Joint meeting of the Kidney in Health and Disease Network and the Renal
Scientists Group of the Australian and New Zealand Society of Nephrology
The Kidney: Present and Future
11-12th December 2020
Scenic Hotel, Blenheim, Marlborough, New Zealand
This is an interactive scientific meeting open to all those interested in Kidney function in
health and disease.
We wish to acknowledge with thanks the support of the Maurice and Phyllis
Paykel Trust
PROGRAM
Thursday 10th December
6.30-8.00 pm
Welcome reception Chart room, Scenic Hotel
Friday 11th December
9.30 am Registration
10.00-
10.15 am
Health and safety
Conference Welcome
STUART SMITH, MP for Kaikoura
10.15-
10.45am
Session 1: New Science
Chair: Rob Walker
ROB MACGINLEY
Checkpoint inhibitors – a new success with a new problem
Eastern Health Clinical School, Monash University, Melbourne, Australia
10.45-
11.00am Morning tea break
Session 2: Developmental nephrology and genetics
Chair: Rob Walker
11.00-
11.20am
VERONIKA SANDER, JENNY DIGBY, THITINEE VANICHAPOL,
ALAN J. DAVIDSON
Using kidney organoids to model cisplatin-induced nephrotoxicity
Department of Molecular Medicine and Pathology, University of Auckland, NZ
11.20-
11.40am
CHERIE STAYNER1, SARAH BOWDEN1,2, EUAN RODGER1,3,
ANIRUDDHA CHATTERJEE1,3, MICHAEL ECCLES1,3
What does DNA methylome analysis tell us about ADPKD? 1Department of Pathology, Dunedin School of Medicine, University of Otago,
Dunedin, New Zealand, 2Renal Division, Department of Medicine, University
Hospital Freiburg, Freiburg University Faculty of Medicine, Germany, 3Maurice
Wilkins Centre for Molecular Biodiscovery, Auckland, New Zealand
11.30-
12.00pm
MEGAN LEASK1,2, NICHOLAS SUMPTER1,2, ALEXA LUPI3, JUSTIN
O’SULLIVAN4, TAYAZA FADASON4, MATT BIXLEY1, AMANDA
PHIPPS-GREEN1, MURRAY CADZOW1, MARILYN MERRIMAN1,
RUTH TOPLESS1, LISA STAMP5, NICOLA DALBETH6, ANA
VAZQUEZ3, RICHARD REYNOLDS2, TONY MERRIMAN1,2
Decoding GWAS to combat renal disease in Māori and Pacific 1Biochemistry Department, University of Otago, Dunedin, NZ, 2University of Alabama
at Birmingham, Birmingham, Alabama, USA, 3Department of Epidemiology and
Biostatistics, Michigan State University, East Lansing, Michigan, USA, 4Liggins
Institute, University of Auckland, Auckland, NZ, 5Department of Medicine, University
of Otago, Christchurch, NZ, 6Department of Medicine, University of Auckland,
Auckland, NZ
12.00-
1.10pm Lunch break
Session 3: Pharmacology
Chair: Cherie Stayner
1.10-
1.30pm
H PILMORE1, N CROSS2, J SCHOLLUM3, C HOOD4, A SALMON5
(NEW ZEALAND INVESTIGATORS)
CARSK study (Canadian-Australasian randomised trial of
screening kidney transplant candidates for coronary artery
disease) 1Auckland District Health Board, Auckland, New Zealand; 2Canterbury District
Health Board, Christchurch, New Zealand, 3Southern District Health Board,
Dunedin, New Zealand; 4Counties Manukau District Health Board Renal, Auckland,
New Zealand; 5Waitemata District Health Board Renal Services, Auckland, New
Zealand
1.30-
1.50pm
ISABELLE H.S. KUAN1, LUKE C. WILSON2, JED C. LEISHMAN2,
SAMUEL COSGROVE2, ROBERT J. WALKER2, TRACEY L. PUTT2,
JOHN B.W. SCHOLLUM2, DANIEL F.B. WRIGHT1.
Metformin dosing in kidney impairment 1School of Pharmacy, Otago Medical School, University of Otago, Dunedin, New
Zealand, 2Department of Medicine, Otago Medical School, University of Otago,
Dunedin, New Zealand
Session 4: Physiology
Chair: Reshma Shettigar
1.50-
2.10pm
JENNIFER A HOLLYWOOD, PANG YUK CHEUNG, ALAN J
DAVIDSON
A new rat model to study the rare kidney disease, cystinosis
Department of Molecular Medicine and Pathology, University of Auckland
2.10-
2.30pm
PANG YUK CHEUNG, JENNIFER HOLLYWOOD, ALAN J.
DAVIDSON
Optimisation of oral cysteamine dosing in ctns knockout rats
Department of Molecular Medicine and Pathology, University of Auckland,
Auckland, New Zealand
2.30-
2.50pm
SHAH, V.K, FRONIUS, M.
Increased expression of epithelial sodium channel affects
mechanical properties of endothelial cells by reorganising the f-
actin cytoskeleton.
Department of Physiology and Heart Otago, University of Otago, Dunedin, New
Zealand
2.50-
3.20 Afternoon tea break
Session 5: Trainee Presentations
Chair: Tracey Putt
3.20-
3.40pm
QINGHUA CAO1, HAO YI1, ANTHONY J. GILL2, MICHAEL
FOLEY3,4, CHUNLING HUANG1, XIN-MING CHEN1, CAROL A.
POLLOCK1
A unique Fc-Fusion protein i-body AD-214 ameliorated kidney
fibrosis 1Kolling Institute of Medical Research, Royal North Shore Hospital, Sydney Medical
School, University of Sydney, Sydney, New South Wales, Australia, 2Department of
Anatomical Pathology, NSW Health Pathology, Royal North Shore Hospital, Sydney,
NSW, Australia, 3AdAlta Pty. Ltd., 15/2 Park Dr., Bundoora, Victoria, Australia, 4Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science,
La Trobe University, Melbourne, Victoria, Australia
3.40-
4.00pm
AMELIA TEKITEKI, TINA SUN, HLA THEIN
Reviewing the perioperative calcium management post
parathyroidectomy in renal patients at Middlemore Hospital
Renal Department, Middlemore Hospital, Auckland, New Zealand; Renal
Department, Auckland City Hospital, Auckland, New Zealand
4.00-
4.20pm
SHETTIGAR R1, SCHOLLUM J2, DERETT S3, SAMARNAYAKA A3,
WALKER R2.
Predictors of health outcomes in elderly dialysis patients. 1Department of Nephrology, Christchurch Hospital, Christchurch, NZ, 2Department
of Nephrology, Dunedin Hospital, Dunedin, NZ, 3Department of Preventative and
Social Medicine, University of Otago, Dunedin, NZ
7.00 pm
Conference dinner:
Arbour Restaurant
(bus leaves from outside the Scenic hotel at
6.45 pm)
Saturday 12th December
Session 6: Cardiology
Chair: Megan Leask
9.00-
9.20 am
LEADER, C., WILKINS, G., WALKER, R.
Effect of spironolactone on cardiac and renal fibrosis following
myocardial infarction in a rat model with established
hypertension
Department of Medicine, University of Otago, Dunedin, New Zealand
9.20-
9.40am
PUJA PAUDEL1,2, FIONA J MCDONALD1, MARTIN FRONIUS1,2
Role of vascular ENaC in human hypertension 1Department of Physiology, University of Otago, Dunedin, New Zealand; 2HeartOtago, University of Otago, Dunedin, New Zealand
9.40-
10.00am
GROUND, M.B.1, WAQANIVAVALAGI, S.W.F.R.2,3, MILSOM, P.F.4,
WALKER, R.J.1, CORNISH, J.2
Optimising recellularisation of tissue engineered heart valves 1Department of Medicine, Dunedin School of Medicine, University of Otago, Dunedin,
New Zealand, 2Department of Medicine, Faculty of Medical and Health Sciences,
University of Auckland, Auckland, New Zealand, 3Adult Emergency Department,
Auckland City Hospital, Auckland District Health Board, Auckland, New
Zealand,4Green Lane Cardiothoracic Surgical Unit, Auckland City Hospital,
Auckland District Health Board, Auckland, New Zealand
Session 7: Clinical Trials Update
Chair: Suetonia Palmer
10.00-
10.10 am
DE ZOYSA, J.R.1, 2; GALLAGHER, M.3,4; WALSH, M.5, 6, 7 FOR THE
ACHIEVE INVESTIGATORS.
ACHIEVE: Aldosterone blockade for health improvement
evaluation in end-stage renal disease. 1Renal Service, Waitemata District Health Board, Auckland, New
Zealand;2Department of Medicine, University of Auckland, Auckland, New
Zealand;3The George Institute for Global Health, University of New South Wales,
Sydney, Australia; 4Concord Repatriation and General Hospital, Sydney,
Australia;5Department of Medicine, McMaster University, Hamilton, Canada; 6Population Health Research Institute, McMaster University/Hamilton Health
Sciences, Hamilton, Canada;7Department of Health Research Methods, Evidence and
Impact, McMaster University, Hamilton, Canada
10.10-
10.20 am
DE ZOYSA, J.R.1, 2; YOUNG, T.3; KRISHNASAMY R.4, 5, JARDINE
M.J.6,7 FOR THE BEAT-CALCI INVESTIGATORS.
BEAT-CALCI: Better evidence and translation for calciphylaxis 1 Renal Service, Waitemata District health Board, Auckland, New Zealand; 2Department of Medicine, University of Auckland, New Zealand;3 The George
Institute for Global Health, Sydney, Australia;4 Sunshine Coast University Hospital,
Queensland, Australia;5 Australasian Clinical Trials Network, University of
Queensland, Australia;6NHMRC Clinical Trials Centre, the University of Sydney,
Australia;7 Concord Repatriation General Hospital, Sydney, Australia
10.20-
10.50 am
M.MARSHALL1, M. J WOLLEY2, T. M MA2, S. CURD1, D. KUMAR1,
S. LEE1, K.PIREVA1, O. TAULE’ALO1, P. TIAVALE1, A. L KAM2, J. S
SUH2, J. KENNEDY1, T. ASPDEN1
Medication adherence in dialysis patients at Middlemore Hospital
– mediators and moderators from a survey study 1School of Medicine, Faculty of Medical and Health Sciences, The University of Auckland,
Auckland, New Zealand, 2Counties Manukau District Health Board, Auckland, New Zealand
10.50-
11.20 am Morning tea break
Session 8: Lithium
Chair: Jennifer Hollywood
11.20-
11.40 am
JOHN LEADER
The multifarious actions of lithium in biological systems
Department of Medicine, Dunedin School of Medicine, University of Otago,
Dunedin, New Zealand
11.40
12.10 pm
ROBERT WALKER1, JENNY BEDFORD1, JOHN LEADER1,
PAULOMI MEHTA2, TANIA SLATTER2, RICHARD COWARD3
Lithium induced kidney injury 1Department of Medicine, Dunedin School of Medicine, University of Otago,
Dunedin, New Zealand; 2Department of Pathology, Dunedin School of Medicine,
University of Otago, Dunedin, New Zealand; 3Bristol Renal, Dorothy Hodgkin
Building, University of Bristol, Bristol, United Kingdom
12.10-
12.30 pm
MEHTA PM1, GREGORY GIMINEZ1, SLATTER TL1, WALKER RJ2
Investigating pathways in lithium induced chronic kidney disease. 1Department of Pathology, Otago Medical School, Dunedin, New Zealand; 2Department of Medicine, Otago Medical School, Dunedin, New Zealand
12.30-
1.30 pm Lunch
Session 8: Clinical Trials continued
Chair: Amelia Tekiteki and Veronika Sander
1.30-
1.50pm
FRANCIS, A.
Understanding the life course and impact of ESDK during
childhood.
Child and Adolescent Renal Unit, Queensland Children’s Hospital, University of
Queensland, Brisbane, Australia
1.50-
2.10pm
ROBERT WALKER1, SUETONIA PALMER2, JANAK DE ZOYSA3,
DAVID JOHNSON4 on behalf of the AKTN investigators
The incremental dialysis to improve health outcomes in people
initiating haemodialysis (INCH-HD) 1Department of Medicine, University of Otago, Dunedin, New Zealand, 2Department
of Medicine, University of Otago, Christchurch, New Zealand; 3Renal Service,
Waitemata District Health Board, Auckland, New Zealand; 4Department of
Nephrology, Division of Medicine, Princess Alexandra Hospital, Queensland,
Australia
2.10-
2.30pm
DHARMENAAN PALAMUTHUSINGAM1,2,3, CARMEL M.
HAWLEY2,4, DAVID W. JOHNSON2,4,6, ELAINE PASCOE5, MAGID
FAHIM3,4,7
Perioperative risk and outcomes in patients on chronic kidney
replacement therapy – reconciling comorbidities in ANZDATA
and hospital admission datasets 1Metro South Integrated Nephrology and Transplant Services, Logan Hospital,
Queensland, Australia, 2Faculty of Medicine, University of Queensland, Australia, 3School of Medicine, Griffith University, Queensland, Australia, 4Metro South
Integrated Nephrology and Transplant Services Queensland, Australia, 5Centre for
Health Services Research, University of Queensland, Australia, 6Translational
Research Institute, Queensland, Australia, 7Metro North Hospital and Health Service,
Royal Brisbane and Women’s Hospital, Queensland, Australia
2.30-
2.50pm
PALMER, SC.1,2
Increasing capacity in kidney disease trials in New Zealand 1Department of Medicine, University of Otago, Christchurch, NZ, 2Department of
Nephrology, Canterbury District Health Board, Christchurch, NZ
2.50-
3.10pm
MICHAEL G COLLINS1, COLIN J MCARTHUR2, RACHAEL C
MCCONNOCHIE2, HELEN L PILMORE1, JOHN IRVINE3, CAROLYN
CLARK4 AND CHANEL PRESTIDGE5 (NEW ZEALAND BASED
INVESTIGATORS) ON BEHALF OF THE BEST-FLUIDS
INVESTIGATORS AND THE AUSTRALASIAN KIDNEY TRIALS
NETWORK (AKTN)
Better evidence for selecting transplant fluids (BEST-FLUIDS): A
pragmatic double-blind randomised controlled trial of plasmalyte-
148 versus 0.9% saline in deceased donor kidney transplantation 1Department of Renal Medicine, Auckland District Health Board, New
Zealand,2Department of Critical Care Medicine, Auckland District Health
Board;3Department of Nephrology, Canterbury District Health Board, New Zealand; 4Department of Nephrology, Capital and Coast District Health Board, Wellington,
New Zealand; 5Department of Pediatric Nephrology, Starship Hospital, Auckland
District Health Board, New Zealand
3.10-
3.30pm Closing comments: Rob Walker
7pm Closing Dinner:
Dodson Street Beer Garden
Abstracts:
Depicted is William E. Clarke’s colourful and dramatic trade cards used to advertise Hunt’s
Remedy (1872-1881) - a cure-all wonder drug. The front of the card shows a hale and hearty
male patient wielding a bottle of Hunt’s Remedy against death, personified as a skeleton
with a scythe and hourglass. The reverse lists no end of ailments against which the wonder
drug has “never been known to fail,” including back pain, kidney problems, and “female
diseases.” Little is known about the ingredients in Hunt’s Remedy beyond the claim made
on the back of Clarke’s trade card that it was “purely vegetable” and based on a recipe that
descended from the original Dutch inhabitants of New Amsterdam. Hunt’s Remedy was
still being sold as late as 1908, when a Kansas State Board of Health Report described it as
“a brown solution of bitter vegetable drugs, containing 17.2% alcohol.”
A UNIQUE FC-FUSION PROTEIN I-BODY AD-214 AMELIORATED KIDNEY
FIBROSIS
QINGHUA CAO1, HAO YI1, ANTHONY J. GILL2, MICHAEL FOLEY3,4, CHUNLING
HUANG1, XIN-MING CHEN1, CAROL A. POLLOCK1
1Kolling Institute of Medical Research, Royal North Shore Hospital, Sydney Medical School, University of
Sydney, Sydney, New South Wales, Australia; 2Department of Anatomical Pathology, NSW Health Pathology, Royal North Shore Hospital, Sydney, NSW,
2065, Australia; 3AdAlta Pty. Ltd., 15/2 Park Dr., Bundoora, Victoria, Australia; 4Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University,
Melbourne, Victoria, Australia.
Aim: To define the role of i-body AD-214 in renal fibrosis.
Background: Tissue fibrosis is the common pathological pathway in progressive chronic
kidney disease (CKD). Current clinical practices are ineffective in limiting renal fibrosis.
CXCR4 has been demonstrated to be central to the development of fibrosis. I-body AD-
214, a redesigned form of i-body AD-114, is an Fc-Fusion protein that contains two AD-
114 i-body molecules that bind with high affinity to CXCR4. The Fc Fragment of AD-214
greatly extends its half-life and therefore efficacy. AD-214 has been shown to be effective
in limiting lung fibrosis. However, the role of AD-214 in renal fibrosis has not been
investigated.
Methods: PTC cells were incubated with TGFβ1 (2ng/ml) with/without AD-214 (1M or
2M) for 48 hours. Supernatant was collected and collagen 3 (Col 3) and collagen 4 (Col
4) were measured by Western blot. Mice with unilateral ureteral obstruction (UUO) were
administrated AD-214 every two days starting from one day after UUO for 14 days.
Changes in renal morphology were examined by H&E staining. Renal histology, mRNA,
analysed by qRT-PCR and extracellular matrix (ECM) protein expression detected by
immunohistochemistry (IHC) were examined.
Results: AD-214 (2µM) suppressed TGFβ1-induced overexpression of Col 3 and Col 4
compared to a negative control i-body (P<0.05, n=4). In UUO model, AD-214 markedly
ameliorated fibrotic kidney remodeling (P<0.05) and attenuated the UUO-induced
overexpression of ECM including fibronectin (P<0.05) and collagens (P<0.05) in kidneys
compared to negative control i-body (n=6-8).
Conclusions: Blocking CXCR4 using the i-body AD-214 is a promising therapeutic
strategy to prevent the development of CKD.
OPTIMISATION OF ORAL CYSTEAMINE DOSING IN CTNS KNOCKOUT
RATS
PANG YUK CHEUNG, JENNIFER HOLLYWOOD, ALAN J. DAVIDSON
Department of Molecular Medicine and Pathology, University of Auckland, Auckland, New Zealand.
Nephropathic cystinosis is a rare lysosomal storage disorder caused by mutations in CTNS,
which encodes for the cystine transporter, cystinosin. Loss of cystinosin results in the
accumulation of cystine within the lysosomes of all cells of the body. Although cystinosis
is a systemic disease, the kidney is the first organ affected with proximal tubule dysfunction
followed by renal failure if left untreated. Patients receive a cystine-depleting drug
cysteamine from diagnosis, however, despite life-long treatment cysteamine only slows the
progression of renal failure with the need for transplant inevitable. Therefore, there is an
urgent need to develop better therapies for cystinosis. We have previously shown that
combination treatment of cysteamine and the mTOR inhibitor, everolimus, was able to
rescue the cystinotic phenotype in our induced pluripotent stem cell and kidney organoid
models. To evaluate the therapeutic potential of this therapy in vivo, we will perform pre-
clinical testing in our rodent model of cystinosis which faithfully recapitulates the human
conditon. To determine any synergistic effect everolimus may have we first set out to
identify the optimal dose of cysteamine that results in a 50% reduction of cystine levels.
Cysteamine is a difficult drug as it has a very short half-life (6hrs), has an unpleasant
sulphur odour and causes nausea at higher doses. To overcome the distastefulness we
delivered the drug in raspberry flavoured jelly pills. Following conditioning, Ctns KO rats
were fed cysteamine in jelly pills twice daily for 10 days. On the final day of treatment,
blood and tissues were harvested and cystine levels measured using HPLC-MS/MS. Ctns
KO rats tolerated cysteamine in a dose dependant manner with higher doses resulting in
avoidance or incomplete consumption of the jelly pill most likely owing to the unpleasant
sulphur odour of the drug. There was a 50% decrease in cystine levels in some tissues
including the kidney, however, further optimisation is required. If successful, this study
will pave the way for better treatments for cystinosis patients.
BETTER EVIDENCE FOR SELECTING TRANSPLANT FLUIDS (BEST-
FLUIDS): A PRAGMATIC DOUBLE-BLIND RANDOMISED CONTROLLED
TRIAL OF PLASMALYTE-148 VERSUS 0.9% SALINE IN DECEASED DONOR
KIDNEY TRANSPLANTATION
MICHAEL G COLLINS1, COLIN J MCARTHUR2, RACHAEL C MCCONNOCHIE2, HELEN
L PILMORE1, JOHN IRVINE3, CAROLYN CLARK4, CHANEL PRESTIDGE5 (NEW
ZEALAND BASED INVESTIGATORS) ON BEHALF OF THE BEST-FLUIDS
INVESTIGATORS AND THE AUSTRALASIAN KIDNEY TRIALS NETWORK (AKTN)
1Department of Renal Medicine, Auckland District Health Board, Auckland, New Zealand; 2Department of Critical Care Medicine, Auckland District Health Board, Auckland; 3Department of Nephrology, Canterbury District Health Board, Christchurch, New Zealand; 4Department of Nephrology, Capital and Coast District Health Board, Wellington, New Zealand; 5Department of Paediatric Nephrology, Starship Hospital, Auckland District Health Board, Auckland, New
Zealand
BEST-Fluids is an investigator-initiated, pragmatic, registry-based, multi-centre, double-
blind, randomised controlled trial. The primary objective is to compare the effect of
intravenous fluid therapy with Plasma-Lyte 148 (Plasmalyte), a balanced, low-chloride
solution, with the effect of 0.9% saline on the incidence of delayed graft function (DGF) in
deceased donor kidney transplant recipients.
Participants admitted for deceased donor kidney transplantation at participating hospitals
are invited to participate. Participants are randomized 1:1 to either intravenous Plasmalyte
or 0.9% saline peri-operatively and until 48 h post-transplant, or until fluid was no longer
required; whichever came first. Follow up is for 1 year. The primary outcome is the
incidence of delayed graft function, defined as dialysis in the first 7 days post-transplant.
Secondary outcomes include early kidney transplant function (composite of dialysis
duration and rate of improvement in graft function when dialysis is not required),
hyperkalaemia, mortality, graft survival, graft function, quality of life, healthcare resource
use, and cost-effectiveness. Participants are enrolled, randomized, and followed up using
the Australia and New Zealand Dialysis and Transplant (ANZDATA) Registry.
This presentation will provide an overview of the rationale and design of BEST-Fluids, and
an update on the current status of the trial. It will also review some of the lessons learned
through the conduct of the trial thus far.
UNDERSTANDING THE LIFE COURSE AND IMPACT OF ESKD DURING
CHILDHOOD.
FRANCIS, A.
Child and Adolescent Renal Unit, Queensland Children’s Hospital, University of Queensland, Brisbane,
Australia
Background
The 30-fold increased risk of mortality in children with kidney failure compared to the
general population is well known. However, we do not have a full understanding of the
lifecourse impact of CKD in childhood or young adulthood.
Aims
For children and young adults with kidney transplants in the modern transplant era: i) To
describe the incidence and risk factors of non-fatal cardiovascular events and serious
infections; ii) To describe the incidence and risk factors of cause-specific mortality; and iii)
To describe the burden of mental illness requiring inpatient admission.
Methods
This will require data linkage between ANZDATA and state and federal (AIHW) health
data, including admitted patient data from Australia and New Zealand. The incidence of
cause-specific hospitalization and death will be estimated using survival analysis,
accounting for the competing risk of (other causes of) death. Comparison with the general
age-matched population will be done via standardised incidence ratios and time trends
analysed using Poisson regression.
Conclusion
This comprehensive linked dataset will provide a rich source of data to understand the life
course impact of kidney failure early in life and hopefully reveal modifiable risk factors for
poor outcomes.
OPTIMISING RECELLULARISATION OF TISSUE ENGINEERED HEART
VALVES
GROUND, M.B.1, WAQANIVAVALAGI, S.W.F.R.2,3, MILSOM, P.F.4, WALKER, R.J.1,
CORNISH, J.2
1Department of Medicine, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand,
2Department of Medicine, Faculty of Medical and Health Sciences, University of Auckland, Grafton,
Auckland, New Zealand,
3Adult Emergency Department, Auckland City Hospital, Auckland District Health Board, Grafton, Auckland,
New Zealand, 4Green Lane Cardiothoracic Surgical Unit, Auckland City Hospital, Auckland District Health Board,
Grafton, Auckland, New Zealand
Current options for heart valve replacement are wanting. For the 300,000 patients
undergoing surgical aortic valve replacement annually1, the choice of prosthesis is between
a mechanical valve and the lifelong anticoagulation therapy it necessitates, or a tissue valve
with a lifespan of only 15 years2. Neither option is attractive to paediatric patients, who
must undergo multiple reoperations as they outgrow their prostheses. The world needs a
valve graft that is both durable enough to last a lifetime, and haemodynamically stable
enough to use without anticoagulants3. Ideally, this valve would support a population of
living autologous cells, giving the graft that ability to remodel and grow with the patient.
Tissue engineering may hold the solution. Our group has developed a decellularisation
protocol that effectively removes cellular material from animal tissue, leaving behind an
extracellular matrix scaffold: a tissue engineered heart valve (TEHV). We treated whole
porcine aortic roots and bovine pericardium with detergent and enzyme washes to remove
cellular material, rendering the tissue non-immunogenic. Effectiveness of the
decellularisation protocol was evaluated histologically, and by DNA quantification. The
retention of native biomechanical properties was also assessed.
Now our group is focused on recellularisation – the repopulating of the blank scaffold with
human cells. We have isolated and cultured human valvular interstitial cells from patients
undergoing valve replacement surgery at Auckland City Hospital. We have optimised the
culture conditions and demonstrated that molecular cues (namely FGF-2) are able to retain
these cells in their healthy phenotype. We hypothesise the combination of chemical and
mechanical stimulation in our novel bioreactor will ensure improved cell survival and
phenotype of cells seeded on our TEHV when compared to static culture conditions.
1. Cheung, D. Y., Duan, B., Butcher, J. T. Current progress in tissue engineering of heart valves:
multiscale problems, multiscale solutions. Expert Opin. Biol. Ther. 15, 1155–1172 (2015)
2. Baumgartner, H. et al. 2017 ESC/EACTS Guidelines for the management of valvular heart disease.
European Heart Journal vol. 38 (2017)
3. Nachlas, A. L. Y., Li, S. , Davis, M. E. Developing a Clinically Relevant Tissue Engineered Heart
Valve—A Review of Current Approaches. Adv. Healthc. Mater. 6, 1–30 (2017)
A NEW RAT MODEL TO STUDY THE RARE KIDNEY DISEASE, CYSTINOSIS
JENNIFER A HOLLYWOOD, PANG YUK CHEUNG, ALAN J DAVIDSON
1Department of Molecular Medicine and Pathology, University of Auckland, Auckland, New Zealand
The lysosomal storage disease nephropathic cystinosis results from mutations in CTNS,
encoding a cystine transporter, and initially causes kidney proximal tubule dysfunction
followed by kidney failure. Patients receive the drug-based therapy Cysteamine from
diagnosis, however, despite long-term treatment, patients still progress to kidney failure
with the need for transplant inevitable. There is an urgent need for alternative treatments as
there is increasing evidence that secondary complications are associated with loss of CTNS
that are unrelated to the accumulation of cystine. Using our stem cell and kidney organoid
model we have discovered a drug combination (Cysteamine + Everolimus) that ‘rescues’
cystinotic cells in vitro. To evaluate the therapeutic potential of this therapy, pre-clinical
testing in a rodent model of cystinosis is required. As there are limitations associated with
current animal models that make them unsuitable for drug trials, we have utilised gene-
editing to generate a cystinotic rat model. These rats display classic hallmark characteristics
of a cystinosis phenotype within 3-6 months as seen by: failure to gain weight, excessive
thirst and urination, cystine accumulation and kidney dysfunction. In depth urine analysis
revealed high levels of glucose, calcium, albumin and total protein are being excreted at 6
months (consistent with the onset of Fanconi syndrome) as well as progressive diminution
of urea and creatinine clearance indicative of chronic kidney damage. Slit lamp
examination of the eyes of 3-month old animals revealed the presence of cystine crystals
and histology shows the presence of ‘swan neck’ lesions in kidney tissues both hallmarks
of cystinosis disease. This novel rat model offers the promise of faithfully recapitulating
the human disease and facilitating the testing of new treatment regimens.
EFFECT OF SPIRONOLACTONE ON CARDIAC AND RENAL FIBROSIS
FOLLOWING MYOCARDIAL INFARCTION IN A RAT MODEL WITH
ESTABLISHED HYPERTENSION
LEADER, C., WILKINS, G., WALKER, R.
Department of Medicine, University of Otago, Dunedin, New Zealand
Patients with a myocardial infarction (MI) often have a history of hypertension, both
exacerbating the development of renal dysfunction and failure (cardiorenal syndrome). The
RAAS has been shown to play a key role, and while mineralocorticoid receptor blockade
has been revealed to be beneficial in cardiac dysfunction, it is less well quantified in renal
disease or cardiorenal syndrome. This study investigated the development of cardiac and
renal fibrosis following MI in animals with established progressive hypertension (more
accurately representing the clinical setting), and whether spironolactone can modify this.
Hypertension was established and maintained in Cyp1a1Ren2 rats. Hypertensive animals
underwent MI surgery before being treated with a clinically relevant daily dose of
spironolactone and monitored for 28 days (including systolic blood pressure (SBP),
echocardiograms and metabolic studies). Cardiac and renal tissue was extracted for
histological and immunohistochemical comparative analysis.
Superimposing a MI on established hypertension resulted in a significant increase, above
hypertension alone, in remote interstitial cardiac fibrosis (p<0.001), renal cortical
interstitial fibrosis (p<0.01) and glomerulosclerosis (p<0.01). Increased fibrosis was
accompanied a significant increase in myofibroblasts and macrophage infiltration in both
the heart and the kidney, and a decline in kidney function. In comparison, treatment with
spironolactone after MI, significantly diminished the progression of fibrosis (p<0.001) and
inflammation (myofibroblasts (p<0.05) and macrophages (p<0.01)) in both the heart and
the kidney, even with the persistently elevated SBP (182±19 mmHg). However, despite
the reduction in inflammation and fibrosis, spironolactone did not modify ejection fraction,
proteinuria, or renal function when compared to untreated animals with a MI.
By establishing hypertension before superimposing myocardial infarction, we created a
progressive model of cardiorenal dysfunction more closely representing that seen in a
clinical setting. The addition of an equivalent clinically relevant dose of spironolactone in
this model, blunted the progression of cardiac and kidney fibrosis which was associated
with reduced cardiac and kidney inflammatory infiltration by myofibroblasts and
macrophages.
THE MULTIFARIOUS ACTIONS OF LITHIUM IN BIOLOGICAL SYSTEMS
JOHN LEADER
Department of Medicine, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand
Lithium is the smallest of the cations, formed early in the Big Bang. Although lithium
concentration is not required in the body, it has many interactions with proteins. Here we
shall review the known biological effects of lithium and what is known about its mechanism
of action.
DECODING GWAS TO COMBAT RENAL DISEASE IN MĀORI AND PACIFIC
MEGAN LEASK1,2, NICHOLAS SUMPTER1,2, ALEXA LUPI3, JUSTIN O’SULLIVAN4,
TAYAZA FADASON4, MATT BIXLEY1, AMANDA PHIPPS-GREEN1, MURRAY
CADZOW1, MARILYN MERRIMAN1, RUTH TOPLESS1, LISA STAMP5, NICOLA
DALBETH6, ANA VAZQUEZ3, RICHARD REYNOLDS2, TONY MERRIMAN1,2
1. Biochemistry Department, University of Otago, Dunedin, NZ
2. University of Alabama at Birmingham, Birmingham, Alabama, USA
3. Department of Epidemiology and Biostatistics, Michigan State University, East Lansing, Michigan, USA
4. Liggins Institute, University of Auckland, Auckland, NZ
5. Department of Medicine, University of Otago, Christchurch, NZ
6. Department of Medicine, University of Auckland, Auckland, NZ
Previous large genome-wide association studies (GWAS) have identified dozens of
genomic regions (loci) that influence both serum urate levels and renal function (eGFR and
sCr) indicating a shared genetic etiology that is consistent with clinical and observational
data. The large majority of these loci are non-coding (>90%), such that the molecular
mechanisms are unclear. However, they likely represent gene regulatory elements that
control gene expression. An additional caveat is that GWAS are limited to the use of mainly
to the very large European or East Asian cohorts available, and therefore any disease-
relevant genetic variation specific to Māori and Pacific people will be missed by these
studies. Using novel bioinformatic methods (CoDeS3D and COLOC) and gene expression
data (GTEx), we have assigned causal genes to shared renal/urate GWAS non-coding loci.
Querying genome sequencing data from Māori and Pacific peoples (n = 55), we have
identified missense variants specific to these populations that alter these causal renal/urate
GWAS genes. Finally, we have carried out genotyping and quantitative analyses to test
whether these missense variants associate with renal disease traits, urate levels and/or gout
in these populations.
We identified three missense variants in genes CBLB, MECOM and LRP2 that are specific
to Māori and Pacific peoples which associate with serum urate, kidney function and/or gout.
A CBLB missense variant (linked to the CYP1A1 SU and sCr GWAS locus in trans)
associates with a decrease in serum creatinine (improved kidney function) and an increase
in serum urate in people of Eastern Polynesian ancestry (βsCr = -115.9, p = 2.8 X 10-9, βSU
0.092, p = 4.0 x 10-7). At MECOM, there are GWAS signals which are associated with the
expression of MECOM. We identified a MECOM missense variant specific to Māori and
Pacific peoples that lowers serum urate (βSU = -0.014, p = 0.009) and reduces kidney
function (eGFR) (βeGFR = -2.135, p = 0.049) in people of Polynesian ancestry. At LRP2,
there are multiple GWAS signals for SU, kidney function (sCr and eGFR), CKD and gout.
The gout, sCr and SU GWAS signals are associated with LRP2 expression. We have
identified an LRP2 missense variant that increases the risk of gout (ORgout 1.3, p = 0.014)
in people of Polynesian ancestry.
CHECKPOINT INHIBITORS – A NEW SUCCESS WITH A NEW PROBLEM
ROB MACGINLEY
Eastern Health Clinical School, Monash University, Melbourne, Australia
Acute interstitial nephritis (AIN) is a rare cause of acute kidney injury (AKI) and is
characterized by inflammatory infiltrates within the interstitium. AIN is most often induced
by drugs, particularly antimicrobial agents, proton pump inhibitors, nonsteroidal anti-
inflammatory drugs and now the new therapies for cancer. An important function of the
immune system is its ability to tell between normal cells in the body and those it sees as
“foreign.” This lets the immune system attack the foreign cells while leaving the normal
cells alone. To do this, it uses “checkpoints.” Immune checkpoints are molecules on certain
immune cells that need to be activated (or inactivated) to start an immune response. This
talk explores the new science behind this and how for the kidney a new challenge has
occurred.
MEDICATION ADHERENCE IN DIALYSIS PATIENTS AT MIDDLE MORE
HOSPITAL – MEDIATORS AND MODERATORS FROM A SURVEY STUDY
1M.MARSHALL, 2M. J WOLLEY, 2T. M MA, 1S. CURD, 1D. KUMAR, 1S. LEE, 1K.PIREVA, 1O. TAULE’ALO, 1P. TIAVALE, 2A. L KAM, 2J. S SUH, 1J. KENNEDY, 1T. ASPDEN
1School of Medicine, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New
Zealand, 2Counties Manukau District Health Board, Auckland, New Zealand
The issue of adherence to medication is generally an under-researched one, and important
for dialysis patients due to their large burden of medication, often limited means and health
literacy, poor illness and medication comprehension, limited self-management and sick role
adoption, and competing health needs due to their multimorbidity. In the literature,
medication adherence is only about 50% (3 to 80% depending on definitions). The only
local audit in the literature showed medication adherence of 66% on average, with
significantly higher proportions in NZ Maori, Pacific People, and the elderly.
A variety of prospective clinical studies have shown that certain interventions can increase
medication adherence in dialysis settings, although these are without exception only short
term, and usually pharmacy-based with an emphasis on medication education and
reconciliation. Such measures might improve patient behaviour through operant
conditioning, and certainly minimise and abrogate factors related to access to care and
comprehension. Such interventions, however, have uncertain effects on internal loci of
control and learning, and little prospect for affecting behaviour in a sustained way through
humanistic psychology. Our own experience of pharmacy-based clinics at MMH is
consistent with other literature. Medication education and reconciliation clinics were
effective in the short term, but had no clearly observable effect on long-term behaviour.
They were also resource intensive, accepting that their even short-term success may have
had downstream benefits on healthcare and resource consumption, in a manner that might
offset their ongoing cost. A formal health outcomes and economics research project with
cost-benefit analyses is needed as a next step, to assess the feasibility of long-term
pharmacy-based interventions such as these.
In this study, we assessed a stratified random sample of MMH dialysis patients (n=100) to
better understand the psychological drivers of non-adherence in dialysis patients, with a
view to a more evidence based suite of interventions to modify behaviour. We assessed
self-reported medication adherence (Morisky Medication Adherence Scale), and related it’s
distribution to the following psychological constructs: illness perception (cognitive and
emotional representations, illness comprehensibility, from the Brief Illness Perception
Questionnaire), beliefs about medication (medication necessity versus medication
concerns, from the Beliefs about Medication Questionnaire), medication knowledge
(Medication Knowledge Evaluation Test), and health literacy. All of these constructs were
assessed by validated instruments, which were re-validated in the local population. The
results were analysed using structural equations modelling, using beliefs about medication
as mediating variables on the basis of previous clinical trials in the literature, and the others
as moderating variables. Results of modelling and their insights will be presented, as well
as next steps in analysis.
INVESTIGATING PATHWAYS IN LITHIUM INDUCED CHRONIC KIDNEY
DISEASE.
MEHTA PM1, GREGORY GIMINEZ1, SLATTER TL1, WALKER RJ2
1Department of Pathology, Otago Medical School, Dunedin, New Zealand; 2Department of Medicine, Otago Medical School, Dunedin, New Zealand
Lithium is used to manage bipolar mood disorders. Long-term lithium therapy is associated
with the development of nephrogenic diabetes insipidus, interstitial fibrosis and dilated
microcystic distal tubules. Cellular changes include proliferating tubular epithelial cells
arrested in G2/M phase. We have demonstrated that the diuretic drug amiloride slows the
rate of development of lithium-induced interstitial fibrosis associated with reduced
expression of profibrotic cytokines, but does not modify the microcystic tubules. The
pathways of how lithium mediates the cellular changes evident within the microcystic
tubular dilations and how amiloride down-regulates the lithium-induced inflammation and
interstitial fibrosis has not been elucidated.
Using kidney tissue from a rat model (n = 10) of long-term (6 months) and shorter-term (14
days and 28 days) lithium-induced chronic kidney disease with or without amiloride, RNA
sequencing was performed. Pathways predicted from the transcriptome-wide analyses were
validated using in situ based techniques on kidney tissues from the rat model, and in vitro
using cell lines treated with lithium, amiloride, or lithium and amiloride. The transcriptome
results suggested greater gene expression differences were evident between lithium and
lithium and amiloride treated kidneys at 6 months compared to the shorter treatment term
periods. A role for lithium in up-regulating inflammation and immune genes, and a role for
induction of early developmental genes were evident. A role for amiloride in modulating
inflammation and upregulating cell damage response pathways were evident.
Immunohistochemistry and RNAscope validation analyses validated the increase in
inflammation signature with lithium (increased PDGF, Ki67, and Notch1), and an anti-
inflammatory and pro-cell damage response pathways with amiloride (increased p53 and
p21).
Results suggest a role for lithium-induced up-regulation of inflammatory and immune
genes and a role for early developmental genes. Amiloride appears to modify these
pathways and may reduce inflammation.
PERIOPERATIVE RISK AND OUTCOMES IN PATIENTS ON CHRONIC
KIDNEY REPLACEMENT THERAPY – RECONCILING COMORBIDITIES IN
ANZDATA AND HOSPITAL ADMISSION DATASETS
DHARMENAAN PALAMUTHUSINGAM1,2,3, CARMEL M. HAWLEY2,4, DAVID W.
JOHNSON2,4,6, ELAINE PASCOE5, MAGID FAHIM3,4,7
1Metro South Integrated Nephrology and Transplant Services, Logan Hospital, Queensland, Australia 2Faculty of Medicine, University of Queensland, Queensland, Australia 3School of Medicine, Griffith University, Queensland, Australia 4Metro South Integrated Nephrology and Transplant Services Queensland, Australia 5Centre for Health Services Research, University of Queensland, Queensland, Australia 6Translational Research Institute, Queensland, Australia 7Metro North Hospital and Health Service, Royal Brisbane and Women’s Hospital, Queensland, Australia
BACKGROUND: Patients on chronic dialysis have an increased odds for postoperative
mortality and morbidity following elective surgery across all surgical
disciplines[1]. Similarly, kidney transplant recipients are also at increased odds for
postoperative mortality and acute kidney injury following elective surgery[2]. Current
perioperative outcome estimations stem predominantly from North American and the
generalisability of these findings is questionable as large cohort studies have also
demonstrated that the survival of North American dialysis patients is significantly inferior
to their Australasian counterparts. As such, the poor surgical outcomes of North American
dialysis patients may be confounded by the underlying poor dialysis outcomes in those
regions[3]. Furthermore, there is a dearth of information on perioperative outcomes in
Australasian dialysis patients who undergo surgery[4]. These knowledge gaps can be
addressed using the national data‐linkage infrastructure to combine the Australia and New
Zealand Dialysis and Transplant Registry (ANZDATA) registry, a clinical quality registry
(CQR), and all state‐ and territory‐based Admitted Patient Data Collection (APDC) data
sets that collect information on all hospitalisations.
AIM: The aim of this study was to compare recording of comorbidities in ANZDATA
compared to state-based hospital admission data sets (APDC - the reference standard).
METHODS: All adult patients that started KRT (Haemodialysis, peritoneal dialysis or
kidney transplant) in South Australia, Tasmania, Victoria and Western Australia as
identified in ANZDATA were linked to APDC datasets. Comparison between ANZDATA
and APDC datasets were made at each ANZDATA census data. Comorbidities were
classified as absent or present in APDC datasets by identifying the relevant ICD-AM code
after concatenating all hospital admissions (>1day) between ANZDATA census dates[5].
Agreement between both datasets were compared using kappa statistic.
RESULTS: 19, 329 patients were included in the analysis. Recording of comorbidities in
ANZDATA was compared to APDC datasets on 66, 408 different occasions. Baseline
comorbidity accuracy included: ischaemic heart disease [sensitivity 76% (75-76),
specificity 59% (59-60), PPV 30% (30-31), NPV 95% (94-95)], diabetes mellitus
[sensitivity 93% (93-94), specificity 91% (91-91), PPV 90% (89-90), NPV 94% (93-94)],
cerebrovascular disease [sensitivity 54% (51-57), specificity 82% (82-82), PPV 5% (4-5),
NPV 99% (99-99)], peripheral vascular disease [sensitivity 55% (52-58), specificity 70%
(69-70), PPV 3% (3-4), NPV 99% (99-99)] and chronic airway disease [sensitivity 49%
(47-50), specificity 82% (82-83), PPV 19% (18-20), NPV 97% (97-97)]. Agreement was
almost perfect for diabetes mellitus and slight to fair for other comorbidities.
CONCLUSION: The very low positive predictive values suggest there remains room for
improvement in data quality and assurance in ANZDATA.
1. Palamuthusingam, D., et al., Postoperative mortality in patients on chronic dialysis following
elective surgery: A systematic review and meta-analysis. PLOS ONE, 2020. 15(6): p. e0234402.
2. Palamuthusingam, D., et al., Postoperative outcomes of kidney transplant recipients undergoing
non-transplant-related elective surgery: a systematic review and meta-analysis. BMC Nephrology,
2020. 21(1): p. 365.
3. Goodkin, D.A., et al., Mortality among hemodialysis patients in Europe, Japan, and the United
States: case-mix effects. Am J Kidney Dis, 2004. 44(5 Suppl 2): p. 16-21.
4. Palamuthusingam, D., et al., Perioperative outcomes and risk assessment in dialysis patients:
current knowledge and future directions. Internal medicine journal, 2019. 49(6): p. 702-710.
5. Palamuthusingam, D., et al., Idenitfying New-Onset Conditions And Pre-Exisiting Conditions
Using Lookback Periods In Australian Health Administrative Datasets. International Journal for
Quality in Health Care, 2020.
INCREASING CAPACITY IN KIDNEY DISEASE TRIALS IN NEW ZEALAND
PALMER, SC.1,2
1 Department of Medicine, University of Otago, Christchurch, New Zealand, 2Department of Nephrology,
Canterbury District Health Board, Christchurch, New Zealand
Randomised controlled trials are a central tool to evaluate the effectiveness and cost-
effectiveness of treatments for people with chronic kidney disease and kidney failure.
However, clinical trials require considerable infrastructure, resources and teams to be
successful and include sufficient sample sizes to generate new knowledge.
Recently, a number of randomised controlled trials have been funded and completed or
underway in Aotearoa New Zealand, leading to the development of national governance,
coordination and delivery across all renal units in New Zealand District Health Boards.
These trials have increased the capacity of nursing teams, electronic data capture, registry-
based trial conduct and international collaboration to build capacity and infrastructure in
Aotearoa New Zealand.
Recent trials conducted with Australian and New Zealand partners include the
PHOSPHATE trial, TEACH-PD, CKD-FIX, SWIFT and INCH-HD. In this presentation,
the specific features of these trials to increase skills, resources, team-based research,
clinically-embedded research, Māori health advancement and network-based practice will
be discussed to show the opportunities for future trials in Aotearoa New Zealand to increase
the applicability and New Zealand-centred relevance of trial-based knowledge to New
Zealand nephrology practice.
ROLE OF VASCULAR ENAC IN HUMAN HYPERTENSION
PUJA PAUDEL1,2, FIONA J MCDONALD1, MARTIN FRONIUS1,2
1Department of Physiology, University of Otago, Dunedin, New Zealand; 2HeartOtago, University of Otago,
Dunedin, New Zealand
The human epithelial sodium channel (ENaC) is a trimeric molecule composed of a
different combination of 4 subunits (α, β, γ, and δ). Recent research in mice and rats has
demonstrated the role of vascular αβγ ENaC in the regulation of vascular tone and blood
pressure. However, the absence of the δ subunit in these animal models makes it difficult
to translate these findings into clinical settings. In this study, we aimed to characterise the
expression and function of ENaC subunits in the human arteries and their potential role in
hypertension.
Human internal mammary arteries (HIMA) from patients undergoing coronary artery
bypass graft (CABG) surgery were collected through the Heart Otago network. The patients
were divided into 3 groups: normotensive, uncontrolled hypertensive, and controlled
hypertensive based on their blood pressure measurement. Expression of ENaC subunits was
analysed by qPCR and western blot analysis. Primary endothelial cells isolated and cultured
from HIMA were used for the functional analysis of ENaC channels using whole-cell and
single-channel patch-clamp electrophysiology. Finally, human umbilical vein endothelial
cells (HUVECs) were treated with common beta-blockers (Metoprolol and Carvedilol) and
angiotensin-converting enzyme (ACE) inhibitor (Cilazapril) to reveal if the common
antihypertensive medication affects ENaC expression.
For the first time, we detected both mRNA and protein expression of all 4 ENaC subunits
in HIMA. In primary endothelial cells, whole-cell patch-clamp electrophysiology revealed
the presence of amiloride-sensitive current. Single-channel patch-clamp experiment
identified channels with two different conductance ~5pS (n=2) and ~12pS (n=10), which
are similar to the conductance of αβγ- and δβγ-ENaC respectively.
Interestingly, the δ subunit was significantly elevated in the uncontrolled hypertensive
group compared to controlled hypertensive groups at both mRNA (p=0.0322) and protein
levels (p=0.028). However, the normotensive groups also had increased δ-ENaC expression
compared to the control hypertensive group at both mRNA (p=0.0322) and protein
(p=0.028) levels. Furthermore, Carvedilol and Metoprolol significantly reduced α-ENaC
(p=0.027) and γ-ENaC (p=0.0027) mRNA expression respectively in HUVECs.
These data suggest that functional ENaC channels are expressed in HIMA and δ-ENaC
might have an important role in human hypertension. Furthermore, the antihypertensive
drugs differentially influence ENaC expression and this could be the reason for the reduced
ENaC expression in the hypertensive group compared to the normotensive group. Hence,
further research should be carried out on healthy tissue without any influence of drugs to
identify the role of αβγ- and δβγ-ENaC for vascular function.
CARSK STUDY (CANADIAN-AUSTRALASIAN RANDOMISED TRIAL OF
SCREENING KIDNEY TRANSPLANT CANDIDATES FOR CORONARY
ARTERY DISEASE)
H PILMORE1, N CROSS2, J SCHOLLUM3, C HOOD4, A SALMON5 (NEW ZEALAND
INVESTIGATORS)
1Auckland District Health Board, Auckland, New Zealand; 2Canterbury District Health Board, Christchurch, New Zealand 3Southern District Health Board, Dunedin, New Zealand; 4Counties Manukau District Health Board Renal, Auckland, New Zealand; 5Waitemata District Health Board Renal Services, Auckland, New Zealand Update on CARSK study – RCT of targeted versus routine cardiac stress testing in renal
transplant wait listed patients
CARSK aims to:
1. Test the hypothesis that after screening for wait list entry, no further screening for
coronary artery disease (CAD) is non-inferior to the current standard care which is
screening all asymptomatic wait-listed patients for CAD at regular intervals.
2. Compare the benefits and costs of not screening versus regular CAD screening from a
health system perspective.
USING KIDNEY ORGANOIDS TO MODEL CISPLATIN-INDUCED
NEPHROTOXICITY
VERONIKA SANDER, JENNY DIGBY, THITINEE VANICHAPOL, ALAN J. DAVIDSON
Department of Molecular Medicine and Pathology, University of Auckland, New Zealand
Disease studies are traditionally undertaken in monolayer cell cultures or rodents.
Organoids are 3D mini-organs grown in vitro. They contain many of the cell types and the
complex microarchitecture of human organs, such as the kidney. Acute kidney injury (AKI)
is defined as the sudden loss of kidney function and can be caused by various types of
insults, such as the toxic side-effects of clinical drugs. Despite being a serious health
burden, no targeted therapies are currently available for AKI. This is partly due to a lack of
clinically-relevant models. We have established a simple method to generate large numbers
of kidney organoids from human induced pluripotent stem cells. At their optimal state of
maturation, the organoids contain the main renal cell types including proximal and distal
tubule cells and podocytes. We tested the applicability of the organoids for modelling drug-
induced nephrotoxicity and found that treatment with the chemotherapeutic drug cisplatin
induced a robust injury response, including expression of AKI biomarkers and
inflammatory cytokines, DNA damage and cell death, reminiscent of the drug’s injurious
effects seen in AKI patients. Transcriptional profiling of control and cisplatin-treated
organoids revealed differential gene expression that significantly overlapped with datasets
obtained from mouse AKI-models and patient studies. This work validates the use of kidney
organoids as human models for nephrotoxicity/AKI. As such, the organoid system holds
promise for improving our understanding of AKI pathology, identifying reliable
biomarkers, and ultimately, developing much-needed new therapies.
INCREASED EXPRESSION OF EPITHELIAL SODIUM CHANNEL AFFECTS
MECHANICAL PROPERTIES OF ENDOTHELIAL CELLS BY
REORGANISING THE F-ACTIN CYTOSKELETON.
SHAH, V.K, FRONIUS, M.
Department of Physiology and Heart Otago, University of Otago, Dunedin, New Zealand
Epithelial sodium channel (ENaC) in the kidney maintain body salt/water balance and
regulate blood pressure. Recent finding suggests that endothelial cells express ENaC. Here
elevated ENaC contributes to increased endothelial cell stiffness (ECS) that associates with
endothelial dysfunction and hypertension. However, the mechanism how exactly ENaC
influence ECS remains unknown. This study aims to investigate the potential role of ENaC
subunits in mediating ECS by cytoskeletal changes. I hypothesize ENaC mediated ECS via
an increased expression of F-actin. To challenge our hypothesis, ENaC protein expression
was quantified by Western blot in human umbilical vein endothelial cells (HUVECs)
treated with aldosterone under static condition (0 dyn/cm²) and under laminar shear stress
(LSS, 10 dyn/cm², 24 h). Atomic Force Microscopy (AFM) was used to measure cell
stiffness and changes of F-actin were assessed by immunofluorescence microscopy. Under
static condition, aldosterone significantly increased α-, and δ-ENaC protein levels. On the
other hand, under LSS conditions aldosterone increased β-, and δ-ENaC protein levels. Also
static condition, a significantly increased Young’s modulus was determined in both fixed
and live HUVEC cells treated with aldosterone. Furthermore, the increased stiffness in
aldosterone treated cells revealed increased F-actin levels. Overall, these findings indicate
that aldosterone has different effects on ENaC subunit expression in HUVECs grown under
static and LSS conditions. The increased ENaC expression does increase ECS. This seems
to involve an increased F-actin expression as a major determinant of ECS. Therefore, this
study may provide a new mechanism for ENaC-mediated ECS and blood pressure
regulation.
PREDICTORS OF HEALTH OUTCOMES IN ELDERLY DIALYSIS PATIENTS.
SHETTIGAR R1, SCHOLLUM J2, DERETT S3, SAMARNAYAKA A3, WALKER R2.
1Department of Nephrology, Christchurch Hospital, Christchurch, New Zealand, 2Department of
Nephrology, Dunedin Hospital, Dunedin, New Zealand, 3Department of Preventative and Social Medicine,
University of Otago, Dunedin, New Zealand
Background: The DOS65+ (Dialysis Outcomes in Those Aged ≥65 Years) Study is an
accelerated cohort study of older New Zealanders with chronic kidney disease stage 5
(CKD5). The overall aim of this study was to examine health related quality of life and
patient experience outcomes prospectively.
Aim: In this paper, our aim was to identifying patient-reported health outcomes in patients
more than 65 years of age at 24 months and 36 months of dialysis relative to characteristics
at 12 months and 24 months.
Methods: We recruited dialysis patients over the age of 65 years from three Nephrology
units in New Zealand. We conducted interviews at baseline, and then follow up interviews
were conducted at 12, 24, and 36 months, respectively. The health outcome question was
compared to one year ago, how would you rate your health in general now? Answers were
grouped into the same or better or worse. Patients who died in the preceding year were
group in the worse health outcome. Data collected included demographics, social factors
like the degree of satisfaction with social relationships, sense of community, modality of
dialysis, quality of life.
Results: At baseline, there were 225 participants. The total number of participants at 12,
24, and 36 months was 154, 120, and 80. Analysis at 24 months and 36 months showed
patients who were of Maori and Pacific ethnicity (p =0.01), less than three comorbidities
(p =0.01), on peritoneal dialysis (p=0.01), with no problems with ADLs (p= 0.03), who
reported strong sense of community and satisfaction with social relationships reported less
worse health outcomes. 58% of the study population at 24 months and 61% at 36 months
reported to be feeling the same or better compared to 12 months ago.
Conclusion: Patient reported health outcomes are critical in informed shared decision-
making regarding invasive therapy such as dialysis. Our paper highlights the importance of
considering factors like burden of comorbidities, social characteristics like satisfaction with
relationships and sense of community amongst other factors in predicting health outcomes.
WHAT DOES DNA METHYLOME ANALYSIS TELL US ABOUT ADPKD?
CHERIE STAYNER1, SARAH BOWDEN1,2, EUAN RODGER1,3, ANIRUDDHA
CHATTERJEE1,3, MICHAEL ECCLES1,3.
1Department of Pathology, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand. 2Renal Division, Department of Medicine, University Hospital Freiburg, Freiburg University Faculty of
Medicine, Germany. 3Maurice Wilkins Centre for Molecular Biodiscovery, Auckland, New Zealand
Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a heritable renal disease that
causes enlargement of the kidneys due to the development of fluid-filled cysts, and results
in end-stage kidney disease in adults and a reduced life expectancy. There are similarities
between cyst development in ADPKD and neoplasia. As epigenetic mechanisms have been
shown to regulate and contribute to every hallmark of cancer, most of which are also
evident in polycystic kidney disease, we were prompted to undertake a methylome analysis
of human ADPKD cystic kidneys to determine the role that DNA methylation may play in
this disease. Our findings have provided insights into both the pathways that are altered in
cystic kidneys, and the potential role of epigenetic variation in cyst development.
REVIEWING THE PERIOPERATIVE CALCIUM MANAGEMENT POST
PARATHYROIDECTOMY IN RENAL PATIENTS AT MIDDLEMORE
HOSPITAL
AMELIA TEKITEKI, TINA SUN, HLA THEIN
Renal Department, Middlemore Hospital, Auckland, New Zealand; Renal Department, Auckland City
Hospital, Auckland, New Zealand
Severe hypocalcemia, also known as hungry bone syndrome (HBS), is a serious
complication post-parathyroidectomy. HBS is more common in patients with end-stage
renal failure (ESRF) with secondary or tertiary hyperparathyroidectomy, compared to those
with primary hyperparathyroidism that undergo parathyroidectomy. There is lack of
evidence regarding the treatment and ideal perioperative management for prevention of
HBS. At Middlemore Hospital (MMH), the protocol for prevention of hypocalcemia in
ESRF patients undergoing parathyroidectomy differs to other hospitals in the Auckland
region. At MMH, all patients are commenced on a continuous calcium infusion via central
venous line (CVL) immediately post-surgery. However, at other centres in the Auckland
region, such as Auckland City Hospital (ACH), CVL insertion and administration of IV
calcium is only commenced in patients at high risk of HBS. The main parameters used to
determine high-risk patients are alkaline phosphatase (ALP) greater than 250 U/L and/or
parathyroid hormone (PTH) > 150 pmol/L. This study aimed to review the perioperative
calcium management for renal patients undergoing parathyroidectomy for secondary or
tertiary hyperparathyroidism at MMH. We reviewed patient demographics, pre- and post-
operative calcium and PTH levels, incidence of hungry bone syndrome, duration of IV
calcium infusion, length of hospital stay and oral calcium supplements required on
discharge. We then reviewed the perioperative calcium management for renal
parathyroidectomy patients at ACH and compared their patient demographics, pre- and
post-operative calcium and PTH levels, incidence of hungry bone syndrome and length of
hospital stay to MMH. We conducted a retrospective study of a total of 171 patients with
renal induced hyperparathyroidism requiring parathyroidectomy between 1st January 2014
to 31st December 2018 at Middlemore Hospital and Auckland City Hospital. There were
88 patients at MMH and 83 patients a ACH. Results showed similar patient demographics
between MMH and ACH. Patients at MMH had higher average pre-operative PTH levels
and longer average length of hospital stay compared to ACH, most likely related to
treatment with an IV calcium infusion. It also showed that more patients at ACH received
pre-operative calcium loading comparted to MMH. The findings of this study suggest that
MMH should consider reviewing their perioperative calcium management for renal
parathyroidectomy. This may help reduce hospital length of stay and need for CVL
insertion and calcium infusion.
LITHIUM INDUCED KIDNEY INJURY
ROBERT WALKER1, JENNY BEDFORD1, JOHN LEADER1, PAULOMI MEHTA2, TANIA
SLATTER2, RICHARD COWARD3
1Department of Medicine, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand; 2Department of Pathology, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand; 3Bristol Renal, Dorothy Hodgkin Building, University of Bristol, Bristol, United Kingdom
Our research group has been interested in the mechanisms and pathways that lead to
changes in kidney function and structure. Our understanding of how lithium induces
nephrogenic diabetes insipidus is now relatively well understood. However long-term
exposure to lithium produces focal glomerulosclerosis with proteinuria, chronic interstitial
fibrosis and cystic dilation of the distal tubules.
The chronic interstitial fibrosis is associated with upregulation of TGFβ and CTGF
expression along with increased numbers of myofibroblasts in the interstitium which is
down-regulated by the use of amiloride. Although the fibrosis is down-regulated, the cystic
dilatation of the distal tubules is not modified. There is increased cell proliferation in these
tubules but the cells are stuck in G2M growth arrest.
Lithium inhibits the action of GSK3 (α and β isoforms) by about 25% at clinically relevant
doses. GSK3 is Glycogen Synthase Kinase 3 (GSK3) is a multi-functional serine/threonine
protein kinase that regulates several distinct biological pathways. GSK3 has two major
biological actions; as a scaffolding protein and a kinase enzyme to catalyse a variety of
down-stream targets. Inhibitory phosphorylation of GSK3 α and β isoforms, leads to
stabilization of β-catenin and upregulation of the Wnt canonical pathway in podocytes and
tubular epithelial cells. These may allow tubular epithelial cells and podocytes to re-enter
cell differentiation and proliferation. Increased Wnt expression is associated with increased
activation and proliferation of myofibroblasts with increased matrix deposition.
We are now exploring these pathways at earlier stages of lithium exposure to identify the
key signalling pathways that are being modified.
THE INCREMENTAL DIALYSIS TO IMPROVE HEALTH OUTCOMES IN
PEOPLE INITIATING HAEMODIALYSIS (INCH-HD)
ROBERT WALKER1, SUETONIA PALMER2, JANAK DE ZOYSA3, DAVID JOHNSON4 on
behalf of the AKTN investigators
1Department of Medicine, University of Otago, Dunedin, New Zealand 2Department of Medicine, University of Otago, Christchurch, New Zealand;
3Renal Service, Waitemata District Health Board, Auckland, New Zealand; 4Department of Nephrology, Division of Medicine, Princess Alexandra Hospital, Brisbane, Queensland,
Australia
The INCremental dialysis to improve Health outcomes in people initiating HaemoDialysis
(INCH-HD) trial plans to compare two strategies for patients commencing long term kidney
replacement therapy: the incremental strategy (incremental HD) twice a week, versus
conventional haemodialysis (conventional HD) three times a week. Commencing
haemodialysis (HD) is an intense period of physiological and social adaptation, incurring a
50-80% excess risk of death in the first 6 months3. It is postulated that early mortality is in
part related to the standard approach to HD initiation three times a week that is used in
clinical practice, regardless of body mass, residual kidney function or kidney failure
symptoms. Incremental HD (commencing HD two times a week instead of three times a
week) is associated with protected residual kidney function in observational studies and a
meta-analysis of cohort studies involving 252,330 people starting HD 8,9. These
uncontrolled data raise the hypothesis that incremental HD may not only have a positive
impact on health-related quality of life for individuals commencing dialysis through
increasing dialysis free time and enabling employment, but also may well be life-saving in
the first 6 months of dialysis care through preservation of kidney function. Though
incremental HD remains an attractive idea to patients, consumers and clinicians and
addresses high priority clinical outcomes, incremental HD has never been subject to a
prospective trial and it is unclear if this is an optimal or comparably safe approach to
starting HD. Robust evidence for the safety and advantages of incremental HD in a properly
conducted randomised, controlled trial, is needed before more widespread application of
this approach can be advocated. If incremental HD is demonstrably proven to be as effective
and safe as standard HD, there is a high likelihood that it will be widely adopted with
consequent cost savings to families and health systems.
INCH-HD is a pragmatic investigator-initiated, clinical quality multicentre, parallel-group,
open-label, blinded outcome, randomised, controlled trial. It will be conducted in dialysis
units in New Zealand Australia and Canada. INCH-HD has been designed, led and
coordinated by the Australasian Kidney Trials Network based at the University of
Queensland in partnership with the University of Otago. An HRC application is seeking
funding for the New Zealand arm of the study which aims to enrol 60 participants. The
primary outcome will be difference between groups in kidney specific component of
KDQOL-SF at 6 months from dialysis commencement as measured using KDQOL-SF
version 1.3 25.
Secondary outcomes include residual kidney function at 6, 12 and 18 months, adverse
events and side effects related to the intervention.
METFORMIN DOSING IN KIDNEY IMPAIRMENT
ISABELLE H.S. KUAN1, LUKE C. WILSON2, JED C. LEISHMAN2, SAMUEL COSGROVE2,
ROBERT J. WALKER2, TRACEY L. PUTT2, JOHN B.W. SCHOLLUM2, DANIEL F.B.
WRIGHT1.
1School of Pharmacy, Otago Medical School, University of Otago, Dunedin, New
Zealand. 2Department of Medicine, Otago Medical School, University of Otago, Dunedin, New
Zealand.
Aims To design a dosing strategy for metformin to ensure efficacy and safety in patients
with kidney impairment.
Materials and methods Metformin data from two open label pharmacokinetic studies
stratified by kidney function were analysed. The relationship between estimated metformin
clearance for each patient and different kidney function estimates (Cockcroft and Gault,
MDRD and CKD-Epi) was explored using a regression analysis. The regression equation
was implemented to predict the maintenance dose range at different bands of kidney
function to achieve an efficacy target for the steady-state plasma concentration of 1 mg/L.
The dose bands were evaluated using stochastic simulations from a published metformin
population pharmacokinetic model to determine the probability of plasma concentrations
exceeding those associated with lactic acidosis risk, i.e. a steady-state average
concentration of 3 mg/L and a maximum plasma concentration of 5 mg/L.
Results The regression analysis indicated a strong relationship between metformin
clearance and estimated kidney function using the Cockcroft and Gault (R2=0.699), 4-
variable MDRD (R2=0.717) and CKD-Epi (R2=0.735) equations. The probability of
exceeding a steady state plasma metformin concentration of 3 mg/L or peak plasma
concentration of 5 mg/L using the dose bands was <5% for most doses and kidney function
levels. However, the lower dose of 500 mg and 250 mg daily was required to maintain
concentrations below the safety limits for patients within the eGFR bands of 15-29 and <
15 mL/min, respectively.
Conclusions The metformin dose bands based on kidney function suggest that a maximum
daily dose of 2250, 1700, 1000, 500, and, 250 mg in patients with normal kidney function,
CKD stage 2, 3, 4 and 5, respectively, will maintain plasma concentrations below those
associated with lactic acidosis while maintaining efficacy.
ACHIEVE: ALDOSTERONE BLOCKADE FOR HEALTH IMPROVEMENT
EVALUATION IN END-STAGE RENAL DISEASE.
DE ZOYSA, J.R.1, 2; GALLAGHER, M.3,4; WALSH, M.5, 6, 7 FOR THE ACHIEVE
INVESTIGATORS.
1Renal Service, Waitemata District Health Board, Auckland, New Zealand; 2Department of Medicine, University of Auckland, Auckland, New Zealand; 3 The George Institute for Global Health, University of New South Wales, Sydney, Australia; 4Concord Repatriation and General Hospital, Sydney, Australia; 5Department of Medicine, McMaster University, Hamilton, Canada; 6 Population Health Research Institute, McMaster University/Hamilton Health Sciences, Hamilton,
Canada; 7Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Canada.
Cardiovascular disease (CVD) accounts for 40%-55% of death in dialysis patients, and is
significantly more frequent than in the general population [1, 2]. Whilst this may be
expected given the high prevalence of hypertension and diabetes in dialysis patients, the
pattern of CVD and death is quite different to that seen in the general population and is
driven by multiple processes including chronic volume overload, hypertension and
myocardial injury that leads to cardiac remodelling, cardiac fibrosis and lethal arrhythmias
[3]. Multiple mechanisms drive the cardiac changes seen in end stage renal disease, and the
pathophysiology for these changes is poorly understood, however, aldosterone excess plays
a key role.
Currently there are no therapies proven to reduce CV morbidity in patients on dialysis. In
non-dialysis patients the mineralocorticoid antagonists (MRA) have been shown to
improve mortality [4]. In small underpowered trials in dialysis patients the MRAs have
been shown to reduce left ventricular hypertrophy and CV mortality and have the potential
to improve clinical outcomes [5].
The ACHIEVE study (Aldosterone bloCkade for Health Improvement EValuation in End-
stage renal disease), is a multi-national, multi-centre trial that will determine whether the
MRA spironolactone, will safely reduce mortality from CVD and heart failure (HF)
hospitalisations in patients requiring dialysis.
1.] Roberts MA et al. Secular trends in cardiovascular mortality rates of patients receiving dialysis
compared with the general population. American Journal of Kidney Diseases, 2011, 58(1): 64-72
2.] Chapter 5: Mortality. American Journal of Kidney Diseases, 2018, 71 (3): S337-S350
3.] Foley RN, Collin AJ. End-stage renal disease in the United States: an update from the United States
Renal Data System. Journal of the American Society of Nephrology, 2007, 18(10): 2644-2648
4.] Ezekowitz JA, McAlister FA. Aldosterone blockade and left ventricular dysfunction: a systematic review
of randomized clinical trials. European Heart Journal, 2009, 30(4): p. 469-477
5.] Quach K et al. The safety and efficacy of mineralocorticoid receptor antagonists in patients who require
dialysis: a systematic review and meta-analysis. American Journal of Kidney Diseases, 2016, 68(4): p. 591-
598
BEAT-CALCI: BETTER EVIDENCE AND TRANSLATION FOR
CALCIPHYLAXIS
DE ZOYSA, J.R.1, 2; YOUNG, T.3; KRISHNASAMY R.4, 5, JARDINE M.J.6,7 FOR THE BEAT-
CALCI INVESTIGATORS.
1 Renal Service, Waitemata District health Board, Auckland, New Zealand; 2Department of Medicine, University of Auckland, Auckland, New Zealand; 3 The George Institute for Global Health, Sydney, Australia; 4 Sunshine Coast University Hospital, Queensland, Australia; 5 Australasian Clinical Trials Network, University of Queensland, Queensland, Australia; 6NHMRC Clinical Trials Centre, the University of Sydney, Sydney, Australia; 7 Concord Repatriation General Hospital, Sydney, Australia.
Vascular calcification is a hallmark of patients with Chronic Kidney Disease and in rare
cases, vascular calcification results in a painful and life-threatening condition known as
calciphylaxis. Calciphylaxis is characterized by medial calcification, intimal proliferation
and fibrosis [1, 2]. The calcified, narrowed micro vessels are thought to trigger chronic
ischaemia with micro-thrombosis leading to painful, necrotic skin plaques and ulcers [1,
2].
Cases of calciphylaxis among End Stage Renal Disease (ESRD) patients have been reported
worldwide, however, the epidemiology of calciphylaxis is imperfectly described. Reported
risk factors for calciphylaxis include ESKD, Caucasian ethnicity, female sex, dialysis
inadequacy, long dialysis vintage, abnormal bone mineral metabolism, hypoalbuminaemia,
diabetes mellitus, obesity, trauma, corticosteroids and vitamin K antagonist therapy (e.g.
warfarin) [3]. Once diagnosed, the prognosis for calciphylaxis patients is poor [4, 5, 6]: in
cohort studies, the reported median survival time varies between 9 weeks and 1.6 years,
with the rate of mortality estimated to be ~30% at 6 months and 50% at 12 months [7, 8].
To date, a considerable variation in clinical practice within and between countries has been
observed. However, the devastating nature of calciphylaxis creates an overwhelming
impetus for treatment despite the absence of any evidence-based treatment options. The
BEAT-Calci multi-domain, adaptive platform trial will investigate the effectiveness of a
range of interventions for the treatment of calciphylaxis in patients with End-Stage Kidney
Disease receiving haemodialysis. In this platform trial, multiple treatments across diverse
domains of therapeutic care will be assessed within the same trial infrastructure. Once
proven, successful interventions will become the standard of care within the trial whilst
additional treatments continue to be tested. This model provides the most efficient structure
for evidence generation in a rare disease, whilst maximising participant access to trial
agents.
1.] Fine, A., Zacharias, J., Calciphylaxis is usually non-ulcerating: risk factors, outcome and therapy.
Kidney International, 2002, 61(6): p. 2210-2217
2.] Selye, H. The dermatologic implications of stress and calciphylaxis. Journal of Investigative
Dermatology, 1962, 39: p. 259-275
3.] Nigwekar, S.U. Calciphylaxis. Current Opinion in Nephrology and Hypertension, 2017, 26(4): p. 276-
281
4.] Nigwekar, S.U., et al. Calciphylaxis: risk factors, diagnosis, and treatment. American Journal of Kidney
Diseases, 2015, 66(1): p. 133-146
5.] Nigwekar, S.U. Multidisciplinary approach to calcific uremic arteriolopathy. Current Opinion in
Nephrology and Hypertension, 2015, 24: p. 531– 537
6.] Brandenburg, V.M., Cozzolino, M., Mazzaferro, S. Calcific uremic arteriolopathy: a call for action.
Seminars in Nephrology, 2014, 34(6): p. 641–647
7.] McCarthy, J.T., et al. Survival, Risk Factors, and Effect of Treatment in 101 Patients With
Calciphylaxis. Mayo Clinic Proceedings, 2016, 91(10): p. 1384-1394
8.] Nigwekar, S.U. et al. Nationally Representative Study of Calcific Uremic Arteriolopathy Risk Factors.
Journal of the American Society of Nephrology, 2016, 27(11): p. 3421-3429
Coffee and Cafes
CPR Café: 18 Wynen St, Blenheim
Marlborough’s boutique coffee roasting company.
Established in 2003, they have perfected the art of roasting
and developing our coffee, including their award winning
signature blend "Accelerator" and recent award winning
blends "Resuscitator", "Marvel" and "Body & Soul".
Roasting premises are located in Wynen St, Blenheim,
where they also created our first coffee-to-go format store.
CBD Eatery: 41 Queen St, Blenheim
An award-winning coffee shop and deli restaurant situated
in the heart of Blenheim's CBD in the beautiful
Marlborough region.
“We specialise in delicious, seasonally inspired food, and
offer a large range of gourmet foods in our cabinet
including gourmet salads, bread products, and delicious
tarts, burritos etc.We also have a great range of gluten free
items and offer an extensive breakfast / brunch / lunch
selection.”
Herb and Olive: 62 High St, Blenheim
“a wholefood cafe based in Blenheim, Marlborough. We
are passionate about coffee, kombucha, and seasonal local
food. Come and visit!”
The Goodhome:70 Queen St, Blenhiem
“We are a pub with an eye for the different and the
delicious. We are your new local, look forward to our
enticing array of drinks at the bar, the tempting treats on
the menu and the smiles of the friendly folk who'll serve
them to you. It’s about lunch with no plans for the
afternoon; it’s a cocktail or two after five; an easy dinner
with the family or a beer while watching the code.”
Figaro’s: 8 Scott St, Blenheim
“Figaros Cafe has been serving the best supreme roasted
coffee in Blenheim for over 10 years. Our cafe serves a
range of delicious breakfast, lunch & tapas menu using
fresh seasonal produce put together by our creative team of
chefs. At Figaros Cafe all of our food is made from scratch
from local produce, which is why we are a favourite among
locals, visitors & businesses who use our catering service.”
Wind down and Drinks
Bamboo Tiger: 50 Queen St, Blenheim
“This 1930's Asian fusion Jazz & Cocktail lounge will be
sure to tick all of your boxes.
Situated in the iconic building Hotel d'Urville in sunny
Marlborough. Great tunes, vibrant staff, elegant decor, live
music and exquisite cocktails.”
The Wine Station: Sinclair St, Blenheim
“At the core of The Wine Station concept is the ability to
showcase an incredible variety of 80 premium wines from
Marlborough. Visitors can sample a tasting, a half or a full
glass of wine. Vineyards without cellar doors also have the
opportunity to present their wines in a satellite cellar door
location they can call their own. Located in a newly
renovated 1906 heritage building, the Blenheim Railway
Station”
Scotch: 24-26 Maxwell Rd, Blenheim
A Cuisine 1-Hat Restaurant and Wine Bar located in
Blenheim and offers a great selection of wine, craft beer
and food.
The Yardbar: 30 Maxwell Rd, Blenheim
“The Yard Bar and Bistro is a a great place to come for a
drink and pizza.”
Public House: 51 Scott St, Blenheim
“With 2 large outdoor areas including a covered balcony
and al fresco courtyard plus a lovely formal dining area and
separate bar area there is plenty of places to relax and enjoy
a great meal, or try one of our fantastic cocktails or
numerous beers on tap. Happy hour is from 4pm till 6pm
during the week”
5-Tapped: 30 Scott St, Blenheim
(Entrance on Tenth Lane behind Harvey Norman)
Specialty Coffee, Craft Beer (Specialty/Limited Release),
Misty Cove Wine, Boutique Ciders, Vintage/ Classic and
Custom Moto's on display
Things to browse
02 Market Street, Blenheim
Welcome to Cerise where you can expect to find all things
beautiful, from our gorgeous gifts and homeware to our
amazing range of jewellery and accessories
18 Scott Street, Blenheim
Still Books for a huge range of second-hand books and all
your homebrewing supplies
21 Queen Street, Blenheim
“At Tango's Shoes you'll just about always find what you're
looking for or even what didn't know you were looking for.
We have the latest in European fashion in colour, textures
and beautiful styles and all at the best prices.
We spend all year every year researching the best leathers,
the best fits and the best styles to suit the New Zealand
market but straight from Europe. Each season we offer
gorgeous fashion and comfort and endeavour to give the
ultimate customer service”
54 Market Street, Blenheim
Thomas’s is a modern provincial city department store
retailing Women’s Fashion including shoes, accessories
and cosmetics, Women’s and Men’s Lifestyle Clothes,
Men’s Clothing, Homewares and JETZ Urban Streetwear
Store
