Histologic Features Associated with Kidney Survival in Scleroderma Renal Crisis.

Abstract

BACKGROUND Scleroderma renal crisis is a severe complication of systemic sclerosis that is associated with higher morbidity and mortality. However, limited data are currently available regarding the factors affecting renal outcome during scleroderma renal crisis. The objective of this study is to describe renal histopathology in scleroderma renal crisis and to evaluate its association with kidney failure. METHODS We performed a French multicenter retrospective study that included 65 patients who underwent a kidney biopsy in the context of scleroderma renal crisis, between 2006 and 2020. Non-supervised hierarchical cluster analysis was used to identify histologic patterns. Cox model was performed to estimate the hazard ratios associated with histologic parameters for kidney failure, defined as the need for long-term dialysis therapy of or eGFR <15 ml/min/1.73m2 at last follow-up. Multiplexed sequential Immunofluorescence and proximity ligation assay was used in kidney biopsies to analyze complement system activation. RESULTS Renal pathology in scleroderma renal crisis was more heterogeneous than expected, with 3 histological patterns of kidney injury identified by cluster analysis. Multivariable analysis showed that together with creatinine at presentation, acute arteriolar thrombotic microangiopathy and onion skinning in small arteries were independently associated with the risk of kidney failure. Multiplex immunofluorescence identified fractions from the complement classical pathway in arterioles and arteries in scleroderma renal crisis, while proximity ligation experiments confirmed the in situ activation of classical pathway C3 convertase. Complement terminal pathway fraction C5b-9 was localized in injured arteries. CONCLUSIONS This study shows that the clinical definition of scleroderma renal crisis encompasses heterogeneity in the patterns of kidney injury. Acute arteriolar thrombotic microangiopathy and onion skinning were associated with kidney failure. Complement system was activated in these injured vessels.