs to know what measure of renal function was used in that dosing equation so they're putting in the appropriate value to arrive at the right dose for the patient."
Now there are a variety of methods available and emerging, and there is a lack of prospective data to confirm that all the methods are equivalent.
One key is to study the product's FDA label. If the label says the drug dosage adjustment is by creatinine clearance, the pharmacist at this time should use creatinine clearance, especially for drugs with a narrow therapeutic range, Matzke suggests.
If the label is not specific as to the renal function estimation methodology, then the pharmacist might be able to substitute the MDRD-estimated GFR or use a serum cystatin C method, he adds.
Finally, it's important that pharmacy directors keep up with the latest studies on this topic since it's been evolving so rapidly.
"There are at least 10 to 15 other equations that have been proposed in the last few years, while we used to have one predominant one until MDRD was developed in 1999," he adds.