Variation in Access to Kidney Transplantation Across Renal Programs in Ontario, Canada.

In the United States, kidney transplant rates vary significantly across end-stage renal disease (ESRD) networks. We conducted a population-based cohort study to determine whether there was variability in kidney transplant rates across renal programs in a health care system distinct from the United States. We included incident chronic dialysis patients in Ontario, Canada, from 2003 to 2013 and determined the 1-, 5-, and 10-year cumulative incidence of kidney transplantation in 27 regional renal programs (similar to U.S. ESRD networks). We also assessed the cumulative incidence of kidney transplant for "healthy" dialysis patients (aged 18-50 years without diabetes, coronary disease, or malignancy). We calculated standardized transplant ratios (STRs) using a Cox proportional hazards model, adjusting for patient characteristics (maximum possible follow-up of 11 years). Among 23 022 chronic dialysis patients, the 10-year cumulative incidence of kidney transplantation ranged from 7.4% (95% confidence interval [CI] 4.8-10.7%) to 31.4% (95% CI 16.5-47.5%) across renal programs. Similar variability was observed in our healthy cohort. STRs ranged from 0.3 (95% CI 0.2-0.5) to 1.5 (95% CI 1.4-1.7) across renal programs. There was significant variation in kidney transplant rates across Ontario renal programs despite patients having access to the same publicly funded health care system.

PP039. The importance of intentionally considering class 1 HELLP syndrome outcomes versus all other categories of HELLP syndrome or severe preeclampsia.

INTRODUCTION: Combining HELLP syndrome patient groups in publications and presentations may obfuscate any potential differences among patient groups with regard to maternal-perinatal outcomes and rendered therapies. OBJECTIVES: We explored the prevalence of major maternal morbidity (MMM) for patients with severe preeclampsia (SPRE) and each defined group of HELLP syndrome. METHODS: Retrospective cohort study 2000-2007 of patients categorized either as class 1 HELLP syndrome (HELLP1, platelets⩽50,000, AST⩽70,LDH⩽600), class 2 (HELLP2, platelets>50,000 to ⩽100,000), class 3 (HELLP3, platelets>100,000 to ⩽150,000), or partial/incomplete (HELLP4) with only 2 of 3 diagnostic parameters present. All SPRE patients (no HELLP) of 2005-2007 were also evaluated. Total MMM for each group was determined. MMM included cardiopulmonary [cardiogenic or noncardiogenic pulmonary edema, pleural or pericardial effusion, pulmonary embolus, indicated intubation, myocardial infarction or arrest], hematologic/coagulation [DIC, transfused blood products], central nervous system/visual [stroke, cerebral edema, hypertensive encephalopathy, vision loss], hepatic [subcapsular hematoma or rupture] or renal complications [acute tubular necrosis or renal failure]. All HELLP1 and HELLP2 patients received corticosteroids, magnesium sulfate and anti-hypertensives. Comparison among groups was done using Chi-square or Fisher exact test at 95% CI. RESULTS: Four hundred and twenty patients had a form of HELLP syndrome 2000-2007; 688 patients had SPRE 2005-2007.The prevalence of MMM for each patient group was determined: HELLP1=41.5%; HELLP2=10.3%; HELLP3=20.0%; HELLP4=21.0%; and SPRE=17.7%. MMM in HELLP1 was significantly increased over all other groups (P<0.001). Combining MMM for HELLP1+HELLP2 produced a prevalence of 22.1% MMM, insignificantly different from all others including HELLP3, HELLP4 and SPRE (p=0.19), thereby obscuring the significantly elevated MMM of HELLP1 patients. CONCLUSION: Only patients with HELLP1 have significantly increased MMM compared to other HELLP groups or SPRE. Failing to separately evaluate patients with HELLP1 in studies of HELLP syndrome could lead to mistaken conclusions about the effectiveness of a treatment to reduce MMM. All publications reviewing HELLP syndrome management should address how well it functions to reduce patient development of HELLP1 and thus minimize MMM.

PP137. Posterior reversible encephalopathy syndrome (PRES) is a constant component of eclampsia.

INTRODUCTION: Posterior reversible encephalopathy syndrome (PRES) has been reported to occur in patients with eclampsia. In both conditions there is evidence to suggest disordered cerebral autoregulation. OBJECTIVES: We sought to investigate the concurrence of PRES with eclampsia and to describe the associated obstetric, radiologic and critical care correlates. METHODS: Single center 2001-2010 retrospective cohort study of all patients with eclampsia who underwent neuroimaging via magnetic resonance imaging (MRI) or computerized tomography (CT) with or without contrast. The medical records of all patients with eclampsia during the study interval were identified, evaluated and extracted for pertinent data; a diagnosis of PRES was made by radiologists using standard criteria. RESULTS: Forty-six of forty-seven (97.9%) patients with eclampsia revealed PRES on neuroimaging using one or more modalities: MRI without contrast=41 (87.2%), MRI with contrast=27 (57.4%), CT without contrast=16 (34%), CT with contrast=7 (14.8%) and/or MRA/MRV=2 (4.3%). PRES was identified within the parietal (36, 78.3%), occipital (35, 76.1%), frontal (29, 63%), temporal (13, 28.3%) and basal ganglia/ brainstem/cerebellum (12, 26.1%). Eclampsia occurred antepartum in 23 patients, postpartum in 24 patients with 22 vaginal/25 cesarean deliveries at a mean maternal age of 21.8 years (range 15-39) and a mean gestational age of 33.9 weeks (range 22.4-41.7 weeks). Ethnicity was African-American in 38 patients. Headache was the most common presenting symptom (87.2%) followed by altered mental status (51.1%), visual disturbances (34%) and nausea/vomiting (19.1%). Severe systolic hypertension was present in 22 (47%) of patients.Use of antihypertensives (87%), magnesium sulfate (100%), diuretics (66%) and corticosteroids (50%) facilitated maternal recovery in all cases with usually a brief hospitalization (mean 3.9 days, range 1-20 days). CONCLUSION: The common finding of PRES in patients with eclampsia suggests that PRES may be part of the pathogenesis of eclampsia. We speculate that therapy targeted at prevention or reversal of PRES pathogenesis will prevent or facilitate recovery from eclampsia.

Receptor-interacting protein 2 is a marker for resolution of peritoneal dialysis-associated peritonitis.

There are no predictive factors for peritoneal dialysis-associated peritonitis; however, its resolution correlates with a cell-mediated Th1 immune response. We tested the hypothesis that induction of receptor-interacting protein 2 (RIP2), an assumed kinase linked with Th1 responses, is a useful marker in this clinical setting. Basal RIP2 expression was measured in human immune cells and during dialysis-associated peritonitis. RIP2 increased with bacterial toxin cell activation and the temporal profile for this differed depending on immune cell involvement in the innate or adaptive phases of the response. Importantly, RIP2 expression increased in peritoneal immune cells during dialysis-associated peritonitis and this upregulation correlated with clinical outcome. An early induction in peritoneal CD14(+) cells correlated with rapid resolution, whereas minimal induction correlated with protracted infection and with catheter loss in 36% of patients. These latter patients had higher levels of MCP-1 consistent with a delayed transition from innate to adaptive immunity. Our study shows that upregulation of RIP2 is a useful marker to monitor dialysis-associated peritonitis and in predicting the clinical outcome of these infections.

Non-Pseudomonas Gram-negative peritonitis.

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.

Characterization of human peritoneal dendritic cell precursors and their involvement in peritonitis.

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.

Peritoneal dialysis adequacy and risk of death.

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.

Association between renal insufficiency and malnutrition in older adults: results from the NHANES III.

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.

Trends in CAPD technique failure: Canada, 1981-1997.

OBJECTIVE: Although important enhancements to continuous ambulatory peritoneal dialysis (CAPD) have occurred since its inception, few studies have explicitly evaluated trends over time in CAPD technique failure rates. To assist in quantifying the net benefit of improvements to CAPD for patient outcomes, we examined trends in technique failure rates among Canadian CAPD patients. PATIENTS: Patients initiating renal replacement therapy on CAPD (n = 7110) between 1981 and 1997. MAIN OUTCOME MEASURES: Technique failure (i.e., switch to hemodialysis). RESULTS: Total follow-up was 12,831 patient-years (pt-yr). There were 1976 technique failures, for a crude CAPD failure rate of 154.0/1000 pt-yr. Technique failure rate ratios (RR) estimated using Poisson regression and adjusted for age, gender, race, province, primary renal diagnosis, and follow-up time, were significantly reduced for the 1990-93 [RR = 0.75, 95% confidence interval (CI) = (0.68, 0.83)], 1994-95 [RR = 0.83, CI (0.75, 0.93)], and 1996-97 [RR = 0.78, CI (0.70, 0.87)] calendar periods relative to 1981-89 (RR = 1, reference). Among cause-specific technique failure rates, the greatest improvement was observed for peritonitis-attributable technique failure, with RR = 0.46, CI (0.41, 0.50) for 1990-97 relative to 1981-89. However, rates of technique failure due to inadequate dialysis were significantly elevated for the 1990-97 period [RR = 1.68, CI (1.44, 1.96)]. CONCLUSIONS: The collection of more detailed data on practice patterns would enable future studies to elucidate the cause-and-effect relationship between CAPD descriptors and technique failure, and hence assist in clinical decision-making.

Effect of renal center characteristics on mortality and technique failure on peritoneal dialysis.

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.

Integrated end-stage renal disease care: the role of peritoneal dialysis.

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.

Predictors of erythropoietin responsiveness in chronic hemodialysis patients.

The impact of dialysis intensity on erythropoietin (EPO) requirements is unclear. Previous work suggests that increased dialysis is associated with increased erythropoietin responsiveness (ERSP), but average dialysis intensity has increased since those publications. We hypothesized that ERSP would be independent of delivered Kt/V(urea) at current intensities of hemodialysis. We prospectively studied 135 stable chronic hemodialysis patients who receive iron and subcutaneous EPO dosed according to current guidelines. We collected biochemical, hematologic, and single pool urea kinetics data. ERSP was expressed as units per kilogram per week of EPO administered. Simple and multiple linear regression were used to identify characteristics predictive of ERSP. The mean age of the patients was 62 +/- 17 years (range, 17-90 years); 68 of 135 (50.3%) were women, and 120 of 135 (88.9%) were Caucasian. Mean delivered Kt/V(urea) was 1.60 +/- 0.49, with 102 of 135 (75.6%) of patients with a delivered Kt/V(urea) > 1.3. Univariate linear regression showed seven significant independent predictors of erythropoietin requirements. Low serum albumin (p < 0.001), low serum calcium (p = 0.002), high serum phosphate (p = 0.004), and high serum iPTH (p = 0.007) were all associated with lower levels of ERSP. Lower ERSP was also correlated with lower hemoglobin and lower serum iron and transferrin saturation. Delivered dialysis (Kt/ V(urea)) was not a significant predictor of ERSP (p = 0.61). Multivariate regression confirmed low serum albumin (p < 0.01), high serum phosphate (p = 0.001), high immunoreactive parathyroid hormone (p = 0.025), and low transferrin saturation (p < 0.0005) as predictors of low ERSP, and also found high serum ferritin to be correlated with low ERSP (p = 0.016). We found no relationship between erythropoietin responsiveness and intensity of hemodialysis in this population of patients with a mean delivered Kt/V(urea) of 1.6. This may indicate a threshold effect beyond which more dialysis will not improve ERSP. However, markers of an underlying inflammatory state and of secondary hyperparathyroidism were associated with decreased response to erythropoietin.

What do American nephologists think about dialysis modality selection? .

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.

A look at dialysis delivery in Australia.

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.