Kidney Week

Abstract: SA-PO004

Calcineurin Inhibitors, Macrolides, and the Risk of Adverse Drug Events in Kidney Transplant Recipients

Session Information

• Transplantation: Clinical Outcomes
  October 27, 2018 | Location: Exhibit Hall, San Diego Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Transplantation

• 1802 Transplantation: Clinical

Authors

• Jeong, Rachel H., University of Alberta, Edmonton, Alberta, Canada

Rachel H. Jeong,

• Quinn, Robert R., University of Calgary, Calgary, Alberta, Canada

Robert R. Quinn,

• Lentine, Krista L., Saint Louis University , St. Louis, Missouri, United States

Krista L. Lentine,

• Lloyd, Anita, University of Alberta, Edmonton, Alberta, Canada

Anita Lloyd,

• Ravani, Pietro, University of Calgary, Calgary, Alberta, Canada

Pietro Ravani,

• Hemmelgarn, Brenda, University of Calgary, Calgary, Alberta, Canada

Brenda Hemmelgarn,

• Braam, Branko, University of Alberta, Edmonton, Alberta, Canada

Branko Braam,

• Garg, Amit X., London Health Sciences Centre, London, Ontario, Canada

Amit X. Garg,

• Wen, Kevin C., University of Alberta, Edmonton, Alberta, Canada

Kevin C. Wen,

• Wong, Anita, Alberta Health Services, Edmonton, Alberta, Canada

Anita Wong,

• Gourishankar, Sita, University of Alberta, Edmonton, Alberta, Canada

Sita Gourishankar,

• Lam, Ngan, University of Alberta, Edmonton, Alberta, Canada

Ngan Lam,

Background

Calcineurin inhibitors (CNI; cyclosporine, tacrolimus) are critical for kidney transplant immunosuppression, but have multiple potential drug interactions, such as with macrolide antibiotics. Clarithromycin and erythromycin inhibit CNI metabolism and increase the risk of CNI nephrotoxicity, while azithromycin does not.

Methods

We conducted a retrospective cohort study using linked healthcare databases in Alberta, Canada to study kidney transplant recipients from 2008-2015. We identified CNI-macrolide co-prescriptions and compared outcomes in those who received clarithromycin/erythromycin vs. azithromycin. The primary outcome was a composite of all-cause hospitalization, acute kidney injury (creatinine increase ≥0.3 mg/dL or 1.5-times baseline), or death within 30 days of the macrolide prescription.

Results

Of the 293 recipients who were co-prescribed a CNI and a macrolide, 38% (n=112) were prescribed clarithromycin/erythromycin while 62% (n=181) were prescribed azithromycin. Over half of the clarithromycin/erythromycin prescriptions were from general practitioners. There was no significant difference in the primary outcome between the two groups (17% vs. 11%, p=0.11); however, the risk of all-cause hospitalization was 3-times higher in the clarithromycin/erythromycin group than in the azithromycin group (10% vs. 3%; odds ratio [OR] 3.18, 95% CI 1.14 to 8.84, p=0.02). The odds of having an outpatient serum creatinine measurement within 30-days of the macrolide prescription were 41% less likely for clarithromycin/erythromycin users compared to azithromycin users (56% vs. 69%; OR 0.59, 95% CI 0.36 to 0.96, p=0.03). Although there was no difference in acute kidney injury between the two groups, there was a significantly greater decrease in eGFR in the clarithromycin/erythromycin group compared to the azithromycin group (-5.4 vs. -1.9 mL/min/1.73 m², p<0.05).

Conclusion

In conclusion, clarithromycin and erythromycin were frequently co-prescribed in kidney transplant recipients on CNIs despite known drug interactions. Clarithromycin/erythromycin users were at higher risk of hospitalization compared to azithromycin users. Safer prescribing practices in kidney transplant recipients are warranted.