Association Between CKD and Major Hemorrhage in Older Persons: Data From the Aspirin in Reducing Events in the Elderly Randomized Trial.

Introduction: Data on the association between chronic kidney disease (CKD) and major hemorrhage in older adults are lacking. Methods: We used data from a double-blind randomized controlled trial of aspirin in persons aged ≥ 70 years with prospective capture of bleeding events, including hemorrhagic stroke and clinically significant bleeding. CKD was defined as an estimated glomerular filtration rate (eGFR) < 60 ml/min per 1.73 m2 and/or urinary albumin-to-creatinine ratio (UACR) ≥ 3 mg/mmol (26.6 mg/g). We compared bleeding rates in those with and without CKD, undertook multivariable analyses, and explored effect modification with aspirin. Results: Of 19,114 participants, 17,976 (94.0%) had CKD status recorded, of whom 4952 (27.5%) had CKD. Participants with CKD had an increased rate of major bleeding events compared with those without CKD (10.4/1000 vs. 6.3/1000 person-years [py], respectively) and increased bleeding risk (risk ratio [RR] 1.60; 95% confidence interval [CI]: 1.40, 1.90 for eGFR < 60 ml/min per 1.73 m2) and RR (2.10; 95% CI: 1.70, 2.50) for albuminuria. In adjusted analyses, CKD was associated with a 35% increased risk of bleeding (hazard ratio [HR] 1.37; 95% CI: 1.15, 1.62; P < 0.001). Other risk factors were older age, hypertension, smoking, and aspirin use. There was no differential effect of aspirin on bleeding by CKD status (test of interaction P = 0.65). Conclusion: CKD is independently associated with an increased risk of major hemorrhage in older adults. Increased awareness of modifiable risk factors such as discontinuation of unnecessary aspirin, blood pressure control, and smoking cessation in this group is warranted.

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.

A pilot study comparing the efficiency of a novel asymmetric cellulose triacetate (ATA) dialyser membrane (Solacea-190H) to a standard high flux polysulfone dialyser membrane (FX-80) in the setting of extended hours haemodialysis.

AIM: To compare small, middle and large-middle molecule clearance; and expression of markers of inflammation, between Solacea-190H (asymmetric cellulose triacetate [ATA]) and FX-80 dialysers in long-hour haemodialysis patients. METHODS: This pilot, randomized cross-over trial recruited 10 home haemodialysis patients. The total study duration was 8 weeks, using each dialyser for 4 weeks. Removal of small (urea, phosphate, creatinine and indoxyl sulfate [IS]), middle and large-middle molecules (beta-2 microglobulin [ß2M], albumin), markers of inflammation (interleukin-6 [IL-6], malondialdehyde-modified low density lipoprotein [MDA-LDL] and alpha-1 microglobulin [α1M]), was evaluated in serum and dialysate samples. RESULTS: Reduction ratios [RR] were calculated for variables at the fourth week of each dialyzer sequence and results expressed as difference in mean RR between dialyzers. There was no difference in clearance of small molecules, with difference in mean RR for urea -2.43 (95% CI -6.44, 1.57; p = .19), creatinine -1.82 (95% CI -5.50, 1.85; p = .28) and phosphate -2.61 (95% CI -12.45, 7.23; p = .55); clearance of middle and large-middle molecules with difference in mean RR (range) for ß2M 2.2 (95% CI -3.2, 7.7; p = .35), IS 1.8 (95% CI -9.5, 13; p = .72) and albumin -0.6 (95% CI -5.5, 4.2; p = .77). There was lack of induction of markers of inflammation, including IL-6 15.2 (95% CI -31.9, 62.2; p = .47), MDA-LDL -8.1 (95% CI -22.1, 5.8; p = .21) and α1M -3.50 (95% CI -29.2, 22.2; p = .76). Dialysate removal results were concurrent. CONCLUSION: This study showed no difference in clearance of small, middle and large-middle molecules, nor expression of markers of inflammation between dialysers.

Risk factors for major adverse kidney events in the first year after acute kidney injury.

BACKGROUND: Acute kidney injury (AKI) survivors are at increased risk of major adverse kidney events (MAKEs), including chronic kidney disease (CKD), end-stage kidney disease (ESKD) and death. High-risk AKI patients may benefit from specialist follow-up, but factors associated with increased risk have not been reported. METHODS: We conducted a retrospective study of AKI patients admitted to a single centre between 2012 and 2016 who had a baseline estimated glomerular filtration rate (eGFR) >30 mL/min/1.73 m2 and were alive and independent of renal replacement therapy (RRT) at 30 days following discharge. AKI was identified using International Classification of Diseases, Tenth Revision codes and staged according to the Kidney Disease: Improving Global Outcomes criteria. Patients were excluded if they were kidney transplant recipients or if AKI was attributed to intrinsic kidney disease. We performed Cox regression models to examine MAKEs in the first year, defined as the composite of CKD (sustained 25% drop in eGFR), ESKD (requirement for chronic RRT or sustained eGFR <15 mL/min/1.73 m2) or death. We examined secondary outcomes (CKD, ESKD and death) using Cox and competing risk regression analyses. RESULTS: We studied 2101 patients (mean ± SD age 69 ± 15 years, baseline eGFR 72 ± 23 mL/min/1.73 m2). Of these, 767 patients (37%) developed at least one MAKE (429 patients developed CKD, 21 patients developed ESKD, 375 patients died). MAKEs occurred more frequently with older age [hazard ratio (HR) 1.16 per decade, 95% confidence interval (CI) 1.10-1.24], greater severity of AKI (Stage 2 HR 1.38, 95% CI 1.16-1.64; Stage 3 HR 1.62, 95% CI 1.31-2.01), higher serum creatinine at discharge (HR 1.04 per 10 µmol/L, 95% CI 1.03-1.06), chronic heart failure (HR 1.41, 95% CI 1.19-1.67), liver disease (HR 1.68, 95% CI 1.39-2.03) and malignancy (non-metastatic HR 1.44, 95% CI 1.14-1.82; metastatic HR 2.26, 95% CI 1.80-2.83). Traditional risk factors (e.g. diabetes and cardiovascular disease) had limited predictive value. CONCLUSIONS: More than a third of AKI patients develop MAKEs within the first year. Clinical variables available at the time of discharge can help identify patients at increased risk of such events.

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.

Home and facility haemodialysis patients: a comparison of outcomes in a matched cohort.

BACKGROUND: Home haemodialysis (HHD) is utilized significantly less often than facility HD globally with few exceptions, despite being associated with improved survival and better quality of life. Previously HHD was exclusively offered to younger patients with a few comorbidities. However, with the increasing burden of end-stage kidney disease (ESKD) alongside an ageing population, increasing numbers of older patients are being treated with HHD. This study aims to re-evaluate survival and related outcomes in the context of this epidemiological shift. METHODS: A matched cohort design was used to compare all-cause mortality, transplantation, average biochemical values and graft survival 6 months post-transplant between HHD and facility HD patients. A total of 181 HHD patients from a major hospital network were included with 413 facility HD patients from the Australia and New Zealand Dialysis and Transplant Registry matched by age, gender and cause of ESKD. Survival analysis and competing risks analysis (for transplantation) were performed. RESULTS: After adjusting for body mass index, smoking status, racial group and comorbidities, HHD was associated with a significantly reduced risk of death compared with facility HD patients [hazard ratio 0.47 (95% confidence interval 0.30-0.74)]. Transplantation rates were comparable, with high rates of graft survival at 6 months in both groups. Haemoglobin, calcium and parathyroid hormone levels did not vary significantly. However, HHD patients had significantly lower phosphate levels. CONCLUSIONS: In this study, improved survival outcomes were observed in patients on home compared with facility dialysis, with comparable rates of transplantation, graft survival and biochemical control.

Conversion of Urine Protein-Creatinine Ratio or Urine Dipstick Protein to Urine Albumin-Creatinine Ratio for Use in Chronic Kidney Disease Screening and Prognosis : An Individual Participant-Based Meta-analysis.

BACKGROUND: Although measuring albuminuria is the preferred method for defining and staging chronic kidney disease (CKD), total urine protein or dipstick protein is often measured instead. OBJECTIVE: To develop equations for converting urine protein-creatinine ratio (PCR) and dipstick protein to urine albumin-creatinine ratio (ACR) and to test their diagnostic accuracy in CKD screening and staging. DESIGN: Individual participant-based meta-analysis. SETTING: 12 research and 21 clinical cohorts. PARTICIPANTS: 919 383 adults with same-day measures of ACR and PCR or dipstick protein. MEASUREMENTS: Equations to convert urine PCR and dipstick protein to ACR were developed and tested for purposes of CKD screening (ACR ≥30 mg/g) and staging (stage A2: ACR of 30 to 299 mg/g; stage A3: ACR ≥300 mg/g). RESULTS: Median ACR was 14 mg/g (25th to 75th percentile of cohorts, 5 to 25 mg/g). The association between PCR and ACR was inconsistent for PCR values less than 50 mg/g. For higher PCR values, the PCR conversion equations demonstrated moderate sensitivity (91%, 75%, and 87%) and specificity (87%, 89%, and 98%) for screening (ACR >30 mg/g) and classification into stages A2 and A3, respectively. Urine dipstick categories of trace or greater, trace to +, and ++ for screening for ACR values greater than 30 mg/g and classification into stages A2 and A3, respectively, had moderate sensitivity (62%, 36%, and 78%) and high specificity (88%, 88%, and 98%). For individual risk prediction, the estimated 2-year 4-variable kidney failure risk equation using predicted ACR from PCR had discrimination similar to that of using observed ACR. LIMITATION: Diverse methods of ACR and PCR quantification were used; measurements were not always performed in the same urine sample. CONCLUSION: Urine ACR is the preferred measure of albuminuria; however, if ACR is not available, predicted ACR from PCR or urine dipstick protein may help in CKD screening, staging, and prognosis. PRIMARY FUNDING SOURCE: National Institute of Diabetes and Digestive and Kidney Diseases and National Kidney Foundation.

Survival in Living Kidney Donors: An Australian and New Zealand Cohort Study Using Data Linkage.

BACKGROUND: Living kidney donors are a highly selected healthy population expected to have high survival postdonation, but mortality studies are limited. Our study aimed to compare mortality in living kidney donors with the general population in Australia and New Zealand, hypothesizing that donor survival would exceed average survival. METHODS: All living kidney donors in Australia, 2004-2013, and New Zealand, 2004-2012, from the Australian and New Zealand Living Kidney Donor Registry were included. We ascertained primary cause of death from data linkage with national death registers. Standardized mortality ratios and relative survival were estimated, matching on age, sex, calendar year, and country. RESULTS: Among 3253 living kidney donors, there were 32 deaths over 20 331 person-years, with median follow-up 6.2 years [interquartile range: 3.9-8.4]. Only 25 donors had diabetes-fasting blood sugar level predonation, of which 3 had impaired glucose tolerance. At discharge, the median creatinine was 108 µmol/L and estimated glomerular filtration rate was 58 mL/min/1.72 m2. Four deaths occurred in the first year: 2 from immediate complications of donation, and 2 from unrelated accidental causes. The leading cause of death was cancer (n = 16). The crude mortality rate was 157 (95% confidence interval [CI], 111-222)/100 000 person-y, and the standardized mortality ratio was 0.33 (95% CI, 0.24-0.47). The 5-year cumulative relative survival was 1.019 (95% CI, 1.014-1.021), confirming that the survival probability in living kidney donors was 2% higher relative to the general population. CONCLUSIONS: As expected, mortality in living kidney donors was substantially lower than the general population and is reassuring for potential donor counseling. The Living Donor Registry only captured a third of the deaths, highlighting the benefit of data linkage to national death registries in the long-term follow-up of living kidney donors.

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.

Associations of Chronic Kidney Disease Markers with Cognitive Function: A 12-Year Follow-Up Study.

BACKGROUND: The role of chronic kidney disease (CKD) as a risk factor for cognitive impairment independent of their shared antecedents remains controversial. OBJECTIVE: To determine whether kidney damage (indicated by albuminuria) or kidney dysfunction (estimated glomerular filtration rate [eGFR] <60 ml/min/1.73 m2) predict future (12-year) cognitive function independently of their shared risk factors. METHODS: We studied 4,128 individuals from the 1999/00 population-based Australian Diabetes, Obesity, and Lifestyle (AusDiab) Study who returned in 2011/12 for follow-up cognitive function testing. Albuminuria was defined by urinary albumin:creatinine≥3.5 (women) or≥2.5 mg/mmol (men). Kidney dysfunction was indicated by eGFR <60 ml/min/1.73 m2. Cognitive function domains assessed included memory (California Verbal Learning Test [CVLT]) and processing speed (Symbol Digit Modalities Test [SDMT]). RESULTS: Baseline albuminuria and kidney dysfunction were identified in 142 (3.4%) and 39 (0.9%) individuals, respectively, with minimal overlap (n = 7). Those with albuminuria demonstrated concurrently reduced 12-year SDMT (p = 0.084) and CVLT scores (p = 0.005) following adjustment for age, sex, and education. However, only CVLT performance remained worse (p = 0.027) following additional adjustment for myocardial infarction, stroke, and related risk factors (hypertension, diabetes, dyslipidemia, smoking, BMI, physical activity, and alcohol intake). Indeed, these collective covariates were responsible for 47% of the effect of albuminuria on SDMT, but only 21% of its effect on CVLT. Kidney dysfunction was not associated with either SDMT or CVLT performance (p > 0.10). CONCLUSIONS: Albuminuria predicted worse memory function at 12 years follow-up, whereas its effect on processing speed was driven largely by differences in cardiovascular risk. Kidney dysfunction based on eGFR predicted neither cognitive domain.

Comparing dialysis centre mortality outcomes across Australia and New Zealand: identifying unusually performing centres 2008-2013.

BACKGROUND: Comparing the mortality profiles of dialysis centres is important to ensure that high standards of care are maintained. We compare the performance of dialysis centres in Australia and New Zealand in their treatment of haemodialysis patients, accounting for the competing risks of kidney transplantation and transfer to peritoneal dialysis. METHODS: Observational cohort study. We included data from all adult patients (5574 patients) commencing haemodialysis at home or in a facility between 2008 and 2010 across 62 dialysis centres, from the Australia and New Zealand Dialysis and Transplant Registry. Standardised mortality ratios were calculated by estimating mortality probabilities from a pooled random effects logistic regression model, accounting for the competing risk of transplantation using an inverse probability weighting approach. Models were adjusted for patient comorbidities, sex, height, weight, late referral to a nephrologist, age, race, primary kidney disease, smoking status, and serum creatinine (µmol/l). RESULTS: Two dialysis centres were found to have relatively higher levels of risk-adjusted mortality lying outside the prediction intervals for "usual" performance. Risk adjusted mortality rates were not associated with centres' compliance with guidelines for vascular access and biochemical and haematological targets. CONCLUSIONS: We demonstrate that standardised mortality ratios are useful to identify facilities that have statistically outlying mortality risk. Our criterion for determining whether a centre has better or worse performance than expected is statistical, and thus analyses such as ours can serve only as a screening tool, and are only one aspect of assessment of "quality" of performance.

Patient reported barriers are associated with low physical and mental well-being in patients with co-morbid diabetes and chronic kidney disease.

BACKGROUND: Little is known about how patient reported barriers to health care impact the quality of life (HRQoL) of patients with comorbid disease. We investigated patient reported barriers to health care and low physical and mental well-being among people with diabetes and chronic kidney disease (CKD). METHODS: Adults with diabetes and CKD (estimated Glomerular Filtration Rate < 60 ml/min/1.73m2) were recruited and completed a questionnaire on barriers to health care, the 12-Item HRQoL Short Form Survey and clinical assessment. Low physical and mental health status were defined as mean scores < 50. Logistic regression models were used. RESULTS: Three hundred eight participants (mean age 66.9 ± 11 years) were studied. Patient reported 'impact of the disease on family and friends' (OR 2.07; 95% CI 1.14 to 3.78), 'feeling unwell' (OR 4.23; 95% CI 1.45 to 12.3) and 'having other life stressors that make self-care a low priority' (OR 2.59; 95% CI 1.20 to 5.61), were all associated with higher odds of low physical health status. Patient reported 'feeling unwell' (OR 2.92; 95% CI 1.07 to 8.01), 'low mood' (OR 2.82; 95% CI 1.64 to 4.87) and 'unavailability of home help' (OR 1.91; 95% CI 1.57 to 2.33) were all associated with higher odds of low mental health status. The greater the number of patient reported barriers the higher the odds of low mental health but not physical health status. CONCLUSIONS: Patient reported barriers to health care were associated with lower physical and mental well-being. Interventions addressing these barriers may improve HRQoL among people with comorbid diabetes and CKD.

Seroresponses and safety of 13-valent pneumococcal conjugate vaccination in kidney transplant recipients.

BACKGROUND: Conjugated pneumococcal vaccine is recommended for kidney transplant recipients, however, their immunogenicity and potential to trigger allograft rejection though generation of de novo anti-human leukocyte antigen antibodies has not been well studied. METHODS: Clinically stable kidney transplant recipients participated in a prospective cohort study and received a single dose of 13-valent conjugate pneumococcal vaccine. Anti-pneumococcal IgG was measured for the 13 vaccine serotypes pre and post vaccination and functional anti-pneumococcal IgG for 4 serotypes post vaccination. Anti-human leukocyte antigen antibodies antibodies were measured before and after vaccination. Kidney transplant recipients were followed clinically for 12 months for episodes of allograft rejection or invasive pneumococcal disease. RESULTS: Forty-five kidney transplant recipients participated. Median days between pre and post vaccination serology was 27 (range 21-59). Post vaccination, there was a median 1.1 to 1.7-fold increase in anti-pneumococcal IgG antibody concentrations for all 13 serotypes. Kidney transplant recipients displayed a functional antibody titer ≥1:8 for a median of 3 of the 4 serotypes. Post vaccination, there were no de novo anti-human leukocyte antigen antibodies, no episodes of biopsy proven rejection or invasive pneumococcal disease. CONCLUSION: A single dose of 13-valent conjugate pneumococcal vaccine elicits increased titers and breadth of functional anti-pneumococcal antibodies in kidney transplant recipients without stimulating rejection or donor-specific antibodies.

Early serum creatinine accurately predicts acute kidney injury post cardiac surgery.

BACKGROUND: Acute Kidney Injury (AKI) is a well recognized complication of cardiac surgery. It is associated with significant morbidity and mortality. The aims of our study are twofold; 1. To define the incidence of AKI post cardiac surgery. 2. To identify pre-morbid and operative risk factors for developing AKI and to determine if immediate post operative serum creatinine (IPOsCr) accurately predicts the development of AKI. METHODS: We prospectively studied 196 consecutive patients undergoing elective (on-pump) cardiac surgery. Baseline patient characteristics, including medical co-morbidities, proteinuria, procedural data and kidney function (serum creatinine (sCr) were collected. Internationally standardised criteria for AKI were used (sCr >1.5 times baseline, elevation in sCr >26.4 µmmol/L (0.3 mg/dl). Measurements were collected pre-operatively, within 2 h of surgical completion (IPOsCr) and daily for two days. Logistic regression was used to assess predictive factors for AKI including IPOsCr. Model discrimination was assessed using ROC AUC curves. RESULTS: Forty (20.4%) patients developed AKI postoperatively. Hypertension (OR 2.64, p = 0.02), diabetes (OR 2.25, p = 0.04), proteinuria (OR 2.48, p = 0.02) and a lower baseline eGFR (OR 0.74, p = 0.002) were associated with AKI in univariate analysis. A multivariate logistic model with preoperative and surgical factors (age, gender, eGFR, proteinuria, hypertension, diabetes and type of cardiac surgery) demonstrated moderate discrimination for AKI (ROC AUC 0.76). The addition of IPOsCr improved model discrimination for AKI (AUC 0.82, p = 0.07 versus baseline AUC) and was independently associated with AKI (OR 7.17; 95% CI 1.27-40.32; p = 0.025). CONCLUSIONS: One in 5 patients developed AKI post cardiac surgery. These patients have significantly increased morbidity and mortality. IPOsCr is significantly associated with the development of AKI, providing a cheap readily available prognostic marker.

Effect of Fish Oil Supplementation and Aspirin Use on Arteriovenous Fistula Failure in Patients Requiring Hemodialysis: A Randomized Clinical Trial.

Importance: Vascular access dysfunction is a leading cause of morbidity and mortality in patients requiring hemodialysis. Arteriovenous fistulae are preferred over synthetic grafts and central venous catheters due to superior long-term outcomes and lower health care costs, but increasing their use is limited by early thrombosis and maturation failure. ω-3 Polyunsaturated fatty acids (fish oils) have pleiotropic effects on vascular biology and inflammation and aspirin impairs platelet aggregation, which may reduce access failure. Objective: To determine whether fish oil supplementation (primary objective) or aspirin use (secondary objective) is effective in reducing arteriovenous fistula failure. Design, Setting, and Participants: The Omega-3 Fatty Acids (Fish Oils) and Aspirin in Vascular Access Outcomes in Renal Disease (FAVOURED) study was a randomized, double-blind, controlled clinical trial that recruited participants with stage 4 or 5 chronic kidney disease from 2008 to 2014 at 35 dialysis centers in Australia, Malaysia, New Zealand, and the United Kingdom. Participants were observed for 12 months after arteriovenous fistula creation. Interventions: Participants were randomly allocated to receive fish oil (4 g/d) or matching placebo. A subset (n = 406) was also randomized to receive aspirin (100 mg/d) or matching placebo. Treatment started 1 day prior to surgery and continued for 12 weeks. Main Outcomes and Measures: The primary outcome was fistula failure, a composite of fistula thrombosis and/or abandonment and/or cannulation failure, at 12 months. Secondary outcomes included the individual components of the primary outcome. Results: Of 1415 eligible participants, 567 were randomized (359 [63%] male, 298 [53%] white, 264 [47%] with diabetes; mean [SD] age, 54.8 [14.3] y). The same proportion of fistula failures occurred in the fish oil and placebo arms (128 of 270 [47%] vs 125 of 266 [47%]; relative risk [RR] adjusted for aspirin use, 1.03; 95% CI, 0.86-1.23; P = .78). Fish oil did not reduce fistula thrombosis (60 [22%] vs 61 [23%]; RR, 0.98; 95% CI, 0.72-1.34; P = .90), abandonment (51 [19%] vs 58 [22%]; RR, 0.87; 95% CI, 0.62-1.22; P = .43), or cannulation failure (108 [40%] vs 104 [39%]; RR, 1.03; 95% CI, 0.83-1.26; P = .81). The risk of fistula failure was similar between the aspirin and placebo arms (87 of 194 [45%] vs 83 of 194 [43%]; RR, 1.05; 95% CI, 0.84-1.31; P = .68). Conclusions and Relevance: Neither fish oil supplementation nor aspirin use reduced failure of new arteriovenous fistulae within 12 months of surgery. Trial Registration: anzctr.org.au Identifier: CTRN12607000569404.

Cystatin C estimated glomerular filtration rate and all-cause and cardiovascular disease mortality risk in the general population: AusDiab study.

AIMS: Uncertainties about the role of cystatin C-based estimated glomerular filtration rate (eGFR) in the prediction of cardiovascular disease (CVD) beyond traditional CVD risk factors remain. We assessed contributions of eGFR to CVD and mortality in the general population. METHODS: Using 14 year follow-up data on 9353 adults without a reported history of CVD from the Australian Diabetes, Obesity and Lifestyle study, we assessed the contributions of eGFR (assessed by cystatin C (eGFRcysC ) and serum creatinine (eGFRcr ) and albuminuria (uACR) to total and CVD mortality. RESULTS: After adjusting for age, sex, CVD risk factors and uACR, compared with an eGFRcysC >90 mL/min per 1.73 m2 , eGFRcysC <60 mL/min per 1.73 m2 was associated with 56% and 73% increases in the risks for all-cause and CVD mortality, respectively. The respective changes for the c-statistic when eGFRcysC was added to a risk prediction model were 0.003 (95% confidence interval: 0.001 to 0.005) and 0.002 (95% confidence interval: -0.001 to 0.006). The net proportion of non-events assigned a lower-risk category significantly improved with the addition of eGFR (non-event net reclassification index eGFRcr : 1.0% and eGFRcysC : 1.5%) for all-cause mortality, but for CVD mortality, improvements were only significant when eGFR was combined with uACR. The net proportion of events assigned a higher-risk category was not significantly improved. CONCLUSION: In our community-based cohort, reduced eGFRcysC was associated with all-cause and CVD mortality. The addition of chronic kidney disease measures to risk prediction models improved overall risk stratification among those at low risk as opposed to those at high baseline risk of mortality.

The Omega-3 fatty acids (Fish Oils) and Aspirin in Vascular access OUtcomes in REnal Disease (FAVOURED) study: the updated final trial protocol and rationale of post-initiation trial modifications.

BACKGROUND: The FAVOURED study is an international multicentre, double-blind, placebo-controlled trial which commenced recruitment in 2008 and examines whether omega-3 polyunsaturated fatty acids (omega-3 PUFAs) either alone or in combination with aspirin will effectively reduce primary access failure of de novo arteriovenous fistulae (AVF) in patients with stage 4 and 5 chronic kidney disease. Publication of new evidence derived from additional studies of clopidogrel and a high screen failure rate due to prevalent aspirin usage prompted an updated trial design. METHODS/DESIGN: The original trial protocol published in 2009 has undergone two major amendments, which were implemented in 2011. Firstly, the primary outcome 'early thrombosis' at 3 months following AVF creation was broadened to a more clinically relevant outcome of 'AVF access failure'; a composite of thrombosis, AVF abandonment and cannulation failure at 12 months. Secondly, participants unable to cease using aspirin were allowed to be enrolled and randomised to omega-3 PUFAs or placebo. The revised primary aim of the FAVOURED study is to test the hypothesis that omega-3 PUFAs will reduce rates of AVF access failure within 12 months following AVF surgery. The secondary aims are to examine the effect of omega-3 PUFAs and aspirin on the individual components of the primary end-point, to examine the safety of study interventions and assess central venous catheter requirement as a result of access failure. DISCUSSION: This multicentre international clinical trial was amended to address the clinically relevant question of whether the usability of de novo AVF at 12 months can be improved by the early use of omega-3 PUFAs and to a lesser extent aspirin. This study protocol amendment was made in response to a large trial demonstrating that clopidogrel is effective in safely preventing primary AVF thrombosis, but ineffective at increasing functional patency. Secondly, including patients taking aspirin will enroll a more representative cohort of haemodialysis patients, who are significantly older with a higher prevalence of cardiovascular disease and diabetes which may increase event rates and the power of the study. TRIAL REGISTRATION: Australia & New Zealand Clinical Trial Register (ACTRN12607000569404).