Study Identifies Drugs of Concern for Patients With CKD

Researchers Highlight Medications to Be Adjusted, Avoided

February 12, 2020 10:49 am News Staff

Chronic kidney disease occurs in about 15% of all adults and about one in five adults older than 65. Like many chronic conditions, CKD can progress from one stage to another without a patient being aware of what's happening. And, because patients with CKD often have other comorbidities, it's common for patients with CKD to take multiple medications.(academic.oup.com)

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Polypharmacy carries considerable health risks, however. As such, it's essential that family physicians and other primary care clinicians keep up to date on the latest recommendations for patients who have CKD or are at increased risk for the disease.

A team of Canadian investigators, after conducting a systematic literature review and additional research, recently published in the Annals of Pharmacotherapy(journals.sagepub.com) a list of two dozen commonly used medications that they contend must be dose-adjusted or avoided in patients with CKD and a secondary list of 12 common medications that could be dose-adjusted or avoided.

Study Design

The research consisted of three phases.

First, the investigators developed an initial medication list drawn from previously published research and a comprehensive literature review that encompassed several health literature databases, including PubMed, MEDLINE and the Cochrane Database of Systematic Reviews.

Story Highlights
  • Patients with chronic kidney disease often take multiple medications, a practice that can carry substantial health risks.
  • After a lengthy review process, Canadian researchers developed a list of two dozen commonly used medications that must be dose-adjusted or avoided in patients with CKD.
  • The researchers also developed a secondary list of 12 medications that could be dose-adjusted or avoided.

Next, they assembled a three-round modified Delphi panel consisting of primary care physicians, nephrologists, renal pharmacists, clinical pharmacologists and other health care professionals to obtain consensus regarding medications that require dose adjustment or avoidance in these patients.

Finally, to build on the consensus reached using that iterative process, the investigators conducted an expert consensus workshop with a second group of experts who were not involved in the Delphi panel, charging them with prioritizing the medication list. These individuals were charged with grouping the medications into those that "must," "could," or "do not" need to be considered for dose-adjustment or avoidance.

Throughout the study, the researchers used estimated glomerular filtration rate to measure kidney function and guide their recommendations.

Primary Results

Of the 66 medications recommended by the Delphi panel, the consensus workshop group identified three dozen drugs that are routinely used in primary care and that must or could be dose-adjusted or avoided in patients with CKD.

Routinely used medications in primary care that the workshop members categorized as those that must be considered for dose adjustment or avoidance based on estimated GFR were

  • antibiotics: ciprofloxacin, co-trimoxazole (trimethoprim/sulfamethoxazole), levofloxacin, nitrofurantoin;
  • anticoagulants: apixaban, dabigatran, edoxaban, rivaroxaban;
  • anticonvulsants: gabapentin, pregabalin;
  • antivirals: acyclovir, valacyclovir;
  • oral hypoglycemics: canagliflozin, dapagliflozin, empagliflozin, glyburide and metformin; and
  • various other drugs: baclofen, colchicine, digoxin, duloxetine, fibrates, lithium and spironolactone.

Routinely used medications in primary care that they said could be considered for dose adjustment or avoidance based on estimated GFR were

  • antimuscarinics: solifenacin, tolterodine;
  • antivirals: famciclovir, oseltamivir;
  • oral hypoglycemics: gliclazide, saxagliptin, sitagliptin; and
  • various other drugs: bisphosphonates, escitalopram, metoclopramide, rosuvastatin, venlafaxine.

Additional Findings and Conclusions

During the review process, the research also team identified three classes of medications (ACE inhibitors, angiotensin receptor blockers and NSAIDs) as broadly requiring additional consideration in patients with CKD, citing the risk of acute kidney injury in certain circumstances.

Similarly, the Delphi panel also determined that opioids deserve special attention when used in patients with CKD.

The researchers acknowledged limitations in the study, most notably the use of estimated GFR to measure kidney function. In some patients, they wrote, medication dosage should be adjusted based on estimated creatine clearance in addition to or instead of estimated GFR.

Even so, said the authors, the medication list serves as an updated, user-friendly resource that can help clinicians avoid adverse outcomes in individuals with CKD.

"The ultimate goal of this work is to reduce harmful medication prescribing in those with CKD through knowledge translation and dissemination strategies among primary care providers," the authors wrote, adding that more research is needed to confirm the list's usefulness.

More From AAFP
Familydoctor.org: Chronic Kidney Disease(familydoctor.org)

Additional Resources
Choosing Wisely: Chronic Kidney Disease(www.choosingwisely.org)

National Institute of Diabetes and Digestive and Kidney Diseases: Chronic Kidney Disease (CKD)(www.niddk.nih.gov)