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Colakerol A. et al., 2021: 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.

Colakerol A, Suzan S, Temiz MZ, Gonultas S, Aykan S, Ozsoy S, Kucuk SH, Yuruk E, Kandırali E, Semercioz A.
Department of Urology, Bagcilar Training and Research Hospital, Merkez Mah., Dr. Sadik Ahmet Cad., Bagcilar, Istanbul, Turkey.
Department of Pathology, Bagcilar Training and Research Hospital, Bagcilar, Istanbul, Turkey.
Department of Biochemistry, Bagcilar Training and Research Hospital, Bagcilar, Istanbul, Turkey.
Department of Urology, Bagcilar Training and Research Hospital, Merkez Mah., Dr. Sadik Ahmet Cad., Bagcilar, Istanbul, Turkey.

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 efects 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 fndings 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 infammation, 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 signifcant improvements. On the other hand, the administration of sivelestat 50 mg/kg decreased serum creatinine and urine KIM-1 and KIM-1/creatinine levels signifcantly in rats treated with ESWL, during the early and late periods. Signifcant decreases in tissue infammation, 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.
Urolithiasis. 2021 Nov 15. doi: 10.1007/s00240-021-01287-x. Online ahead of print. PMID: 34778918

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Comments 1

Peter Alken on Tuesday, 10 May 2022 10:30

Basic research does not have to ask or answer medical, clinical questions. However, it should at least deal with actual problems or delineate how the evaluated experimental setting contributes to the understanding of contemporary problems or future developments.
The present study evaluates the effect of standard ESWL - a 40-year-old setting - on rat kidneys. The effects are well known and of negligible clinical importance. Sivelestat, a synthetic NE inhibitor shows some protective effects. The drug is known since 20 years and was initially thought to be beneficial in the treatment of the acute respiratory distress syndrome (ARDS), a life-threatening condition caused by direct or indirect lung injury. A look into the actual literature seems to suggest that the drug is looking for a disease to be tretaed. In a recent Cochrane review on the treatment of ARDS Silvestat is of minor importance (1).
Evaluating the effect a 20 year old drug on a 40 year old clinical setting seems to be a waste of time and money.

1 Lewis SR, Pritchard MW, Thomas CM, Smith AF. Pharmacological agents for adults with acute respiratory distress syndrome. Cochrane Database Syst Rev. 2019 Jul 23;7(7):CD004477. doi: 10.1002/14651858.CD004477.pub3. PMID: 31334568; PMCID: PMC6646953.

Peter Alken

Basic research does not have to ask or answer medical, clinical questions. However, it should at least deal with actual problems or delineate how the evaluated experimental setting contributes to the understanding of contemporary problems or future developments. The present study evaluates the effect of standard ESWL - a 40-year-old setting - on rat kidneys. The effects are well known and of negligible clinical importance. Sivelestat, a synthetic NE inhibitor shows some protective effects. The drug is known since 20 years and was initially thought to be beneficial in the treatment of the acute respiratory distress syndrome (ARDS), a life-threatening condition caused by direct or indirect lung injury. A look into the actual literature seems to suggest that the drug is looking for a disease to be tretaed. In a recent Cochrane review on the treatment of ARDS Silvestat is of minor importance (1). Evaluating the effect a 20 year old drug on a 40 year old clinical setting seems to be a waste of time and money. 1 Lewis SR, Pritchard MW, Thomas CM, Smith AF. Pharmacological agents for adults with acute respiratory distress syndrome. Cochrane Database Syst Rev. 2019 Jul 23;7(7):CD004477. doi: 10.1002/14651858.CD004477.pub3. PMID: 31334568; PMCID: PMC6646953. Peter Alken
Saturday, 18 May 2024