Postoperative Outcomes After Gastrointestinal Surgery in Patients Receiving Chronic Kidney Replacement Therapy: A Population-based Cohort Study.

OBJECTIVE: This study evaluated the postoperative mortality and morbidity outcomes following the different subtypes of gastrointestinal (GI) surgery over a 15-year period. BACKGROUND: Patients receiving chronic kidney replacement therapy (KRT) experience higher rates of general surgery compared with other surgery types. Contemporary data on the types of surgeries and their outcomes are lacking. KRT was defined as patients requiring chronic dialysis (hemodialysis or peritoneal dilaysis) or having a functioning kidney transplant long-term. METHODS: All incident and prevalent patients aged greater than 18 years identified in the Australia and New Zealand Dialysis and Transplant (ANZDATA) Registry as receiving chronic KRT were linked with jurisdictional hospital admission datasets between January 1, 2000 until December 31, 2015. Patients were categorized by their KRT modality [hemodialysis (HD), peritoneal dialysis (PD), home hemodialysis (HHD), and kidney transplant (KT)]. GI surgeries were categorized as upper gastrointestinal (UGI), bowel (small and large bowel), anorectal, hernia surgery, cholecystectomy, and appendicectomy. The primary outcome was the rates of the different surgeries, estimated using Poisson models. Secondary outcomes were risks of 30-day/in-hospital postoperative mortality risk and nonfatal outcomes and were estimated using logistic regression. Independent predictors of 30-day mortality were examined using comorbidity-adjusted Cox models. RESULTS: Overall, 46,779 patients on chronic KRT were linked to jurisdictional hospital datasets, and 9,116 patients were identified as having undergone 14,540 GI surgeries with a combined follow-up of 76,593 years. Patients on PD had the highest rates of GI surgery (8 per 100 patient years), with hernia surgery being the most frequent. Patients on PD also had the highest risk of 30-day postoperative mortality following the different types of GI surgery, with the risk being more than 2-fold higher after emergency surgery compared with elective procedures. Infective postoperative complications were more common than cardiac complications. This study also observed a U-shaped association between body mass index (BMI) and mortality, with a nadir in the 30 to 35 kg/m 2 group. CONCLUSIONS: Patients on chronic KRT have high rates of GI surgery and morbidity, particularly in those who receive PD, are older, or are either underweight or moderately obese.

Balanced crystalloid solution versus saline in deceased donor kidney transplantation (BEST-Fluids): a pragmatic, double-blind, randomised, controlled trial.

BACKGROUND: Delayed graft function (DGF) is a major adverse complication of deceased donor kidney transplantation. Intravenous fluids are routinely given to patients receiving a transplant to maintain intravascular volume and optimise graft function. Saline (0·9% sodium chloride) is widely used but might increase the risk of DGF due to its high chloride content. We aimed to test our hypothesis that using a balanced low-chloride crystalloid solution (Plasma-Lyte 148) instead of saline would reduce the incidence of DGF. METHODS: BEST-Fluids was a pragmatic, registry-embedded, multicentre, double-blind, randomised, controlled trial at 16 hospitals in Australia and New Zealand. Adults and children of any age receiving a deceased donor kidney transplant were eligible; those receiving a multi-organ transplant or weighing less than 20 kg were excluded. Participants were randomly assigned (1:1) using an adaptive minimisation algorithm to intravenous balanced crystalloid solution (Plasma-Lyte 148) or saline during surgery and up until 48 h after transplantation. Trial fluids were supplied in identical bags and clinicians determined the fluid volume, rate, and time of discontinuation. The primary outcome was DGF, defined as receiving dialysis within 7 days after transplantation. All participants who consented and received a transplant were included in the intention-to-treat analysis of the primary outcome. Safety was analysed in all randomly assigned eligible participants who commenced surgery and received trial fluids, whether or not they received a transplant. This study is registered with Australian New Zealand Clinical Trials Registry, (ACTRN12617000358347), and ClinicalTrials.gov (NCT03829488). FINDINGS: Between Jan 26, 2018, and Aug 10, 2020, 808 participants were randomly assigned to balanced crystalloid (n=404) or saline (n=404) and received a transplant (512 [63%] were male and 296 [37%] were female). One participant in the saline group withdrew before 7 days and was excluded, leaving 404 participants in the balanced crystalloid group and 403 in the saline group that were included in the primary analysis. DGF occurred in 121 (30%) of 404 participants in the balanced crystalloid group versus 160 (40%) of 403 in the saline group (adjusted relative risk 0·74 [95% CI 0·66 to 0·84; p<0·0001]; adjusted risk difference 10·1% [95% CI 3·5 to 16·6]). In the safety analysis, numbers of investigator-reported serious adverse events were similar in both groups, being reported in three (<1%) of 406 participants in the balanced crystalloid group versus five (1%) of 409 participants in the saline group (adjusted risk difference -0·5%, 95% CI -1·8 to 0·9; p=0·48). INTERPRETATION: Among patients receiving a deceased donor kidney transplant, intravenous fluid therapy with balanced crystalloid solution reduced the incidence of DGF compared with saline. Balanced crystalloid solution should be the standard-of-care intravenous fluid used in deceased donor kidney transplantation. FUNDING: Medical Research Future Fund and National Health and Medical Research Council (Australia), Health Research Council (New Zealand), Royal Australasian College of Physicians, and Baxter.

Trends in Rates of Surgery and Postoperative Mortality Among Patients Receiving Chronic Kidney Replacement Therapy: A Population-based Cohort Study.

OBJECTIVE: To estimate the incidence and postoperative mortality rates of surgery, and variations by age, diabetes, kidney replacement therapy (KRT) modality, and time over a 15-year period. BACKGROUND: Patients with kidney failure receiving chronic KRT (dialysis or kidney transplantation) have increased risks of postoperative mortality and morbidity. Contemporary data on the incidence and types of surgery these patients undergo are lacking. METHODS: This binational population cohort study evaluated all incident and prevalent patients receiving chronic KRT using linked data between Australia and New Zealand Dialysis and Transplant (ANZDATA) Registry and jurisdictional hospital admission datasets between 2000 and 2015. Patients were categorized by their KRT modality (hemodialysis, peritoneal dialysis, home hemodialysis, and kidney transplant) for each calendar year. Incidence rates for overall surgery and subtypes were estimated using Poisson models. Logistic regression was used to estimate 30-day/in-hospital mortality risk. RESULTS: Overall, 46,497 patients over a median (interquartile range) follow-up of 6.3 years (3.5-10.2 years) underwent 81,332 surgeries. The median incidence rate of surgery remained stable over this period with a median of 14.9 surgeries per 100 patient-years. Annual incidence rate was higher in older people and those with diabetes mellitus. Patients receiving hemodialysis had a higher incidence rate of surgery compared with kidney transplant recipients (15.8 vs 10.0 surgeries per 100 patient-years, respectively). Overall adjusted postoperative mortality rates decreased by >70% over the study period, and were lowest in kidney transplant recipients (1.7%, 95% confidence interval, 1.4-2.0). Postoperative mortality following emergency surgery was >3-fold higher than elective surgery (8.4% vs 2.3%, respectively). CONCLUSIONS: Patients receiving chronic KRT have high rates of surgery and morbidity. Further research into strategies to mitigate perioperative risk remain a priority.

Pre-dialysis levels of inflammation and endotoxin in people receiving hemodialysis are not associated with blood pressure variability.

There are multiple risk factors for inflammation in dialysis. One potential cause is the presence of circulating levels of Gram-negative bacteria-derived endotoxin which is a strong inducer of inflammation. Gut-associated endotoxin may enter the circulation via a defective blood-gut barrier during episodes of hypotension or reduced perfusion. MATERIALS AND METHODS: In this study, 165 patients receiving outpatient-based hemodialysis in a facility (FHD) or at home (HHD), were studied. Levels of inflammation were quantified by developing an inflammatory score derived from the measurement of pro-inflammatory cytokines, high-sensitivity C-reactive protein (hsCRP), tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6). Intradialytic blood pressure (BP) variability and hypotension events were recorded. This included the final session of dialysis, at the commencement of which the blood samples were drawn, as well as the five preceding sessions. RESULTS: The median inflammatory score was 2 (range 0 - 3), and 30% of patients had an inflammatory score of three suggesting significant levels of inflammation. Only 8.5% had an inflammatory score of 0. Endotoxin was measured in all participants and was only positive in N = 3. The mean systolic blood pressure (SBP) was 134 ± 20 mmHg and the BP variability was 11.7 ± 3.5. In a multivariable ordinal regression model, a higher inflammatory score was significantly associated with younger age (OR 0.95, 95% CI 0.95 - 0.99, p = 0.03), higher ultrafiltration volume (OR 1.62, CI 1.04 - 2.54, p = 0.03) and lower body mass index (OR 0.9, CI 0.86 - 0.96, p = 0.01). There was no association between inflammatory score and dialysis modality, access type, kidney replacement therapy (KRT), BP variability, or endotoxin. Endotoxin was detected in only 3 of 165 patients and was not associated with inflammation. CONCLUSION: Pre-dialysis levels of inflammation are prevalent in the hemodialysis population after the long break but are not related to intradialytic BP variability or hypotension in the preceding 2 weeks. However, endotoxemia is uncommon and unlikely to be a significant driver of inflammation.

Morbidity after elective surgery in patients on chronic dialysis: a systematic review and meta-analysis.

BACKGROUND: Patients on chronic dialysis are at increased risk of postoperative mortality following elective surgery compared to patients with normal kidney function, but morbidity outcomes are less often reported. This study ascertains the excess odds of postoperative cardiovascular and infection related morbidity outcomes for patients on chronic dialysis. METHODS: Systematic searches were performed using MEDLINE, Embase and the Cochrane Library to identify relevant studies published from inception to January 2020. Eligible studies reported postoperative morbidity outcomes in chronic dialysis and non-dialysis patients undergoing major non-transplant surgery. Risk of bias was assessed using the Newcastle-Ottawa Scale and the certainty of evidence was summarised using GRADE. Random effects meta-analyses were performed to derive summary odds estimates. Meta-regression and sensitivity analyses were performed to explore heterogeneity. RESULTS: Forty-nine studies involving 10,513,934 patients with normal kidney function and 43,092 patients receiving chronic dialysis were included. Patients on chronic dialysis had increased unadjusted odds of postoperative cardiovascular and infectious complications within each surgical discipline. However, the excess odds of cardiovascular complications was attenuated when odds ratios were adjusted for age and comorbidities; myocardial infarction (general surgery, OR 1.83 95% 1.29-2.36) and stroke (general surgery, OR 0.95, 95%CI 0.84-1.06). The excess odds of infectious complications remained substantially higher for patients on chronic dialysis, particularly sepsis (general surgery, OR 2.42, 95%CI 2.12-2.72). CONCLUSION: Patients on chronic dialysis are at increased odds of both cardiovascular and infectious complications following elective surgery, with the excess odds of cardiovascular complications attributable to being on dialysis being highest among younger patients without comorbidities. However, further research is needed to better inform perioperative risk assessment.

Identifying new-onset conditions and pre-existing conditions using lookback periods in Australian health administrative datasets.

BACKGROUND: The condition onset flag (COF) variable was introduced into the hospitalization coding practice in 2008 to help distinguish between the new and pre-existing conditions. However, Australian datasets collected prior to 2008 lack the COF, potentially leading to data waste. The aim of this study was to determine if an algorithm to lookback across the previous admissions could make this distinction. METHODS: All patients requiring kidney replacement therapy (KRT) identified in the Australia and New Zealand Dialysis and Transplant Registry in New South Wales, South Australia and Tasmania between July 2008 and December 2015 were linked with hospital admission datasets using probabilistic linkage. Three different lookback periods entailing either one, two or three admissions prior to the index admission were investigated. Conditions identified in an index admission but not in the lookback periods were classified as a new-onset condition. Conditions identified in both the index admission and the lookback period were deemed to be pre-existing. The degrees of agreement were determined using the kappa statistic. Conditions examined for new onset were myocardial infarction, pulmonary embolism and pneumonia. Conditions examined for prior existence were diabetes mellitus, hypertension and kidney failure. Secondary analyses evaluated whether the conditions identified as pre-existing using COF were captured consistently in the subsequent admissions. RESULTS: 11 140 patients on KRT with 69 403 admissions were analysed. Lookback over a single admission interval (Period 1) provided the highest rates of true positives with COF for all three new-onset conditions, ranging from 89% to 100%. The levels of agreement were almost perfect for all conditions (k = 0.94-1.00). This was consistent across the different time eras. All lookback periods identified additional new-onset conditions that were not classified by COF: Lookback Period 1 picked up a further 474 myocardial infarction, 84 pulmonary embolism and 1092 pneumonia episodes. Lookback Period 1 had the highest percentage of true positives when identifying the pre-existing conditions (64-80%). The level of agreement was moderate to strong and was similar across the time eras. Secondary analysis showed that not all pre-existing conditions identified using COF carried forward to the subsequent admission (61-82%) but increased when looking forward across >1 admission (87-95%). CONCLUSION: The described algorithm using a lookback period is a pragmatic, reliable and robust means of identifying the new-onset and pre-existing patient conditions, thereby enriching the existing datasets predating the availability of the COF. The findings also highlight the value of concatenating a series of hospital patient admissions to more comprehensively adjudicate the pre-existing conditions, rather than assessing the index admission alone.

Postoperative outcomes of kidney transplant recipients undergoing non-transplant-related elective surgery: a systematic review and meta-analysis.

BACKGROUND: Reliable estimates of the absolute and relative risks of postoperative complications in kidney transplant recipients undergoing elective surgery are needed to inform clinical practice. This systematic review and meta-analysis aimed to estimate the odds of both fatal and non-fatal postoperative outcomes in kidney transplant recipients following elective surgery compared to non-transplanted patients. METHODS: Systematic searches were performed through Embase and MEDLINE databases to identify relevant studies from inception to January 2020. Risk of bias was assessed by the Newcastle Ottawa Scale and quality of evidence was summarised in accordance with GRADE methodology (grading of recommendations, assessment, development and evaluation). Random effects meta-analysis was performed to derive summary risk estimates of outcomes. Meta-regression and sensitivity analyses were performed to explore heterogeneity. RESULTS: Fourteen studies involving 14,427 kidney transplant patients were eligible for inclusion. Kidney transplant recipients had increased odds of postoperative mortality; cardiac surgery (OR 2.2, 95%CI 1.9-2.5), general surgery (OR 2.2, 95% CI 1.3-4.0) compared to non-transplanted patients. The magnitude of the mortality odds was increased in the presence of diabetes mellitus. Acute kidney injury was the most frequently reported non-fatal complication whereby kidney transplant recipients had increased odds compared to their non-transplanted counterparts. The odds for acute kidney injury was highest following orthopaedic surgery (OR 15.3, 95% CI 3.9-59.4). However, there was no difference in the odds of stroke and pneumonia. CONCLUSION: Kidney transplant recipients are at increased odds for postoperative mortality and acute kidney injury following elective surgery. This review also highlights the urgent need for further studies to better inform perioperative risk assessment to assist in planning perioperative care.

Health data linkage research in Australia remains challenging.

Data linkage is a valuable technique for uniting information from multiple sources that relates to the same person, place, family or event. Despite its value, establishing such linkages in Australia remains challenging. Existing policies are a missed opportunity for research and innovation and engender a negative attitude among researchers when considering data linkage as a research means. Greater leadership from the Population Health Research Network and cooperation from data custodians and Human Research Ethics Committees are necessary to access optimally Australia's enormous data potential.

Perioperative outcomes and risk assessment in dialysis patients: current knowledge and future directions.

Perioperative medicine is rapidly emerging as a key discipline to address the specific needs of high-risk surgical groups, such as those on chronic dialysis. Crude hospital separation rates for chronic dialysis patients are considerably higher than patients with normal renal function, with up to 15% of admission being related to surgical intervention. Dialysis dependency carries substantial mortality and morbidity risk compared to patients with normal renal function. This group of patients has a high comorbid burden and complex medical need, making accurate perioperative planning essential. Existing perioperative risk assessment tools are unvalidated in chronic dialysis patients. Furthermore, they fail to incorporate important dialysis treatment-related characteristics that could potentially influence perioperative outcomes. There is a dearth of information on perioperative outcomes of Australasian dialysis patients. Current perioperative outcome estimates stem predominantly from North American literature; however, the generalisability of these findings is limited, as the survival of North American dialysis patients is significantly inferior to their Australasian counterparts and potentially confounds reported perioperative outcomes; let alone regional variation in surgical indication and technique. We propose that data linkage between high-quality national registries will provide more complete data with more detailed patient and procedural information to allow for more informative analyses to develop and validate dialysis-specific risk assessment tools.

Carvedilol and Cardiac Biomarkers in Dialysis Patients: Secondary Analysis of a Randomized Controlled Trial.

BACKGROUND/AIMS: Cardiac biomarkers are associated with cardiac abnormalities and adverse outcomes in dialysis patients. Our aim was to report the effect of the beta-blocker carvedilol on cardiac biomarkers in adult dialysis patients. METHODS: The Beta-Blocker to Lower Cardiovascular Dialysis Events Feasibility Study was a randomized controlled trial comparing carvedilol to placebo. Serum and plasma were collected before the run-in, then 6 and 12 months post-randomization to measure B-type Natriuretic Peptide (BNP), N-terminal BNP (NT-ProBNP), high-sensitivity cardiac troponins I (hs-TnI) and T (hs-TnT), and galectin-3. Left ventricular global longitudinal strain (GLS) was measured by echocardiography at baseline. RESULTS: Seventy-two participants were recruited of whom 49 completed the run-in and were randomized to carvedilol (n=26) or placebo (n=23). Baseline echocardiography demonstrated median (inter-quartile range) GLS of -14.27% (-16.63 to -11.93). NTproBNP and hs-TnT correlated with GLS (Spearman's rho=0.34 [p=0.018] and rho=0.28 [p=0.049], respectively). Median change scores from baseline to 12 months did not differ significantly between participants with complete biomarker data randomized to carvedilol (n=15) or placebo (n=16) for any biomarkers. CONCLUSIONS: NT-proBNP and hs-TnT were associated with GLS. However, changes in levels of the biomarkers from baseline to 12 months were not different between groups randomized to carvedilol and placebo.

Biological variation of high sensitivity cardiac troponin-T in stable dialysis patients: implications for clinical practice.

BACKGROUND: Changes in high sensitivity cardiac troponin-T (hs-cTnT) concentrations may reflect either acute myocardial injury or biological variation. Distinguishing between these entities is essential to accurate diagnosis, however, the biological variation of hs-cTnT in dialysis population is currently unknown. We sought to estimate the within- and between-person coefficients of variation of hs-cTnT in stable dialysis patients, and derive the critical difference between measurements needed to exclude biological variation with 99% confidence. METHODS: Fifty-five prevalent haemo- and peritoneal-dialysis patients attending two metropolitan hospitals were assessed on 10 consecutive occasions; weekly for 5 weeks then monthly for 4 months. Assessments were conducted at the same dialysis cycle time-point and entailed hs-cTnT testing, clinical review, electrocardiography, and bioimpedance spectroscopy. Patients were excluded if they developed clinical or physiological instability. RESULTS: In total 137 weekly and 114 monthly hs-cTnT measurements from 42 stable patients were analysed. Respective between- and within-person coefficients of variation were 83% and 7.9% for weekly measurements, and 79% and 12.6% for monthly measurements. Within-person variation was unaffected by dialysis modality or cardiac co-morbidity. The bidirectional 99% reference change value was -25% and +33% for weekly measurements, and -37% and +58% for monthly measurements. CONCLUSIONS: The between-person variation of hs-cTnT in the dialysis population is markedly greater than within-person variation indicating that hs-cTnT testing is best applied in this population using a relative change strategy. An increase of 33% or a reduction of 25% in serial hs-cTnT concentrations measured at weekly intervals excludes change due to analytical and biological variation alone with 99% confidence.

Revised cardiac risk index in predicting cardiovascular complications in patients receiving chronic kidney replacement therapy undergoing elective general surgery.

INTRODUCTION: The Revised Cardiac Risk Index (RCRI) is a six-parameter model that is commonly used in assessing individual 30-day perioperative cardiovascular risk before general surgery, but its use in patients on chronic kidney replacement therapy (KRT) is unvalidated. This study aimed to externally validate RCRI in this patient group over a 15-year period. METHODS: Data linkage was used between the the Australia and New Zealand Dialysis and Transplant (ANZDATA) Registry and jurisdictional hospital admisisons data across Australia and New Zealand to identify all incident and prevalent patients on chronic KRT between 2000 and 2015 who underwent elective abdominal surgery. Chronic KRT was categorised as haemodialysis (HD), peritoneal dialysis (PD), home haemodialysis (HHD) and kidney transplant. The outcome of interest was major adverse cardiovascular event (MACE) which was defined as nonfatal myocardial infarction, nonfatal stroke, non-fatal cardiac arrest and cardiovascular mortality at 30 days. Logistic regression was used with the RCRI score included as a continuous variable to estimate discrimination by area under the receiver operating curve (AUROC). Calibration was evaluated using a calibration plot. Clinical utility was assessed using a decision curve analysis to determine the net benefit. RESULTS: A total of 5094 elective surgeries were undertaken, and MACE occurred in 153 individuals (3.0%). Overall, RCRI had poor discrimination in patients on chronic KRT undergoing elective surgery (AUROC 0.67), particularly in patients aged greater than 65 years (AUROC 0.591). A calibration plot showed that RCRI overestimated risk of MACE. The expected-to-observed outcome ratio was 6.0, 5.1 and 2.5 for those with RCRI scores of 1, 2 and ≥ 3, respectively. Discrimination was moderate in patients under 65 years and in kidney transplant recipients, with AUROC values of 0.740 and 0.718, respectively. Overestimation was common but less so for kidney transplant recipients. Decision curve analysis showed that there was no net benefit of using the tool in neither the overall cohort nor patients under 65 years, but a slight benefit associated with threshold probability > 5.5% in kidney transplant recipients. CONCLUSIONS: The RCRI tool performed poorly and overestimated risk in patients on chronic dialysis, potentially misinforming patients and clinicians about the risk of elective surgery. Further research is needed to define a more comprehensive means of estimating risk in this unique population.

PD peritonitis in patients undergoing capsule endoscopy: A descriptive study.

Peritoneal dialysis (PD) patients who undergo gastroendoscopy and colonoscopy are at increased risk of peritoneal dialysis-associated peritonitis (PD peritonitis) following the procedure (defined as occurring within 7 days of intervention). As per current International Society for PD (ISPD) guidelines, antibiotic prophylaxis is currently recommended pre-colonoscopy in PD patients given the risk of post-colonoscopy PD peritonitis. The risk of PD peritonitis in patients undergoing capsule endoscopy (CE) is unknown. This binational data-linkage study between the Australia and New Zealand Dialysis and Transplant Registry and all hospital admission data sets in Australia and New Zealand evaluated all patients with PD who underwent CE between 2006 and 2015. The objective of the study was to assess the risk of PD peritonitis in patients undergoing CE. Descriptive statistics were used to describe patient characteristics and clinical outcomes. Overall, 23 patients with PD underwent CE. Twelve patients underwent CE alone (i.e. no other concomitant procedures) and none of these patients experienced an episode of PD peritonitis. The remaining 11 patients underwent CE and other invasive endoscopic/abdominal surgical procedures, of whom 2 suffered PD peritonitis. CE is likely a relatively safe procedure in PD patients. PD patients undergoing CE may not require prior antibiotic prophylaxis. Given their relative safety, CE may be an appealing diagnostic tool in a select group of PD patients for the investigation of gastrointestinal disease.

Evaluating data quality in the Australian and New Zealand dialysis and transplant registry using administrative hospital admission datasets and data-linkage.

Background: Clinical quality registries provide rich and useful data for clinical quality monitoring and research purposes but are susceptible to data quality issues that can impact their usage. Objective: This study assessed the concordance between comorbidities recorded in the Australia and New Zealand Dialysis and Transplant (ANZDATA) Registry and those in state-based hospital admission datasets. Method: All patients in New South Wales, South Australia, Tasmania, Victoria and Western Australia recorded in ANZDATA as requiring chronic kidney replacement therapy (KRT) between 01/07/2000 and 31/12/2015 were linked with state-based hospital admission datasets. Coronary artery disease, diabetes mellitus, cerebrovascular disease, chronic lung disease and peripheral vascular disease recorded in ANZDATA at each annual census date were compared overall, over time and between different KRT modalities to comorbidities recorded in hospital admission datasets, as defined by the International Classification of Diseases (ICD-10-AM), using both the kappa statistic and logistic regression analysis. Results: 29, 334 patients with 207,369 hospital admissions were identified. Comparison was made at census date for every patient comparison. Overall agreement was "very good" for diabetes mellitus (92%, k = 0.84) and "poor" to "fair" (21-61%, k = 0.02-0.22) for others. Diabetes mellitus recording had the highest accuracy (sensitivity 93% (±SE 0.2) and specificity 93% (±SE 0.2)), and cerebrovascular disease had the lowest (sensitivity 54% (±SE 0.2) and specificity 21% (±SE 0.3)). The false positive rates for cerebrovascular disease, peripheral vascular disease and chronic airway disease ranged between 18 and 33%. The probability of a false positive was lowest for kidney transplant patients for all comorbidities and highest for patients on haemodialysis. Conclusions and Implications: Agreement between the clinical quality registry and hospital admission datasets was variable, with the prevalence of comorbidities being higher in ANZDATA.

Effect of a Hemodialysis Session on Markers of Inflammation and Endotoxin.

Background: People receiving hemodialysis (HD) treatment have higher cardiovascular morbidity and mortality, ascribed to an increased prevalence of traditional cardiovascular risk factors. However, the role of nontraditional risk factors, such as inflammation, has become increasingly recognized. The origin of this inflammation remains elusive and one putative cause is elevated levels of circulating bacterial endotoxin. Methods: In this study, serum concentrations of endotoxin and inflammatory biomarkers, including high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), interleukin-1ß (IL1ß), ferritin and tumor necrosis factor (TNF), were measured in 30 adults receiving HD and 10 healthy individuals without kidney disease. In people receiving HD, samples were collected immediately before dialysis (preHD), after dialysis (postHD), and 48 hours after (postHD48hrs). Results: Endotoxin was detectable in only 1 of 90 samples analyzed. There were no significant differences in serum hsCRP, IL1ß, and IL6 levels, before and after dialysis. Serum TNF levels decreased significantly from 30.9 (8.0, 39.5) pg/mL preHD to 13.9 (8.5, 17.3) pg/mL post-HD (p=0.002) and then increased back to 27.37 (14.5, 35) pg/mL 2 days later (p < 0.001). Ferritin increased from 1153 ng/mL (782, 1458) preHD to 1313 ng/mL (657, 1638) post HD (p < 0.001) and then decreased back to 1186 ng/mL (754, 1597) (p=0.66) postHD48hrs. Compared to controls, people receiving HD had significantly elevated levels of hsCRP [6.16 mg/L (2.1, 16.8) vs. 1.1 mg/L (0.81, 3.63) p=0.015], IL1ß [1.5 pg/mL (0.05, 2.51) vs. 0.5 pg/mL (1.81, 2.95) p ≤ 0.001], and ferritin [1153 (782, 1458) vs. 132.9 (111, 257) ng/mL p ≤ 0.001], but comparable levels of in IL6 [6.15 pg/mL (4.82, 9.12) vs. 7.49 pg/mL (4.56, 10.39), p=0.77] and TNF [27.35 pg/mL ± 17.48 vs. 17.87 pg/mL ± 12.28, p < 0.12]. In conclusion, people on HD have elevated levels of inflammatory biomarkers, which are not associated with endotoxemia (which is rare) or the dialysis procedure.

Statistical analysis plan for Better Evidence for Selecting Transplant Fluids (BEST-Fluids): a randomised controlled trial of the effect of intravenous fluid therapy with balanced crystalloid versus saline on the incidence of delayed graft function in deceased donor kidney transplantation.

BACKGROUND: Delayed graft function, or the requirement for dialysis due to poor kidney function, is a frequent complication of deceased donor kidney transplantation that is associated with inferior outcomes. Intravenous fluids with a high chloride content, such as isotonic sodium chloride (0.9% saline), are widely used in transplantation but may increase the risk of poor kidney function. The primary objective of the BEST-Fluids trial is to compare the effect of a balanced low-chloride crystalloid, Plasma-Lyte 148 (Plasmalyte), versus 0.9% saline on the incidence of DGF in deceased donor kidney transplant recipients. This article describes the statistical analysis plan for the trial. METHODS AND DESIGN: BEST-Fluids is an investigator-initiated, pragmatic, registry-based, multi-centre, double-blind, randomised controlled trial. Eight hundred patients (adults and children) in Australia and New Zealand with end-stage kidney disease admitted for a deceased donor kidney transplant were randomised to intravenous fluid therapy with Plasmalyte or 0.9% saline in a 1:1 ratio using minimization. The primary outcome is delayed graft function (dialysis within seven days post-transplant), which will be modelled using a log-binomial generalised linear mixed model with fixed effects for treatment group, minimization variables, and ischaemic time and a random intercept for study centre. Secondary outcomes including early kidney transplant function (a ranked composite of dialysis duration and the rate of graft function recovery), treatment for hyperkalaemia, and graft survival and will be analysed using a similar modelling approach appropriate for the type of outcome. DISCUSSION: BEST-Fluids will determine whether Plasmalyte reduces the incidence of DGF and has a beneficial effect on early kidney transplant outcomes relative to 0.9% saline and will inform clinical guidelines on intravenous fluids for deceased donor kidney transplantation. The statistical analysis plan describes the analyses to be undertaken and specified before completion of follow-up and locking the trial databases. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12617000358347 . Prospectively registered on 8 March 2017 ClinicalTrials.gov identifier NCT03829488 . Registered on 4 February 2019.

Baseline Characteristics and Representativeness of Participants in the BEST-Fluids Trial: A Randomized Trial of Balanced Crystalloid Solution Versus Saline in Deceased Donor Kidney Transplantation.

Delayed graft function (DGF) is a major complication of deceased donor kidney transplantation. Saline (0.9% sodium chloride) is a commonly used intravenous fluid in transplantation but may increase the risk of DGF because of its high chloride content. Better Evidence for Selecting Transplant Fluids (BEST-Fluids), a pragmatic, registry-based, double-blind, randomized trial, sought to determine whether using a balanced low-chloride crystalloid solution (Plasma-Lyte 148) instead of saline would reduce DGF. We sought to evaluate the generalizability of the trial cohort by reporting the baseline characteristics and representativeness of the trial participants in detail. Methods: We compared the characteristics of BEST-Fluids participants with those of a contemporary cohort of deceased donor kidney transplant recipients in Australia and New Zealand using data from the Australia and New Zealand Dialysis and Transplant Registry. To explore potential international differences, we compared trial participants with a cohort of transplant recipients in the United States using data from the Scientific Registry of Transplant Recipients. Results: During the trial recruitment period, 2373 deceased donor kidney transplants were performed in Australia and New Zealand; 2178 were eligible' and 808 were enrolled in BEST-Fluids. Overall, trial participants and nonparticipants were similar at baseline. Trial participants had more coronary artery disease (standardized difference [d] = 0.09; P = 0.03), longer dialysis duration (d = 0.18, P < 0.001), and fewer hypertensive (d = -0.11, P = 0.03) and circulatory death (d = -0.14, P < 0.01) donors than nonparticipants. Most key characteristics were similar between trial participants and US recipients, with moderate differences (|d| ≥ 0.2; all P < 0.001) in kidney failure cause, diabetes, dialysis duration, ischemic time, and several donor risk predictors, likely reflecting underlying population differences. Conclusions: BEST-Fluids participants had more comorbidities and received slightly fewer high-risk deceased donor kidneys but were otherwise representative of Australian and New Zealand transplant recipients and were generally similar to US recipients. The trial results should be broadly applicable to deceased donor kidney transplantation practice worldwide.