Effects of Elobixibat on Constipation and Lipid Metabolism in Patients With Moderate to End-Stage Chronic Kidney Disease

Objective:The aim of this study was to investigate the effects of elobixibat on constipation and lipid metabolism; and determine the factors associated with the effect of elobixibat on constipation in patients with moderate to end-stage chronic kidney disease (CKD).Methods:Stool frequency and serum lipid parameters were retrospectively analyzed before and after 4 weeks of elobixibat administration in 42 patients (CKD stage G3, 6; stage G4, 9; stage G5, 9; stage G5D, 18). Relationships between the change in stool frequency after initiation of elobixibat and various clinical parameters were analyzed by using linear regression analysis.Results:Elobixibat increased stool frequency from 0.5 ± 0.4 per day to 1.1 ± 0.6 per day (p < 0.001) regardless of whether patients were undergoing dialysis, on concomitant laxatives, or were administered elobixibat before or after breakfast. Elobixibat reduced low-density lipoprotein cholesterol concentration (from 90.9 ± 37.2 mg/dL to 77.5 ± 34.8 mg/dL, p < 0.05) and increased high-density lipoprotein cholesterol concentration (from 44.9 ± 14.3 mg/dL to 57.0 ± 25.8 mg/dL, p < 0.05), but did not change triglyceride concentration. Adverse effects were observed in two patients (nausea and diarrhea). Only phosphate concentration was correlated with the change in stool frequency after initiation of elobixibat (standard coefficient = 0.321, p = 0.043).Conclusions:Elobixibat improved constipation and lipid metabolism in patients with moderate to end-stage CKD, without serious adverse events.

Role of miRNA-671-5p in Mediating Wnt/β-Catenin-Triggered Podocyte Injury

Podocyte injury and proteinuria are the most common features of glomerular disease, which is the leading cause of end-stage renal failure. Hyperactivated Wnt/β-catenin signaling is closely associated with podocyte injury, but the underlying mechanisms are incompletely understood. Here we show that miRNA-671-5p (miR-671-5p) plays a crucial role in mediating β-catenin-triggered podocyte injury by targeting Wilms tumor 1 (WT1). Microarray-based expression profiling revealed that miR-671-5p was the most upregulated miRNA in podocytes after β-catenin activation. MiR-671-5p was colocalized with β-catenin in the glomeruli of proteinuric CKD in vivo. Bioinformatics analyses and luciferase reporter assays confirmed that miR-671-5p targeted WT1 mRNA. Overexpression of miR-671-5p mimics inhibited WT1 and impaired podocyte integrity, whereas miR-671-5p antagomir preserved the expression of WT1 and other podocyte-specific proteins under basal conditions or after β-catenin activation. In mouse remnant kidney model, overexpression of miR-671-5p aggravated podocyte injury, worsened kidney dysfunction and exacerbated renal fibrosis after 5/6 nephrectomy. In contrast, miR-671-5p antagomir alleviated podocyte injury and attenuated proteinuria and renal fibrotic lesions after glomerular injury in vivo. These studies underscore a pivotal role of miR-671-5p in mediating WT1 depletion and podocyte injury induced by β-catenin. Targeting miR-671-5p may serve as a new approach to prevent podocyte injury and proteinuria in proteinuric CKD.

Patients’ experiences of cannulation of arteriovenous access for haemodialysis: A qualitative systematic review

Introduction: Cannulation is an essential part of haemodialysis with arteriovenous access. Patients’ experiences of cannulation for haemodialysis are problematic but poorly understood. This review aims to synthesise findings related to patients’ experiences of cannulation for haemodialysis from qualitative studies, providing a fuller description of this phenomenon. Methods: Eligibility criteria defined the inclusion of studies with a population of patients with end-stage kidney disease on haemodialysis. The phenomena of interest was findings related to patients’ experiences of cannulation for haemodialysis and the context was both in-centre and home haemodialysis. MedLine, CINAHL, EMBASE, EMCARE, BNI, PsycInfo and PubMed were last searched between 20/05/2019 and 23/05/2019. The quality of studies was assessed using the using Joanna Briggs Critical Appraisal Checklist for Qualitative Research. Meta-aggregation was used to synthesise findings and CERQual to assess the strength of accumulated findings. Results: This review included 26 studies. The subject of included studies covered cannulation, pain, experiences of vascular access, experiences of haemodialysis and a research priority setting exercise. From these studies, three themes were meta-aggregated: (1) Cannulation for haemodialysis is an unpleasant, abnormal and unique procedure associated with pain, abnormal appearance, vulnerability and dependency. (2) The necessity of cannulation for haemodialysis emphasises the unpleasantness of the procedure. Success had multiple meanings for patients and patients worry about whether the needle insertion will be successful. (3) Patients survive unpleasant, necessary and repetitive cannulation by learning to tolerate cannulation and exerting control over the procedure. Feeling safe can help them tolerate cannulation better and the cannulator can invoke feeling safe. However, some patients still avoid cannulation, due to its unpleasantness. Conclusions: Cannulation is a pervasive procedure that impacts on patients’ experiences of haemodialysis. This review illuminates further patients’ experiences of cannulation for haemodialysis, indicating how improvements can be made to cannulation. Registration: PROSPERO (CRD42019134583).

Genome-wide Analysis Reflects Novel 5-Hydroxymethylcytosines Implicated in Diabetic Nephropathy

Long-term complications of type 2 diabetes (T2D) are the major causes for T2D-related disability and mortality. Notably, diabetic nephropathy (DN) has become the most frequent cause of end-stage renal disease (ESRD) in most countries. Understanding epigenetic contributors to DN can provide novel insights into this complex disorder and lay the foundation for more effective monitoring tools and preventive interventions, critical for achieving the ultimate goal of improving patient care and reducing healthcare burden. We have used a selective chemical labeling technique (5hmC-Seal) to profile genome-wide distributions of 5-hydroxymethylcytosines (5hmC), a gene activation mark, in patient-derived circulating cell-free DNA (cfDNA). Differentially modified 5hmC genes were identified across T2D patients with DN (n = 12), T2D patients with non-DN vascular complications (non-DN) (n = 29), and T2D patients with no complications (controls) (n = 14). Specifically, differential 5hmC markers between DN and controls revealed relevant pathways such as NOD-like receptor signaling pathway and tyrosine metabolism. A ten-gene panel was shown to provide differential 5hmC patterns between controls and DN, as well as between controls and non-DN patients using a machine learning approach. The 5hmC profiles in cfDNA reflected novel DN-associated epigenetic modifications relevant to the disease pathogenesis of DN. Importantly, these findings in cfDNA, a convenient liquid biopsy, have the potential to be exploited as a clinically useful tool for predicting DN in high risk T2D patients. Keywords: diabetes, nephropathy, epigenetics, 5-hydroxymethylcytosine, cfDNA

A study on evaluating blood urea and serum creatinine in diabetes mellitus patients

Diabetes is one of the leading causes for end stage renal disease and nephropathy. Increases of blood urea and serum creatinine are due to abnormal renal function and also reduction in glomerular filtration rate. So, Urea and Creatinine are the ideal biomarkers to correlate the progression of diabetic nephropathy. Aim of the study is to evaluate the blood urea & serum creatinine with HbA1C in Diabetes mellitus patients.: A total of 50 cases and 30 controls were selected in our study. Blood samples were collected for blood urea, serum creatinine, HbA1C, Fasting plasma glucose and Post prandial blood sugar with age limit of 35-65 years. Mean ±SD was calculated for all these parameters. Blood urea and Serum creatinine are statistically significant in Diabetic patients when compared to the controls.Our study shows that blood urea and serum creatinine can be used as biomarkers in the early detection of diabetic nephropathy. These parameters help in reducing the severity of renal failure.

Mechanisms of liver injury in high fat sugar diet fed mice that lack hepatocyte X-box binding protein 1

Nonalcoholic fatty liver disease (NAFLD) is one of the most common causes of liver diseases in the United States and can progress to cirrhosis, end-stage liver disease and need for liver transplantation. There are limited therapies for NAFLD, in part, due to incomplete understanding of the disease pathogenesis, which involves different cell populations in the liver. Endoplasmic reticulum stress and its adaptative unfolded protein response (UPR) signaling pathway have been implicated in the progression from simple hepatic steatosis to nonalcoholic steatohepatitis (NASH). We have previously shown that mice lacking the UPR protein X-box binding protein 1 (XBP1) in the liver demonstrated enhanced liver injury and fibrosis in a high fat sugar (HFS) dietary model of NAFLD. In this study, to better understand the role of liver XBP1 in the pathobiology of NAFLD, we fed hepatocyte XBP1 deficient mice a HFS diet or chow and investigated UPR and other cell signaling pathways in hepatocytes, hepatic stellate cells and immune cells. We demonstrate that loss of XBP1 in hepatocytes increased inflammatory pathway expression and altered expression of the UPR signaling in hepatocytes and was associated with enhanced hepatic stellate cell activation after HFS feeding. We believe that a better understanding of liver cell-specific signaling in the pathogenesis of NASH may allow us to identify new therapeutic targets.

Hallux Valgus Recurrence After Simple Bunionectomy: Algorithm Treatment

Background: Recurrences of hallux valgus can be difficult to manage, especially after a prior simple bunionectomy. This study aimed to present a treatment algorithm for the correction of recurrences after a simple bunionectomy.Methods: This was a single-center, descriptive, and retrospective comparative study. Thirty-four consecutive patients were classified according to the bone stock and the presence or absence of end-stage arthritis of the first metatarsophalangeal joint (MTPJ). According to our algorithm, we only performed an osteotomy as the salvage procedure in cases with sufficient bone stock and absence of or mild arthritis. In the other cases, we performed an MTPJ fusion. Exceptionally, we chose a Keller-Brandes arthroplasty for patients with advanced age and comorbidities. Results: We performed 17 scarf osteotomies (50%), 15 MTPJ arthrodeses (44.1%), and 2 Keller-Brandes arthroplasties (5.9%). Following the algorithm, we achieved an improvement of the AOFAS score of >30 points without severe complications in all groups.Conclusions: The proposed operative algorithm successfully addresses the recurrences considering the lack of bone stock and the presence of MTPJ arthritis.Level of EvidenceLevel 3: retrospective comparative study