Kidney Week

Abstract: TH-PO1118

Effect of Pirfenidone on Kidney Fibrosis by MRI and Urine Biomarkers: TOP-CKD Trial

Session Information

• CKD: Therapies, Innovations, and Insights
  November 06, 2025 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

• 2302 CKD (Non-Dialysis): Clinical, Outcomes, and Trials

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

Kidney tubule-interstitial fibrosis is highly prognostic for CKD progression. Pirfenidone is FDA approved to treat idiopathic pulmonary fibrosis in humans, and has prevented kidney fibrosis in animal models. Whether pirfenidone prevents kidney fibrosis in humans with CKD is unknown

Methods

We conducted a two-site, double blind, randomized clinical trial testing pirfenidone 1335 mg/day vs. matched placebo in 98 participants with CKD. Inclusion required eGFR > 20 and 5 year KFRE risk > 1% at baseline. Key exclusions included ADPKD, liver disease, active smoking, and QTc > 500msec. After a 2-week active run-in, participants were randomized and treated for 12 months. Kidney fibrosis was assessed by apparent diffusion coefficient (ADC) of the kidney cortex by MRI (1° outcome), assessment of 8 urine biomarkers (exploratory outcomes), and albuminuria. Linear mixed models evaluated changes over 12 months by treatment arm.

Results

Mean age was 73±13 years, 87% were men, 59% had diabetes, mean eGFR was 36±11 ml/min/1.73m², and median urine ACR was 145 (IQR 35, 549) mg/g. Characteristics were well balanced at baseline. Ninety-two participants had acceptable baseline MRIs, and 73 (79%) had month 12 MRI. All 98 provided baseline urine biomarker data, and 84 (86%) provided month 12 biomarker data. Seventy-nine percent of participants completed the 12-month study on study medication per protocol. Randomization to pirfenidone was not associated with changes in ADC by MRI over 12 months, urine biomarkers of kidney damage or albuminuria (Table).

Conclusion

Treatment with pirfenidone for 12 months did not improve MRI imaging of kidney fibrosis or urine biomarkers of kidney tubule damage in this trial among persons with moderate CKD.

Funding

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

Digital Object Identifier (DOI)

• doi: 10.1681/ASN.2025cfv4nn85