Renal and vascular outcomes in patients with isolated antiphospholipid syndrome nephropathy.

BACKGROUND: Antiphospholipid syndrome (APS) nephropathy (APSN) is a rare pattern with specific features resulting from microvascular lesions. The prognosis of APSN, outside of lupus nephritis, is unknown. The aim of this study was to describe the renal, vascular and overall outcomes of patients with APSN. METHODS: Retrospective multicenter study of patients with antiphospholipid antibodies (aPL) associated with histological APSN lesions and no other nephropathy, identified through a national call for medical records. End-stage renal disease (ESRD)-free survival, thrombosis recurrence-free survival and overall survival were assessed. RESULTS: Thirty patients were included (19 women) with a median age of 40 years (34-52 years). Fifteen patients had APS, 26/28 had lupus anticoagulant, and 15/26 had triple positivity for aPL. Median eGFR was 50 (31-60) mL/min/1.73 m2. Glomerular thrombotic microangiopathy was found in 12/24 cases, fibrous intimal hyperplasia in 12/22 cases and focal cortical atrophy in 17/29 cases. Nineteen patients had moderate to severe interstitial fibrosis (>25%). Six patients developed ESRD at a median follow-up of 6.2 (1.8-9.1) years. The ESRD-free survival rates at 5 and 10 years were 80.0% (95% CI 57.6%-91.4%) and 72.7% (95% CI, 46.9%-87.4%) respectively. None of the histological factors considered was significantly associated with a decrease in eGFR at 12 months. Thrombosis recurrence-free survival was 77.8% (95% CI 48.2%-91.6%) at 10 years. Overall survival was 94% at 10 years (95% CI 65.0%-99.2%). CONCLUSIONS: The renal prognosis of isolated APSN is poor. The severe fibrotic lesions observed are suggestive of late diagnosis.

An early increase in endothelial protein C receptor is associated with excess mortality in pneumococcal pneumonia with septic shock in the ICU.

BACKGROUND: This study investigated changes in plasma level of soluble endothelial protein C receptor (sEPCR) in association with outcome in patients with septic shock. We explored sEPCR for early sepsis prognosis assessment and constructed a scoring system based on clinical and biological data, in order to discriminate between surviving at hospital discharge and non-surviving patients. METHODS: Clinical data and samples were extracted from the prospective "STREPTOGENE" cohort. We enrolled 278 patients, from 50 intensive care units (ICUs), with septic shock caused by pneumococcal pneumonia. Patients were divided into survivors (n = 194) and non-survivors (n = 84) based on in-hospital mortality. Soluble EPCR plasma levels were quantified at day 1 (D1) and day 2 (D2) by ELISA. The EPCR gene A3 haplotype was determined. Patients were followed up until hospital discharge. Univariate and multivariate analyses were performed. A scoring system was constructed using least absolute shrinkage and selection operator (lasso) logistic regression for selecting predictive variables. RESULTS: In-hospital mortality was 30.2% (n = 84). Plasma sEPCR level was significantly higher at D1 and D2 in non-surviving patients compared to patients surviving to hospital discharge (p = 0.0447 and 0.0047, respectively). Early increase in sEPCR at D2 was found in non-survivors while a decrease was observed in the survival group (p = 0.0268). EPCR A3 polymorphism was not associated with mortality. Baseline sEPCR level and its variation from D1 to D2 were independent predictors of in-hospital mortality. The scoring system including sEPCR predicted mortality with an AUC of 0.75. CONCLUSIONS: Our findings confirm that high plasma sEPCR and its increase at D2 are associated with poor outcome in sepsis and thus we propose sEPCR as a key player in the pathogenesis of sepsis and as a potential biomarker of sepsis outcome.