Biomedical subjects
Publications and source records attributed to P G Blake.
Non-Pseudomonas Gram-negative organisms account for over 10% of cases of peritoneal dialysis-associated peritonitis. The key findings from a paper by Szeto et al. are discussed and compared with those from previous publications. This type of peritonitis has a high rate of catheter removal and technique failure. Results may be better with more aggressive antibiotic treatment. Other developments in the field are reviewed.
Scattered evidence suggests that the human peritoneal cavity contains cells of the dendritic cell (DC) lineage but their characterization is missing. Here, we report that the peritoneal cavity of normal subjects and of stable patients on peritoneal dialysis (PD) contains a population of CD14(+) cells that can differentiate into DCs or macrophages. Within this pool, we characterized a CD14(+)CD4(+) cell subset (2.2% of the peritoneal cells) fulfilling the definition of myeloid DC precursors or pre-DC1 cells. These cells expressed high levels of HLA-DR, CD13, CD33, and CD86, and low levels of CD40, CD80, CD83, CD123, CD209, TLR-2 and TLR-4. These cells retained CD14 expression until late stages of differentiation, despite concomitant up-regulation of DC-SIGN (CD209), CD1a, CD80 and CD40. Peritoneal pre-DC1 cells had endocytic capacity that was down-regulated upon LPS/IFN-gamma stimulation, were more potent allo-stimulators than peritoneal CD14(+)CD4(-/lo) cells and monocyte-derived macrophages, and induced Th1 cytokine responses. More importantly, the number of peritoneal pre-DC1 cells increased during PD-associated peritonitis, with a different profile for Gram positive and Gram negative peritonitis, suggesting that these cells participate in the induction of peritoneal adaptive immune responses, and may be responsible for the bias towards Th1 responses during peritonitis.
BACKGROUND: The extent to which relevant confounding variables influence the recognized association between renal insufficiency and malnutrition is not known. This study examined whether renal insufficiency was associated with malnutrition, independent of relevant demographic, social, and medical conditions in noninstitutionalized adults 60 years of age and older. METHODS: Participants (5248) in the United States Third National Health and Nutrition Examination Survey (NHANES III, 1988 to 1994), a cross-sectional study, were examined in a multivariate logistic regression model. Participants were stratified into three groups of glomerular filtration rate (GFR) by serum creatinine. Dietary and nutritional factors were estimated from 24-hour dietary recall, biochemistry measurements, anthropometry, and bioelectrical impedance. Participants were malnourished if they demonstrated at least three of the following five criteria: (1) serum albumin < or =37 g/L, (2) male weight < or =63.9 kg, female weight < or =51.8 kg, (3) serum cholesterol <4.1 mmol/L, (4) energy intake <15 kcal/kg/day, and (5) protein intake <0.5 g/kg/day. RESULTS: A GFR <30 mL/min/1.73 m(2) was present in 2.3% of men and 2.6% of women; these participants demonstrated low energy and protein intake and higher serum markers of inflammation. Thirty-one percent of individuals with malnutrition demonstrated a GFR <60 mL/min/1.73 m(2). In multivariate analysis, a GFR <30 mL/min/1.73 m(2) was independently associated with malnutrition [odds ratio 3.6 (2.0 to 6.6)] after adjustment for relevant demographic, social and medical conditions. CONCLUSIONS: It is probable that renal insufficiency is an important independent risk factor for malnutrition in older adults. Malnutrition should be considered, prevented, and treated as possible in persons with clinically important renal insufficiency. These results should be confirmed in a prospective longitudinal cohort study.
BACKGROUND: Recent studies report decreased mortality in patients on peritoneal dialysis (PD) over time, suggesting that advances in PD have resulted in improved patient outcomes. Our investigation sought to assess the effect of renal center characteristics on mortality and technique failure (TF) rates. METHODS: Covariates of interest included center-specific cumulative number of PD patients treated, percentage of patients who initiated dialysis on PD, and academic status. Using data obtained from the Canadian Organ Replacement Register, the 17,900 patients who received PD during the 1981 to 1997 period were studied. Mortality and TF rate ratios (RR) were estimated using Poisson regression, adjusting for age, gender, race, primary renal diagnosis, province, follow-up time, and type of PD. RESULTS: As the cumulative number of PD patients treated increased, covariate-adjusted mortality significantly decreased (P < 0.05); a weaker yet significant association was observed between number of PD patients treated and TF. As the percentage of patients initiating dialysis on PD increased, TF rates decreased significantly. No association was observed between center academic status and PD mortality or TF rates. CONCLUSIONS: These results imply that a center's experience with and degree of specialization toward PD impact strongly on PD outcomes. One hypothesis is that a center's propensity to exploit technical and non-technical advances in PD increases directly with these variables. It is also possible that, through experience, centers become more adept at identifying appropriate patients to receive PD. More detailed research is required to evaluate these hypotheses.
In the United States, 87.3% of the patients with end-stage renal disease (ESRD) requiring dialysis are treated with hemodialysis (HD) and 12.7% with peritoneal dialysis (PD). This represents a greater use of HD than in many other nations. We mailed a survey questionnaire to members of the National Kidney Foundation Council on Dialysis to better understand the attitudes of American nephrologists toward dialysis modality decisions. We received responses from 240 of 507 nephrologists (47.3%). The respondents were heavily involved in clinical dialysis work. Results showed that decisions regarding modality selection were strongly based on patient preference (4.54 on a scale of 1 to 5), quality of life (4.18), morbidity (4.02), and mortality (3.90), whereas the least important factors reported were facility reimbursement (2.09) and physician reimbursement (1.98). When asked about the current use of modalities, hospital-based HD and full-care HD were believed to be overused (2.63 for each on a scale of 1 [vastly overused] to 5 [vastly underused]), whereas home HD (4.29), continuous ambulatory PD (3.71), and cycler PD (3.59) were underused. A hypothetical question about optimal modality distribution to maximize survival or cost-effectiveness showed that HD should constitute 71% or 66% of dialysis (with 11% or 14% in the form of home HD, respectively). PD use would increase between two- and threefold over current practices. Our results suggest that American nephrologists believe home therapies are underused. Because modality distribution is an important determinant of costs and possibly outcomes in patients with ESRD, there is an urgent need for further research in this area.
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This paper reviews the rationale behind the proposed policy of using peritoneal dialysis (PD) as the initial treatment modality in patients with end-stage renal disease (ESRD). The better preservation of residual renal function associated with PD is emphasized along with its potential cardiovascular benefits. The superior patient survival on PD, relative to hemodialysis, during the first 2 years on dialysis in both the United States and Canada is discussed, as are the potential advantages of PD in terms of hepatitis C prevention, anaemia management and quality of life. The lower cost of PD in association with these clinical advantages lead to the modality being more cost-effective in the early years on dialysis. The relatively high technique failure rate on PD, however, subsequently leads to an increasing need for haemodialysis. A policy of integrated dialysis care with PD first and then haemodialysis, as required, is advocated as a more cost-effective approach to ESRD in suitable patients.
The debate on the relationship between small solute clearance and patient outcome on peritoneal dialysis has intensified in the past year with the publication or presentation of a number of important new studies. Previous studies had found a correlation between clearances and subsequent patient survival. However, this effect was all accounted for by residual renal clearance. The failure to detect an independent effect of peritoneal clearance on outcomes had been attributed to a lack of well-done studies with sufficient variation in peritoneal clearance to detect such an effect. New prospective and randomized studies suggest, however, that the relationship between peritoneal clearance and outcome is weak or absent within the usual dose ranges delivered in clinical practice. Existing clearance targets may need to be reviewed.
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Australia, in a sense, has as many dialysis delivery systems as it has states, with the differences in delivery systems being far greater between those states than is the case, for example, in the U.S. However, if common trends are apparent across the nation in dialysis delivery, they include: an increasing tendency to move HD delivery out of major teaching hospital centres into the community a modest decrease in PD use as more HD becomes available an increased role for the private sector in terms of HD delivery, ranging from direct facility ownership to pay-per-treatment arrangements in public hospitals an awareness of a need to make particular provision for the Aboriginal population, given their high rate of ESRD, their geographical dispersion, and their socio-economic deprivation. It will be interesting to observe how these processes evolve in the years ahead and whether these initiatives lead to "catch up" in Australia's incidence of treated ESRD relative to that of other Western countries.
Recent evidence suggested that noncompliance (NC) with continuous ambulatory peritoneal dialysis (CAPD) exchanges may be more common in US than in Canadian dialysis centers. This issue was investigated using a questionnaire-based method in 656 CAPD patients at 14 centers in the United States and Canada. NC was defined as missing more than one exchange per week or more than two exchanges per month. Patients were ensured of the confidentiality of their individual results. Mean patient age was 56 +/- 16 years, 52% were women, and 39% had diabetes. The overall admitted rate of NC was 13%, with a rate of 18% in the United States and 7% in Canada (P < 0.001). NC was more common in younger patients (P < 0.0001), those without diabetes (P < 0.001), and employed patients (P < 0.05). It was also more common in black and Hispanic than in Asian and white patients (P < 0.001). NC was more common in patients prescribed more than four exchanges daily (P < 0.0001) but was not affected by dwell volume. On multiple regression analysis, the independent predictors of NC, in order of importance, were being prescribed more than four exchanges per day, black race, being employed, younger age, and not having diabetes. Being treated in a US unit did not quite achieve significance as a multivariate independent predictor. These findings suggest that NC is not uncommon in CAPD patients and is more frequent in US than in Canadian patients. However, country of residence is less powerful as a predictor of NC than a variety of other demographic and prescription factors.
The creatinine excretion (CrEx) ratio was first described as a method for detecting noncompliance in peritoneal dialysis (PD) patients. However, a high CrEx ratio is not specific for noncompliance and may also be found in compliant patients with a relatively greater lean body mass (LBM). A cohort of 44 PD patients was followed up for a mean of 13 +/- 8 months after measurement of baseline CrEx ratio to investigate whether greater values were predictive of good or poor clinical outcomes. During this follow-up, 11 patients died, 12 patients transferred to hemodialysis, 4 patients underwent transplantation, 1 patient recovered renal function, and 16 patients continued on PD. The mean CrEx ratio in all patients was 1.14 +/- 0.32. It did not differ between men and women (1.15 versus 1.13, respectively; P = 0.76) but showed a trend toward being less in patients with diabetes (1.03 versus 1.19; P = 0. 19). The mean weekly Kt/V, weekly creatinine clearance, normalized protein equivalent of nitrogen appearance, and serum albumin values were 2.18 +/- 0.57, 73.57 +/- 33.75 L/1.73 m(2), 0.80 +/- 0.22 g/kg/d, and 3.22 +/- 0.59 g/dL, respectively. Technique failure (P < 0.001) and death (P < 0.05) were significantly more common in patients with a CrEx ratio less than 1 compared with those with a CrEx ratio greater than 1. On Cox regression analysis, the CrEx ratio was the only significant predictor of technique failure and was also an independent predictor of death. High CrEx ratio is a predictor of good, rather than poor, outcome in PD patients, perhaps because it is primarily an index of nutrition. This further weakens the argument that it is a reliable or useful marker of noncompliance.
The best data on long term trends in patient and technique survival on dialysis come from North America. Mortality rates on both peritoneal (PD) and hemodialysis (HD) have fallen over the past one to two decades in both the US and Canada with the decline in the US being relatively greater in older and diabetic patients. There is some suggestion that this improvement may be proportionately greater in PD, relative to HD, patients in both the US and Canada. Overall, mortality rates on PD are similar to, or better than, those on HD in the early years of treatment, except in older US diabetic patients. In later years, patients on HD do relatively better than those on PD in the US but not in Canada. The biggest cause of mortality on dialysis is cardiovascular disease and the risk factors for this in the dialysis population generally, and particularly on PD, are reviewed, including newly appreciated ones such as hyperhomocysteinemia, high lipoprotein (a) levels and inflammation/malnutrition. Possible preventative and therapeutic strategies are also considered. Technique failure (TF) rates are high in PD but Canadian data suggest they have fallen over the past 20 years, primarily due to a reduction in cases due to peritonitis. TF rates due to inadequate dialysis have increased and an interpretation of this as well as an approach to reducing it are suggested.
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The overall conclusion is that neither creatinine clearance nor urea clearance is the perfect index for predicting outcome in PD patients. In the absence of indices that are better validated and more convenient, creatinine and urea are what we have to use. They are best seen as two imperfect, but potentially complementary, measurements. On balance, creatinine clearance is the better of the two indices, in that it gives greater weight to residual renal function, and residual renal function is probably a stronger predictor of patient outcome than peritoneal clearance per se. However, creatinine clearance has a particular weakness in low transporters; values have to be interpreted with discretion in this group. Furthermore, both indices are flawed because of the manner in which they are conventionally normalized. Research into more appropriate methods of normalization, or into whether normalization is required at all, would be helpful. The complex relationship between these clearance indices, protein intake, and lean body mass also needs to be kept in mind. While this paper argues in favour of creatinine clearance as the better index, it still suggests that both indices be used, together with a large measure of clinical judgment.
Peritoneal clearance has not yet been proven to predict clinical outcome in peritoneal dialysis patients independent of residual renal function. Studies looking at the relationship between clearance and outcome have not been adequately powered to detect an effect. Pending better studies, clearance targets have been established, and higher clearances are being delivered. This article reviews existing literature on the topic and discusses the problems associated with carrying out a randomized controlled trial to address the issue.
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