Background-Atheroembolic renal disease (AERD) is caused by showers of cholesterol crystals released by eroded atherosclerotic plaques. Embolization may occur spontaneously or after angiographic/surgical procedures. We sought to determine clinical features and prognostic factors of AERD. Methods and Results-Incident cases of AERD were enrolled at multiple sites and followed up from diagnosis until dialysis and death. Diagnosis was based on clinical suspicion, confirmed by histology or ophthalmoscopy for all spontaneous forms and for most iatrogenic cases. Cox regression was used to model time to dialysis and death as a function of baseline characteristics, AERD presentation (acute/subacute versus chronic renal function decline), and extrarenal manifestations. Three hundred fifty-four subjects were followed up for an average of 2 years. They tended to be male (83%) and elderly (60% Ͼ70 years) and to have cardiovascular diseases (90%) and abnormal renal function at baseline (83%). AERD occurred spontaneously in 23.5% of the cases. During the study, 116 patients required dialysis, and 102 died. Baseline comorbidities, ie, reduced renal function, presence of diabetes, history of heart failure, acute/subacute presentation, and gastrointestinal tract involvement, were significant predictors of event occurrence.

Chikungunya Virus in Aedes albopictus , Italy

BackgroundInflammation in skeletal muscle is implicated in the pathogenesis of insulin resistance and cachexia but why uremia up‐regulates pro‐inflammatory cytokines is unknown. Toll‐like receptors (TLRs) regulate locally the innate immune responses, but it is unknown whether in chronic kidney disease (CKD) TLR4 muscle signalling is altered. The aim of the study is to investigate whether in CKD muscle, TLRs had abnormal function and may be involved in transcription of pro‐inflammatory cytokine.MethodsTLR4, phospho‐p65, phospho‐ikBα, tumour necrosis factor (TNF)‐α, phospho p38, Murf 1, and atrogin were studied in skeletal muscle from nondiabetic CKD stage 5 patients (n = 29) and controls (n = 14) by immunohistochemistry, western blot, and RT–PCR. Muscle cell cultures (C2C12) exposed to uremic serum were employed to study TLR4 expression (western blot and RT–PCR) and TLR‐driven signalling. TLR4 signalling was abrogated by a small molecule chemical inhibitor or TLR4 siRNA. Phospho AKT and phospho p38 were evaluated by western blot.ResultsCKD subjects had elevated TLR4 gene and protein expression. Also expression of NFkB, p38 MAPK and the NFkB‐regulated gene TNF‐α was increased. At multivariate analysis, TLR4 protein content was predicted by eGFR and Subjective Global Assessment, suggesting that the progressive decline in renal function and wasting mediate TLR4 activation. In C2C12, uremic serum increased TLR4 as well as TNF‐α and down‐regulated pAkt. These effects were prevented by blockade of TLR4.ConclusionsCKD promotes muscle inflammation through an up‐regulation of TLR4, which may activate downward inflammatory signals such as TNF‐α and NFkB‐regulated genes.

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