US Pharm. 2010;35(3):HS16-HS21.
The pharmacist is a crucial member of the health care team and is often the last line of defense in catching excessive or incorrect drug dosing for patients. Chronic kidney disease (CKD) affects many people in the United States, and more than 500,000 Americans have end-stage renal disease (ESRD) requiring dialysis.1,2 The most common risk factors for developing CKD are diabetes and hypertension. Patients with CKD are at increased risk for cardiovascular disease and complications. This brief review will focus on risk factors, assessing renal function, and dosage adjustments.
Risk Factors for Acute Kidney Injury
Drugs are a frequent cause of acute kidney injury (AKI). It is estimated that nearly 50% of all medicines are not used appropriately.3 Many drug clearances are affected by kidney function, and especially in the elderly population, drugs need to be adjusted due to reduced kidney function as part of the aging process. Drug-induced kidney injury can be as high as 70% in elderly patients.4 Patients increasingly take more medications and have more comorbid conditions today than ever before. They are also getting older and receiving more diagnostic and therapeutic procedures that could potentially harm their kidneys.5
Medications that cause kidney injury tend to be more common in certain patient groups and certain specific clinical scenarios. For example, if a patient is dehydrated, avoid using a nonsteroidal anti-inflammatory drug (NSAID) or a nephrotoxic drug that can lead to development of an AKI. It is important to recognize mechanisms of kidney injury and medication-related and patient-related risk factors. For instance, gentamicin can cause acute tubular necrosis if used concomitantly with furosemide for patients in the intensive care unit (ICU). Both of these drugs can increase the chance of acute kidney injury occurring in ICU patients who already have multiple comorbid conditions. Prevention and constant assessment are important, while targeting early treatment is essential to saving kidneys from further damage. When reviewing and assessing drug therapies, pharmacists should familiarize themselves with important risk factors that could potentially harm the kidneys (TABLE 1).6-10
Patients with poor kidney function are at an increased risk of developing kidney injury from nephrotoxic medications. Pharmacists should recognize that the threat of kidney injury increases if the patient has multiple risk factors. For instance, if a patient has a glomerular filtration rate (GFR) of less than 60 mL/min/1.73 m2 and comorbid conditions such as diabetes and hypertension, he or she will experience a higher chance of developing kidney injury. Pharmacists must thoroughly review the patient medication profile and assess for risks versus benefits when a nephrotoxic drug is added. TABLE 2 lists drugs with a high potential for causing kidney injury.11
Combining two or more nephrotoxic drugs can enhance the risk of kidney injury.12 Patients should be closely monitored for any changes in kidney function such as a rise in serum creatinine, a decrease in GFR, a change in urine output, and other signs and symptoms of kidney injury.
Assessing Renal Function
Patients with CKD have higher risks of drug dosing errors and experiencing adverse drug events. Traditionally, drugs that are renally cleared should be adjusted according to the calculated creatinine clearance level (CrCl) using the Cockcroft-Gault equation.13 The Cockcroft-Gault equation is the most widely used and acceptable method for drug dosage adjustment according to the FDA.14 An alternative method for assessing kidney function is the Modification of Diet in Renal Disease (MDRD) equation.15 Recently, the National Kidney Disease Education Program suggested that the MDRD equation, if adjusted for body surface area, may also be recommended to guide drug dosage adjustment.16 For drugs that have narrow therapeutic indexes or are difficult to dose or whose serum concentration is unpredictable, and for those patients with unreliable markers for estimating CrCl or GFR, clinicians should consider using more reliable alternative methods to help guide drug dosing. Many online tools are available for pharmacists to calculate CrCl or GFR, including information provided on the National Kidney Foundation’s Web site ( www.kidney.org).
Patients who have low CrCl or GFR and receive renally excreted maintenance drugs should have either the dose reduced, the dosing interval extended, or both. For example, the recommended digoxin maintenance dose for patients with normal kidney function is usually 0.25 mg administered orally daily. In patients with severe kidney disease, the digoxin dose should be decreased to 0.125 mg orally every other day.17 This is an example of a renally excreted drug that requires reduction of both the dose and the frequency. Loading doses do not usually need to be adjusted in patients with CKD. Many renally excreted drugs require a dosage adjustment when the CrCl falls below 50 mL/min.18 Pharmacists should become familiar with commonly used drugs that required dosage adjustments (TABLE 3).
Recommendations for Pharmacists
Pharmacists play a vital role in the overall management of patient care. The following are general recommendations for practicing pharmacists to observe when reviewing drug therapies:
• Assess and identify underlying risk factors
• Recognize combination nephrotoxic medications
• Use alternative nonnephrotoxic drugs (e.g., avoid the use of NSAIDs)
• Assess baseline kidney function
• Adjust the dosage as needed
• Monitor kidney functions and vital signs during nephrotoxic therapy.
Therapy may not be effective and toxicity can occur if inappropriate drug dosing is taking place in patients with kidney disease. In particular, older patients are at a higher risk of developing advanced kidney disease and related adverse events with the use of multiple medications to treat multiple conditions. Pharmacists should pay careful attention to patient kidney function when assessing drug therapies in order to use the appropriate dosage and avoid complications for this vulnerable patient population. Awareness of CKD in the U.S. is low,19 and pharmacists can help influence and educate consumers about the importance of protecting the kidneys. When encountering a prescription, pharmacists should be reminded to screen the patient’s kidney function, as they are the last line of defense for these patients.
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21. Munar MY, Singh H. Drug dosing adjustments in patients with chronic kidney disease. Am Fam Physician. 2007;75:1487-1496.
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