Protective effect of ischaemic preconditioning on acute and chronic renal damage following ischaemia reperfusion injury: characterisation of fibrosis development after inflammation resolution

Brown, Charlotte V. M., Pino-Chavez, Gilda, Zaidi, Aeliya, Grigorieva, Irina, Woods, Emma, Steadman, Robert ORCID: https://orcid.org/0000-0002-1303-2496, Chavez, Rafael, Meran, Soma ORCID: https://orcid.org/0000-0003-3408-3978 and Khalid, Usman 2024. Protective effect of ischaemic preconditioning on acute and chronic renal damage following ischaemia reperfusion injury: characterisation of fibrosis development after inflammation resolution. International Journal of Clinical and Experimental Pathology 17 (4) , pp. 151-164. 10.62347/MFJG1164

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Abstract

Objectives: Acute Kidney Injury (AKI) and Chronic Kidney Disease (CKD) are increasingly recognised as one disease continuum, rather than distinct entities, and are associated with a huge burden to healthcare services. The leading cause of AKI worldwide is Ischaemia Reperfusion Injury (IRI), most commonly seen in clinical settings of sepsis-driven hypotension. Ischaemic Preconditioning (IPC) is a strategy aimed at reducing the deleterious effects of IRI. The objectives of this study were to demonstrate an efficacious in vivo model of Kidney IRI, and the protec�tive influence of IPC in attenuating AKI and development of renal fibrosis. Methods: A rat model of bilateral kidney IRI was used: Male Lewis rats (n=84) were assigned to IRI, sham or IPC. In IRI, renal pedicles were clamped for 45 minutes. IPC groups underwent pulsatile IPC prior to IRI. Kidneys were retrieved at 24 hours, 48 hours, 7 days, 14 days and 28 days, and assessed histologically. Results: IRI led to marked AKI (24-48 h) and renal fibrosis development by 28 days. IPC attenuated this damage, with 66% less fibrosis. Interestingly, at 14-days, the histological appearance of both IRI and IPC kidneys was rather similar, potentially representing an important transitional point at which kidneys commit to either fibrosis or recovery. This may provide a suitable inflexion point for introduction of novel anti-fibrotic therapies. Conclusions: In conclusion, we have characterised a model of kidney injury from acute to chronic phases, allowing detailed mechanistic understanding and which can be manipulated by effective treatment strategies such as IPC.

Item Type:	Article
Date Type:	Published Online
Status:	Published
Schools:	Medicine
Publisher:	e-Century Publishing
ISSN:	1936-2625
Date of First Compliant Deposit:	19 August 2024
Date of Acceptance:	17 January 2024
Last Modified:	28 Aug 2024 10:00
URI:	https://orca.cardiff.ac.uk/id/eprint/171469

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