The impact of obesity on body surface area adjusted estimated glomerular filtration rate in patients with chronic kidney disease.

BACKGROUND: Assessment of kidney function is necessary for prescribing renally excreted drugs. The estimated glomerular filtration rate (eGFR) routinely reported by laboratories is indexed to a body surface area (BSA) of 1.73 m2. In obese patients, the indexed eGFR may underestimate directly measured GFR. AIMS: To determine the prevalence of obesity in patients with chronic kidney disease (CKD) and examine the effect of adjusting the indexed eGFR for patient BSA (deindexing) across CKD Stages 2-5. METHODS: We conducted a cross-sectional study of 575 adults with stable CKD from two general nephrology clinics over 6 months. Dialysis and kidney transplant patients were excluded. We used four equations (Mosteller, Dubois, Haycock and Schlich) to determine BSA based on actual body weight and applied Bland-Altman plots and piecewise linear regression to examine the relationship between deindexed and indexed eGFR. RESULTS: The median age was 68 years (58% male). The prevalence of overweight and obesity was 31% and 47% respectively. Mean body mass index was 29.7 kg/m2. The Schlich equation for BSA produced the smallest adjustment in eGFR, while the Haycock equation produced the largest adjustment. Males experienced the largest change in eGFR from deindexing because of larger BSAs. Although bias became increasingly positive with higher eGFR, the linear regression stratified by CKD stage indicated that deindexing had little impact with eGFR <45 mL/min/1.73 m2. CONCLUSIONS: In CKD, deindexing the Chronic Kidney Disease Epidemiology Collaboration eGFR may not be necessary when the eGFR is <45 mL/min/1.73 m2, particularly if the patient is female.

Genomic testing for suspected monogenic kidney disease in children and adults: A health economic evaluation.

PURPOSE: To assess the relative cost-effectiveness of genomic testing compared with standard non-genomic diagnostic investigations in patients with suspected monogenic kidney disease from an Australian health care system perspective. METHODS: Diagnostic and clinical information was used from a national cohort of 349 participants. Simulation modelling captured diagnostic, health, and economic outcomes during a time horizon from clinical presentation until 3 months post-test results based on the outcome of cost per additional diagnosis and lifetime horizon based on cost per quality-adjusted life-year (QALY) gained. RESULTS: Genomic testing was Australian dollars (AU$) 1600 more costly per patient and led to an additional 27 diagnoses out of a 100 individuals tested, resulting in an incremental cost-effectiveness ratio of AU$5991 per additional diagnosis. Using a lifetime horizon, genomic testing resulted in an additional cost of AU$438 and 0.04 QALYs gained per individual compared with standard diagnostic investigations, corresponding to an incremental cost-effectiveness ratio of AU$10,823 per QALY gained. Sub-group analyses identified that the results were largely driven by the cost-effectiveness in glomerular diseases. CONCLUSION: Based on established or expected thresholds of cost-effectiveness, our evidence suggests that genomic testing is very likely to be cost saving for individuals with suspected glomerular diseases, whereas no evidence of cost-effectiveness was found for non-glomerular diseases.

A codesigned integrated kidney and diabetes model of care improves patient activation among patients from culturally and linguistically diverse backgrounds.

BACKGROUND: Little is known about the relationship between patients' cultural and linguistic backgrounds and patient activation, especially in people with diabetes and chronic kidney disease (CKD). We examined the association between culturally and linguistically diverse (CALD) background and patient activation and evaluated the impact of a codesigned integrated kidney and diabetes model of care on patient activation by CALD status in people with diabetes and CKD. METHODS: This longitudinal study recruited adults with diabetes and CKD (Stage 3a or worse) who attended a new diabetes and kidney disease service at a tertiary hospital. All completed the patient activation measure at baseline and after 12 months and had demographic and clinical data collected. Patients from CALD backgrounds included individuals who spoke a language other than English at home, while those from non-CALD backgrounds spoke English only as their primary language. Paired t-tests compared baseline and 12-month patient activation scores by CALD status. RESULTS: Patients from CALD backgrounds had lower activation scores (52.1 ± 17.6) compared to those from non-CALD backgrounds (58.5 ± 14.6) at baseline. Within-group comparisons showed that patient activation scores for patients from CALD backgrounds significantly improved by 7 points from baseline to 12 months follow-up (52.1 ± 17.6-59.4 ± 14.7), and no significant change was observed for those from non-CALD backgrounds (58.5 ± 14.6-58.8 ± 13.6). CONCLUSIONS: Among patients with diabetes and CKD, those from CALD backgrounds report worse activation scores. Interventions that support people from CALD backgrounds with comorbid diabetes and CKD, such as the integrated kidney and diabetes model of care, may address racial and ethnic disparities that exist in patient activation and thus improve clinical outcomes. PATIENT OR PUBLIC CONTRIBUTION: Patients, caregivers and national consumer advocacy organisations (Diabetes Australia and Kidney Health Australia) codesigned a new model of care in partnership with healthcare professionals and researchers. The development of the model of care was informed by focus groups of patients and healthcare professionals and semi-structured interviews of caregivers and healthcare professionals. Patients and caregivers also provided a rigorous evaluation of the new model of care, highlighting its strengths and weaknesses.

A co-designed integrated kidney and diabetes model of care improves mortality, glycaemic control and self-care.

BACKGROUND: Current healthcare models are ill-equipped for managing people with diabetes and chronic kidney disease (CKD). We evaluated the impact of a new diabetes and kidney disease service (DKS) on hospitalization, mortality, clinical and patient-relevant outcomes. METHODS: Longitudinal analyses of adult patients with diabetes and CKD (Stages 3a-5) were performed using outpatient and hospitalization data from January 2015 to October 2018. Data were handled according to whether patients received the DKS intervention (n = 196) or standard care (n = 7511). The DKS provided patient-centred, coordinated multidisciplinary assessment and management of patients. Primary analyses examined hospitalization and mortality rates between the two groups. Secondary analyses evaluated the impact of the DKS on clinical target attainment, changes in estimated glomerular filtration rate (eGFR), glycated haemoglobin A1c (HbA1c), self-care and patient activation at 12 months. RESULTS: Patients who received the intervention had a higher hospitalization rate {incidence rate ratio [IRR] 1.20 [95% confidence interval (CI) 1.13-1.30]; P < 0.0001}, shorter median length of stay {2 days [interquartile range (IQR) 1-6] versus 4 days [IQR 1-9]; P < 0.0001} and lower all-cause mortality rate [IRR 0.4 (95% CI 0.29-0.64); P < 0.0001] than those who received standard care. Improvements in overall self-care [mean difference 2.26 (95% CI 0.83-3.69); P < 0.001] and in statin use and eye and feet examinations were observed. The mean eGFR did not change significantly after 12 months [mean difference 1.30 mL/min/1.73 m2 (95% CI -4.17-1.67); P = 0.40]. HbA1c levels significantly decreased by 0.40, 0.35, 0.34 and 0.23% at 3, 6, 9 and 12 months of follow-up, respectively. CONCLUSIONS: A co-designed, person-centred integrated model of care improved all-cause mortality, kidney function, glycaemic control and self-care for patients with diabetes and CKD.

Smad4 promotes diabetic nephropathy by modulating glycolysis and OXPHOS.

Diabetic nephropathy (DN) is the leading cause of end-stage kidney disease. TGF-ß1/Smad3 signalling plays a major pathological role in DN; however, the contribution of Smad4 has not been examined. Smad4 depletion in the kidney using anti-Smad4 locked nucleic acid halted progressive podocyte damage and glomerulosclerosis in mouse type 2 DN, suggesting a pathogenic role of Smad4 in podocytes. Smad4 is upregulated in human and mouse podocytes during DN. Conditional Smad4 deletion in podocytes protects mice from type 2 DN, independent of obesity. Mechanistically, hyperglycaemia induces Smad4 localization to mitochondria in podocytes, resulting in reduced glycolysis and oxidative phosphorylation and increased production of reactive oxygen species. This operates, in part, via direct binding of Smad4 to the glycolytic enzyme PKM2 and reducing the active tetrameric form of PKM2. In addition, Smad4 interacts with ATPIF1, causing a reduction in ATPIF1 degradation. In conclusion, we have discovered a mitochondrial mechanism by which Smad4 causes diabetic podocyte injury.

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.

Dietary habits in Australian, New Zealand and Malaysian patients with end stage kidney failure: A pre-specified cross-sectional study of the FAVOURED trial participants.

BACKGROUND: Dietary management plays an important role in patients with kidney failure. Current dietary habits of Australians and New Zealanders (ANZ) and Malaysians with chronic kidney disease (CKD Stage 4-5) have not been adequately investigated. We report the dietary habits of people with advanced CKD and their adherence to country-specific dietary guidelines. METHODS: Participants with CKD Stage 4-5, enrolled in the Omega-3 Fatty Acids (Fish oils) and Aspirin in Vascular access Outcomes in Renal Disease (FAVOURED) trial, completed a lifestyle questionnaire at baseline on their dietary intake. RESULTS: Of 567 participants, 538 (ANZ, n = 386; Malaysian, n = 152; mean ± SD age 54.8 ± 14.3 years, 64% male) completed the questionnaire. Dietary fruit and vegetable intakes were higher in ANZ participants; 49% (n = 189) consumed ≥2 serves day-1 of fruit and 61% (n = 235) ate ≥2 serves day-1 of vegetables compared to 24% (n = 36) and 34% (n = 52) of Malaysians, respectively (p < 0.0001). Only 4% (n = 15) of ANZ participants met Australian Dietary recommendations of two fruit and five vegetable serves day-1 . Fish consumption was higher in Malaysians with 83% (n = 126) consuming ≥2 serves week-1 compared to 21% (n = 81) of ANZ participants (p < 0.001). Red meat intake was higher in ANZ participants; however, chicken consumption was similar; 48% (n = 185) consumed >2 chicken serves week-1 and 65% (n = 251) ate >2 serves week-1 of red meat compared to 43% (n = 65) and 15% (n = 23) of Malaysians, respectively. CONCLUSIONS: Significant regional variation in dietary intake for fruit, vegetables and animal protein is described that likely reflects cultural and economic differences. Barriers to meeting recommended dietary intakes require further investigation.

Oral Anticoagulant Use in Patients With Atrial Fibrillation and Chronic Kidney Disease: A Review of the Evidence With Recommendations for Australian Clinical Practice.

Chronic kidney disease is common in patients with atrial fibrillation (AF) and is associated with heightened risks of stroke/systemic embolisation and bleeding. In this review we outline the evidence for AF stroke prevention in kidney disease, identify current knowledge gaps, and give recommendations for anticoagulation at various stages of chronic kidney disease. Overall, anticoagulation is underused. Warfarin use becomes increasingly difficult with advancing kidney disease, with difficulty maintaining international normalised ratio (INR) in therapeutic range, increased risk of intracranial and fatal bleeding compared to non-vitamin K oral anticoagulants (NOACs), and high rates of discontinuation. Similarly, the direct thrombin inhibitor dabigatran is not recommended as it is predominantly renally excreted with consequent increased plasma levels and bleeding risk with advanced kidney disease. The Factor Xa inhibitors apixaban and rivaroxaban have less renal excretion (25-35%), modest increases in plasma levels with advancing kidney disease, and are the preferred first line choice for anticoagulation in moderate kidney disease based on strong evidence from randomised clinical trials (RCTs). In severe kidney disease there is a paucity of RCT data, but extrapolation of the pharmacokinetic and RCT data for moderate kidney disease, and observational studies, support the considered use of dose-adjusted Factor Xa inhibitors unless the bleeding risk is prohibitive. In Australia, apixaban is approved for creatinine clearance down to 25 mL/min, and rivaroxaban down to 15 mL/min. For end-stage kidney disease warfarin is the only agent approved, but we recommend against anticoagulation (except in selected cases) due to high bleeding risk, multiple co-morbidities, and questionable benefit.

Clinical impact of genomic testing in patients with suspected monogenic kidney disease.

PURPOSE: To determine the diagnostic yield and clinical impact of exome sequencing (ES) in patients with suspected monogenic kidney disease. METHODS: We performed clinically accredited singleton ES in a prospectively ascertained cohort of 204 patients assessed in multidisciplinary renal genetics clinics at four tertiary hospitals in Melbourne, Australia. RESULTS: ES identified a molecular diagnosis in 80 (39%) patients, encompassing 35 distinct genetic disorders. Younger age at presentation was independently associated with an ES diagnosis (p < 0.001). Of those diagnosed, 31/80 (39%) had a change in their clinical diagnosis. ES diagnosis was considered to have contributed to management in 47/80 (59%), including negating the need for diagnostic renal biopsy in 10/80 (13%), changing surveillance in 35/80 (44%), and changing the treatment plan in 16/80 (20%). In cases with no change to management in the proband, the ES result had implications for the management of family members in 26/33 (79%). Cascade testing was subsequently offered to 40/80 families (50%). CONCLUSION: In this pragmatic pediatric and adult cohort with suspected monogenic kidney disease, ES had high diagnostic and clinical utility. Our findings, including predictors of positive diagnosis, can be used to guide clinical practice and health service design.

Hemodialysis Use and Practice Patterns: An International Survey Study.

RATIONALE & OBJECTIVE: Hemodialysis (HD) is the most common form of kidney replacement therapy. This study aimed to examine the use, availability, accessibility, affordability, and quality of HD care worldwide. STUDY DESIGN: A cross-sectional survey. SETTING & PARTICIPANTS: Stakeholders (clinicians, policy makers, and consumer representatives) in 182 countries were convened by the International Society of Nephrology from July to September 2018. OUTCOMES: Use, availability, accessibility, affordability, and quality of HD care. ANALYTICAL APPROACH: Descriptive statistics. RESULTS: Overall, representatives from 160 (88%) countries participated. Median country-specific use of maintenance HD was 298.4 (IQR, 80.5-599.4) per million population (pmp). Global median HD use among incident patients with kidney failure was 98.0 (IQR, 81.5-140.8) pmp and median number of HD centers was 4.5 (IQR, 1.2-9.9) pmp. Adequate HD services (3-4 hours 3 times weekly) were generally available in 27% of low-income countries. Home HD was generally available in 36% of high-income countries. 32% of countries performed monitoring of patient-reported outcomes; 61%, monitoring of small-solute clearance; 60%, monitoring of bone mineral markers; 51%, monitoring of technique survival; and 60%, monitoring of patient survival. At initiation of maintenance dialysis, only 5% of countries used an arteriovenous access in almost all patients. Vascular access education was suboptimal, funding for vascular access procedures was not uniform, and copayments were greater in countries with lower levels of income. Patients in 23% of the low-income countries had to pay >75% of HD costs compared with patients in only 4% of high-income countries. LIMITATIONS: A cross-sectional survey with possibility of response bias, social desirability bias, and limited data collection preventing in-depth analysis. CONCLUSIONS: In summary, findings reveal substantial variations in global HD use, availability, accessibility, quality, and affordability worldwide, with the lowest use evident in low- and lower-middle-income countries.

Peritoneal Dialysis Use and Practice Patterns: An International Survey Study.

RATIONALE & OBJECTIVE: Approximately 11% of people with kidney failure worldwide are treated with peritoneal dialysis (PD). This study examined PD use and practice patterns across the globe. STUDY DESIGN: A cross-sectional survey. SETTING & PARTICIPANTS: Stakeholders including clinicians, policy makers, and patient representatives in 182 countries convened by the International Society of Nephrology between July and September 2018. OUTCOMES: PD use, availability, accessibility, affordability, delivery, and reporting of quality outcome measures. ANALYTICAL APPROACH: Descriptive statistics. RESULTS: Responses were received from 88% (n=160) of countries and there were 313 participants (257 nephrologists [82%], 22 non-nephrologist physicians [7%], 6 other health professionals [2%], 17 administrators/policy makers/civil servants [5%], and 11 others [4%]). 85% (n=156) of countries responded to questions about PD. Median PD use was 38.1 per million population. PD was not available in 30 of the 156 (19%) countries responding to PD-related questions, particularly in countries in Africa (20/41) and low-income countries (15/22). In 69% of countries, PD was the initial dialysis modality for≤10% of patients with newly diagnosed kidney failure. Patients receiving PD were expected to pay 1% to 25% of treatment costs, and higher (>75%) copayments (out-of-pocket expenses incurred by patients) were more common in South Asia and low-income countries. Average exchange volumes were adequate (defined as 3-4 exchanges per day or the equivalent for automated PD) in 72% of countries. PD quality outcome monitoring and reporting were variable. Most countries did not measure patient-reported PD outcomes. LIMITATIONS: Low responses from policy makers; limited ability to provide more in-depth explanations underpinning outcomes from each country due to lack of granular data; lack of objective data. CONCLUSIONS: Large inter- and intraregional disparities exist in PD availability, accessibility, affordability, delivery, and reporting of quality outcome measures around the world, with the greatest gaps observed in Africa and South Asia.

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.

Relationship between measured and prescribed dialysate sodium in haemodialysis: a systematic review and meta-analysis.

BACKGROUND: Dialysate sodium (DNa) prescription policy differs between haemodialysis (HD) units, and the optimal DNa remains uncertain. We sought to summarize the evidence on the agreement between prescribed and delivered DNa, and whether the relationship varied according to prescribed DNa. METHODS: We searched MEDLINE and PubMed from inception to 26 February 2020 for studies reporting measured and prescribed DNa. We analysed results reported in aggregate with random-effects meta-analysis. We analysed results reported by individual sample, using mixed-effects Bland-Altman analysis and linear regression. Pre-specified subgroup analyses included method of sodium measurement, dialysis machine manufacturer and proportioning method. RESULTS: Seven studies, representing 908 dialysate samples from 10 HD facilities (range 16-133 samples), were identified. All but one were single-centre studies. Studies were of low to moderate quality. Overall, there was no statistically significant difference between measured and prescribed DNa {mean difference = 0.73 mmol/L [95% confidence interval (CI) -1.12 to 2.58; P = 0.44]} but variability across studies was substantial (I2 = 99.3%). Among individually reported samples (n = 295), measured DNa was higher than prescribed DNa by 1.96 mmol/L (95% CI 0.23-3.69) and the 95% limits of agreement ranged from -3.97 to 7.88 mmol/L. Regression analysis confirmed a strong relationship between prescribed and measured DNa, with a slope close to 1:1 (ß = 1.16, 95% CI 1.06-1.27; P < 0.0001). CONCLUSIONS: A limited number of studies suggest that, on average, prescribed and measured DNa are similar. However, between- and within-study differences were large. Further consideration of the precision of delivered DNa is required to inform rational prescribing.

Availability, coverage, and scope of health information systems for kidney care across world countries and regions.

BACKGROUND: Health information systems (HIS) are fundamental tools for the surveillance of health services, estimation of disease burden and prioritization of health resources. Several gaps in the availability of HIS for kidney disease were highlighted by the first iteration of the Global Kidney Health Atlas. METHODS: As part of its second iteration, the International Society of Nephrology conducted a cross-sectional global survey between July and October 2018 to explore the coverage and scope of HIS for kidney disease, with a focus on kidney replacement therapy (KRT). RESULTS: Out of a total of 182 invited countries, 154 countries responded to questions on HIS (85% response rate). KRT registries were available in almost all high-income countries, but few low-income countries, while registries for non-dialysis chronic kidney disease (CKD) or acute kidney injury (AKI) were rare. Registries in high-income countries tended to be national, in contrast to registries in low-income countries, which often operated at local or regional levels. Although cause of end-stage kidney disease, modality of KRT and source of kidney transplant donors were frequently reported, few countries collected data on patient-reported outcome measures and only half of low-income countries recorded process-based measures. Almost no countries had programs to detect AKI and practices to identify CKD-targeted individuals with diabetes, hypertension and cardiovascular disease, rather than members of high-risk ethnic groups. CONCLUSIONS: These findings confirm significant heterogeneity in the global availability of HIS for kidney disease and highlight important gaps in their coverage and scope, especially in low-income countries and across the domains of AKI, non-dialysis CKD, patient-reported outcomes, process-based measures and quality indicators for KRT service delivery.

Kidney transplant recipient perspectives on telehealth during the COVID-19 pandemic.

The COVID-19 pandemic has challenged the delivery of health services. Telehealth allows delivery of care without in-person contacts and minimizes the risk of vial transmission. We aimed to describe the perspectives of kidney transplant recipients on the benefits, challenges, and risks of telehealth. We conducted five online focus groups with 34 kidney transplant recipients who had experienced a telehealth appointment. Transcripts were thematically analyzed. We identified five themes: minimizing burden (convenient and easy, efficiency of appointments, reducing exposure to risk, limiting work disruptions, and alleviating financial burden); attuning to individual context (depending on stability of health, respect patient choice of care, and ensuring a conducive environment); protecting personal connection and trust (requires established rapport with clinicians, hampering honest conversations, diminished attentiveness without incidental interactions, reassurance of follow-up, and missed opportunity to share lived experience); empowerment and readiness (increased responsibility for self-management, confidence in physical assessment, mental preparedness, and forced independence); navigating technical challenges (interrupted communication, new and daunting technologies, and cognizant of patient digital literacy). Telehealth is convenient and minimizes time, financial, and overall treatment burden. Telehealth should ideally be available after the pandemic, be provided by a trusted nephrologist and supported with resources to help patients prepare for appointments.

A Randomized Trial on the Effect of Phosphate Reduction on Vascular End Points in CKD (IMPROVE-CKD).

BACKGROUND: Hyperphosphatemia is associated with increased fibroblast growth factor 23 (FGF23), arterial calcification, and cardiovascular mortality. Effects of phosphate-lowering medication on vascular calcification and arterial stiffness in CKD remain uncertain. METHODS: To assess the effects of non-calcium-based phosphate binders on intermediate cardiovascular markers, we conducted a multicenter, double-blind trial, randomizing 278 participants with stage 3b or 4 CKD and serum phosphate >1.00 mmol/L (3.10 mg/dl) to 500 mg lanthanum carbonate or matched placebo thrice daily for 96 weeks. We analyzed the primary outcome, carotid-femoral pulse wave velocity, using a linear mixed effects model for repeated measures. Secondary outcomes included abdominal aortic calcification and serum and urine markers of mineral metabolism. RESULTS: A total of 138 participants received lanthanum and 140 received placebo (mean age 63.1 years; 69% male, 64% White). Mean eGFR was 26.6 ml/min per 1.73 m2; 45% of participants had diabetes and 32% had cardiovascular disease. Mean serum phosphate was 1.25 mmol/L (3.87 mg/dl), mean pulse wave velocity was 10.8 m/s, and 81.3% had abdominal aortic calcification at baseline. At 96 weeks, pulse wave velocity did not differ significantly between groups, nor did abdominal aortic calcification, serum phosphate, parathyroid hormone, FGF23, and 24-hour urinary phosphate. Serious adverse events occurred in 63 (46%) participants prescribed lanthanum and 66 (47%) prescribed placebo. Although recruitment to target was not achieved, additional analysis suggested this was unlikely to have significantly affected the principle findings. CONCLUSIONS: In patients with stage 3b/4 CKD, treatment with lanthanum over 96 weeks did not affect arterial stiffness or aortic calcification compared with placebo. These findings do not support the role of intestinal phosphate binders to reduce cardiovascular risk in patients with CKD who have normophosphatemia. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: Australian Clinical Trials Registry, ACTRN12610000650099.

Biochemical comparison of 8 h haemodialysis and 4 h haemodiafiltration, and two dialysis membranes, in a randomized cross-over trial.

AIM: Extended-hours haemodialysis has long been regarded as the optimal form of dialysis for solute clearance. With emerging benefits of haemodiafiltration, we wanted to compare these two head-to-head. METHODS: In this randomized cross-over trial, we recruited existing nocturnal haemodialysis patients, who had not been hospitalized in the prior 3 months. After a baseline 8 h haemodialysis session, subjects were randomized to either 2 weeks of 8 h haemodialysis or 4 h haemodiafiltration with cross-over to the alternative treatment after a 2-week washout period. Subjects were additionally randomized to the Fresenius FX80 or Nipro Elisio in a parallel design. Blood and dialysate samples were collected at baseline and at the end of both study periods. RESULTS: Twelve patients completed the study. Mean (SD) age and body mass index were 55.1 ± 11.5 years and 36.4 ± 10.8, respectively. Urea and creatinine reduction ratios were higher with extended-hours haemodialysis compared to haemodiafiltration (difference 14.0%, 95% CI = 10.6, 17.3; P < 0.001 and 9.1%, 95% CI = 11.0, 7.2; P < 0.001). Fibroblast growth factor 23 (FGF23) clearance was superior with haemodiafiltration (difference 20.1%, 95% CI = 8.7, 31.6; P = 0.001). No difference was seen in reduction ratios for phosphate, retinol binding protein, alpha-1-microglobulin, beta-2-microglobulin and fetuin with both modalities. Compared to Nipro Elisio, Fresenius FX80 dialyser achieved higher beta-2-microglobulin clearance (Period 1: difference 7.8%, 95% CI = 1.3, 14.4; P = 0.02, Period 2:7.5%, 95% CI = 1.0, 14.1; P = 0.02). CONCLUSIONS: Small solute clearance was superior with extended-hours haemodialysis while haemodiafiltration enhanced FGF23 clearance. Beta-2-microglobulin clearance was improved with Fresenius FX80 dialyser, but this difference is unlikely to be clinically significant.

Renal genetics in Australia: Kidney medicine in the genomic age.

There have been few new therapies for patients with chronic kidney disease in the last decade. However, the management of patients affected by genetic kidney disease is rapidly evolving. Inherited or genetic kidney disease affects around 10% of adults with end-stage kidney disease and up to 70% of children with early onset kidney disease. Advances in next-generation sequencing have enabled rapid and cost-effective sequencing of large amounts of DNA. Next-generation sequencing-based diagnostic tests now enable identification of a monogenic cause in around 20% of patients with early-onset chronic kidney disease. A definitive diagnosis through genomic testing may negate the need for prolonged diagnostic investigations and surveillance, facilitate reproductive planning and provide accurate counselling for at-risk relatives. Genomics has allowed the better understanding of disease pathogenesis, providing prognostic information and facilitating development of targeted treatments for patients with inherited or genetic kidney disease. Although genomic testing is becoming more readily available, there are many challenges to implementation in clinical practice. Multidisciplinary renal genetics clinics serve as a model of how some of these challenges may be overcome. Such clinics are already well established in most parts of Australia, with more to follow in future. With the rapid pace of new technology and gene discovery, collaboration between expert clinicians, laboratory and research scientists is of increasing importance to maximize benefits to patients and health-care systems.

Identifying patient-important outcomes in polycystic kidney disease: An international nominal group technique study.

AIM: Patients with autosomal dominant polycystic kidney disease (ADPKD) are at increased risk of premature mortality, morbidities and complications, which severely impair quality of life. However, patient-centered outcomes are not consistently reported in trials in ADPKD, which can limit shared decision-making. We aimed to identify outcomes important to patients and caregivers and the reasons for their priorities. METHODS: Nominal group technique was adopted involving patients with ADPKD and caregivers who were purposively selected from eight centres across Australia, France and the Republic of Korea. Participants identified, ranked and discussed outcomes for trials in ADPKD. We calculated an importance score (0-1) for each outcome and conducted thematic analyses. RESULTS: Across 17 groups, 154 participants (121 patients, 33 caregivers) aged 19 to 78 (mean 54.5 years) identified 55 outcomes. The 10 highest ranked outcomes were: kidney function (importance score 0.36), end-stage kidney disease (0.32), survival (0.21), cyst size/growth (0.20), cyst pain/bleeding (0.18), blood pressure (0.17), ability to work (0.16), cerebral aneurysm/stroke (0.14), mobility/physical function (0.12), and fatigue (0.12). Three themes were identified: threatening semblance of normality, inability to control and making sense of diverse risks. CONCLUSION: For patients with ADPKD and their caregivers, kidney function, delayed progression to end-stage kidney disease and survival were the highest priorities, and were focused on achieving normality, and maintaining control over health and lifestyle. Implementing these patient-important outcomes may improve the meaning and relevance of trials to inform clinical care in ADPKD.