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

Abstract

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.

Keywords: Acute kidney injury; Complement; Scleroderma renal crisis; Systemic sclerosis; Thrombotic microangiopathy.

Fig. 1

Worldwide prevalence of anti-RNA polymerase III antibody according to French systematic review and meta-analysis. Reproduced with permission from Sobanski et al. [14]

Fig. 2

Proposed pathogenesis of SRC. Modified from Denton et al. [18]. Created with BioRender.com

Fig. 3

UKSSG guidelines on the diagnosis and management of scleroderma renal crisis Reproduced with permission from Lynch et al. [56]