Renal involvement in HCV related cirrhosis evidenced as glomerular and tubular derangement

Introduction and Aims: The relation between HCV infection and glomerular damage is well recognized, with evidences of negative impact on renal function. HCV replication in renal tubular cells on kidney biopsies has been reported but very limited data are available on HCV-mediated tubular damage. The aim of the study was to assess the presence of renal involvement (RI), glomerular or tubular, in patients with HCV cirrhosis. Methods: 98 patients with HCV cirrhosis Child Pugh-A were consecutively enrolled. Glomerular filtration rate (eGFR) was estimated with CKD-EPI 2009 equation. Urinary albumin/creatinine (ACR) and alpha1microglobulin/creatinine (a1MCR) ratios were calculated. Glomerular involvement was defined based on ACR>20μg/mg, tubular involvement based on a1MCR>14μg/mg plus fractional sodium excretion (FeNa)>1%. Urine concentration of Liver-type Fatty Acid-Binding Protein (L-FABP) and Kidney injury molecule-1 (KIM-1) were examined in morning midstream urine samples (ELISA) and the values normalized to urine creatinine concentration as expression of tubular derangement. Results: eGFR was ≥60 mL/min/1.73 m2 in 92 patients (93.8%) and between 45-59 mL/min/1.73 m2 in 6 patients (6.1%). Glomerular involvement was found in 19 patients (19.4%), tubular involvement in 31 patients (31.6%) and these co-occurred in 10 patients ( p=0.034). Patients with glomerular or tubular involvement, or both, considered as patients with RI, showed significantly lower eGFR values ( p=0.005) (Tab 1). A ROC curve was drafted and a cut point of 90 ml/min predicted RI (AUC: 0.700; sensitivity 63%, specificity 75%). Patients with RI were older, had higher ACR and a1MCR levels and exhibited a higher KDIGO stage (Tab 1). No association was found between RI and: HCV-RNA levels, liver stiffness and liver function tests. L-FABP and KIM-1 levels were significantly higher in patients with RI. Conclusions: Tubular and/or glomerular involvement is quite frequent in HCV cirrhotic patients, despite a normal eGFR. The evidence of tubular involvement suggests an alternative localization of HCV as renal disease

Chronic Kidney Disease as a Systemic Inflammatory Syndrome: Update on Mechanisms Involved and Potential Treatment

Chronic kidney disease (CKD) is characterized by manifestations and symptoms involving systemic organs and apparatus, associated with elevated cardiovascular morbidity and mortality, bone disease, and other tissue involvement. Arterial hypertension (AH), diabetes mellitus (DM), and dyslipidemia, with glomerular or congenital diseases, are the traditional risk factors recognized as the main causes of progressive kidney dysfunction evolving into uremia. Acute kidney injury (AKI) has recently been considered an additional risk factor for the worsening of CKD or the development of CKD de novo. Evidence underlies the role of systemic inflammation as a linking factor between AKI and CKD, recognizing the role of inflammation in AKI evolution to CKD. Moreover, abnormal increases in oxidative stress (OS) and inflammatory status in CKD seem to exert an important pathogenetic role, with significant involvement in the clinical management of this condition. With our revision, we want to focus on and update the inflammatory mechanisms responsible for the pathologic conditions associated with CKD, with particular attention on the development of AKI and AKI-CKD de novo, the alteration of calcium-phosphorus metabolism with bone disease and CKD-MBD syndrome, the status of malnutrition and malnutrition-inflammation complex syndrome (MICS) and protein-energy wasting (PEW), uremic sarcopenia, the status of OS, and the different inflammatory pathways, highlighting a new approach to CKD. The depth comprehension of the mechanisms underlying the development of inflammation in CKD may present new possible therapeutic approaches in CKD and hopefully improve the management of correlated morbidities and provide a reduction in associated mortality

The unusual association of three autoimmune diseases in a patient with Noonan’s syndrome

report on a 26-year-old female affected by Noonan syndrome (NS), a congenital disorder characterized by various phenotypic features and congenital anomalies) associated with a variety of autoimmune diseases, including systemic lupus erythematosus, celiac disease, and Hashimoto thyroiditis. Autoimmunity is seldom described in NS and the association between this congenital disease and three autoimmune disorders has not been previously report