The impact of peritoneal dialysis on oxypurinol and urate elimination in people with gout.

Gout affects 15%-30% of individuals with advanced kidney disease. Allopurinol which is rapidly and extensively metabolised to an active metabolite, oxypurinol, is the most commonly prescribed urate-lowering therapy. Oxypurinol is almost entirely eliminated by the kidneys (>95%) and has an elimination half-life of 18-30 h in those with normal kidney function. However, oxypurinol pharmacokinetics are poorly understood in individuals with kidney failure on peritoneal dialysis. This study characterised the elimination of oxypurinol and urate in people with gout receiving peritoneal dialysis. Oxypurinol steady-state oral clearance (CL/F), elimination half-life as well as kidney (CLk) and peritoneal (CLpd) clearances for oxypurinol and urate were calculated from the plasma, urine and dialysate concentration data for each individual. Our results demonstrate that oxypurinol and urate are removed by peritoneal dialysis, accounting for more than 50% of oxypurinol and urate clearances. An allopurinol dose about 50%-60% lower than the usual dose used for a patient with normal kidney function will provide adequate urate-lowering therapy.

Actioning the findings of hard endpoint clinical trials as they emerge in the realm of chronic kidney disease care: a review and a call to action.

Fewer than half of patients treated with hemodialysis survive 5 years. Multiple therapeutics are used to address the complications of advanced chronic kidney disease but most have not been found to improve clinical outcomes. Clinical trials of treatment innovations for chronic kidney diseases and dialysis care have been suboptimal in number and quality. Recent trials are changing this trend. Practice and policy change when new evidence emerges remains frequently impeded by resource and organizational constraints and accordingly, clinical practice guidelines are updated years or decades after definitive evidence is produced. Ultimately, practice change in health systems is slow, leading to impaired uptake of effective medical interventions and lower value healthcare, although innovations in rapid guideline production are emerging. What can be done to ensure that conclusive evidence is taken up in practice, policy and healthcare funding? We use the example of the recently published hard endpoint study "Comparison of high-dose HDF with high-flux HD" (CONVINCE) (hemodiafiltration versus hemodialysis), to explain how a new trial can impact on medical knowledge and change in practices. We (i) assess how the trial can be placed in the context of the totality of the evidence, (ii) define whether or not further trials of convective dialysis therapies are still needed and (iii) examine whether the evidence for convective therapies is now ready to inform practice, policy and funding change. When looking at CONVINCE in the context of the totality of evidence, we show that it addresses dialysis quality improvement priorities and is consistent with other trials evaluating convective dialysis therapies, and that the evidence for convective dialysis therapies is now definitive. Once updated evidence for cost-effectiveness in specific healthcare settings and patient-reported outcomes become available, we should therefore determine whether or not clinical practice guidelines should recommend uptake of convective dialysis therapies routinely, and move on to evaluating other treatments.

Management of chronic kidney disease for Maori in Aotearoa New Zealand: a summary of clinical practice guidelines.

AIMS: The kaupapa of the Caring for Australians and New Zealanders with Kidney Impairment (CARI) Clinical practice guidelines for management of chronic kidney disease for Maori in Aotearoa New Zealand is to provide whanau-centred and evidence-based recommendations to healthcare systems, healthcare providers and healthcare workers. The guidelines include screening, identification, management and system-level responses to chronic kidney disease (CKD) to deliver best practice care to Maori affected by CKD across community, primary and secondary services. METHODS: The guidelines are funded by the Ministry of Health - Manatu Hauora and are written by a panel of Maori and non-Maori clinicians and literacy experts across Aotearoa New Zealand from Kaupapa Maori organisations, general practice and nephrology units using standardised methods. The guidelines methodology included consultation with whanau Maori with lived experience of CKD and primary and secondary care practitioners. Additional guideline development would be required to inform management of CKD for non-Maori in Aotearoa New Zealand. RESULTS: The guidelines provide recommendations about equity, governance and accountability, cultural safety, case management, information systems, social determinants of equity and wellbeing and screening. CONCLUSIONS: Recommendations to health services for Maori with CKD are based on giving effect to Te Tiriti o Waitangi and best practice care to prevent CKD, delaying its progression, treating kidney failure through timely transplantation, delivering in community and providing high-quality symptom management.