312. Perturbed Response to Experimental Renal Injury in a Mouse Model of Systemic Sclerosis

Derrett-Smith, Emma; Neal, M. Pinson; Abraham, David A.; Salama, Alan D.; Little, Mark; Denton, Christopher

doi:10.1093/rheumatology/keu127.009

Cited by 4 publications

(1 citation statement)

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“…The TβRIIΔk-fib transgenic mouse model replicates hypertension and large vessel fibrosis. The model demonstrates exaggerated fibrotic response to hypertensive injury and provides opportunity for further studies into the specific mechanism of injury in SRC [39].…”

Section: Animal Models Of Srcmentioning

confidence: 97%

Renal Disease and Systemic Sclerosis: an Update on Scleroderma Renal Crisis

Cole

Ong

Denton

2022

Clinic Rev Allerg Immunol

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Scleroderma renal crisis (SRC) is a life-threatening complication of systemic sclerosis (SSc) with a mortality of 20% at 6 months. Once the leading cause of mortality in scleroderma (SSc), it remains a serious complication, often necessitating level three care for patients affected. Whilst renal outcomes have significantly improved following the advent of angiotensin-converting enzyme inhibitor (ACEi) therapy, SRC remains a precarious challenge for clinicians, due to lack of preventative measures and the fact that patients can rapidly decline despite best medical management. Large cohort studies spanning decades have allowed clear identification of phenotypes particularly at risk of developing SRC thus allowing enhanced monitoring and early identification in those individuals. Novel urinary biomarkers for renal disease in SSc may offer a new window for early identification of SRC patients and response to treatment. Multiple studies have demonstrated increased activity of complement pathways in SRC with some anecdotal cases exhibiting serological response to treatment with eculizumab where ACEi and therapeutic plasma exchange (TPE) were not successful. Endothelin-1 blockade, a therapeutic strategy in other SSc vasculopathies, has shown potential as a target but clinical trials are yet to show a clear treatment benefit. Clear guidelines for the management of SRC are in place to standardise care and facilitate early collaboration between rheumatology and renal physicians. Outcomes following renal transplant have improved but the mortality of SRC remains high, indicating the need for continued exploration of the mechanisms precipitating and exacerbating SRC in order to develop novel therapies.

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Section: Animal Models Of Srcmentioning

confidence: 97%