The MDRD equations were more accurate in predicting the group mean GFR in patients with ESRD than the Cockcroft and Gault formula. However, the predicted GFR using either formula was related to the basal GFR and percentage body fat.
Background
Trimethylamine N-oxide (TMAO), a metabolite from red meat and fish consumption, plays a role in promoting cardiovascular events. However, data regarding TMAO and its impact on clinical outcomes are inconclusive, possibly due to its undetermined dietary source.
Objective
We hypothesized circulating TMAO derived from fish intake might cause less harm compared to red meat source by examining the concomitant level of 3-carboxy-4-methyl-5-propyl-2-furanpropionate (CMPF), a known biomarker of fish intake, and investigated the association between TMAO, CMPF and outcomes.
Design
Patients were recruited from the European QUALity study on treatment in advanced CKD (EQUAL) among individuals ≥65 years whose eGFR had dropped for the first time to ≤20mL/min/1.73m2 during last 6 months. The association between TMAO, CMPF and outcomes including all-cause mortality and kidney replacement therapy (KRT) was assessed among 737 patients. Patients were further stratified by median cut-offs of TMAO and CMPF, suggesting high/low red meat and fish intake.
Results
During a median of 39 months’ follow-up, 232 patients died. Higher TMAO was independently associated with an increased risk of all-cause mortality (multivariable-hazard ratio (HR) 1.46, 95% confidence interval (CI) 1.17, 1.83). Higher CMPF was associated with a reduced risk of both all-cause mortality (HR 0.79, 95%CI 0.71, 0.89) and KRT (HR 0.80, 95%CI 0.71, 0.90), independent of TMAO and other clinically relevant confounders. In comparison to patients with low TMAO and CMPF, patients with low TMAO and high CMPF had reduced risk of all-cause mortality (adjusted HR 0.49, 95% CI 0.31, 0.73), whereas those with high TMAO and high CMPF showed no association across adjusted models.
Conclusions
High CMPF conferred an independent role in health benefits and might even counteract the unfavorable association between TMAO and outcomes. Whether higher circulating CMPF are due to fish consumption, and/or CMPF is a protective factor remains to be verified.
Background
Patients with stage 4/5 chronic kidney disease (CKD) suffer from various symptoms. The retention of uremic solutes is thought to be associated with those symptoms. However, there are relatively few rigorous studies on the potential links between uremic toxins and symptoms in patients with CKD.
Methods
The EQUAL study is an ongoing observational cohort study of non-dialyzed patients with stage 4/5 CKD. EQUAL patients from Germany, Poland, Sweden, and the United Kingdom were included in the present study (n = 795). Data and symptoms self-report questionnaires were collected between April 2012 and September 2020. Baseline uric acid and parathyroid hormone and ten uremic toxins were quantified. We tested the association between uremic toxins and symptoms, and adjusted p-values for multiple testing.
Results
Symptoms were more frequent in women than in men with stage 4/5 CKD, while levels of various uremic toxins were higher in men. Only trimethylamine-N-oxide (positive association with fatigue), p-cresylsulfate with constipation, and 3 carboxy-4-methyl-5-propyl-2-furanpropionic acid (negative association with shortness of breath) demonstrated moderately strong associations with symptoms in adjusted analysis. The association of phenylacetylglutamine with shortness of breath was consistent in both sexes, although only reached statistical significance in the full population. By contrast, trimethylamine-N-oxide (fatigue) and p-cresyl sulfate and phenylacetylglutamine (constipation) were only associated with symptoms in men, who presented higher serum levels than women.
Conclusion
Only a limited number of toxins were associated with symptoms in persons with stage 4/5 CKD. Other uremic toxins, uremia related factors or psychosocial factors not yet explored might contribute to symptom burden.
Background: End-stage kidney disease (ESKD) is an overwhelming illness that impacts not just patients, but also their informal carers. Patients who opt for conservative management rather than dialysis experience difficult symptoms and the psychosocial consequences of their condition. Informal carers of patients who choose conservative management can also experience high levels of psychosocial burden, yet there is little guidance on how best to support informal carers, and no evidence on psychosocial interventions to address unmet needs. Aim: The aim of this study is to explore the experiences and unmet needs of informal carers of patients with ESKD receiving conservative management in order to inform the development of a psychosocial intervention. Methods: This qualitative study will consist of three stages: (I) semi-structured interviews with informal carers in England and Northern Ireland, (II) focus groups with healthcare professionals and informal carers, and (III) national workshops to refine the components of a psychosocial intervention. Discussion: Informal carers of patients with ESKD who are receiving conservative management experience a high psychosocial burden, but there is limited evidence on how best to provide support, particularly as the patient nears the end of life. To our knowledge this study will be the first to address this gap by exploring the experiences and unmet needs of informal carers, with the aim of informing the development of a psychosocial intervention to support the health and wellbeing of informal carers.
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