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The following cases demonstrate a proof of concept for the safe and effective use of the glucagon‐like‐peptide‐1 receptor agonist (GLP‐1 RA) semaglutide for weight loss in obese, non‐diabetic, end stage kidney disease (ESKD) patients on haemodialysis (HD), who are unable to undergo renal transplantation due to obesity. Obesity is a common barrier to wait‐listing for renal transplantation with effective, broadly applicable weight loss strategies lacking. GLP‐1 RAs have been shown to be effective adjuncts to achieve weight loss in non‐diabetic obese people. However, the major clinical trials excluded patients with ESKD on dialysis. This paper outlines the successful use of semaglutide to achieve a target body mass index (BMI) prior to renal transplant wait‐listing in two obese, non‐diabetic, HD patients. These patients achieved a 16% and 12.6% weight loss in under 9 months with one now waitlisted and the other transplanted. This strategy has the potential for broader use in this patient cohort to improve wait‐list times by overcoming this common barrier to renal transplantation. [ABSTRACT FROM AUTHOR]

Introduction: Hemodialysis (HD) with medium cut‐off (MCO) dialyzers may expand molecular clearance, predominantly larger middle molecules (molecular weight 25–60 kDa). However, the impact of MCO dialyzers on long‐term clearance of various other components of the uremic milieu is unknown. The tRial Evaluating Mid cut‐Off Value membrane clearance of Albumin and Light chains in HemoDialysis patients (REMOVAL‐HD) provided an opportunity to assess the effect of MCO dialyzers on protein‐bound uremic toxins and novel markers of mineral metabolism. Methods: This exploratory sub‐study of REMOVAL‐HD evaluated changes in protein‐bound solutes (total and free indoxyl sulfate [IS] and p‐cresyl sulfate [PCS]) and mineral metabolism markers (intact fibroblast growth factor‐23 [iFGF23], fetuin‐A and endogenous calciprotein particles [CPP‐1 and CPP‐2]). Mid‐week, pre‐HD serum samples were collected at baseline and after 12 and 24 weeks of MCO use in stable adult patients. Change from baseline to Week 12 and 24 was estimated using linear mixed effects models. Findings: Eighty‐nine participants were studied (mean age 67 ± 15 years, 38% female, 51% diabetic, median urine output 200 ml/24 h). Serum iFGF23 was reduced at Week 12 compared to baseline (−26.8% [95%CI −39.7, −11.1], p = 0.001), which was sustained at Week 24 (−21.7% [95%CI ‐35.7, −4.5], p = 0.012). There was no significant change in serum IS, PCS, fetuin‐A, CPP‐1, or CPP‐2. Discussion: The use of a MCO dialyzer over 24 weeks was associated with a sustained reduction in FGF23, while other measured components of the uremic milieu were not significantly altered. Further studies are required to determine whether FGF23 reduction is associated with improved patient outcomes. [ABSTRACT FROM AUTHOR]

Background: A new class of dialysis membrane, the mid cut-off (MCO) dialyzer, has been developed to improve the clearance of uremic toxins in hemodialysis (HD). The a tRial Evaluating Mid cut-Off Value membrane clearance of Albumin and Light chains in HemoDialysis patients (REMOVAL-HD) study aimed to determine if regular use of MCO dialyzer was safe and specifically did not result in a significant loss of albumin. Methods: This investigator initiated, crossover, longitudinal, device study was conducted across 9 centers in Australia and New Zealand (n = 89). Participants had a 4-week wash-in with high-flux HD, followed by 24-week intervention with MCO HD and a subsequent 4-week wash-out with high-flux HD. The primary outcome was change in serum albumin between weeks 4 and 28. Secondary outcomes included trends in serum albumin, changes in kappa- and lambda-free light chains (FLC), 6-min walk test (6MWT), malnutrition inflammation score (MIS), restless legs score and quality of life. Results: Participants had a mean age of 66 ± 14 years, 62% were men, 45% were anuric, and 51% had -diabetes. There was no reduction in serum albumin following treatment with MCO HD (mean reduction –0.7 g/L, 95% CI –1.5 to 0.1). A sustained, unexplained reduction in serum albumin (>25%) was not observed in any participant. A reduction in FLC was observed 2 weeks into MCO HD (lambda-FLC: Δ –9.1 mg/L, 95% CI –14.4 to –3.7; kappa-FLC: Δ –5.7 mg/L, 95% CI –9.8 to –1.6) and was sustained for the rest of the study intervention. Both FLC increased after the cessation of MCO use. There was no improvement in restless legs symptoms, quality of life, 6MWT or MIS scores. Conclusions: Regular HD using the MCO dialyzer did not result in a significant fall in serum albumin. There were no effects on quality of life, functional status or nutrition. Trial Registration: Australian New Zealand Clinical Trials Registry Number (ANZCTRN) 12616000804482. [ABSTRACT FROM AUTHOR]

Background: Secondary hyperparathyroidism (SHPT) in chronic kidney disease is associated with cardiovascular and bone pathology. Measures to achieve parathyroid hormone (PTH) target values and control biochemical abnormalities associated with SHPT require complex therapies, and severe SHPT often requires parathyroidectomy or the calcimimetic cinacalcet. In Australia, cinacalcet was publicly funded for dialysis patients from 2009 to 2015 when funding was withdrawn following publication of the EVOLVE study, which resulted in most patients on cinacalcet ceasing therapy. We examined the clinical and biochemical outcomes associated with this change at Australian renal centres. Aim: To assess changes to biochemical and clinical outcomes in dialysis patients following cessation of cinacalcet. Methods: We conducted a retrospective study of dialysis patients who ceased cinacalcet after August 2015 in 11 Australian units. Clinical outcomes and changes in biochemical parameters were assessed over a 24‐ and 12‐month period, respectively, from cessation of cinacalcet. Results: A total of 228 patients was included (17.7% of all dialysis patients from the units). Patients were aged 63 ± 15 years with 182 patients on haemodialysis and 46 on peritoneal dialysis. Over 24 months following cessation of cinacalcet, we observed 26 parathyroidectomies, 3 episodes of calciphylaxis, 8 fractures and 50 deaths. Eight patients recommenced cinacalcet, meeting criteria under a special access scheme. Biochemical changes from baseline to 12 months after cessation included increased levels of serum PTH from 54 (interquartile range 27–90) pmol/L to 85 (interquartile range 41–139) pmol/L (P < 0.0001), serum calcium from 2.3 ± 0.2 mmol/L to 2.5 ± 0.1 mmol/L (P < 0.0001) and alkaline phosphatase from 123 (92–176) IU/L to 143 (102–197) IU/L (P < 0.0001). Conclusion: Significant increases in serum PTH, calcium and alkaline phosphatase occurred over a 12‐month period following withdrawal of cinacalcet. Longer‐term follow up will determine if these biochemical and therapeutic changes are associated with altered rates of parathyroidectomies and cardiovascular mortality and morbidity. [ABSTRACT FROM AUTHOR]

Background: There are limited published data on the types and appropriateness of oral and intravenous (IV) antibiotics prescribed to patients receiving haemodialysis. This information is critical to optimise antibiotic prescribing. Therefore this study aims to describe the patterns of use and the appropriateness of oral and IV antibiotics prescribed to patients receiving haemodialysis.Methods: This was a prospective, observational study across four community and two hospital inpatient haemodialysis units in Melbourne, Australia. Data were collected from July 2014 to January 2015 from participants. Antibiotic regimens prescribed were compared with nationally available antibiotic guidelines and then classified as being either appropriate, inappropriate or not assessable by an expert multidisciplinary team using the National Antimicrobial Prescribing Survey tool.Results: Overall, 114 participants consented to this study where 55.3% (63/114) received antibiotics and 235 antibiotic regimens were prescribed at a rate of 69.1 antibiotic regimens/100 patient-months. The most common oral antibiotics prescribed were amoxycillin/clavulanic acid and cephalexin. The most common IV antibiotics prescribed were vancomycin, piperacillin/tazobactam, cephazolin and ceftriaxone. The percentage of inappropriate antibiotic regimens prescribed were 34.9% (15/43) in the community setting and 22.1% (40/181) in the hospital setting. Furthermore, 29.4% (30/102) of oral and 20.5% (25/122) of IV antibiotic regimens were inappropriate with incorrect dosing as the primary reason.Conclusion: Although this study is limited by the sample size, it describes the high antibiotic exposure that patients receiving haemodialysis experience. Of concern is inappropriate dose and frequency being a major issue. This requires interventions focused on the quality use of medicines and antimicrobial stewardship aspects of prescribing in this population. [ABSTRACT FROM AUTHOR]