Peritoneal Protein and Albumin Excretion as Markers of Cardiovascular Risk and Systemic Endothelial Dysfunction

BackgroundMicroalbuminuria is a marker of systemic endothelial dysfunction. We studied the relationship between peritoneal protein loss in peritoneal dialysis (PD) patients, which is conceptually analogous to microalbuminuria in non-uremic patients, and pre-existing vascular disease in new PD patients.MethodsPeritoneal total protein and albumin loss were quantified within 2 months of initiation of dialysis in 44 consecutive new PD patients, together with a standard peritoneal equilibration test. The results were compared according to the presence of cardiovascular disease (CVD) prior to initiation of dialysis, lean body mass, and serum albumin and C-reactive protein (CRP) concentrations.ResultsThe dialysate albumin concentration was closely correlated with the creatinine dialysate-to-plasma ratio at 4 hours (r = 0.601, p < 0.001). It was higher in patients with pre-existing CVD than in those without, when patients were analyzed according to diabetic status (one-way ANOVA, p = 0.004). In diabetic patients, the dialysate albumin concentration was significantly higher in patients with pre-existing CVD than in those without (0.754 ± 0.273 vs 1.088 ± 0.280 mg/μmol creatinine, p = 0.04). Multivariate analysis showed that only diabetic status and dialysate albumin concentration, but not peritoneal transport status or serum CRP, were independent predictors of pre-existing CVD. Although dialysate protein loss accounted for only 10.5 ± 4.4% of total protein catabolism, the dialysate protein level was significantly correlated with serum albumin concentration (r = −0.457, p = 0.002), percentage of lean body mass (r = −0.558, p < 0.001), and serum CRP concentration (r = 0.434, p = 0.003).ConclusionsPatients with CVD prior to initiation of dialysis have higher levels of dialysate albumin and total protein excretion, indicating that dialysate protein loss is a marker of underlying CVD. Dialysate protein and albumin excretion may provide a simple and convenient measure of vascular disease and endothelial dysfunction in PD patients

Piperacillin/tazobactam Induced Myelosuppression

Neutropenia, secondary to immune destruction or maturation arrest, is the most commonly described adverse haematological effect of beta-lactam antibiotics. We describe a case of reversible pancytopenia, with evidence of hypocellular marrow, after a prolonged course of piperacillin/tazobactam for 26 days

A prospective cohort study of the long-term effects of CPAP on carotid artery intima-media thickness in Obstructive sleep apnea syndrome

<p>Abstract</p> <p>Objective</p> <p>To examine the long-term effect of CPAP on carotid artery intima-media thickness (IMT) in patients with Obstructive sleep apnea syndrome(OSAS).</p> <p>Methods</p> <p>A prospective observational study over 12 months at a teaching hospital on 50 patients newly diagnosed with OSAS who received CPAP or conservative treatment (CT). Carotid IMT was assessed with B-mode Doppler ultrasound from both carotid arteries using images of the far wall of the distal 10 mm of the common carotid arteries at baseline, 6 months and 12 months.</p> <p>Measurements and results [mean (SE)]</p> <p>Altogether 28 and 22 patients received CPAP and CT respectively without significant differences in age 48.8(1.8) vs 50.5(2.0)yrs, BMI 28.2(0.7) vs 28.0(1.2)kg/m2, ESS 13.1(0.7) vs 12.7(0.6), AHI 38(3) vs 39(3)/hr, arousal index 29(2) vs 29(2)/hr, minimum SaO₂75(2) vs 77(2)% and existing co-morbidities. CPAP usage was 4.6(0.3) and 4.7(0.4)hrs/night over 6 months and 1 year respectively. Carotid artery IMT at baseline, 6 months, and 12 months were 758(30), 721(20), and 705(20)micron for the CPAP group versus 760(30), 770(30), and 778(30)micron respectively for the CT group, p = 0.002.</p> <p>Among those free of cardiovascular disease(n = 24), the carotid artery IMT at baseline, 6 months and 12 months were 722(40), 691(40), and 659(30)micron for the CPAP group (n = 12) with usage 4.5(0.7) and 4.7(0.7) hrs/night over 6 months and 12 months whereas the IMT data for the CT group(n = 12) were 660(20), 685(10), and 690(20)micron respectively, p = 0.006.</p> <p>Conclusions</p> <p>Reduction of carotid artery IMT occurred mostly in the first 6 months and was sustained at 12 months in patients with reasonable CPAP compliance.</p

Prevalence of complications among Chinese diabetic patients in urban primary care clinics: A cross-sectional study

Background: A territory-wide diabetes management program (Risk Assessment Management Program - RAMP) was recently established, providing comprehensive management for all diabetics, helping to delineate current level of control and complications prevalence among primary care diabetic patients in Hong Kong. Method. This cross-sectional study captured anonymous clinical data from RAMP patients. Data obtained include sociodemographic details, type of diabetes, illness duration, family history, drug usage, coexisting illnesses, diabetic complications and other clinical parameters. Results: Data from 15,856 type 2 diabetic patients were analyzed. 57.1% were above 60 years old, with mean disease duration of 7.3 years. Hypertension was the commonest coexisting chronic illness (57.6%). 30.2% and 61.8% have their systolic and diastolic pressure controlled to below 130 mmHg and 80 mmHg respectively. Over half (51.5%) had an HbA1c level of less than 7.0%. 88.4% did not achieve target lipid level. 15% were on diet control alone. Only 22.2% were on statins. In patients with microalbuminuria and macroalbuminuria, 40.7% and 54.5% were on angiotensin converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) respectively. 12.9%, 38.8% and 2.4% had diabetic retinopathy, nephropathy and neuropathy respectively. Overall, 37.9%, 7.3% and 0.4% had single, two and three concurrent microvascular complications respectively. Conclusion: The level of diabetic control is comparable with other developed countries. We demonstrated a high prevalence of microvascular complications among Chinese primary care patients despite achieving adequate HbA1c levels, highlighting the importance of managing all aspects of diabetes including weight, lipid and blood pressure. Efforts to improve holistic management must be tailored according to the needs of our population, with the challenges that the majority have low educational background and in the older age group. © 2014 Kung et al.; licensee BioMed Central Ltd.link_to_subscribed_fulltex

Endotoxaemia in Haemodialysis: A Novel Factor in Erythropoetin Resistance?

Background/Objectives Translocated endotoxin derived from intestinal bacteria is a driver of systemic inflammation and oxidative stress. Severe endotoxaemia is an underappreciated, but characteristic finding in haemodialysis (HD) patients, and appears to be driven by acute repetitive dialysis induced circulatory stress. Resistance to erythropoietin (EPO) has been identified as a predictor of mortality risk, and associated with inflammation and malnutrition. This study aims to explore the potential link between previously unrecognised endotoxaemia and EPO Resistance Index (ERI) in HD patients. Methodology/Principal Findings 50 established HD patients were studied at a routine dialysis session. Data collection included weight, BMI, ultrafiltration volume, weekly EPO dose, and blood sampling pre and post HD. ERI was calculated as ratio of total weekly EPO dose to body weight (U/kg) to haemoglobin level (g/dL). Mean haemoglobin (Hb) was 11.3±1.3 g/dL with a median EPO dose of 10,000 [IQR 7,500–20,000] u/wk and ERI of 13.7 [IQR 6.9–23.3] ((U/Kg)/(g/dL)). Mean pre-HD serum ET levels were significantly elevated at 0.69±0.30 EU/ml. Natural logarithm (Ln) of ERI correlated to predialysis ET levels (r = 0.324, p = 0.03) with a trend towards association with hsCRP (r = 0.280, p = 0.07). Ln ERI correlated with ultrafiltration volume, a driver of circulatory stress (r = 0.295, p = 0.046), previously identified to be associated with increased intradialytic endotoxin translocation. Both serum ET and ultrafiltration volume corrected for body weight were independently associated with Ln ERI in multivariable analysis. Conclusions This study suggests that endotoxaemia is a significant factor in setting levels of EPO requirement. It raises the possibility that elevated EPO doses may in part merely be identifying patients subjected to significant circulatory stress and suffering the myriad of negative biological consequences arising from sustained systemic exposure to endotoxin

Establishing a core outcome set for peritoneal dialysis : report of the SONG-PD (standardized outcomes in nephrology-peritoneal dialysis) consensus workshop

Outcomes reported in randomized controlled trials in peritoneal dialysis (PD) are diverse, are measured inconsistently, and may not be important to patients, families, and clinicians. The Standardized Outcomes in Nephrology-Peritoneal Dialysis (SONG-PD) initiative aims to establish a core outcome set for trials in PD based on the shared priorities of all stakeholders. We convened an international SONG-PD stakeholder consensus workshop in May 2018 in Vancouver, Canada. Nineteen patients/caregivers and 51 health professionals attended. Participants discussed core outcome domains and implementation in trials in PD. Four themes relating to the formation of core outcome domains were identified: life participation as a main goal of PD, impact of fatigue, empowerment for preparation and planning, and separation of contributing factors from core factors. Considerations for implementation were identified: standardizing patient-reported outcomes, requiring a validated and feasible measure, simplicity of binary outcomes, responsiveness to interventions, and using positive terminology. All stakeholders supported inclusion of PD-related infection, cardiovascular disease, mortality, technique survival, and life participation as the core outcome domains for PD

Down-Regulated NOD2 by Immunosuppressants in Peripheral Blood Cells in Patients with SLE Reduces the Muramyl Dipeptide-Induced IL-10 Production

Pattern recognition receptors (PRRs) such as Toll-like receptors are aberrantly expressed of peripheral blood mononuclear cells (PBMCs) in systemic lupus erythematosus (SLE) patients, for playing immunopathological roles. basal productions of cytokines (IL-6, IL-8 and IL-10) were significantly increased in immunosuppressant naïve patients and patients with active disease despite immunosuppressants compared with HCs. Upon MDP stimulaiton, relative induction (%) of cytokines (IL-1β) from PBMC was significantly increased in immunosuppressant naïve patients with inactive disease, and patients with active disease despite immunosuppressant treatment compared with HCs. Immunosuppressant usage was associated with a decreased basal production and MDP induced relative induction (%) of IL-10 in patients with inactive disease compared with immunosuppressant naïve patients and HCs.Bacterial exposure may increase the NOD2 expression in monocytes in immunosuppressant naïve SLE patients which can subsequently lead to aberrant activation of PBMCs to produce proinflammatory cytokines, implicating the innate immune response for extracellular pathogens in the immunopathological mechanisms in SLE. Immunosuppressant therapy may downregulate NOD2 expression in CD8+ T lymphocytes, monocytes, and DCs in SLE patients which subsequently IL-10 reduction, contributing towards the regulation of immunopathological mechanisms of SLE, at the expense of increasing risk of bacterial infection

Randomized trial on the effect of an oral spleen tyrosine kinase inhibitor in the treatment of IgA nephropathy

Introduction We reported increased spleen tyrosine kinase (SYK) expression in kidney biopsies of patients with IgA nephropathy (IgAN) and that inhibition of SYK reduces inflammatory cytokines production from IgA stimulated mesangial cells. Methods This study was a double-blind, randomised, placebo-controlled phase 2 trial of fostamatinib (an oral SYK inhibitor) in 76 patients with IgAN. Patients were randomised to receive placebo, fostamatinib at 100 mg or 150 mg twice daily for 24 weeks on top of maximum tolerated dose of renin-angiotensin system inhibitors (RASi). The primary end point was reduction of proteinuria. Secondary endpoints included change from baseline in eGFR and kidney histology. Results While we could not detect significant reduction in proteinuria with fostamatinib overall, in a pre-determined subgroup analysis, there was a trend for dose-dependent reduction in median proteinuria (from baseline to 24 weeks by 14%, 27% and 36% in the placebo, fostamatinib 100 mg and 150 mg groups respectively) in patients with baseline urinary protein to creatinine ratios (UPCR) more than 1000 mg/g. Kidney function (eGFR) remained stable in all groups. Fostamatinib was well tolerated. Side effects included diarrhea, hypertension and increased liver enzymes. Thirty-nine patients underwent repeat biopsy showing reductions in SYK staining associated with therapy at low dose (-1.5 v 1.7 SYK+ cells/glomerulus in the placebo group, p<0.05). Conclusions There was a trend towards reduction in proteinuria with fostamatinib in a predefined analysis of high risk patients with IgAN despite maximal care, as defined by baseline UPCR greater than 1000 mg/g. Further study may be warranted

A Genome-Wide Association Study of Diabetic Kidney Disease in Subjects With Type 2 Diabetes

dentification of sequence variants robustly associated with predisposition to diabetic kidney disease (DKD) has the potential to provide insights into the pathophysiological mechanisms responsible. We conducted a genome-wide association study (GWAS) of DKD in type 2 diabetes (T2D) using eight complementary dichotomous and quantitative DKD phenotypes: the principal dichotomous analysis involved 5,717 T2D subjects, 3,345 with DKD. Promising association signals were evaluated in up to 26,827 subjects with T2D (12,710 with DKD). A combined T1D+T2D GWAS was performed using complementary data available for subjects with T1D, which, with replication samples, involved up to 40,340 subjects with diabetes (18,582 with DKD). Analysis of specific DKD phenotypes identified a novel signal near GABRR1 (rs9942471, P = 4.5 x 10(-8)) associated with microalbuminuria in European T2D case subjects. However, no replication of this signal was observed in Asian subjects with T2D or in the equivalent T1D analysis. There was only limited support, in this substantially enlarged analysis, for association at previously reported DKD signals, except for those at UMOD and PRKAG2, both associated with estimated glomerular filtration rate. We conclude that, despite challenges in addressing phenotypic heterogeneity, access to increased sample sizes will continue to provide more robust inference regarding risk variant discovery for DKD.Peer reviewe