DOI: 10.1177/09612033261479120 ISSN: 0961-2033

Interstitial palladin is associated with tubulointerstitial chronicity and adverse outcomes in patients with lupus nephritis

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

Tubulointerstitial lesions predict kidney prognosis in lupus nephritis (LN), but the molecular features of interstitial fibrosis remain incompletely defined. We previously showed that palladin, an actin-associated protein, drives kidney fibrosis through actin dynamics. This study examined whether interstitial palladin expression is associated with histopathology and prognosis in LN.

Methods

We retrospectively analyzed Japanese patients with biopsy-proven LN at Kanazawa University Hospital between 1990 and 2018. Palladin-positive area was quantified by immunohistochemistry and log2-transformed (log2 palladin). The colocalization of palladin and α-smooth muscle actin (αSMA) was investigated by immunofluorescence. Associations with modified NIH activity and chronicity indices were assessed using Spearman correlation. Event-free survival for renal replacement therapy (RRT) initiation or all-cause death was evaluated by Kaplan-Meier analysis.

Results

Thirty-four patients were included. Palladin was predominantly expressed in the kidney interstitium and colocalized with αSMA-positive cells. Log2 palladin correlated with the modified NIH chronicity index (ρ = 0.61, p < 0.01), tubular atrophy (ρ = 0.53, p < 0.01), interstitial fibrosis (ρ = 0.56, p < 0.01), and interstitial inflammation (ρ = 0.55, p < 0.01), but not with the total activity index (ρ = 0.24, p = 0.16). During a median follow-up of 10.1 years (IQR, 3.3–17.5), seven patients reached the composite outcome. The composite outcome occurred in five patients in the high-palladin group and two patients in the low-palladin group, and high palladin expression was associated with poorer event-free survival by Kaplan–Meier analysis (log-rank p = 0.04).

Conclusion

Interstitial palladin expression may reflect tubulointerstitial chronicity and be associated with poor outcomes in LN; however, its independent prognostic value could not be established due to the limited number of events.

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