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.

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.

Effect of lanthanum carbonate on serum calciprotein particles in patients with stage 3-4 CKD-results from a placebo-controlled randomized trial.

BACKGROUND: Calciprotein particles (CPP) are colloidal aggregates of calcium phosphate and the mineral-binding protein fetuin-A, and are potential mediators of cardiovascular disease in chronic kidney disease (CKD). Emerging evidence suggests non-calcium-containing phosphate binders may reduce serum CPP in patients with kidney failure who require dialysis; however, it is unclear whether similar interventions are effective in patients with earlier stages of CKD. METHODS: The IMpact of Phosphate Reduction On Vascular End-points in CKD (IMPROVE-CKD) was a multi-centre, placebo-controlled, randomized trial of lanthanum carbonate on cardiovascular markers in 278 participants with stage 3b/4 CKD. In this pre-specified exploratory analysis, primary (CPP-I) and secondary CPP (CPP-II) were measured in a sub-cohort of participants over 96 weeks. Treatment groups were compared using linear mixed-effects models and the relationship between serum CPP and pulse wave velocity (PWV) and abdominal aortic calcification (AAC) was examined. RESULTS: A total of 253 participants had CPP data for baseline and at least one follow-up timepoint and were included in this analysis. The mean age was 62.4 ± 12.6 years, 32.0% were female and the mean estimated glomerular filtration rate (eGFR) was 26.6 ± 8.3 mL/min/1.73 m2. Baseline median serum CPP-I was 14.9 × 104 particles/mL [interquartile range (IQR) 4.6-49.3] and median CPP-II was 3.3 × 103 particles/mL (IQR 1.4-5.4). There was no significant difference between treatment groups at 96 weeks in CPP-I [22.8% (95% confidence interval -39.2, 36.4), P = 0.65] or CPP-II [-18.3% (95% confidence interval -40.0, 11.2), P = 0.20] compared with a placebo. Serum CPP were not correlated with baseline PWV or AAC, or with the progression of either marker. CONCLUSIONS: Lanthanum carbonate was not associated with a reduction of CPP at 96 weeks when compared with a placebo in a CKD cohort.

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.

A comparison of arteriovenous fistula failure between Malaysian and Australian and New Zealand participants enrolled in the FAVOURED trial.

AIM: To describe and compare de novo arteriovenous fistula (AVF) failure rates between Australia and New Zealand (ANZ), and Malaysia. BACKGROUND: AVFs are preferred for haemodialysis access but are limited by high rates of early failure. METHODS: A post hoc analysis of 353 participants from ANZ and Malaysia included in the FAVOURED randomised-controlled trial undergoing de novo AVF surgery was performed. Composite AVF failure (thrombosis, abandonment, cannulation failure) and its individual components were compared between ANZ (n = 209) and Malaysian (n = 144) participants using logistic regression adjusted for patient- and potentially modifiable clinical factors. RESULTS: Participants' mean age was 55 ± 14.3 years and 64% were male. Compared with ANZ participants, Malaysian participants were younger with lower body mass index, higher prevalence of diabetes mellitus and lower prevalence of cardiovascular disease. AVF failure was less frequent in the Malaysian cohort (38% vs 54%; adjusted odds ratio (OR) 0.53, 95% confidence interval (CI) 0.31-0.93). This difference was driven by lower odds of cannulation failure (29% vs 47%, OR 0.45, 95% CI 0.25-0.80), while the odds of AVF thrombosis (17% vs 20%, OR 1.24, 95% CI 0.62-2.48) and abandonment (25% vs 23%, OR 1.17, 95% CI 0.62-2.16) were similar. CONCLUSIONS: The risk of AVF failure was significantly lower in Malaysia compared to ANZ and driven by a lower risk of cannulation failure. Differences in practice patterns, including patient selection, surgical techniques, anaesthesia or cannulation techniques may account for regional outcome differences and warrant further investigation.

Relationship Between Dietary Phosphate Intake and Biomarkers of Bone and Mineral Metabolism in Australian Adults With Chronic Kidney Disease.

OBJECTIVE: Higher serum phosphate is associated with increased adverse outcomes including cardiovascular disease. Abnormalities of bone and mineral metabolism in chronic kidney disease (CKD), including higher serum phosphate, are important risk factors for increased cardiovascular disease. Associations between dietary phosphate intake and biochemical and cardiovascular parameters in non-dialysis CKD patients, however, have not been adequately studied. This study aimed to explore associations between phosphate intake and biomarkers of bone and mineral metabolism and intermediate cardiovascular markers in adults with stage 3-4 CKD. DESIGN AND METHODS: One hundred thirty-two participants enrolled in the IMpact of Phosphate Reduction On Vascular End-points in Chronic Kidney Disease trial were invited to participate in this sub-study. At baseline, dietary phosphate intake and its source (animal, plant, or a mixture of animal and plant) were determined using a 7-day self-administered diet food record, and measurements were made of serum and urinary phosphate, serum calcium, parathyroid hormone, fibroblast growth factor-23, and the intermediate cardiovascular markers pulse wave velocity (PWV) and abdominal aortic calcification. The relationships between dietary phosphate intake and these bone metabolism and cardiovascular markers were explored using Pearson's correlation and linear regression. The effect of source of phosphate intake was analyzed using compositional data analysis. RESULTS: Ninety participants (age 64 ± 12 years, 68% male, estimated glomerular filtration rate 26.6 ± 7.6 mL/min/1.73 m2, daily phosphate intake 1,544 ± 347 mg) completed the study. Correlations among dietary phosphate intake and biochemical measures, PWV, and abdominal aortic calcification ranged from r = -0.13 to r = +0.13. Linear regression showed no association between dietary phosphate measurements and biochemical or cardiovascular parameters. Source of phosphate intake was associated with PWV (P = .01), but not with other biomarkers of bone and mineral metabolism. Higher PWV values were associated with higher intake of plant-based relative to animal-based phosphate (1.058 [1.020-1.098], P = .003). CONCLUSION: Levels of total dietary phosphate intake measured by dietary food record show no statistically significant relationship with biochemical markers of bone and mineral metabolism or intermediate cardiovascular markers. Higher PWV levels associated with higher intake of plant-based relative to animal-based phosphate intake were an unexpected finding and further research is needed in this area.

Characteristics of the gastrointestinal microbiota in paired live kidney donors and recipients.

BACKGROUND: There are few studies that have examined whether dysbiosis occurs in kidney donors and transplant recipients following kidney transplant surgery. AIM: To ascertain whether changes occur in the gastrointestinal microbiota of the kidney donor and recipient following kidney transplantation. METHODS: Kidney transplant recipients and their donors were prospectively enrolled in a pilot study to collect one faecal sample prior to, and another faecal sample between four to eight weeks following surgery. Gastrointestinal microbiota richness, Shannon diversity measures and functional assessments of kidney donors and recipients were analysed via metagenomic sequencing. RESULTS: The study included 12 donors (median age 56 years, 6 females) and 12 recipients (median age 51 years, 3 females). Donor microbiota showed no significant changes in gastrointestinal microbiota richness, Shannon diversity, or functional assessments before and after nephrectomy. Recipient microbiota was altered post-transplant, reflected in reductions of the mean (±SD) richness values (156 ± 46.5 to 116 ± 38.6, p = 0.002), and Shannon diversity (3.57 ± 0.49 to 3.14 ± 0.52, p = 0.007), and a dramatic increase in Roseburia spp. abundance post-transplant (26-fold increase from 0.16 ± 0.0091 to 4.6 ± 0.3; p = 0.006; FDR = 0.12). Functionally, the post-transplant microbial community shifted towards those taxa using the glycolysis pathway (1.2-fold increase; p = 0.02; FDR = 0.26) for energy metabolism, while those functions involved with reactive oxygen species degradation decreased (2.6-fold; p = 0.006; FDR = 0.14). CONCLUSION: Live donor kidney transplantation and standard care post-transplant result in significant alterations in gut microbiota richness, diversity, composition and functional parameters in kidney transplant recipients but not in their kidney donors.

Center-Effect of Incident Hemodialysis Vascular Access Use: Analysis of a Bi-national Registry.

Background: Commencing hemodialysis (HD) with an arteriovenous access is associated with superior patient outcomes compared with a catheter, but the majority of patients in Australia and New Zealand initiate HD with a central venous catheter. This study examined patient and center factors associated with arteriovenous fistula/graft access use at HD commencement. Methods: We included all adult patients starting chronic HD in Australia and New Zealand between 2004 and 2015. Access type at HD initiation was analyzed using logistic regression. Patient-level factors included sex, age, race, body mass index (BMI), smoking status, primary kidney disease, late nephrologist referral, comorbidities, and prior RRT. Center-level factors included size; transplant capability; home HD proportion; incident peritoneal dialysis (average number of patients commencing RRT with peritoneal dialysis per year); mean weekly HD hours; average blood flow; and achievement of phosphate, hemoglobin, and weekly Kt/V targets. The study included 27,123 patients from 61 centers. Results: Arteriovenous access use at HD commencement varied four-fold from 15% to 62% (median 39%) across centers. Incident arteriovenous access use was more likely in patients aged 51-72 years, males, and patients with a BMI of >25 kg/m2 and polycystic kidney disease; but use was less likely in patients with a BMI of <18.5 kg/m2, late nephrologist referral, diabetes mellitus, cardiovascular disease, chronic lung disease, and prior RRT. Starting HD with an arteriovenous access was less likely in centers with the highest proportion of home HD, and no center factor was associated with higher arteriovenous access use. Adjustment for center-level characteristics resulted in a 25% reduction in observed intercenter variability of arteriovenous access use at HD initiation compared with the model adjusted for only patient-level characteristics. Conclusions: This study identified several patient and center factors associated with incident HD access use, yet these factors did not fully explain the substantial variability in arteriovenous access use across centers.

Dietary Phosphate Consumption in Australians With Stages 3b and 4 Chronic Kidney Disease.

OBJECTIVE: Dietary phosphate modification is a common therapy to treat hyperphosphatemia in individuals with chronic kidney disease (CKD). However, current dietary intake and common food sources of phosphate typically consumed by individuals with CKD are not well characterized. This study examined a cohort of CKD patients to determine total dietary intake and common food sources of phosphate, including phosphate additives. DESIGN AND METHODS: Participants with CKD stages 3b and 4 recruited to a substudy of the "IMPROVE-CKD (IMpact of Phosphate Reduction On Vascular End-points in Chronic Kidney Disease) Study" completed a 7-day self-administered diet record at baseline. Diet histories were analyzed and daily phosphate intakes determined using FoodWorks V.9 (Xyris). The proportion of phosphate contributed by each food group was determined using the AUSNUT 2011-2013 Food Classification System. Ingredient lists of packaged food items consumed were reviewed to determine frequency of phosphate-based additives. RESULTS: Ninety participants (mean eGFR 26.5 mL/min/1.73 m2) completed this substudy. Mean phosphate intake of participants was 1544 ± 347 mg/day, with 96% of individuals exceeding the recommended daily intake of phosphate (1000 mg/day). The highest sources of dietary phosphate were milk-based products (25%) and meat and poultry products/dishes (25%). Phosphate-based food additives were identified in 39% (n = 331/845) of packaged foods consumed by participants. CONCLUSION: Dietary phosphate intakes of Australians with CKD are high and come from a variety of sources. Managing dietary phosphate intake requires a patient-centered, tailored approach with an emphasis on maintaining nutritional adequacy and awareness of phosphate additives.

Perioperative antibiotics for preventing post-surgical site infections in solid organ transplant recipients.

BACKGROUND: Solid organ transplant recipients are at high risk for infections due to the complexity of surgical procedures combined with the impact of immunosuppression. No consensus exists on the role of antibiotics for surgical site infections in solid organ transplant recipients. OBJECTIVES: To assess the benefits and harms of prophylactic antimicrobial agents for preventing surgical site infections in solid organ transplant recipients. SEARCH METHODS: The Cochrane Kidney and Transplant Register of Studies was searched up to 21 April 2020 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal, and ClinicalTrials.gov. SELECTION CRITERIA: All randomised controlled trials (RCTs) and quasi-RCTs in any language assessing prophylactic antibiotics in preventing surgical site infections in solid organ transplant recipients at any time point after transplantation. DATA COLLECTION AND ANALYSIS: Two authors independently determined study eligibility, assessed quality, and extracted data. Primary outcomes were surgical site infections and antimicrobial resistance. Other outcomes included urinary tract infections, pneumonias and septicaemia, death (any cause), graft loss, graft rejection, graft function, adverse reactions to antimicrobial agents, and outcomes identified by the Standardised Outcomes of Nephrology Group (SONG), specifically graft health, cardiovascular disease, cancer and life participation. Summary effect estimates were obtained using a random-effects model and results were expressed as risk ratios (RR) and 95% confidence intervals (CI). The quality of the evidence was assessed using the risk of bias and the GRADE approach. MAIN RESULTS: We identified eight eligible studies (718 randomised participants). Overall, five studies (248 randomised participants) compared antibiotics versus no antibiotics, and three studies (470 randomised participants) compared extended duration versus short duration antibiotics. Risk of bias was assessed as high for performance bias (eight studies), detection bias (eight studies) and attrition bias (two studies). It is uncertain whether antibiotics reduce the incidence of surgical site infections as the certainty of the evidence has been assessed as very low (RR 0.42, 95% CI 0.21 to 0.85; 5 studies, 226 participants; I2 = 25%). The certainty of the evidence was very low for all other reported outcomes (death, graft loss, and other infections). It is uncertain whether extended duration antibiotics reduces the incidence of surgical site infections in either solid organ transplant recipients (RR 1.19, 95% CI 0.58 to 2.48; 2 studies, 302 participants; I2 = 0%) or kidney-only transplant recipients (RR 0.50, 95% CI 0.05 to 5.48; 1 study, 205 participants) as the certainty of the evidence has been assessed as very low. The certainty of the evidence was very low for all other reported outcomes (death, graft loss, and other infections). None of the eight included studies evaluated antimicrobial agent adverse reactions, graft health, cardiovascular disease, cancer, life participation, biochemical and haematological parameters, intervention cost, hospitalisation length, or overall hospitalisation costs. AUTHORS' CONCLUSIONS: Due to methodological limitations, risk of bias and significant heterogeneity, the current evidence for the use of prophylactic perioperative antibiotics in transplantation is of very low quality. Further high quality, adequately powered RCTs would help better inform clinical practice.

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.

Effects of Allopurinol on the Progression of Chronic Kidney Disease.

BACKGROUND: Elevated serum urate levels are associated with progression of chronic kidney disease. Whether urate-lowering treatment with allopurinol can attenuate the decline of the estimated glomerular filtration rate (eGFR) in patients with chronic kidney disease who are at risk for progression is not known. METHODS: In this randomized, controlled trial, we randomly assigned adults with stage 3 or 4 chronic kidney disease and no history of gout who had a urinary albumin:creatinine ratio of 265 or higher (with albumin measured in milligrams and creatinine in grams) or an eGFR decrease of at least 3.0 ml per minute per 1.73 m2 of body-surface area in the preceding year to receive allopurinol (100 to 300 mg daily) or placebo. The primary outcome was the change in eGFR from randomization to week 104, calculated with the Chronic Kidney Disease Epidemiology Collaboration creatinine equation. RESULTS: Enrollment was stopped because of slow recruitment after 369 of 620 intended patients were randomly assigned to receive allopurinol (185 patients) or placebo (184 patients). Three patients per group withdrew immediately after randomization. The remaining 363 patients (mean eGFR, 31.7 ml per minute per 1.73 m2; median urine albumin:creatinine ratio, 716.9; mean serum urate level, 8.2 mg per deciliter) were included in the assessment of the primary outcome. The change in eGFR did not differ significantly between the allopurinol group and the placebo group (-3.33 ml per minute per 1.73 m2 per year [95% confidence interval {CI}, -4.11 to -2.55] and -3.23 ml per minute per 1.73 m2 per year [95% CI, -3.98 to -2.47], respectively; mean difference, -0.10 ml per minute per 1.73 m2 per year [95% CI, -1.18 to 0.97]; P = 0.85). Serious adverse events were reported in 84 of 182 patients (46%) in the allopurinol group and in 79 of 181 patients (44%) in the placebo group. CONCLUSIONS: In patients with chronic kidney disease and a high risk of progression, urate-lowering treatment with allopurinol did not slow the decline in eGFR as compared with placebo. (Funded by the National Health and Medical Research Council of Australia and the Health Research Council of New Zealand; CKD-FIX Australian New Zealand Clinical Trials Registry number, ACTRN12611000791932.).

Postoperative mortality in patients on chronic dialysis following elective surgery: A systematic review and meta-analysis.

RATIONALE & OBJECTIVE: The prognostic significance of dialysis-dependent end-stage kidney disease on postoperative mortality is unclear. This study aims to estimate the odds of postoperative mortality in patients receiving chronic dialysis undergoing elective surgery compared to patients with normal kidney function, and to examine the influence of comorbidities on the excess mortality risk. METHODS: A systematic search of studies published up to January 2020 was conducted using MEDLINE, EMBASE and CENTRAL databases. Eligible studies reported postoperative 30-day or in-hospital mortality in chronic dialysis patients compared to patients with normal kidney function undergoing elective surgery. Two investigators independently reviewed all abstracts and performed risk of bias assessments using the Newcastle-Ottawa Scale. Quality of evidence was summarised in accordance with GRADE methodology (grading of recommendations, assessment, development and evaluation). Relative mortality risk estimates were obtained using random effects meta-analysis. Heterogeneity was explored using meta-regression. (PROSPERO CRD42017076565). RESULTS: Forty-nine studies involving 41, 822 chronic dialysis and 10, 476, 321 non-dialysis patients undergoing elective surgery were included. Patients on chronic dialysis had a greatly increased postoperative mortality odds compared to patients with normal kidney function. The excess risk ranged from OR 10.8 (95%CI 7.3-15.9) following orthopaedic surgery to OR 4.0 (95%CI 3.2-4.9) after vascular surgery. Adjustment for age and comorbidity attenuated the excess odds but remained higher for patients on chronic dialysis, irrespective of surgical discipline. Meta-regression analysis demonstrated an inverse linear relationship between excess mortality risk and study-level mean age (slope -0.06; P = 0.001) and diabetes prevalence (slope -0.02; p = 0.001). CONCLUSIONS: Patients on chronic dialysis have an increased odds for postoperative mortality following elective surgery across all surgical disciplines. This relationship is consistent among all studies, with the excess postoperative mortality attributable to end-stage kidney disease and chronic dialysis treatment may be lower among older patients with diabetes.

Aortic Calcification and Arterial Stiffness Burden in a Chronic Kidney Disease Cohort with High Cardiovascular Risk: Baseline Characteristics of the Impact of Phosphate Reduction On Vascular End-Points in Chronic Kidney Disease Trial.

Chronic kidney disease (CKD) is associated with excess cardiovascular morbidity and mortality compared to the general population. Hyperphosphataemia, associated with vascular calcification and arterial stiffness, may play a key role in the pathogenesis of cardiovascular disease (CVD) associated with CKD, although phosphate reduction strategies have not consistently proven to beneficially affect clinically relevant outcomes. The IMpact of Phosphate Reduction On Vascular End-points in CKD (IMPROVE-CKD) study is an international, multi-centre, randomized, placebo-controlled trial investigating the effect of the phosphate binder lanthanum carbonate on intermediate cardiovascular markers in patients with stage 3b-4 CKD. The primary end-point is change in carotid-femoral pulse wave velocity (PWV, SphygmoCor) after 96 weeks. Secondary outcomes include change in abdominal aortic calcification (AAC, computed tomography), serum phosphate and fibroblast growth factor 23 (FGF-23). In total, 278 participants were recruited and randomized, mean age 63 ± 13 years, 69% male, 45% diabetes, 32% CVD, 33% stage 3b CKD and 67% stage 4 CKD. Mean estimated glomerular filtration rate and serum phosphate were 26.6 ± 8.3 mL/min/1.72 m2 and 1.25 ± 0.20 mmol/L, respectively. Median (interquartile range) intact and c-terminal FGF-23 levels were 133.0 (89.1-202) pg/mL and 221.1 (154.3-334.1) RU/mL, respectively. Mean PWV was 10.8 ± 3.6 m/s and 81% had AAC (median Agatston score 1,535 [63-5,744] Hounsfield units). PWV ≥10 m/s was associated with older age, diabetes, CVD, presence of AAC, higher systolic blood pressure (BP), larger waist circumference and higher alkaline phosphatase. AAC was associated with older age, male sex, diabetes, CVD, higher diastolic BP, dyslipidaemia (and use of statins), smoking, larger waist circumference and increased PWV. In conclusion, IMPROVE-CKD participants had high baseline risk for cardiovascular events, as suggested by high baseline PWV and AAC values.

Fish oil and aspirin effects on arteriovenous fistula function: Secondary outcomes of the randomised omega-3 fatty acids (Fish oils) and Aspirin in Vascular access OUtcomes in REnal Disease (FAVOURED) trial.

BACKGROUND: Arteriovenous fistulas (AVF) for haemodialysis often experience early thrombosis and maturation failure requiring intervention and/or central venous catheter (CVC) placement. This secondary and exploratory analysis of the FAVOURED study determined whether omega-3 fatty acids (fish oils) or aspirin affected AVF usability, intervention rates and CVC requirements. METHODS: In 567 adult participants planned for AVF creation, all were randomised to fish oil (4g/d) or placebo, and 406 to aspirin (100mg/d) or placebo, starting one day pre-surgery and continued for three months. Outcomes evaluated within 12 months included AVF intervention rates, CVC exposure, late dialysis suitability failure, and times to primary patency loss, abandonment and successful cannulation. RESULTS: Final analyses included 536 participants randomised to fish oil or placebo (mean age 55 years, 64% male, 45% diabetic) and 388 randomised to aspirin or placebo. Compared with placebo, fish oil reduced intervention rates (0.82 vs 1.14/1000 patient-days, incidence rate ratio [IRR] 0.72, 95% confidence interval [CI] 0.54-0.97), particularly interventions for acute thrombosis (0.09 vs 0.17/1000 patient-days, IRR 0.53, 95% CI 0.34-0.84). Aspirin significantly reduced rescue intervention rates (IRR 0.45, 95% CI 0.27-0.78). Neither agent significantly affected CVC exposure, late dialysis suitability failure or time to primary patency loss, AVF abandonment or successful cannulation. CONCLUSION: Although fish oil and low-dose aspirin given for 3 months reduced intervention rates in newly created AVF, they had no significant effects on CVC exposure, AVF usability and time to primary patency loss or access abandonment. Reduction in access interventions benefits patients, reduces costs and warrants further study.

Predictors of new-onset chronic kidney disease in patients managed surgically for T1a renal cell carcinoma: An Australian population-based analysis.

BACKGROUND: New-onset chronic kidney disease (CKD) following surgical management of kidney tumors is common. This study evaluated risk factors for new-onset CKD after nephrectomy for T1a renal cell carcinoma (RCC) in an Australian population-based cohort. METHODS: There were 551 RCC patients from the Australian states of Queensland and Victoria included in this study. The primary outcome was new-onset CKD (eGFR <60 mL/min per 1.73 m2 ) and the secondary outcome was new-onset moderate-severe CKD (<45 mL/min per 1.73 m2 ). Multivariable logistic regression was used to evaluate associations between patient, tumor and health-service characteristics and these outcomes. RESULTS: Forty percent (219/551) of patients developed new-onset CKD, and 12% (68/551) experienced new-onset moderate-severe CKD. Risk factors for new-onset CKD were age, lower preoperative eGFR, tumor size >20 mm, radical nephrectomy, lower hospital caseloads (<20 cases/year), and rural place of residence. The associations between rural place of residence and low center volume were a consequence of higher radical nephrectomy rates. CONCLUSION: Risk factors for CKD after nephrectomy generally relate to worse baseline health, or likelihood of undergoing radical nephrectomy. Surgeons in rural centres and hospitals with low caseloads may benefit from formalized integration with specialist centers for continued professional development and case-conferencing, to assist in management decisions.

Factors associated with acutely elevated serum creatinine following radical tumour nephrectomy: the Correlates of Kidney Dysfunction-Tumour Nephrectomy Database study.

BACKGROUND: To identify factors associated with acutely elevated serum creatinine (SCr) within 7 days of radical tumour nephrectomy. METHODS: The study population consisted of 130 consecutive patients managed for renal tumours. The primary outcome was acute kidney injury (AKI) (defined as SCr increase ≥50% above baseline), assessed using multivariable logistic regression analysis. The secondary outcome was SCr percentage increase, assessed using multivariable linear regression analysis. RESULTS: Following nephrectomy, the mean percentage increase in SCr in the first week was 55%±29%, and 77 (59%) patients experienced AKI. Independent predictors of AKI post-nephrectomy were male gender [adjusted odds ratio (OR): 2.67; 95% confidence interval (95% CI): 1.01, 6.93], urine albumin-creatinine ratio (OR: 0.66; 95% CI: 0.47, 0.91), preoperative estimated glomerular filtration rate (eGFR) (OR: 1.03; 95% CI: 1.00, 1.05), laparoscopic nephrectomy (OR: 3.02; 95% CI: 1.00, 9.12), and non-clear cell renal cell carcinoma (RCC) (OR: 2.93; 95% CI: 1.04, 8.29). Independent predictors of a SCr increase were male gender (ß: 12.0; 95% CI: 2.69, 21.3), urine albumin-creatinine ratio (ß: -3.36; 95% CI: -6.55, -0.16), preoperative eGFR (ß: 0.38; 95% CI: 0.10, 0.66), laparoscopic nephrectomy (ß: 12.7; 95% CI: 1.05, 24.3) and obesity (ß: 9.94, 95% CI: 0.61, 19.3). CONCLUSIONS: Male gender, albuminuria, eGFR and laparoscopic nephrectomy independently associated with acutely elevated serum creatinine following radical tumour nephrectomy.

EARLY PERITONITIS AND ITS OUTCOME IN INCIDENT PERITONEAL DIALYSIS PATIENTS.

BACKGROUND: Early-onset peritonitis is a serious complication of peritoneal dialysis (PD) and is associated with heightened risks of technique failure and death. The risk factors for early peritonitis and its outcomes are unknown. METHODS: This registry study examined all incident Australian PD patients between 2003 and 2014. The primary outcome was early peritonitis, defined as onset within 12 months of starting therapy. Secondary outcomes were medical cure, relapse/recurrence, catheter removal, peritonitis-associated technique failure, and peritonitis-associated death. RESULTS: Of 9,845 patients, 2,615 experienced 3,827 early-peritonitis episodes (0.50 episodes per patient-year). Early peritonitis was more common in patients who were male, obese, had a history of cigarette smoking or cerebrovascular disease, used continuous ambulatory PD, and had received prior renal replacement therapy for > 90 days. Remoteness was a risk modifier for the association between race and early peritonitis; remote Aboriginal, Torres Strait Islander, Maori and Pacific Islander patients had the highest risk. Obese patients were more likely to achieve medical cure. Older patients were less likely to achieve cure and more likely to experience peritonitis-associated death. CONCLUSIONS: In summary, several factors predicted early peritonitis in incident PD patients. Modified approaches to patient selection, training techniques, and prevention strategies should be considered in high-risk individuals.