Kidney Week

Abstract: SA-PO0243

Effect of Penicillin on Proximal Tubule Secretion in Persons with CKD

Session Information

• Pharmacology
  November 08, 2025 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)

• 2000 Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)

Authors

• Garimella, Pranav S., University of California San Diego, La Jolla, California, United States

Pranav S. Garimella, MD, MPH, FASN

• Katz, Ronit, University of Washington, Seattle, Washington, United States

Ronit Katz, PhD

• Seegmiller, Jesse C., University of Minnesota Twin Cities, Minneapolis, Minnesota, United States

Jesse C. Seegmiller, PhD

• Shlipak, Michael, San Francisco VA Health Care System, San Francisco, California, United States

Michael Shlipak, MD, MPH

• Inker, Lesley Ann, Tufts Medical Center, Boston, Massachusetts, United States

Lesley Ann Inker, MD, MS, FASN

• Ix, Joachim H., University of California San Diego, La Jolla, California, United States

Joachim H. Ix, MD, FASN

Background

Organic anion transporters (OAT) and organic cation transporters (OCT) are responsible for the active secretion of many endogenous substances and drugs. Competitive inhibition of OAT and OCT by drugs may increase risk of drug-drug interactions (DDIs). We conducted this proof-of-concept study to evaluate competitive inhibition by penicillin (an OCT substrate) on endogenous proximal tubular secretory solutes in persons with chronic kidney disease (CKD).

Methods

Ten participants with eGFR 30-45 mL/min/1.73m² received 1 million units of intravenous Penicillin G. Ten endogenous solutes marking OAT and nine solutes marking OCT secretion were measured in paired blood and urine by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Tubular secretion was assessed by calculating the urine-to-plasma ratio (UPR) of each solute and creating a summary secretion score for OAT and OCT solutes separately at baseline, and 240 minutes after penicillin infusion.

Results

Mean age was 57 years, and 50% were women. Baseline eGFR was 39 ± 6 ml/min/1.73m² and albuminuria was 164 (60-453) mg/g. Prior to penicillin infusion, the median (IQR) composite OAT secretory score was 17.6 (5.4-28.2) and OCT secretory score was 29.9 (14.7-40.9). Urine to plasma ratio (UPR) levels of all individual secretory metabolites were lower at the 240 minutes post-penicillin infusion compared to baseline (0 minutes). Overall, the absolute suppression of composite markers of OAT clearance was greater (Figure) than that of OCT after penicillin infusion (p= 0.028).

Conclusion

Infusion of penicillin and OAT substrate inhibits proximal tubular solute clearance via OATs and OCTs, with larger effects observed on OAT substrate clearance. Future studies are required to determine if these findings may contribute to drug-drug interactions.

Funding

• NIDDK Support

Digital Object Identifier (DOI)

• doi: 10.1681/ASN.20251bgcg9x0