Kidney Week

Abstract: FR-PO0149

Calcineurin Inhibitor Therapy and Clinical Response in Patients with WT-1-Related Disorders

Session Information

• Hereditary Glomerular and Tubulointerstitial Kidney Diseases
  October 23, 2026 | Location: Exhibit Hall A, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Genetic Diseases of the Kidneys

• 1202 Genetic Diseases of the Kidneys: Non-Cystic (Complex and Non-Cystic Monogenic)

Authors

• Aoyama, Shuhei, Kobe Daigaku Daigakuin Igakukei Kenkyuka Igakubu, Kobe, Hyogo Prefecture, Japan

Shuhei Aoyama, MD

• Nagano, China, Kobe Daigaku Daigakuin Igakukei Kenkyuka Igakubu, Kobe, Hyogo Prefecture, Japan

China Nagano, MD, PhD

• Nishimura, Ryo, Kobe Daigaku Daigakuin Igakukei Kenkyuka Igakubu, Kobe, Hyogo Prefecture, Japan

Ryo Nishimura

• Fujiwara, Ayako, Kobe Daigaku Daigakuin Igakukei Kenkyuka Igakubu, Kobe, Hyogo Prefecture, Japan

Ayako Fujiwara

• Baba, Minato, Kobe Daigaku Daigakuin Igakukei Kenkyuka Igakubu, Kobe, Hyogo Prefecture, Japan

Minato Baba

• Yamamoto, Asahi, Kobe Daigaku Daigakuin Igakukei Kenkyuka Igakubu, Kobe, Hyogo Prefecture, Japan

Asahi Yamamoto, MD

• Kimura, Yuka, Kobe Daigaku Daigakuin Igakukei Kenkyuka Igakubu, Kobe, Hyogo Prefecture, Japan

Yuka Kimura, MD

• Ichikawa, Yuta, Kobe Daigaku Daigakuin Igakukei Kenkyuka Igakubu, Kobe, Hyogo Prefecture, Japan

Yuta Ichikawa

• Inoki, Yuta, Kobe Daigaku Daigakuin Igakukei Kenkyuka Igakubu, Kobe, Hyogo Prefecture, Japan

Yuta Inoki, MD, MEd

• Horinouchi, Tomoko, Kobe Daigaku Daigakuin Igakukei Kenkyuka Igakubu, Kobe, Hyogo Prefecture, Japan

Tomoko Horinouchi, MD, PhD

• Yamamura, Tomohiko, Kobe Daigaku Daigakuin Igakukei Kenkyuka Igakubu, Kobe, Hyogo Prefecture, Japan

Tomohiko Yamamura, MD, PhD

• Sakakibara, Nana, Kobe Daigaku Daigakuin Igakukei Kenkyuka Igakubu, Kobe, Hyogo Prefecture, Japan

Nana Sakakibara, MD, PhD

• Ishimori, Shingo, Kobe Daigaku Daigakuin Igakukei Kenkyuka Igakubu, Kobe, Hyogo Prefecture, Japan

Shingo Ishimori, MD, PhD

• Nozu, Kandai, Kobe Daigaku Daigakuin Igakukei Kenkyuka Igakubu, Kobe, Hyogo Prefecture, Japan

Kandai Nozu, MD, PhD

Background

WT1-related disorders are genetic kidney diseases characterized by early-onset proteinuria, nephrotic syndrome(NS), and progressive kidney dysfunction. Although calcineurin inhibitors(CNI) may reduce proteinuria in some patients, evidence remains limited. This study evaluated CNI use and its association with proteinuria reduction and kidney outcomes in WT1-related disorders.

Methods

We retrospectively reviewed patient background, treatment details, and responsiveness in 39 patients with genetically diagnosed WT1-related disorders from April 2016 to September 2025. Cases were collected through collaboration with multiple institutions and analyzed at our center.

Results

The median age at genetic diagnosis was 8.4 years(range, 2.3–14.3), and the median age at proteinuria onset was 3.0 years(1.4–5.2). 25 patients(64%) presented with concomitant NS. At the time of genetic diagnosis, 21 patients(54%) had already progressed to end-stage kidney disease. Steroids were administered to 18 patients(46%), and 15 patients(38%) received CNI for more than 6 months. Among the CNI-treated patients, 13 received cyclosporine, one received tacrolimus, and one received both cyclosporine and tacrolimus. The median duration of CNI treatment was 8.1 years(1.6–10.6).
Among CNI-treated patients with NS, 8 of 10 patients(80%) achieved remission, including 5 complete remissions and 3 partial remissions. Among CNI-treated patients without NS, 2 of 5 patients(40%) achieved remission, including 1 complete remission and 1 partial remission. Among the 10 patients who achieved remission, 2 had missense variants in exon 8 or 9, 6 had splice-site variants in intron 9, and 2 had nonsense variants in exon 8 or 9. Among the 13 CNI-treated patients with available longitudinal eGFR data, exploratory analysis suggested a less steep decline in eGFR after CNI initiation compared with before initiation (−0.9 vs −8.6 mL/min/1.73 m2/year, p=0.286), although interpretation was limited by sparse pre-treatment data.

Conclusion

In this cohort of patients with WT1-related disorders, urinary protein reduction was observed in 67% of the patients with CNI use. Patients treated with CNI did not show evidence of accelerated kidney function decline after treatment initiation. These findings suggest that CNI may be a therapeutic option for reducing proteinuria in selected patients with WT1-related disorders, without apparent worsening of kidney function decline.