[New Therapeutic Strategies in the Treatment of CKD Anemia: Hypoxia-Induced Factor Prolyl-Hydroxylase Inhibitors].

The link between chronic renal failure and anemia has been known for more than 180 years, negatively impacting the quality of life, cardiovascular risk, mortality, and morbidity of patients with chronic kidney disease (CKD). Traditionally, the management of anemia in CKD has been based on the use of replacement martial therapy, vitamin therapy, and the use of erythropoiesis-stimulating agents (ESAs). In recent years, alongside these consolidated therapies, new molecules known as hypoxia-induced factor prolyl-hydroxylase inhibitors (HIF-PHIs) have appeared. The mechanism of action is expressed through an increased transcriptional activity of the HIF gene with increased erythropoietin production. The drugs currently produced are roxadustat, daprodustat, vadadustat, molidustat, desidustat, and enarodustat; among these only roxadustat is currently approved and usable in Italy. The possibility of oral intake, pleiotropic activity on martial and lipidic metabolism, and the non-inferiority compared to erythropoietins make these drugs a valid alternative to the treatment of anemia associated with chronic kidney disease in the nephrologist practice.

Efficacy of sustained low-efficiency dialysis in the management of topiramate intoxication: case report.

Guidelines on the use of dialysis treatment in patients with chronic kidney disease (CKD) and TPM (Topiramate) intoxication are controversial. A 51-year-old man with epilepsy and CKD was carried to our emergency department for dysuria and sickness. He chronically assumed TPM 100 mg 3/day. Creatinine level was 2.1 mg/dL, blood urea nitrogen 70 mg/dL, and inflammation indexes were increased. We started empirical antibiotic therapy and rehydration. The day two he had diarrhea and an acute insurgence of dizziness, confusion, and bicarbonate levels reduction. Brain CT resulted negative for acute events. During the night his mental status worsened, and urinary output results were about 200 mL in 12h. EEG showed desynchronized brain bioelectric activity. Thereafter, there was an episode of seizure and then anuria, hemodynamic instability, and loss of consciousness. Creatinine value was 5.39 mg/dL with a serious metabolic acidosis non-anion gap. We decided to start 6-hours Sustained Low Efficiency Hemo-Dia-Filtration (SLE-HDF). We assisted in the recovery of consciousness and later in the improvement of kidney function after 4 hours of treatment. TPM levels before SLE-HDF resulted in 123.1 µg/mL. At the end of treatment resulted in 30 µg/mL. To our knowledge, this is the first report of TPM involuntary intoxication in a patient affected by CKD who survived such a high TPM concentration treated with renal replacement therapy. SLE-HDF resulted in moderate elimination of TPM and acidemia resolution, continuous monitoring patient's vital parameters in relation to his hemodynamic instability, since blood flow and dialysate flow are lower than conventional hemodialysis.

Safety and Efficacy of Eculizumab Therapy in Multiple Sclerosis: A Case Series.

(1) Background: Complement system activation has been proposed as one of the different factors that contribute to Multiple Sclerosis (MS) pathogenesis. In this study, we aimed to describe the potential effects of eculizumab, an anticomplement therapy, on MS disease activity in a cohort of relapsing-remitting (RR) MS patients who discontinued IFN-ß therapy due to IFN-ß-related thrombotic microangiopathy (TMA) onset. (2) Methods: In this retrospective observational multicentric study, we searched for all patients with MS treated by eculizumab with a survey of several nephrological and neurological centers (over 45 centers). (3) Results: Nine patients were included. The mean follow-up time under eculizumab was 3.72 ± 2.58 years. There were no significant differences in disease activity (EDSS, relapses, new T2, and/or Gd-enhancing lesions at MRI) considering the two years before and after eculizumab therapy. No adverse events potentially related to eculizumab therapy were reported during follow-up. (4) Conclusions: In this preliminary study, we described a good safety profile for eculizumab therapy in MS. However, the available data are not sufficient to make firm conclusions about the possible efficacy of eculizumab as a disease-modifying therapy for MS patients.

Handling High-Throughput Omics Data for Systems Genetics Analysis.

Omics data are being generated and collected at unprecedented scale. During the last decade, single omics, such as genomics, transcriptomics, proteomics, and metabolomics, have already highlighted pathophysiological pathways underpinning a variety of conditions across all the fields of medicine.In fact, high-throughput data generated by the comprehensive and unbiased analysis of an entire segment of the flow of genetic information (i.e., genetic variants in the case of genomics, or gene expression in transcriptomics) certainly provide a plethora of information and a precious support to dissect the mechanisms involved in complex diseases.Yet the most effective approach, set to fully exploit the potential of such big data, lies in the possibility to integrate various omics to unveil previously unappreciated pathways. This approach is the foundation of Systems Biology and allows to overcome the limitations inherent to single omics and traditional biology analyses.A robust and powerful strategy has been developed to integrate genetics and gene expression data in the framework of Systems Genetics. With this technique the first two layers of the flow of genetic information are integrated and specifically it is possible to pinpoint which genetic variants are associated with gene co-expression networks.Here we present a versatile bioinformatic protocol that can be used to study the Systems Genetics of CTLs, in order to identify genes (also known as master regulators) that influence the activation of biological pathways in these cells in a particular state or condition.

Sarcopenia and cardiovascular risk indices in patients with chronic kidney disease on conservative and replacement therapy.

OBJECTIVE: Chronic kidney disease (CKD) is a condition with high cardiovascular mortality associated with emerging risk factors, including sarcopenia. Several mechanisms can affect muscle mass, such as vitamin D deficiency, low protein intake, physical inactivity, metabolic acidosis, and inflammation leading to a worsening of cardiovascular outcomes and cognitive function. We aimed to evaluate the prevalence of sarcopenia in CKD patients on conservative and replacement therapy and the associations between sarcopenia and markers of atherosclerosis, endothelial dysfunction, psychological and cognitive function. METHODS: We enrolled CKD patients (stage 3/5 KDIGO [Kidney Disease: Improving Global Outcomes]) and hemodialysis, peritoneal dialysis, and post-kidney transplant patients. Clinical, laboratory and instrumental assessments, including bioimpedance analysis, hand-grip strength, intima media thickness, flow-mediated dilation, and epicardial adipose tissue, were performed in addition to analysis of psychological and cognitive status by the Montreal Cognitive Assessment, Mini-Mental State Examination, and Geriatric Depression Scale. RESULTS: A total of 77 patients (43 male) with a mean age of 69.6 ± 9.85 y were studied. According to validated criteria (using bioimpedance analysis and hand-grip strength), the prevalence of sarcopenia was 49.4%. Sarcopenic patients had higher values of intima media thickness (P = 0.032) and epicardial adipose tissue (P = 0.012) and lower flow-mediated dilation (P = 0.002), total cholesterol (P = 0.005), and high-density lipoprotein cholesterol (P = 0.008) with respect to non-sarcopenic patients. We found higher Geriatric Depression Scale scores (P = 0.04) in sarcopenic patients, whereas we did not find differences between the two groups in Mini-Mental State Examination and Montreal Cognitive Assessment score. CONCLUSION: Sarcopenia is highly prevalent in CKD/end stage renal disease patients and is associated with changes in early systemic indices of atherosclerosis and endothelial dysfunction, known as markers of worse prognosis.