Patient data collected through registries has been used to evaluate important outcomes in patients with Autosomal Recessive PKD (ARPKD), highlighting the importance of registries to determine best practice for patients and to inform research.
ARegPKD is an international registry that aims to gather the largest collection of detailed longitudinal data on clinical ARPKD courses worldwide, in order to contribute to the fight against this life-threatening disorder(1). Comprehensive prenatal, perinatal, and postnatal information was captured from 385 patients from ARegPKD and analysed for potential risk markers for dialysis during the first year of life. Identifying these risk factors may be helpful in prenatal parental counselling in cases of suspected ARPKD(2).
Conducting studies in rare diseases such as ARPKD and paediatric ADPKD are by nature difficult for many reasons. Registries can help determine optimal management plans and are an important aspect in the path forward for PKD. In the research of rare disease, patient registries have been described as the best tool to close the gap between research and therapeutics(3).
2. Risk Factors for Early Dialysis Dependency in Autosomal Recessive Polycystic Kidney Disease. Burgmaier, KathrinRanguelov, Nadejda et al. The Journal of Pediatrics, Volume 199, 22 – 28.e6
3. EURODIS NORD CORD, Joint Declaration of 10 Key Principles for Rare Disease Patient Registries
PKDA was a signatory last year on a call to the Federal Government to make dialysis more accessible for indigenous patients.
Representing PKDA at the meeting, Helen and Robert heard from experts and indigenous patients that the pressures of undergoing long-term dialysis far from home, away from their families and cultural commitments, can be so great for some Indigenous patients that they would rather die. Patients said that many people were dying a lonely death in cities and towns because of the poor accessibility of treatment centres in remote communities.
Helen expressed her shock and disappointment: “It’s a renal emergency. Why is it happening, and why has it existed for so long?”
Now, the Government has pledged to spend $57.8 million for dialysis in remote communities to help Indigenous patients stay at home.
Helen and Robert said of the Indigenous Patients Voices Forum at the time “it’s been an amazing privilege to be here, especially today, and to hear all of your stories. They’re so powerful and so moving, and I think it takes tremendous courage to stand up and speak from the heart as so many people have done.”
It was the voices, hard work and determination of these strong people and communities, their carers and their supporters that has led to this great outcome, a step towards equitable outcomes for all kidney patients.
As the 2018 Budget was announced we welcomed the new investment into health. A few words stood out to us from the Health Budget: Rare, genetic and chronic.
To us Rare genetic and chronic = PKD. So, we put together a wish list of what we hope the 2018 health Budget could mean for PKD.
“The Government will deliver $6 billion in record funding for Australia’s health and medical research sector, including $3.5 billion for the National Health and Medical Research Council, $2 billion in disbursements from the Medical Research Future Fund and $500 million from the Biomedical Translation Fund.”
Dr Gopala Rangan (the chair of our SAB) is the lead investigator of the PREVENT-ADPKD clinical trial which is funded by NHMRC.
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
Click the button below to watch the video.Watch Video