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Background <p>Kidney fibrosis is a common mechanism of progressive kidney diseases including diabetic kidney disease (DKD). We have revealed that palladin, an actin-associated protein, drives kidney fibrosis through actin dynamics. However, it has not been elucidated whether palladin is related to the pathogenesis of DKD. In this study, we investigated whether palladin is associated with kidney dysfunction, fibrosis, and prognosis in DKD. </p> Methods <p>We conducted a retrospective cohort study of Japanese patients diagnosed with DKD by kidney biopsy between 2000 and 2020. Palladin expression was quantified as the percentage of positive area on immunohistochemistry and log2-transformed (log2 palladin). We assessed its correlation with baseline clinical characteristics and pathological findings. Event-free survival for the initiation of renal replacement therapy (RRT) or all-cause death was analyzed by Kaplan–Meier analysis and Cox proportional hazards regression.</p> Results <p>A total of 38 patients were enrolled with a mean age of 57.4&#xa0;years (10 women). Median follow-up was 2.6&#xa0;years (range 0.01–19.9), during which 12 patients experienced the composite outcome. On immunohistochemistry, palladin is expressed in myofibroblasts in kidneys from patients with DKD<b>.</b> Log2 palladin was independently associated with lower baseline eGFR (<i>B</i> = − 12.3&#xa0;mL/min/1.73 m<sup>2</sup> per doubling; 95% CI − 20.1 to − 4.54; <i>p</i> = 0.003). Higher palladin was associated with poorer event-free survival (log-rank <i>p</i> = 0.003). In Cox analysis, doubling of palladin-positive area was associated with increased risk of RRT initiation or death (age-adjusted HR 2.70; 95% CI 1.36 to 6.33; <i>p</i> = 0.004).</p> Conclusion <p>Interstitial palladin expression may serve as a histopathological prognostic marker in patients with DKD.</p>

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Interstitial palladin expression is associated with increased risk of end-stage kidney disease and death in patients with biopsy-proven diabetic kidney disease

  • 期刊论文

  • 发表日期：

    2026年3月26日

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  • Naoki Yamamoto,
  • Norihiko Sakai,
  • Daichi Kaikoi,
  • Takahiro Matsuno,
  • Akihiko Koshino,
  • Keisuke Sako,
  • Taku Kobayashi,
  • Takahiro Yuasa,
  • Akira Tamai,
  • Taichiro Minami,
  • Yuta Yamamura,
  • Megumi Oshima,
  • Satoshi Hara,
  • Kiyoaki Ito,
  • Akinori Hara,
  • Miho Shimizu,
  • Takashi Wada,
  • Yasunori Iwata

摘要

Background

Kidney fibrosis is a common mechanism of progressive kidney diseases including diabetic kidney disease (DKD). We have revealed that palladin, an actin-associated protein, drives kidney fibrosis through actin dynamics. However, it has not been elucidated whether palladin is related to the pathogenesis of DKD. In this study, we investigated whether palladin is associated with kidney dysfunction, fibrosis, and prognosis in DKD.

Methods

We conducted a retrospective cohort study of Japanese patients diagnosed with DKD by kidney biopsy between 2000 and 2020. Palladin expression was quantified as the percentage of positive area on immunohistochemistry and log2-transformed (log2 palladin). We assessed its correlation with baseline clinical characteristics and pathological findings. Event-free survival for the initiation of renal replacement therapy (RRT) or all-cause death was analyzed by Kaplan–Meier analysis and Cox proportional hazards regression.

Results

A total of 38 patients were enrolled with a mean age of 57.4 years (10 women). Median follow-up was 2.6 years (range 0.01–19.9), during which 12 patients experienced the composite outcome. On immunohistochemistry, palladin is expressed in myofibroblasts in kidneys from patients with DKD. Log2 palladin was independently associated with lower baseline eGFR (B = − 12.3 mL/min/1.73 m2 per doubling; 95% CI − 20.1 to − 4.54; p = 0.003). Higher palladin was associated with poorer event-free survival (log-rank p = 0.003). In Cox analysis, doubling of palladin-positive area was associated with increased risk of RRT initiation or death (age-adjusted HR 2.70; 95% CI 1.36 to 6.33; p = 0.004).

Conclusion

Interstitial palladin expression may serve as a histopathological prognostic marker in patients with DKD.