Kidney Week

Abstract: SA-PO0237

Safety and Tolerability of Pirfenidone in Patients with CKD: TOP-CKD Trial

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

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

Joachim H. Ix, MD, FASN

• Scherzer, Rebecca, University of California San Francisco, San Francisco, California, United States

Rebecca Scherzer, PhD

• Rifkin, Dena E., University of California San Diego, La Jolla, California, United States

Dena E. Rifkin, MD

• Park, Meyeon, University of California San Francisco, San Francisco, California, United States

Meyeon Park, MD, FASN

• Malkina, Anna, University of California San Francisco, San Francisco, California, United States

Anna Malkina, MD

• Wang, Zhen Jane, University of California San Francisco, San Francisco, California, United States

Zhen Jane Wang

• Potok, O. Alison, University of California San Diego, La Jolla, California, United States

O. Alison Potok, MD

• Parsa, Afshin, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland, United States

Afshin Parsa, MD, MPH, FASN

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

Michael Shlipak, MD, MPH

Background

Pirfenidone is approved to treat idiopathic pulmonary fibrosis. Pirfenidone is cleared by the liver, but metabolites are retained in CKD. Previously reported pirfenidone side effects include gastro-intestinal (GI) intolerance and photosensitivity rash. Tolerability and risk of these side effects in persons with CKD are unknown.

Methods

We conducted a two-site, double blind, randomized clinical trial testing pirfenidone 1335 mg/day vs. placebo in 98 persons with CKD. MRI imaging for fibrosis was the primary endpoint. Inclusion required eGFR > 20ml/min/1.73m² and 5-year KFRE risk > 1% at baseline. Exclusions included ADPKD, liver disease, smoking, and QTc > 500msec. After 2-weeks active run-in, participants were randomized and treated for 12 months. Gastrointestinal (GI) and dermatologic (Derm) symptoms (pre-specified symptoms of interest) and adherence were assessed every 3 months.

Results

Mean age was 70±13 years, mean eGFR was 36±11 ml/min/1.73m², and median urine ACR was 145 (IQR 30, 370) mg/g. Characteristics were well balanced by randomization. 5 participants in the pirfenidone arm, and 3 in the placebo arm permanently discontinued study medications for AEs. Deaths, SAEs and AEs, GI symptoms and eGFR trajectories were similar across arms. 5 (10%) in pirfenidone vs. 0 in placebo had photosensitivity rashes, all of which resolved with drug discontinuation. Among those still enrolled at month 12 (N=77), median study drug consumption was 92% and 96% (p 0.34) in pirfenidone and plabebo; 82% and 68% consumed > 80% of study medications in pirfenidone and placebo, respectively (Table).

Conclusion

In persons with CKD, pirfenidone is generally well tolerated with similar rates of adverse events, GI symptoms, and eGFR changes compared to placebo over 12 months. Photosensitivity rash occurred more frequently in persons randomized to pirfenidone.

Funding

• NIDDK Support – Genentech (donated drug and placebo, no financial support)

Digital Object Identifier (DOI)

• doi: 10.1681/ASN.2025bwb96qcy