Estimating risk of encapsulating peritoneal sclerosis accounting for the competing risk of death.

BACKGROUND: Risk of encapsulating peritoneal sclerosis (EPS) is strongly associated with the duration of peritoneal dialysis (PD), such that patients who have been on PD for some time may consider elective transfer to haemodialysis to mitigate the risk of EPS. There is a need to determine this risk to better inform clinical decision making, but previous studies have not allowed for the competing risk of death. METHODS: This study included new adult PD patients in Australia and New Zealand (ANZ; 1990-2010) or Scotland (2000-08) followed until 2012. Age, time on PD, primary renal disease, gender, data set and diabetic status were evaluated as predictors at the start of PD, then at 3 and 5 years after starting PD using flexible parametric competing risks models. RESULTS: In 17 396 patients (16 162 ANZ, 1234 Scotland), EPS was observed in 99 (0.57%) patients, less frequently in ANZ patients (n = 65; 0.4%) than in Scottish patients (n = 34; 2.8%). The estimated risk of EPS was much lower when the competing risk of death was taken into account (1 Kaplan-Meier = 0.0126, cumulative incidence function = 0.0054). Strong predictors of EPS included age, primary renal disease and time on PD. The risk of EPS was reasonably discriminated at the start of PD (C-statistic = 0.74-0.79) and this improved at 3 and 5 years after starting PD (C-statistic = 0.81-0.92). CONCLUSIONS: EPS risk estimates are lower when calculated using competing risk of death analyses. A patient's estimated risk of EPS is country-specific and can be predicted using age, primary renal disease and duration of PD.

A Randomized, Single-Blind, Crossover Trial of Recovery Time in High-Flux Hemodialysis and Hemodiafiltration.

BACKGROUND: The choice between hemodiafiltration (HDF) or high-flux hemodialysis (HD) to treat end-stage kidney disease remains a matter of debate. The duration of recovery time after treatment has been associated with mortality, affects quality of life, and may therefore be important in informing patient choice. We aimed to establish whether recovery time is influenced by treatment with HDF or HD. STUDY DESIGN: Randomized patient-blinded crossover trial. SETTINGS & PARTICIPANTS: 100 patients with end-stage kidney disease were enrolled from 2 satellite dialysis units in Glasgow, United Kingdom. INTERVENTION: 8 weeks of HD followed by 8 weeks of online postdilution HDF or vice versa. OUTCOMES: Posttreatment recovery time, symptomatic hypotension events, dialysis circuit clotting events, and biochemical parameters. MEASUREMENTS: Patient-reported recovery time in minutes, incidence of adverse events during treatments, hematology and biochemistry results, quality-of-life questionnaire. RESULTS: There was no overall difference in recovery time between treatments (medians for HDF vs HD of 47.5 [IQR, 0-240] vs 30 [IQR, 0-210] minutes, respectively; P=0.9). During HDF treatment, there were significant increases in rates of symptomatic hypotension (8.0% in HDF vs 5.3% in HD; relative risk [RR], 1.52; 95% CI, 1.2-1.9; P<0.001) and intradialytic tendency to clotting (1.8% in HDF vs 0.7% in HD; RR, 2.7; 95% CI, 1.5-5.0; P=0.002). Serum albumin level was significantly lower during HDF (3.2 vs 3.3g/dL; P<0.001). Health-related quality-of-life scores were equivalent. LIMITATIONS: Single center; mean achieved HDF convection volume, 20.6L. CONCLUSIONS: Patients blinded to whether they were receiving HD or HDF in a randomized controlled crossover study reported similar posttreatment recovery times and health-related quality-of-life scores.

Incidence and outcome of encapsulating peritoneal sclerosis.

BACKGROUND: Studies report variation in the incidence and outcomes of encapsulating peritoneal sclerosis (EPS). This study reports the incidence and outcome of EPS cases in a national cohort of peritoneal dialysis (PD) patients. METHODS: The incident cohort of adult patients who started PD between 1 January 2000 and 31 December 2007 in Scotland (n = 1238) was identified from the Scottish Renal Registry. All renal units in Scotland identified potential EPS cases diagnosed from 1 January 2000 to 31 December 2014, by which point all patients had a minimum of 7 years follow-up from start of PD. RESULTS: By 31 December 2014, 35 EPS cases were diagnosed in the 1238 patient cohort: an overall incidence of 2.8%. The incidence for subgroups with longer PD duration rises exponentially: 1.1% by 1 year, 3.4% by 3 years, 8.8% at 4 years, 9.4% at 5 years and 22.2% by 7 years. Outcomes are poor with mortality of 57.1% by 1 year after diagnosis. Survival analysis demonstrates an initial above-average survival in patients who later develop EPS, which plummets to well below average after EPS diagnosis. CONCLUSIONS: The incidence of EPS is reassuringly low provided PD exposure is not prolonged and this supports ongoing use of PD. However, continuing PD beyond 3 years results in an exponential rise in the risk of developing EPS and deciding whether this risk is acceptable should be made on an individual patient basis.

Extracorporeal treatment for valproic acid poisoning: systematic review and recommendations from the EXTRIP workgroup.

BACKGROUND: The EXtracorporeal TReatments In Poisoning (EXTRIP) workgroup presents its systematic review and clinical recommendations on the use of extracorporeal treatment (ECTR) in valproic acid (VPA) poisoning. METHODS: The lead authors reviewed all of the articles from a systematic literature search, extracted the data, summarized the key findings, and proposed structured voting statements following a predetermined format. A two-round modified Delphi method was chosen to reach a consensus on voting statements and the RAND/UCLA Appropriateness Method was used to quantify disagreement. Anonymous votes were compiled, returned, and discussed in person. A second vote was conducted to determine the final workgroup recommendations. RESULTS: The latest literature search conducted in November 2014 retrieved a total of 79 articles for final qualitative analysis, including one observational study, one uncontrolled cohort study with aggregate analysis, 70 case reports and case series, and 7 pharmacokinetic studies, yielding a very low quality of evidence for all recommendations. Clinical data were reported for 82 overdose patients while pharmaco/toxicokinetic grading was performed in 55 patients. The workgroup concluded that VPA is moderately dialyzable (level of evidence = B) and made the following recommendations: ECTR is recommended in severe VPA poisoning (1D); recommendations for ECTR include a VPA concentration > 1300 mg/L (9000 µmol/L)(1D), the presence of cerebral edema (1D) or shock (1D); suggestions for ECTR include a VPA concentration > 900 mg/L (6250 µmol/L)(2D), coma or respiratory depression requiring mechanical ventilation (2D), acute hyperammonemia (2D), or pH ≤ 7.10 (2D). Cessation of ECTR is indicated when clinical improvement is apparent (1D) or the serum VPA concentration is between 50 and 100 mg/L (350-700 µmol/L)(2D). Intermittent hemodialysis is the preferred ECTR in VPA poisoning (1D). If hemodialysis is not available, then intermittent hemoperfusion (1D) or continuous renal replacement therapy (2D) is an acceptable alternative. CONCLUSIONS: VPA is moderately dialyzable in the setting of overdose. ECTR is indicated for VPA poisoning if at least one of the above criteria is present. Intermittent hemodialysis is the preferred ECTR modality in VPA poisoning.

Extracorporeal treatment for barbiturate poisoning: recommendations from the EXTRIP Workgroup.

The EXTRIP (Extracorporeal Treatments in Poisoning) Workgroup conducted a systematic review of barbiturate poisoning using a standardized evidence-based process to provide recommendations on the use of extracorporeal treatment (ECTR) in patients with barbiturate poisoning. The authors reviewed all articles, extracted data, summarized key findings, and proposed structured voting statements following a predetermined format. A 2-round modified Delphi method was used to reach a consensus on voting statements, and the RAND/UCLA Appropriateness Method was used to quantify disagreement. 617 articles met the search inclusion criteria. Data for 538 patients were abstracted and evaluated. Only case reports, case series, and nonrandomized observational studies were identified, yielding a low quality of evidence for all recommendations. Using established criteria, the workgroup deemed that long-acting barbiturates are dialyzable and short-acting barbiturates are moderately dialyzable. Four key recommendations were made. (1) The use of ECTR should be restricted to cases of severe long-acting barbiturate poisoning. (2) The indications for ECTR in this setting are the presence of prolonged coma, respiratory depression necessitating mechanical ventilation, shock, persistent toxicity, or increasing or persistently elevated serum barbiturate concentrations despite treatment with multiple-dose activated charcoal. (3) Intermittent hemodialysis is the preferred mode of ECTR, and multiple-dose activated charcoal treatment should be continued during ECTR. (4) Cessation of ECTR is indicated when clinical improvement is apparent. This report provides detailed descriptions of the rationale for all recommendations. In summary, patients with long-acting barbiturate poisoning should be treated with ECTR provided at least one of the specific criteria in the first recommendation is present.

Guidelines for reporting case studies on extracorporeal treatments in poisonings: methodology.

A literature review performed by the EXtracorporeal TReatments In Poisoning (EXTRIP) workgroup highlighted deficiencies in the existing literature, especially the reporting of case studies. Although general reporting guidelines exist for case studies, there are none in the specific field of extracorporeal treatments in toxicology. Our goal was to construct and propose a checklist that systematically outlines the minimum essential items to be reported in a case study of poisoned patients undergoing extracorporeal treatments. Through a modified two-round Delphi technique, panelists (mostly chosen from the EXTRIP workgroup) were asked to vote on the pertinence of a set of items to identify those considered minimally essential for reporting complete and accurate case reports. Furthermore, independent raters validated the clarity of each selected items between each round of voting. All case reports containing data on extracorporeal treatments in poisoning published in Medline in 2011 were reviewed during the external validation rounds. Twenty-one panelists (20 from the EXTRIP workgroup and an invited expert on pharmacology reporting guidelines) participated in the modified Delphi technique. This group included journal editors and experts in nephrology, clinical toxicology, critical care medicine, emergency medicine, and clinical pharmacology. Three independent raters participated in the validation rounds. Panelists voted on a total of 144 items in the first round and 137 items in the second round, with response rates of 96.3% and 98.3%, respectively. Twenty case reports were evaluated at each validation round and the independent raters' response rate was 99.6% and 98.8% per validation round. The final checklist consists of 114 items considered essential for case study reporting. This methodology of alternate voting and external validation rounds was useful in developing the first reporting guideline for case studies in the field of extracorporeal treatments in poisoning. We believe that this guideline will improve the completeness and transparency of published case reports and that the systematic aggregation of information from case reports may provide early signals of effectiveness and/or harm, thereby improving healthcare decision-making.

Pain resulting from arteriovenous fistulae: prevalence and impact.

INTRODUCTION: The burden of pain from cannulation of arteriovenous fistulae (AVF) and the impact it has on quality of life is poorly described in the literature. METHODOLOGY: A pain score questionnaire was employed for all patients in the West of Scotland dialyzing via AVF (n = 461). Pain was assessed using visual analogue score (VAS) and McGill pain score. Patients with severe pain (VAS > 5) were compared to those with minimal pain. RESULTS: The questionnaire as completed by 97.5% of the patients. Median VAS on cannulation was 3 (IQR 0.5 - 4.5). Of those who had completed the questionnaire, 24.4% had severe pain on cannulation and 3.2% experienced severe chronic pain. 53 patients (11.3%) cut a dialysis session short due to pain. Of the patients with severe chronic pain, 46.7% had a physical complication affecting their AVF (e.g., venous stenosis, pseudoaneurysm). Following treatment of the problem, pain improved in 71.4% and resolved completely in 14.3%. Brachiobasilic AVF was associated with a higher incidence of severe pain than either brachiocephalic or radiocephalic AVF (50%, 23.3% and 24.4% respectively; p = 0.03). There was a trend towards more severe pain with rope-ladder cannulation (27.7%) compared to button-hole cannulation (18.2%); however, this difference did not reach statistical significance (p = 0.09). CONCLUSIONS: Pain from AVF is poorly recognized and an under-reported problem. While severe pain resulting in the avoidance of dialysis is rare, it can lead to significant difficulties and ultimate abandonment of AVF. Pain is often suggestive of an underlying anatomical problem.

Extracorporeal treatment for thallium poisoning: recommendations from the EXTRIP Workgroup.

BACKGROUND: The EXtracorporeal TReatments In Poisoning (EXTRIP) workgroup was formed to provide recommendations on the use of extracorporeal treatment (ECTR) in poisoning. To test and validate its methods, the workgroup reviewed data for thallium (Tl). METHODS: After an extensive search, the co-chairs reviewed the articles, extracted the data, summarized findings, and proposed structured voting statements following a predetermined format. A two-round modified Delphi method was chosen to reach a consensus on voting statements and RAND/UCLA Appropriateness Method to quantify disagreement. Blinded votes were compiled, returned, and discussed during a conference call. A second vote determined the final recommendations. RESULTS: Forty-five articles met inclusion criteria. Only case reports and case series were identified, yielding a very low quality of evidence for all recommendations. Data on 74 patients, including 11 who died, were abstracted. The workgroup concluded that Tl is slightly dialyzable and made the following recommendations: ECTR is recommended in severe Tl poisoning (1D). ECTR is indicated if Tl exposure is highly suspected on the basis of history or clinical features (2D) or if the serum Tl concentration is >1.0 mg/L (2D). ECTR should be initiated as soon as possible, ideally within 24-48 hours of Tl exposure (1D), and be continued until the serum Tl concentration is <0.1 mg/L for a minimal duration of 72 hours (2D). CONCLUSION: Despite Tl's low dialyzability and the limited evidence, the workgroup strongly recommended extracorporeal removal in the case of severe Tl poisoning.

The EXTRIP (EXtracorporeal TReatments In Poisoning) workgroup: guideline methodology.

Extracorporeal treatments (ECTRs), such as hemodialysis and hemoperfusion, are used in poisoning despite a lack of controlled human trials demonstrating efficacy. To provide uniform recommendations, the EXTRIP group was formed as an international collaboration among recognized experts from nephrology, clinical toxicology, critical care, or pharmacology and supported by over 30 professional societies. For every poison, the clinical benefit of ECTR is weighed against associated complications, alternative therapies, and costs. Rigorous methodology, using the AGREE instrument, was developed and ratified. Methods rely on evidence appraisal and, in the absence of robust studies, on a thorough and transparent process of consensus statements. Twenty-four poisons were chosen according to their frequency, available evidence, and relevance. A systematic literature search was performed in order to retrieve all original publications regardless of language. Data were extracted on a standardized instrument. Quality of the evidence was assessed by GRADE as: High = A, Moderate = B, Low = C, Very Low = D. For every poison, dialyzability was assessed and clinical effect of ECTR summarized. All pertinent documents were submitted to the workgroup with a list of statements for vote (general statement, indications, timing, ECTR choice). A modified Delphi method with two voting rounds was used, between which deliberation was required. Each statement was voted on a Likert scale (1-9) to establish the strength of recommendation. This approach will permit the production of the first important practice guidelines on this topic.

Peritoneal dialysis-associated peritonitis rates and outcomes in a national cohort are not improving in the post-millennium (2000-2007).

BACKGROUND: Peritoneal dialysis (PD)-related peritonitis remains the leading cause of technique failure and a significant cause of morbidity among PD patients. Rates in the literature vary, reflecting differences in study design and in populations. The objective of the present study was to determine peritonitis incidence and outcomes in Scotland and to compare them with national guidelines. METHODS: All 10 adult renal units in Scotland prospectively collect data relating to peritonitis for all PD patients in Scotland. Complete audit data between 1 January 2000 and 31 December 2007 were analyzed for the study. RESULTS: The 1918 peritonitis episodes in 38 106 PD treatment months yielded a national rate of 1 episode every 19.9 months. The UK Renal Association standard was met every year, but is not consistently improving. The median peritonitis-free survival was 526 days (95% confidence interval: 463 to 589 days). The spectrum of causative organisms reflected those in previous reports, with a culture-negative rate of 19.4%. Nationally, the cure rate was 74.6%, the refractory rate was 22.6%, and the death rate was 2.8%. Outcome varied by organism. Recurrences represented 9.3% of episodes, and technique failure occurred in 14.9%. The peritonitis rate was higher for continuous ambulatory PD patients than for automated PD patients (1 episode every 17.6 months vs 1 episode every 22.3 months, p < 0.001, relative risk: 1.27). There were significant differences between renal units. CONCLUSIONS: This large national PD cohort met targets for peritonitis rates every year during the 8 years covered by the present report, but showed no consistent trend for improvement. Peritonitis remains the main cause of technique failure in Scotland. Peritonitis rates varied widely between the units, which suggests that we should look to the units and countries with lower peritonitis rates to see if we can adopt successful elements of their practice before resigning ourselves to our ongoing peritonitis burden.

Precipitating factors and patient outcomes in acute kidney injury treated with renal replacement therapy.

Acute kidney injury (AKI) is not uncommon in acute hospital admissions. AKI treated with renal replacement therapy (RRT) has a wide spectrum of causes and the mortality rate at 90 days, approaches 50%. This study was performed to analyse the identifiable causes and outcomes of all cases of AKI treated with RRT in the Glasgow Royal Infirmary (GRI) renal wards during 2007. This study identified 65 cases of AKI treated with RRT from the GRI renal unit electronic patient record (EPR). Causes of AKI, modality of RRT and patient outcomes were retrieved from the EPR and discharge letters. The main outcome measures were the mortality rate and the percentage of patients still receiving RRT at 90 days. More than one precipitating factor was identified in half of the cases of dialysis-dependent AKI. Sepsis, hypovolaemia and nephrotoxic drugs were the main contributory factors and were observed in 52%, 40% and 23% of the cases, respectively. The mortality rate was 29% at 90 days. This study shows that the aetiology of AKI is often multifactorial and the 90-day mortality rate of AKI treated with RRT is still high.

AA amyloidosis in a patient with Langerhans cell histiocytosis.

We report the case of a 37-year-old woman who presented with progressive renal dysfunction and proteinuria, in whom renal biopsy confirmed a diagnosis of AA amyloidosis. No evidence of chronic suppurative infection, connective tissue disease or malignancy was found. A past history of Langerhans cell histiocytosis (LCH) diagnosed in childhood was noted for which the patient had been successfully treated with surgical excision, corticosteroids, radiotherapy and chemotherapy. Renal disease in LCH is not widely recognized and thus we describe a patient with LCH in whom AA amyloidosis developed in the absence of any other established cause.

Comparison of patient survival in non-diabetic transplant-listed patients initially treated with haemodialysis or peritoneal dialysis.

BACKGROUND: It is still not known whether patients survive longer on one modality of dialysis compared to the other. We have tried to answer this question using data from the Scottish Renal Registry. METHODS: To avoid the confounding effects of co-morbidity, we limited our survival analysis to those patients listed for a renal transplant and excluded patients with a primary renal diagnosis (PRD) of diabetic nephropathy. We studied patients starting dialysis between 01 January 1982 and 31 December 2006. RESULTS: Three thousand one hundred and ninety-seven patients fulfilled our criteria. A Kaplan-Meier plot showed no difference in survival between initial dialysis modality (log-rank P = 0.996). In the Cox regression model, initial dialysis modality was not a significant predictor of survival; hazard ratio = 0.97 (95% CI 0.80 to 1.18) after adjusting for age, sex and PRD. Age at the start of dialysis, hazard ratio = 1.05 (95% CI 1.04 to 1.06) and a PRD group of 'multi-system disease' or 'unknown' were found to significantly influence survival. When survival was also censored for change in modality, there was no difference in survival over the whole study period with the hazard of death for patients on haemodialysis compared to those on peritoneal dialysis being 1.04 (95% CI 0.78 to 1.38; P = 0.803). Age at the start of dialysis remained a significant predictor of death. CONCLUSIONS: This study shows that there was no survival advantage between initial dialysis modalities in non-diabetic patients who are deemed healthy enough for listing for a renal transplant.

A prospective observational study of catheter-related bacteraemia and thrombosis in a haemodialysis cohort: univariate and multivariate analyses of risk association.

BACKGROUND: Central venous catheterization is a fundamental component in delivering haemodialysis yet is associated with significantly higher complication rates than other methods of vascular access. In this study, we report results of univariate and multivariate analyses designed to identify and quantify independent risk association for catheterization type, clinical variables and laboratory variables with regard to the development of catheter-related bacteraemia (CRB) and catheter failure due to poor haemodialysis flow. METHODS: A 2-year prospective study of all incident haemodialysis vascular access catheter insertions was conducted. Laboratory and clinical variables were recorded at catheter insertion, and the clinical course was followed up to the point of catheter removal. CRB and catheter failure due to poor flow were recorded as outcome events. Univariate and multivariate analyses were used to test for association between clinical and laboratory variables and outcome. RESULTS: Forty-four thousand five hundred seventy-six catheter days were accumulated over the study period. Multivariate analysis demonstrated an independent association between non-tunnelled catheterization procedures and adverse outcomes compared with tunnelled central venous catheter insertions. Elevated modified Charlson comorbidity score was independently associated with the development of CRBc. Elevated C-reactive protein and low haemodialysis blood pump flow were independently associated with catheter failure due to poor flow. CONCLUSIONS: The data demonstrate that tunnelled central venous catheter insertions have an association with lower complication rates than non-tunnelled central venous catheter insertions that is independent of whether patients have acute or chronic renal failure, or high levels of comorbidity.

Encapsulating peritoneal sclerosis in the new millennium: a national cohort study.

BACKGROUND AND OBJECTIVES: The study aim was to establish the incidence and characterize all encapsulating peritoneal sclerosis (EPS) cases in patients treated by peritoneal dialysis (PD). DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The patient cohort, which started PD from January 1, 2000, to December 31, 2007, was identified from the Scottish Renal Registry (n = 1238). Possible EPS cases were identified by the ten adult Scottish renal units. Patient records were examined to ensure cases met diagnostic criteria. RESULTS: Forty-six cases were identified; 19 had their first PD exposure after January 1, 2000. The rate was 1.5%, an incidence of 4.9 per 1000 person-years. The incidence increased with PD duration, with rates of 0, 0.6, 2.0, 3.5, 8.1, 8.8 and 5% at <1, 1 to 2, >2 to 3, >3 to 4, >4 to 5, >5 to 6 and >6 yr PD exposure, respectively. The median PD duration of EPS cases was 5.1 yr (interquartile range [IQR] 3.4 to 6.1 yr). At diagnosis, 12 (26%) were on PD and 33 (72%) were diagnosed <2 yr after PD stopped. The cases had a median of 3.3 episodes of peritonitis (range 0 to 20, IQR 1 to 4.5). Thirty (65%) had used 3.86% dextrose dialysate and 45 (98%) had used Extraneal. The mortality was 42% at 1 yr postdiagnosis with a median survival of 149 d (IQR 61 to 408 d). CONCLUSIONS: The incidence reported in this study may be used to inform patients of the minimum risk of developing EPS on PD.