Graham Woodrow’s research while affiliated with University of Leeds and other places

Rationale & objective: Peritoneal dialysis (PD)-related peritonitis carries high morbidity for PD patients. Understanding the characteristics and risk factors for peritonitis can guide regional development of prevention strategies. We describe peritonitis rates and the associations of selected facility practices with peritonitis risk among countries participating in the Peritoneal Dialysis Outcomes and Practice Patterns Study (PDOPPS). Study design: Observational prospective cohort study. Setting & participants: 7,051 adult PD patients in 209 facilities across 7 countries (Australia, New Zealand, Canada, Japan, Thailand, United Kingdom, United States). Exposures: Facility characteristics (census count, facility age, nurse to patient ratio) and selected facility practices (use of automated PD, use of icodextrin or biocompatible PD solutions, antibiotic prophylaxis strategies, duration of PD training). Outcomes: Peritonitis rate (by country, overall and variation across facilities), microbiology patterns. Analytical approach: Poisson rate estimation, proportional rate models adjusted for selected patient case-mix variables. Results: 2,272 peritonitis episodes were identified in 7,051 patients (crude rate, 0.28 episodes/patient-year). Facility peritonitis rates were variable within each country and exceeded 0.50/patient-year in 10% of facilities. Overall peritonitis rates, in episodes per patient-year, were 0.40 (95% CI, 0.36-0.46) in Thailand, 0.38 (95% CI, 0.32-0.46) in the United Kingdom, 0.35 (95% CI, 0.30-0.40) in Australia/New Zealand, 0.29 (95% CI, 0.26-0.32) in Canada, 0.27 (95% CI, 0.25-0.30) in Japan, and 0.26 (95% CI, 0.24-0.27) in the United States. The microbiology of peritonitis was similar across countries, except in Thailand, where Gram-negative infections and culture-negative peritonitis were more common. Facility size was positively associated with risk for peritonitis in Japan (rate ratio [RR] per 10 patients, 1.07; 95% CI, 1.04-1.09). Lower peritonitis risk was observed in facilities that had higher automated PD use (RR per 10 percentage points greater, 0.95; 95% CI, 0.91-1.00), facilities that used antibiotics at catheter insertion (RR, 0.83; 95% CI, 0.69-0.99), and facilities with PD training duration of 6 or more (vs <6) days (RR, 0.81; 95% CI, 0.68-0.96). Lower peritonitis risk was seen in facilities that used topical exit-site mupirocin or aminoglycoside ointment, but this association did not achieve conventional levels of statistical significance (RR, 0.79; 95% CI, 0.62-1.01). Limitations: Sampling variation, selection bias (rate estimates), and residual confounding (associations). Conclusions: Important international differences exist in the risk for peritonitis that may result from varied and potentially modifiable treatment practices. These findings may inform future guidelines in potentially setting lower maximally acceptable peritonitis rates.

Background: Peritoneal dialysis (PD)-related infections lead to significant morbidity. The International Society for Peritoneal Dialysis (ISPD) guidelines for the prevention and treatment of PD-related infections are based on variable evidence. We describe practice patterns across facilities participating in the Peritoneal Dialysis Outcomes and Practice Patterns Study (PDOPPS). Methods: PDOPPS, a prospective cohort study, enrolled nationally representative samples of PD patients in Australia/New Zealand (ANZ), Canada, Thailand, Japan, the UK and the USA. Data on PD-related infection prevention and treatment practices across facilities were obtained from a survey of medical directors'. Results: A total of 170 centers, caring for >11 000 patients, were included. The proportion of facilities reporting antibiotic administration at the time of PD catheter insertion was lowest in the USA (63%) and highest in Canada and the UK (100%). Exit-site antimicrobial prophylaxis was variably used across countries, with Japan (4%) and Thailand (28%) having the lowest proportions. Exit-site mupirocin was the predominant exit-site prophylactic strategy in ANZ (56%), Canada (50%) and the UK (47%), while exit-site aminoglycosides were more common in the USA (72%). Empiric Gram-positive peritonitis treatment with vancomycin was most common in the UK (88%) and USA (83%) compared with 10-45% elsewhere. Empiric Gram-negative peritonitis treatment with aminoglycoside therapy was highest in ANZ (72%) and the UK (77%) compared with 10-45% elsewhere. Conclusions: Variation in PD-related infection prevention and treatment strategies exist across countries with limited uptake of ISPD guideline recommendations. Further work will aim to understand the impact these differences have on the wide variation in infection risk between facilities and other clinically relevant PD outcomes.

Restriction of dietary protein intake has been used in the management of chronic kidney disease (CKD) for many decades, yet remains controversial, with marked variations in its application in clinical practice. There is extensive literature on the subject, with some expert opinion advocating the use of protein restriction based on the balance of the available evidence. The largest randomized trial of low-protein diets is the Modification of Diet in Renal Disease study. Despite multiple secondary analyses, the essential intention-to-treat analysis failed to demonstrate a benefit in the primary outcome of rate of decline of glomerular filtration rate. There are criticisms of many published studies and meta-analyses, including the likelihood of publication bias and unsuitable biochemical endpoints that may be affected by dietary restriction in the absence of effects on kidney function, leading to false positive findings. It is also uncertain whether any benefits observed in these often older studies would be derived in patients undergoing modern standards of CKD management, including blood pressure control and renin-angiotensin blockade. Thus it is unclear whether, even in the strictly controlled environment of a clinical study, low-protein diets significantly slow CKD progression. Important questions exist regarding the applicability of these diets in routine clinical practice. Even in carefully selected study populations with intensive dietetic input, adherence to low-protein diets is poor. It is likely that only a small minority of CKD patients in routine practice could adhere to these diets, and although risks of malnutrition arising from protein restriction are uncertain, they will be greater in less supervised care outside of studies.

Malnutrition is common in haemodialysis (HD) and is linked to poor outcomes. This study aimed to describe changes in body composition after the initiation of HD and investigate whether any routinely collected parameters were associated with these changes. The study cohort came from the HD population of a single centre between 2009 and 2014. Body composition measurements were obtained from a database of bioimpedance results using the Body Composition Monitor (BCM), while demographics and laboratory values came from the renal unit database. Primary outcomes were changes in normohydration weight, lean tissue mass and adipose tissue mass over the two years after HD initiation. A total of 299 patients were included in the primary analyses, showing an increase in adipose tissue, loss of lean tissue and no significant change in normohydration weight. None of the routinely collected parameters were associated with the lean tissue changes. Loss of lean tissue over the first year of dialysis was associated with increased mortality. The results showing loss of lean tissue that is not limited to those traditionally assumed to be at high risk supports interventions to maintain or improve lean tissue as soon as possible after the initiation of HD. It highlights the importance of monitoring nutrition and the potential for routine use of bioimpedance.

Patients on peritoneal dialysis (PD) develop complex changes in body composition. These changes reflect hydration, nutrition, and body fat, all important elements reflecting patient well-being and efficacy of therapy that should be assessed and monitored as guides to patient management. They are all notoriously difficult to accurately measure in clinical practice and simultaneous abnormalities may obscure detection, as in the malnourished fluid-overloaded patient where body weight is misleadingly stable. Malnutrition is a serious complication in PD that carries an adverse prognosis. Assessment of hydration in PD is important in determining “dry weight” to allow adjustment of dialysis prescription to optimize fluid balance. A number of techniques have been investigated to measure body composition in clinical practice. Of these, bioelectrical impedance analysis (BIA) has attracted most interest and seems to be of greatest promise. Cases illustrating different aspects of the use of BIA in PD patients are described, and the background, possible uses, and limitations of BIA in PD patients are discussed. To be of clinical value, BIA must be used to distinguish between extracellular water (which reflects hydration) and body cell mass, or intracellular water (which declines in wasting and malnutrition). The high precision of BIA is ideally suited to detecting changes in body composition and its main role may be in longitudinal monitoring. However, inaccuracy of absolute measurements and variability of normal values in the general population make precise diagnosis of the degree of normality of body composition in an individual subject a more difficult task for body composition analysis.

Objective This study was carried out to evaluate a procedure for converting bioimpedance spectroscopy (BIS) data to a clinically useful measure of fluid status that is easily interpreted by nursing staff and patients. ♦ Design The ratio of extracellular water (ECW) to total body water (TBW) in a cohort of peritoneal dialysis (PD) patients was compared with the distribution for normal control subjects. The result was expressed as the difference between the measured ECW/TBW ratio and the mean ratio for age- and sex-matched controls divided by the standard deviation for the controls (the “hydration score”). Where possible, interventions were made to reduce the target weight in patients with a hydration score greater than +2.0. ♦ Setting This clinical study was carried out in the nurseled outpatient PD unit at St. James's University Hospital. BIS measurements were carried out during routine clinic visits. The data for the control subjects were obtained in a range of settings in the UK and the Czech Republic. ♦ Patients 31 PD patients (21 M, 10 F; aged 19 – 78 years) who came to the PD unit for routine procedures during the study participated. ♦ Results The mean hydration score for PD patients was significantly higher than for the control subjects (+1.3 vs 0.0, p < 0.0001). 11 (35%) patients had a hydration score greater than +2.0, compared with only 2.5% of the controls; systolic blood pressure was greater than 130 mmHg in only two of these patients. After a 3-month follow-up, a weight reduction of 3.6 ± 2.3 kg had been achieved in 7 patients through modality change and implementation of prescription changes, with no adverse effects. ♦ Conclusions Although this was a small study, all the data collected indicated that the hydration score provides a reliable indication of fluid status in PD patients. BIS measurements are now carried out at 6-month intervals and are used to monitor the effect of interventions.