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Tissue neutrophil elastase contributes to extracorporeal shock wave lithotripsy-induced kidney damage and the neutrophil elastase inhibitor, sivelestat, attenuates kidney damage with gratifying immunohistopathological and biochemical findings: an experimental study

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Abstract

Although the efficacy of extracorporeal shock wave lithotripsy (ESWL) has been well established within the literature, debate continues on the safety of the procedure while focusing on cellular injury and its long-term consequences. Here, we describe the role of neutrophil elastase (NE) in ESWL-related rat kidney damage and investigate the protective effects of sivelestat, an inhibitor of NE, during the early and late phases. Four groups including control, ESWL alone, ESWL with sivelestat 50 mg/kg and ESWL with treatment of 100 mg/kg, each consisting of ten rats were created. Biochemical parameters of kidney function and damage and immunohistopathological findings were compared in the early (72 h after ESWL) and late (1 week after ESWL) periods between the groups. During the early period, serum and urine creatinine levels and urine kidney injury molecule-1 (KIM-1) levels and the KIM-1/creatinine ratio increased in rats treated with ESWL compared to the control group. Furthermore, increased tissue inflammation, ductal dilatation and hemorrhage, and glomerular, tubular, and interstitial damage with increased NE staining were also detected in the ESWL treatment group. During the late phase, although urine KIM-1 levels remained stable at high levels, other parameters showed significant improvements. On the other hand, the administration of sivelestat 50 mg/kg decreased serum creatinine and urine KIM-1 and KIM-1/creatinine levels significantly in rats treated with ESWL, during the early and late periods. Significant decreases in tissue inflammation, tubular, and interstitial tissue damage were also observed during the early period. In conclusion, ESWL-related kidney tissue damage occurs primarily during the early period, and NE is involved in this process. On the other hand, the NE inhibitor sivelestat attenuated this ESWL-induced kidney damage.

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Acknowledgements

We would like to thank the director of our animal laboratory, Duygu Sultan Oran, and her team for their valuable support.

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Authors and Affiliations

  1. Department of Urology, Bagcilar Training and Research Hospital, Merkez Mah., Dr. Sadik Ahmet Cad., Bagcilar, Istanbul, Turkey

    Aykut Colakerol, Serhat Suzan, Mustafa Zafer Temiz, Serkan Gonultas, Serdar Aykan, Emrah Yuruk, Engin Kandırali & Atilla Semercioz

  2. Department of Pathology, Bagcilar Training and Research Hospital, Bagcilar, Istanbul, Turkey

    Sule Ozsoy

  3. Department of Biochemistry, Bagcilar Training and Research Hospital, Bagcilar, Istanbul, Turkey

    Suat Hayri Kucuk

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  1. Aykut Colakerol
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Contributions

AC, EK, and AS designed the study. AC, SZ, SG, EK, and AS coordinated the study. AC and MZT designed and ran the literature search. AC, SZ, SG, SA, SO, and SHK collected and extracted data. AC, MZT, SA, SO and SHK performed the data analysis and data interpretation. AC, MZT, and EY drafted the manuscript. SHK and SO contributed to the writing. EY, EK, and AS supervised the work and critically reviewed the article.

Corresponding author

Correspondence to Atilla Semercioz.

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The authors state that they had no conflict of interest or competing interests.

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All animal experiments and procedures were in accordance with the principles of laboratory animal care and were approved by the Institutional Animal Care and Use Committee (approval ID: 2017/40).

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Colakerol, A., Suzan, S., Temiz, M.Z. et al. Tissue neutrophil elastase contributes to extracorporeal shock wave lithotripsy-induced kidney damage and the neutrophil elastase inhibitor, sivelestat, attenuates kidney damage with gratifying immunohistopathological and biochemical findings: an experimental study. Urolithiasis 50, 103–112 (2022). https://doi.org/10.1007/s00240-021-01287-x

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