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Objective Tissue damage in lupus nephritis (LN) is mediated by activation of the classical complement pathway. Complement-mediated upregulation of endothelial cell adhesion molecules is seen in dermal blood vessels of non-lesional skin of patients with active lupus. In diseases with systemic complement activation, extensive microvascular C5b-9 deposition is seen in non-lesional skin. In this study, we assess the presence of systemic complement pathway activation as determined by non-lesional skin microvascular C5b-9 deposition in patients with LN.Methods Eight patients with active LN and eight patients without active LN underwent non-lesional skin biopsies. Using a diaminobenzidine technique, specimens were evaluated for microvascular C5b-9 consistent with systemic complement pathway activation.Results Five of eight patients with active LN and one of eight patients without active LN demonstrated positive C5b-9 staining in non-lesional skin (p=0.04). Positive non-lesional C5b-9 staining has greater specificity, 87.5%, for active LN than pyuria, low complements, elevated double-stranded DNA (dsDNA) and proteinuria. Urine protein creatinine ratio was significantly higher in patients with positive non-lesional C5b-9 deposition (5.18 vs 1.20; p=0.04). C5b-9 deposition was not associated with a higher NIH Activity Index, interstitial fibrosis, dsDNA or lower complements.Conclusion This is the first study to demonstrate evidence in non-lesional skin of microvascular C5b-9 indicative of systemic complement pathway activation in LN. C5b-9 deposition is statistically more common and demonstrated greater specificity than most historical biomarkers for active LN. The findings support a potential role for microvascular C5b-9 assessment in non-lesional skin as a biomarker for LN activity.

Atypical hemolytic uremic syndrome (aHUS) is a rare form of thrombotic microangiopathy due to inability to regulate the complement cascade, resulting in thrombocytopenia, intravascular hemolysis, and end-organ damage. Over 70% of cases are associated with mutations in complement or complement regulatory proteins, and some two-thirds have recognized complement-activating conditions triggering an aHUS event. We describe a case of aHUS after abdominal myomectomy in a 42-year-old woman that was managed with plasma exchange and eculizumab (an anti-C5 monoclonal antibody). The diagnosis was confirmed by biopsy of normal-appearing deltoid skin that demonstrated microvascular C5b-9 deposition, diagnostic of systemic complement pathway activation. Although extremely uncommon following gynecologic surgery, aHUS should be considered in the setting of postoperative oliguric acute kidney injury, as prompt diagnosis is necessary to prevent significant morbidity and mortality.