Randomized Controlled Clinical Trial of the Effect of Treatment with Vitamin K2 on Vascular Calcification in Hemodialysis Patients (Trevasc-HDK).

Introduction: Vitamin K deficiency among patients on hemodialysis (HD) affects the function of matrix GLA protein (MGP), a potent vitamin K-dependent inhibitor of vascular calcification (VC). Methods: We conducted a single-center randomized controlled trial (RCT) on maintenance HD patients to examine if vitamin K2 supplementation can reduce progression of coronary artery calcification (CAC) over an 18-month study period. Patients were randomized to vitamin K2 group receiving menaquinone-7360 µg 3 times/wk or control group. The primary outcome was CAC scores at the end of the study period. The secondary outcomes were aortic valve calcification (AVC), carotid-femoral pulse wave velocity (cfPWV), aortic augmentation index (AIx), dephosphorylated undercarboxylated MGP (dp-ucMGP) levels, major adverse cardiac events (MACE), and vascular access events. Results: Of the 178 patients randomized, follow-up was completed for 138 patients. The CAC scores between the 2 groups were not statistically different at the end of 18 months (relative mean difference [RMD] 0.85, 95% CI 0.55-1.31). The secondary outcomes did not differ significantly in AVC (RMD 0.82, 95% CI 0.34-1.98), cfPWV (absolute mean difference [AMD] 0.55, 95% CI -0.50 to 1.60), and AIx (AMD 0.13, 95% CI -3.55 to 3.80). Supplementation with vitamin K2 did reduce dp-ucMGP levels (AMD -86, 95% CI -854 to -117). The composite outcome of MACE and mortality was not statistically different between the 2 groups (Hazard ratio = 0.98, 95% CI 0.50-1.94). Conclusion: Our study did not demonstrate a beneficial effect of vitamin K2 in reducing progression of VC in this population at the studied dose and duration.

Treatment to reduce vascular calcification in hemodialysis patients using vitamin K (Trevasc-HDK): A study protocol for a randomized controlled trial.

INTRODUCTION: End stage renal failure patients on hemodialysis have significant vascular calcification This is postulated to be related to sub-clinical vitamin K deficiency, which is prevalent in hemodialysis patients. Vitamin K deficiency result in the failure of the matrix GLA protein (MGP) to undergo carboxylation. MGP is a natural local inhibitor of vascular calcification and the lack of functional carboxylated MGP may contribute to increase vascular calcification. Vitamin K supplement should therefore correct this anomaly and decrease the rate or severity of vascular calcification in this population of patients on long-term maintenance hemodialysis. Our study seeks to evaluate the prevalence and the progression of vascular calcification in a cohort of maintenance hemodialysis patients. It will also evaluate the efficacy of vitamin K supplementation in reducing the progression of vascular calcification in this group of patients. METHODS: This will be a single-center randomized, prospective and open-label interventional clinical trial of end stage renal failure patients on hemodialysis. We aim to recruit 200 patients. Eligible patients will be randomized to either the standard care arm or active treatment arm. Active treatment arm patients will receive standard care plus supplementation with oral vitamin K2 isoform 360 mcg 3 times weekly for a total duration of 18 months. Primary outcome measured will be absolute difference in coronary artery calcification score at 18-month between control and intervention arms. Secondary outcomes will be to compare absolute difference in aortic valve calcification, percentage of patients with regression of coronary artery calcification of at least 10%, absolute difference in aortic and systemic arterial stiffness, mortality from any cause and major adverse cardiovascular over the same period. DISCUSSION: Evidence of successful regression or retardation of vascular calcification will support the conduct of larger and longer-term trials aimed at reducing cardiovascular disease mortality and major adverse cardiovascular events in this high-risk population using a safe and inexpensive strategy TRIAL REGISTRATION:: ClinicalTrials.gov NCT02870829. Registered on 17 August 2016 - Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT02870829National University Hospital's Institutional Review Board (2015/01000).

Perceptions of a night float system for intern doctors in an internal medicine program: an Asian perspective.

Long duty hours have been associated with significant medical errors, adverse events, and physician "burn-out". An innovative night float (NF) system has been implemented in our internal medicine program to reduce the negative effects of long duty hours associated with conventional full-call systems. However, concerns remain if this would result in inadequate training for interns. We developed a structured questionnaire to assess junior doctors' perceptions of the NF system compared to full calls, in areas of patient safety, medical training, and well-being. Ninety-seven (71%) of the 137 doctors polled responded. Ninety-one (94%) felt the NF system was superior to the full call system. A strong majority felt NF was beneficial for patient safety compared to full call (94% vs. 2%, p<0.001). The NF system was also perceived to reduce medical errors (94% vs. 2%, p<0.001) and reduce physician "burn-out" (95% vs. 5%, p<0.001). Beyond being a practical solution to duty-hour limitations, there was a significant perceived benefit of the NF system compared to the full call in terms of overall satisfaction, patient safety, reducing medical errors and physician "burn-out".

The modality of choice, manual or automated, for urgent start peritoneal dialysis.

Over the last decade, urgent start peritoneal dialysis (USPD), defined as initiation of peritoneal dialysis (PD) before the traditionally recommended break-in period of 2-4 weeks, has increasingly been seen as a viable option for late-presenting end-stage renal disease patients, obviating the need for haemodialysis via central venous catheter. Different prescriptions and protocols involving both manual and automated exchanges have been published, but there is no head-to-head comparison of the two modalities and no consensus on the most suitable modality exists. Evaluation of the available evidence suggests that PD can be initiated urgently using either or both options without much difference in the outcome. The two most critical aspects dictating the success of a USPD programme are using low dwell volumes and keeping patients in a strict supine position during the dialysis exchanges in the first couple of weeks of the therapy. These measures are crucial in keeping the intraperitoneal pressure to a minimum and reduce the risk of mechanical complications, including catheter leaks and malpositioning.

Is surgical PD catheter insertion safe for urgent-start peritoneal dialysis?

Urgent-start peritoneal dialysis (USPD) is increasingly seen as a viable alternative to hemodialysis through a central venous catheter for late-presenting end-stage renal disease patients. However, concerns remain about starting dialysis early following the surgical implantation of the peritoneal dialysis (PD) catheter; urgent PD is often thought to be a safe option only after minimally invasive percutaneous catheter insertions. Analysis of the cumulative data from published literature presented in this review appears to negate this general perception and shows that compared to the percutaneous catheter insertions, starting PD urgently following surgically placed catheter is not associated with more catheter leaks, dysfunctions, or other complications. The outcome of USPD is independent of the mode of catheter insertion. Instead, measures to minimize intra-peritoneal pressure including using the low initial dwell volume based on patient's weight and body habitus and keeping patients in strict supine posture during exchanges in the first 2 weeks of treatment are the two most important factors ensuring a minimization of the risk of catheter-related complications.

Peritoneal dialysis as initial dialysis modality: a viable option for late-presenting end-stage renal disease.

Late-presenting end-stage renal disease is a significant problem worldwide. Up to 70% of patients start dialysis in an unplanned manner without a definitive dialysis access in place. Haemodialysis via a central venous catheter is the default modality for the majority of such patients, and peritoneal dialysis is usually not considered as a feasible option. However, in the recent years, some reports on urgent-start peritoneal dialysis in the late-presenting end-stage renal disease have been published. The collective experience shows that PD can be a safe, efficient and cost-effective alternative to haemodialysis in late-presenting end-stage renal disease with comparable outcomes to the conventional peritoneal dialysis and urgent-start haemodialysis. More importantly, as compared to urgent-start haemodialysis via a central venous catheter, urgent-start peritoneal dialysis has significantly fewer incidences of catheter-related bloodstream infections, dialysis-related complications and need for dialysis catheter re-insertions during the initial phase of the therapy. This article examines the rationale and feasibility for starting peritoneal dialysis urgently in late-presenting end-stage renal disease patients and reviews the literature to compare the urgent-start peritoneal dialysis with conventional peritoneal dialysis and urgent-start haemodialysis.

Sustained Increase in Peritoneal Dialysis Prevalence through a Structured PD Initiation Service.

A structured peritoneal dialysis (PD) initiation service provided by a dedicated team of nephrologists, interventionists, and PD nurses, taking patients through the stages of predialysis education and monitoring, dialysis catheter insertion, dialysis initiation, and follow-up in the immediate post-dialysis initiation period, can go a long way in expanding PD prevalence. The authors noticed a rapid expansion of their PD program following the introduction of such a service, and they share their experience in this article. A multidisciplinary team providing 1-stop coordinated care may help in alleviating the differences in patient selection criteria, minimize delays in PD catheter insertions, ensure timely initiation of dialysis, reduce the need to start dialysis urgently, actively identify and sort any teething issues, enhance patients' confidence, and reduce technique failures.

Should antiviral monotherapy with nucleotide analogs be the primary treatment option for focal segmental glomerulosclerosis-related nephrotic syndrome in chronic hepatitis B infection?

Renal involvement is the most common extrahepatic manifestation of chronic hepatitis B virus (HBV) infection. While membranous nephropathy is the most frequent, the association with focal segmental glomerulosclerosis (FSGS) is not as strong, and only a few cases have been described in the literature. In particular, the tip variant FSGS is extremely rare and to our knowledge has not previously been described in association with chronic HBV infection. The management of such cases can be challenging. Immunosuppression may lead to enhanced viral replication and flare-up of the hepatic disease. Antiviral treatment has been reported to induce remission in hepatitis B-associated glomerulonephritis in a few cases. However, their use is primarily restricted to the treatment of associated liver disease, and the current guidelines do not provide specific recommendations on HBV-mediated kidney disease in the absence of hepatic involvement. We describe a case of nephrotic syndrome due to secondary tip variant FSGS in a patient with chronic HBV infection who went into complete remission with antiviral therapy alone and present an argument for the use of oral antiviral agents as the primary treatment option for FSGS-related nephrotic syndrome in chronic HBV-infected patients without progressive liver disease.

Epoetin-ß induced pure red cell aplasia: an unintended consequence.

Pure red cell aplasia is a rare condition associated with the use of recombinant human erythropoietin preparations. It has predominantly been associated with the subcutaneous use of a particular epoetin-α product, Eprex, and is rarely associated with intravenous use or with other commercially available products. Only a few cases of pure red cell aplasia secondary to epoetin-ß have been reported. On account of its rarity, the condition can often be missed on initial presentation, leading to unnecessary investigations and delayed diagnosis. A high index of suspicion is required for timely diagnosis and proper management. We present a case of severe anaemia secondary to the subcutaneous use of epoetin-ß (Recormon) and briefly discuss the pathogenesis, diagnosis and management.

Reliable Quantification of the Potential for Equations Based on Spot Urine Samples to Estimate Population Salt Intake: Protocol for a Systematic Review and Meta-Analysis.

BACKGROUND: Methods based on spot urine samples (a single sample at one time-point) have been identified as a possible alternative approach to 24-hour urine samples for determining mean population salt intake. OBJECTIVE: The aim of this study is to identify a reliable method for estimating mean population salt intake from spot urine samples. This will be done by comparing the performance of existing equations against one other and against estimates derived from 24-hour urine samples. The effects of factors such as ethnicity, sex, age, body mass index, antihypertensive drug use, health status, and timing of spot urine collection will be explored. The capacity of spot urine samples to measure change in salt intake over time will also be determined. Finally, we aim to develop a novel equation (or equations) that performs better than existing equations to estimate mean population salt intake. METHODS: A systematic review and meta-analysis of individual participant data will be conducted. A search has been conducted to identify human studies that report salt (or sodium) excretion based upon 24-hour urine samples and spot urine samples. There were no restrictions on language, study sample size, or characteristics of the study population. MEDLINE via OvidSP (1946-present), Premedline via OvidSP, EMBASE, Global Health via OvidSP (1910-present), and the Cochrane Library were searched, and two reviewers identified eligible studies. The authors of these studies will be invited to contribute data according to a standard format. Individual participant records will be compiled and a series of analyses will be completed to: (1) compare existing equations for estimating 24-hour salt intake from spot urine samples with 24-hour urine samples, and assess the degree of bias according to key demographic and clinical characteristics; (2) assess the reliability of using spot urine samples to measure population changes in salt intake overtime; and (3) develop a novel equation that performs better than existing equations to estimate mean population salt intake. RESULTS: The search strategy identified 538 records; 100 records were obtained for review in full text and 73 have been confirmed as eligible. In addition, 68 abstracts were identified, some of which may contain data eligible for inclusion. Individual participant data will be requested from the authors of eligible studies. CONCLUSIONS: Many equations for estimating salt intake from spot urine samples have been developed and validated, although most have been studied in very specific settings. This meta-analysis of individual participant data will enable a much broader understanding of the capacity for spot urine samples to estimate population salt intake.

A Score for Predicting Acute Kidney Injury After Coronary Artery Bypass Graft Surgery in an Asian Population.

OBJECTIVE: To develop a scoring system to predict acute kidney injury in Asian patients after coronary artery bypass grafting. DESIGN: A retrospective analysis of data collected in an institutional cardiac database. SETTING: A tertiary academic hospital in a large metropolitan city. PARTICIPANTS: The study comprised 954 patients with coronary artery disease. INTERVENTIONS: All patients underwent coronary artery bypass surgery with cardiopulmonary bypass but did not undergo any other concomitant procedures. MEASUREMENTS AND MAIN RESULTS: The main outcome measured was acute kidney injury as defined by the Acute Kidney Injury Network criteria. The following 6 clinical variables were independent predictors of kidney injury: age>60 years, diabetes requiring insulin, estimated glomerular filtration rate<60 mL/min/1.73 m(2), ejection fraction<40%, cardiopulmonary bypass time>140 minutes, and aortic cross-clamp time>100 minutes. These variables were used to develop the Singapore Acute Kidney Injury score. CONCLUSION: The Singapore Acute Kidney Injury score is a simple way to predict, at the time of admission to the intensive care unit, an Asian patient's risk of developing acute kidney injury after coronary artery bypass surgery.

Blood pressure and antihypertensive medication profile in a multiethnic Asian population of stable chronic kidney disease patients.

INTRODUCTION: Clinical practice guidelines recommend different blood pressure (BP) goals for chronic kidney disease (CKD) patients. Usage of antihypertensive medication and attainment of BP targets in Asian CKD patients remain unclear. This study describes the profile of antihypertensive agents used and BP components in a multiethnic Asian population with stable CKD. METHODS: Stable CKD outpatients with variability of serum creatinine levels < 20%, taken > 3 months apart, were recruited. Mean systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured using automated manometers, according to practice guidelines. Serum creatinine was assayed and the estimated glomerular filtration rate (GFR) calculated using the CKD Epidemiology Collaboration equation. BP and antihypertensive medication profile was examined using univariate analyses. RESULTS: 613 patients (55.1% male; 74.7% Chinese, 6.4% Indian, 11.4% Malay; 35.7% diabetes mellitus) with a mean age of 57.8 ± 14.5 years were recruited. Mean SBP was 139 ± 20 mmHg, DBP was 74 ± 11 mmHg, serum creatinine was 166 ± 115 µmol/L and GFR was 53 ± 32 mL/min/1.73 m(2). At a lower GFR, SBP increased (p < 0.001), whereas DBP decreased (p = 0.0052). Mean SBP increased in tandem with the number of antihypertensive agents used (p < 0.001), while mean DBP decreased when ≥ 3 antihypertensive agents were used (p = 0.0020). CONCLUSION: Different targets are recommended for each BP component in CKD patients. A majority of patients cannot attain SBP targets and/or exceed DBP targets. Research into monitoring and treatment methods is required to better define BP targets in CKD patients.