Background. Encapsulating peritoneal sclerosis (EPS) is a disease process that can occur as a complication of peritoneal dialysis (PD). The aim of this study was to make a general assessment of the ...clinical features, diagnosis, management and outcome of PD-related EPS cases from London and South-East England. Methods. Questionnaires were sent to 11 PD units in March 2007; cases were identified retrospectively. Outcome data on surviving patients were collected in March 2008. Results. A total of 111 patients were identified; the mean time on PD was 82 months (range 8–247). Mortality increased with length of time on PD, being 42% at <3 years (n = 12), 32% at 3–4 years (n = 19), 61% at 5–6 years (n = 31), 54% at 7–8 years (n = 24), 75% at 9–10 years (n = 8) and 59% at >10 years (n = 17). Twelve patients had no previous peritonitis episodes, 28 had one previous episode, 30 had two previous episodes and 33 had three or more previous episodes. Of the patients with PD details available, 41/63 were high (>0.81) transporters and 44/71 had ultrafiltration <1 l/24 h, but 7/63 were low average transporters (0.5–<0.65) and 27/71 had ultrafiltration >1 l/24 h and a few had significant residual renal function. Sixty-five (59%) patients had their PD discontinued prior to diagnosis (51 HD; 14 transplanted). CT scans were performed on 91 patients and laparotomy on 47 patients. Drug treatment consisted of tamoxifen, immunosuppression or both. The median survival was 15 months in patients treated with tamoxifen (n = 17), 12 months in patients treated with immunosuppression (n = 24) and 21 months in patients who received both (n = 13), against 13 months (n = 46) in patients who received no specific treatment. Adhesionolysis was performed in 5 patients, and 39 patients were given parenteral nutrition. The overall mortality was 53% with a median survival of 14 months and a median time to death of 7 months. Conclusion. This is one of the largest cohorts of patients with EPS in the literature. Long-term survival occurred in over 50%, regardless of the various treatments strategies undertaken by the centres.
Altered intestinal function is prevalent in patients with heart failure (HF), but its role in adverse outcomes is unclear.
This study investigated the potential pathophysiological contributions of ...intestinal microbiota in HF.
We examined the relationship between fasting plasma trimethylamine-N-oxide (TMAO) and all-cause mortality over a 5-year follow-up in 720 patients with stable HF.
The median TMAO level was 5.0 μM, which was higher than in subjects without HF (3.5 μM; p < 0.001). There was modest but significant correlation between TMAO concentrations and B-type natriuretic peptide (BNP) levels (r = 0.23; p < 0.001). Higher plasma TMAO levels were associated with a 3.4-fold increased mortality risk. Following adjustments for traditional risk factors and BNP levels, elevated TMAO levels remained predictive of 5-year mortality risk (hazard ratio HR: 2.2; 95% CI: 1.42 to 3.43; p < 0.001), as well as following the addition of estimated glomerular filtration rate to the model (HR: 1.75; 95% CI: 1.07 to 2.86; p < 0.001).
High TMAO levels were observed in patients with HF, and elevated TMAO levels portended higher long-term mortality risk independent of traditional risk factors and cardiorenal indexes.
Background
Production of the proatherogenic metabolite, trimethylamine N‐oxide (TMAO), from dietary nutrients by intestinal microbiota enhances atherosclerosis development in animal models and is ...associated with atherosclerotic coronary artery disease in humans. The utility of studying plasma levels of TMAO to risk stratify in patients with peripheral artery disease (PAD) has not been reported.
Methods and Results
We examined the relationship between fasting plasma TMAO and all‐cause mortality (5‐year), stratified by subtypes of PAD and presence of coronary artery disease in 935 patients with PAD who underwent elective angiography for cardiac evaluation at a tertiary care hospital. Median plasma TMAO was 4.8 μmol/L (interquartile range, 2.9–8.0 μmol/L). Elevated TMAO levels were associated with 2.7‐fold increased mortality risk (fourth versus first quartiles, hazard ratio 2.86, 95% CI 1.82–3.97, P<0.001). Following adjustments for traditional risk factors, inflammatory biomarkers, and history of coronary artery disease, the highest TMAO quartile remained predictive of 5‐year mortality (adjusted hazard ratio 2.06, 95% CI 1.36–3.11, P<0.001). Similar prognostic value for elevated TMAO was seen for subjects with carotid artery, non–carotid artery, or lower extremity PAD. TMAO provided incremental prognostic value for all‐cause mortality (net reclassification index, 40.22%; P<0.001) and improvement in area under receiver operator characteristic curve (65.7% versus 69.4%; P=0.013).
Conclusions
TMAO, a pro‐atherogenic metabolite formed by gut microbes, predicts long‐term adverse event risk and incremental prognostic value in patients with PAD. These findings point to the potential for TMAO to help improve selection of high‐risk PAD patients with or without significant coronary artery disease, who likely need more aggressive and specific dietary and pharmacologic therapy.
Volume status can be difficult to assess in dialysis patients. Peripheral edema, elevated venous pressure, lung crackles, and hypertension are taught as signs of fluid overload, but sensitivity and ...specificity are poor. Bioimpedance technology has evolved from early single frequency to multifrequency machines which apply spectroscopic analysis (BIS), modeling data to physics-based mixture theory. Bioimpedance plots can aid the evaluation of hydration status and body composition. The challenge remains how to use this information to manage dialysis populations, particularly as interventions to improve over hydration, sarcopenia, and adiposity are not without side effects. It is therefore of no surprise that validation studies for BIS use in peritoneal dialysis patients are limited, and results from clinical trials are inconsistent and conflicting. Despite these limitations, BIS has clinical utility with potential to accurately evaluate small changes in body tissue components. This article explains the information a BIS plot ("picture") can provide and how it can contribute to the overall clinical assessment of a patient. However, it remains the role of the clinician to integrate information and devise treatment strategies to optimize competing patient risks, fluid and nutrition status, effects of high glucose PD fluids on membrane function, and quality of life issues.
Background
Trimethylamine‐N‐oxide (TMAO), a metabolite derived from gut microbes and dietary phosphatidylcholine, is linked to both coronary artery disease pathogenesis and increased cardiovascular ...risks. The ability of plasma TMAO to predict 5‐year mortality risk in patients with stable coronary artery disease has not been reported. This study examined the clinical prognostic value of TMAO in patients with stable coronary artery disease who met eligibility criteria for a patient cohort similar to that of the Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) trial.
Methods and Results
We examined the relationship between fasting plasma TMAO and all‐cause mortality over 5‐year follow‐up in sequential patients with stable coronary artery disease (n=2235) who underwent elective coronary angiography. We identified the COURAGE‐like patient cohort as patients who had evidence of significant coronary artery stenosis and who were managed with optimal medical treatment. Higher plasma TMAO levels were associated with a 4‐fold increased mortality risk. Following adjustments for traditional risk factors, high‐sensitivity C‐reactive protein, and estimated glomerular filtration rate, elevated TMAO levels remained predictive of 5‐year all‐cause mortality risk (quartile 4 versus 1, adjusted hazard ratio 1.95, 95% CI 1.33–2.86; P=0.003). TMAO remained predictive of incident mortality risk following cardiorenal and inflammatory biomarker adjustments to the model (adjusted hazard ratio 1.71, 95% CI 1.11–2.61; P=0.0138) and provided significant incremental prognostic value for all‐cause mortality (net reclassification index 42.37%, P<0.001; improvement in area under receiver operator characteristic curve 70.6–73.76%, P<0.001).
Conclusions
Elevated plasma TMAO levels portended higher long‐term mortality risk among patients with stable coronary artery disease managed with optimal medical treatment.
Bioimpedance analysis is often routinely performed in any dialysis unit to guide fluid management but can provide a reproduceable assessment of fat and muscle mass. We wished to determine the ...clinical significance of low muscle or high fat mass and the determinants that influence their change.
We performed retrospective analysis of 824 patients on peritoneal dialysis who underwent routine repeated bioimpedance analysis measurements using the body composition monitor (BCM).
Lean tissue index (LTI) was an independent predictor of mortality when sex, age, PD vintage and diabetes status were included in the models (HR 0.93; 95% CI 0.86-1.00, p < 0.05) and when baseline serum albumin was included in a separate model (HR 0.86; 95% CI: 0.79-0.93, p < 0.001). High fat tissue index (FTI) was an independent predictor of mortality when demographic factors were included (HR 0.87; 95% CI: 0.78-0.97, p < 0.02), but not with the addition biochemical parameters. Changes in body composition of 206 patients over a 2-year follow-up period could not be predicted by baseline demographics, functional or biochemical assessments. However, there was a strong inverse relationship between changes in LTI and FTI. There were no associations between changes in body composition with prescribed dialysate glucose.
We showed body composition changes are common and complex. LTI was an independent predictor of survival. Changes in LTI and FTI could not be predicted by baseline parameters. BCM may be a sensitive and accurate tool to monitor changes in body composition during dialysis treatment.
Recent metabolomics and animal model studies show trimethylamine-N-oxide (TMAO), an intestinal microbiota-dependent metabolite formed from dietary trimethylamine-containing nutrients such as ...phosphatidylcholine (PC), choline, and carnitine, is linked to coronary artery disease pathogenesis. Our aim was to examine the prognostic value of systemic choline and betaine levels in stable cardiac patients.
We examined the relationship between fasting plasma choline and betaine levels and risk of major adverse cardiac events (MACE = death, myocardial infraction, stroke) in relation to TMAO over 3 years of follow-up in 3903 sequential stable subjects undergoing elective diagnostic coronary angiography. In our study cohort, median (IQR) TMAO, choline, and betaine levels were 3.7 (2.4-6.2)μM, 9.8 (7.9-12.2)μM, and 41.1 (32.5-52.1)μM, respectively. Modest but statistically significant correlations were noted between TMAO and choline (r = 0.33, P < 0.001) and less between TMAO and betaine (r = 0.09, P < 0.001). Higher plasma choline and betaine levels were associated with a 1.9-fold and 1.4-fold increased risk of MACE, respectively (Quartiles 4 vs. 1; P < 0.01, each). Following adjustments for traditional cardiovascular risk factors and high-sensitivity C-reactive protein, elevated choline 1.34 (1.03-1.74), P < 0.05, and betaine levels 1.33 (1.03-1.73), P < 0.05 each predicted increased MACE risk. Neither choline nor betaine predicted MACE risk when TMAO was added to the adjustment model, and choline and betaine predicted future risk for MACE only when TMAO was elevated.
Elevated plasma levels of choline and betaine are each associated with incident MACE risk independent of traditional risk factors. However, high choline and betaine levels are only associated with higher risk of future MACE with concomitant increase in TMAO.
These guidelines cover all aspects of the care of patients who are treated with peritoneal dialysis. This includes equipment and resources, preparation for peritoneal dialysis, and adequacy of ...dialysis (both in terms of removing waste products and fluid), preventing and treating infections. There is also a section on diagnosis and treatment of encapsulating peritoneal sclerosis, a rare but serious complication of peritoneal dialysis where fibrotic (scar) tissue forms around the intestine. The guidelines include recommendations for infants and children, for whom peritoneal dialysis is recommended over haemodialysis.Immediately after the introduction there is a statement of all the recommendations. These recommendations are written in a language that we think should be understandable by many patients, relatives, carers and other interested people. Consequently we have not reworded or restated them in this lay summary. They are graded 1 or 2 depending on the strength of the recommendation by the authors, and A-D depending on the quality of the evidence that the recommendation is based on.
Peritonitis remains a common clinical problem for patients on peritoneal dialysis (PD). There are, however, retrospective studies with historical controls that suggest that biocompatible PD solutions ...may reduce the rates of peritonitis. We conducted a randomized controlled study comparing the use of biocompatible and conventional solutions, accumulating over 7000 patient-months experience. We included peritonitis episodes from patients who discontinued PD during the follow-up period. The study was powered to detect a reduction in the peritonitis rate of over half in the 267 randomized patients in demographically similar groups. There were no intergroup differences in PD technique survival irrespective of whether the outcome was censored for death. Peritonitis-free survival was 26.7 months using conventional compared to 23.1 months using biocompatible PD solutions. The peritonitis rates were also not statistically different when measured in patient-months. Thus, despite the finding of non-randomized studies suggesting benefits of the biocompatible PD solutions, we could not detect any clinically significant advantages in terms of technique survival or peritonitis. Although our study is the largest randomized study comparing different PD solutions to date, we do not exclude the possibility that our results are a consequence of the lack of statistical power. Meta-analysis of randomized control trials in this field is essential.
It is becoming increasingly evident that the accurate assessment of hydration status is critical to care of a dialysis patient. Using the Body Composition Monitor, different parameters (overhydration ...(OH), extra-cellular water/total body water (ECW/TBW) or OH/ECW) have been proposed to indicate hydration status. We wished to determine which parameter (if any) was most predictive of all-cause mortality, and if this was independent of nutritional indices.
We performed a single-centre retrospective analysis of prospectively collected data of all peritoneal dialysis (PD) patients between 1 January 2008 and 30 March 2012. Record review was undertaken to establish patient survival, clinical and demographic data. Follow-up was continued even after PD technique failure (transfer to haemodialysis) and transplantation.
The study included 529 patients. OH index (OH and OH/ECW) was the independent predictor of mortality in multi-variate analysis. ECW/TBW as a continuous variable was not associated with increased risk of death. In contrast, patients that were severely overhydrated (highest 33%) had hazard ratios (HRs) that were statistically significant irrespective of the parameter used to define hydration. Using OH, severely overhydrated patients had an HR of 1.83 95% confidence interval (CI) 1.19-2.82, P < 0.01, OH/ECW: 2.09 (95% CI 1.36-3.20, P < 0.001) and ECW/TBW: 2.05 (95% CI 1.31-3.22, P < 0.005).
Our results also indicated that there was no influence of body mass index (BMI) on the hydration parameter OH/ECW. OH/ECW remained an independent predictor of mortality when the BMI and lean tissue index were included in multivariate model. However, it remains to be determined if correcting the OH status of a patient will lead to improvement in mortality.
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