Prognostic value of high-sensitive cardiac troponin I in asymptomatic chronic hemodialysis patients.

INTRODUCTION: Increased levels of cardiac troponins (cTn) are a hallmark of acute myocardial infarction (AMI), along with symptoms and electrocardiographic (ECG) changes. Stably elevated cTn concentrations are frequently observed in asymptomatic patients with chronic kidney disease (CKD) and/or on hemodialysis (HD); the meaning of this elevation, as assessed by conventional techniques, remains unclear. Aim of our study was to evaluate the clinical significance of cTnI levels in asymptomatic HD patients by employing a newer high-sensitive cTnI (hs-cTnI) assay. METHODS: We enrolled 49 patients undergoing regular HD treatment for more than 3 months; all patients were asymptomatic for chest pain and had no history of acute coronary syndrome in the past 2 months. For every patient we measured hs-cTnI, cTnI and brain natriuretic peptide (BNP) before initiation of one HD session at baseline (T0), after 3 (T1) and 9 months (T2). Demographic, anamnestic, dialytic and echocardiographic characteristics of the examined population were evaluated. We also recorded the number of cardiovascular events from T0 to 12 months after T2. RESULTS: Fifteen patients were lost to follow-up: 6 died, 2 underwent kidney transplantation, 7 did not match the inclusion criteria later during observation. At T0 (49 patients) we observed 14 hs-cTnI positive patients vs. 4 standard c-TnI positive patients (28,5% vs 8,1%); at T1 (40 patients) 16 vs 3 (26.4% vs 7.5%); at T2 (34 pz) 9 vs 0 (26.4% vs 0%). During the study we recorded 10 cardiovascular events, 8 of which in patients that were hs-cTNI positive, leading to death in 3. Hs-cTnI levels were predictive of cardiovascular events at all times and predictive of cardiovascular mortality at T0 and T1 (p < 0.001). In a multivariate analysis, a history of coronary artery disease (CAD) was an independent variable of high hs-cTnI levels at T0 (p < 0.04) and T1 (p < 0.03). CONCLUSIONS: Our study shows that a novel sensitive assay detects more asymptomatic HD patients compared to previously used methods, being at the same time predictive of cardiovascular mortality and morbidity. The only independent variable of high hs-cTnI concentrations was a positive history of cardiovascular disease, suggesting a possible role of hs-cTnI in identifying a high-risk subset of patients.

[Steroid and cyclosporine therapy in idiopathic membranous nephropathy: monocentric experience and literature review].

INTRODUCTION: Immunosuppressive treatment of patients with idiopathic membranous nephropathy (IMN) is debated due to its possible side effects. The 2012 KDIGO guidelines suggest alkylating agents as first choice therapy. The aim of the study is to retrospectively evaluate the induction and maintenance of clinical remission in patients with histological diagnosis of IMN undergoing steroid and/or cyclosporine therapy at the Nephrology Unit of the Sant'Andrea Hospital in Rome. MATERIALS AND METHODS: Therapy A (conservative) was reserved to low-risk patients. 8 medium and high risk patients were induced by Therapy B (Prednisone 1 mg / kg ≤12-16 weeks plus 8 weeks withdrawal); 6 patients by Therapy C (Prednisone 1 mg /kg ≥20-24 weeks plus 8 week withdrawal) and, finally, 6 steroid-resistent patients by Therapy D (steroid withdrawal + cyclosporine 3-5 mg / kg for 2 years). RESULTS: Complete remission was observed in 37.5% of patients in Therapy B, in 83.3% of patients in Therapy C and in 66.6% of patients in Therapy D. Patients in group B relapsed more frequently than patients in the other groups. Side effects were irrelevant. CONCLUSIONS: In view of the potential cytotoxicity of alkylating agents, steroids are a valid alternative in inducing and maintaining clinical remission over time, when administered with a more aggressive induction scheme. In cases of steroid resistance or rapid relapse, cyclosporine is a valid alternative to alkylating agents.

HDAC1 inhibition by MS-275 in mesothelial cells limits cellular invasion and promotes MMT reversal.

Peritoneal fibrosis is a pathological alteration of the peritoneal membrane occurring in a variety of conditions including peritoneal dialysis (PD), post-surgery adhesions and peritoneal metastases. The acquisition of invasive and pro-fibrotic abilities by mesothelial cells (MCs) through induction of MMT, a cell-specific form of EMT, plays a main role in this process. Aim of this study was to evaluate possible effects of histone deacetylase (HDAC) inhibitors, key components of the epigenetic machinery, in counteracting MMT observed in MCs isolated from effluent of PD patients. HDAC inhibitors with different class/isoform selectivity have been used for pharmacological inhibition. While the effect of other inhibitors was limited to a partial E-cadherin re-expression, MS-275, a HDAC1-3 inhibitor, promoted: (i) downregulation of mesenchymal markers (MMP2, Col1A1, PAI-1, TGFß1, TGFßRI) (ii) upregulation of epithelial markers (E-cadherin, Occludin), (iii) reacquisition of an epithelial-like morphology and (iv) marked reduction of cellular invasiveness. Results were confirmed by HDAC1 genetic silencing. Mechanistically, MS-275 causes: (i) increase of nuclear histone H3 acetylation (ii) rescue of the acetylation profile on E-cadherin promoter, (iii) Snail functional impairment. Overall, our study, pinpointing a role for HDAC1, revealed a new player in the regulation of peritoneal fibrosis, providing the rationale for future therapeutic opportunities.

Metformin associated lactic acidosis (MALA): clinical profiling and management.

Metformin (MF) accumulation during acute kidney injury is associated with high anion gap lactic acidosis type B (MF-associated lactic acidosis, MALA), a serious medical condition leading to high mortality. Despite dose adjustment for renal failure, diabetic patients with chronic kidney disease (CKD) stage III-IV are at risk for rapid decline in renal function by whatever reason, so that MF toxicity might arise if the drug is not timely withdrawn. Sixteen consecutive patients were admitted to our Hospital's Emergency Department with clinical findings consistent with MALA. Fifteen had prior history of CKD, 60 % of them with GFR between 30 and 60 ml/min. Of these, 5 required mechanical ventilation and cardiovascular support; 3 promptly recovered renal function after rehydration, whereas 10 (62 %) required continuous veno-venous renal replacement treatment. SOFA and SAPS II scores were significantly related to the degree of lactic acidosis. In addition, lactate levels were relevant to therapeutic choices, since they were higher in dialyzed patients than in those on conservative treatment (11.92 mmol/l vs 5.7 mmol/l, p = 0.03). The overall death rate has been 31 %, with poorer prognosis for worse acidemia, as serum pH was significantly lower in non-survivors (pH 6.96 vs 7.16, p > 0.04). Our own data and a review of the literature suggest that aged, hemodynamically frail patients, with several comorbidities and CKD, are at greater risk of MALA, despite MF dosage adjustment. Moreover, renal replacement therapy rather than simple acidosis correction by administration of alkali seems the treatment of choice, based on eventual renal recovery and overall outcome.