The new trial, using water to treat PKD, known as PREVENT-ADPKD is led by Dr Annette Wong, Carly Mannix, Professor David Harris and Dr Gopi Rangan at the Westmead Hospital and the Westmead Institute for Medical Research.
The trial will investigate whether drinking the right amount of water can prevent adult polycystic kidney disease (ADPKD) progressing to kidney failure.
“A positive study result will show that water is a cheap, safe and effective treatment,” Dr Rangan explained.
Story originally published by the Westmead Institute for Medical Research, republished on our website with their permission. Photo: Dr Gopi Rangan and his team from the Westmead Institute and the Westmead Hospital from Westmead Medical Research Foundation
The aim was to develop a new test that uses whole genome sequencing (WGS) to diagnose autosomal dominant polycystic kidney disease (ADPKD). Sequencing genes to determine a causative mutation in ADPKD is difficult using traditional gene sequencing methods.
This is due to six ‘pseudogenes’ – which are non-functional genes, almost identical in DNA sequence to the causative genes. Dr Mallawaarachchi and a team of clinicians and scientists trialled WGS and found it more detailed and accurate than current testing. This has led to the establishment of a genetic test for Australian ADPKD families. More accessible genetic testing will allow patients to be diagnosed sooner, allow families to better inform their family planning decisions, help to predict prognosis and allow better selection of living kidney donors for kidney transplantation.
In the long term, improved genetic testing will accelerate our understanding of the underlying cause of ADPKD – an important step in finding a cure. To read Dr Mallawaarachchi final report please see here.
Our bodies depend on a hormone called vasopressin to regulate fluid balance. When our bodies are not hydrated more of the hormone, vasopressin is produced. High vasopressin levels (which occur when we don’t get enough fluid) have been linked to cyst growth in ADPKD. Drinking more fluid can reduce vasopressin levels and may slow the progression of ADPKD.
Tolvaptan is a selective vasopressin type 2 receptor inhibitor and blocks vasopressin’s actions at the cellular level. Results from the Phase 3 REPRISE trial of tolvaptan, which was conducted in 21 countries for treatment of ADPKD were announced late last year by Otsuka Pharmaceutical (Otsuka).
In the REPRISE trial, Tolvaptan reduced the rate of decline of kidney function by 35 percent over a 12-month period, compared to the placebo. These results built upon their previous trial, known as TEMPO 3:4. The REPRISE trial focused on ADPKD patients with more severe kidney disease than those in the TEMPO 3:4 trial. To summarise the TEMPO 3:4 trial, Tolvaptan, when given over a period of 3 years, slowed the increase in total kidney volume and the decline in kidney function (as measured by glomerular filtration rate). Key safety findings were generally consistent in both the REPRISE and TEMPO 3:4 trial.
In these two trials patients who received tolvaptan had a higher frequency of adverse events such as excessive thirst, increased urine production and urination during the night. Furthermore, Tolvaptan led to more instances of increased liver-enzyme levels, which resolved after the discontinuation of the drug. Those who received placebo had higher frequencies of adverse events related to ADPKD, such as kidney pain, haematuria (blood in the urine), urinary tract infection and back pain.
The Australian PBS listing application for Tolvaptan will be reviewed at the March 2018 meeting of the Pharmaceutical Benefits Advisory Committee (PBAC). As part of the review process, the PBAC welcomes input from patients and their families, carers, members of the public, health professionals and members of consumer interest groups. These submissions provide accounts of how the medication under consideration will impact the lives of individuals.
To complete the consumer input form, please go to the PBAC online submission form. Or you may write a letter to the PBAC at the following addresses:
Mail: PBAC Secretariat MDP 952, Department of Health and Ageing GPO Box 9848 Canberra ACT 2601
Facsimile: (02) 6289 4175
The Outcomes of the PBAC meeting will be available on the PBS website six (6) weeks after the meeting. Public submissions for medicines being considered at the March 2018 meeting will be received up until the deadline date of 7 February 2018.
Sources: 1: Torres, V. E. et al. Tolvaptan in patients with autosomal dominant polycystic kidney disease. N. Engl. J. Med. 367, 2407–2418 (2012). 2: Torres, V. E. et al. Tolvaptan in later-stage autosomal dominant polycystic kidney disease. N. Engl. J. Med. 377, 1930–1942 (2017) 3: van Gastel M, D, A, Torres V, E, Polycystic Kidney Disease and the Vasopressin Pathway. Ann Nutr Metab 2017;70(suppl 1):43-50
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