Publications by authors named "Joanna Dunlop"

12 Publications

  • Page 1 of 1

Effect of Low-Sodium versus Conventional Sodium Dialysate on Left Ventricular Mass in Home and Self-Care Satellite Facility Hemodialysis Patients: A Randomized Clinical Trial.

J Am Soc Nephrol 2020 05 18;31(5):1078-1091. Epub 2020 Mar 18.

Department of Renal Medicine, Middlemore Hospital, Counties Manukau District Health Board, Auckland, New Zealand.

Background: Fluid overload in patients undergoing hemodialysis contributes to cardiovascular morbidity and mortality. There is a global trend to lower dialysate sodium with the goal of reducing fluid overload.

Methods: To investigate whether lower dialysate sodium during hemodialysis reduces left ventricular mass, we conducted a randomized trial in which patients received either low-sodium dialysate (135 mM) or conventional dialysate (140 mM) for 12 months. We included participants who were aged >18 years old, had a predialysis serum sodium ≥135 mM, and were receiving hemodialysis at home or a self-care satellite facility. Exclusion criteria included hemodialysis frequency >3.5 times per week and use of sodium profiling or hemodiafiltration. The main outcome was left ventricular mass index by cardiac magnetic resonance imaging.

Results: The 99 participants had a median age of 51 years old; 67 were men, 31 had diabetes mellitus, and 59 had left ventricular hypertrophy. Over 12 months of follow-up, relative to control, a dialysate sodium concentration of 135 mmol/L did not change the left ventricular mass index, despite significant reductions at 6 and 12 months in interdialytic weight gain, in extracellular fluid volume, and in plasma B-type natriuretic peptide concentration (ratio of intervention to control). The intervention increased intradialytic hypotension (odds ratio [OR], 7.5; 95% confidence interval [95% CI], 1.1 to 49.8 at 6 months and OR, 3.6; 95% CI, 0.5 to 28.8 at 12 months). Five participants in the intervention arm could not complete the trial because of hypotension. We found no effect on health-related quality of life measures, perceived thirst or xerostomia, or dietary sodium intake.

Conclusions: Dialysate sodium of 135 mmol/L did not reduce left ventricular mass relative to control, despite improving fluid status.

Clinical Trial Registry Name And Registration Number: The Australian New Zealand Clinical Trials Registry, ACTRN12611000975998.
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http://dx.doi.org/10.1681/ASN.2019090877DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7217404PMC
May 2020

Radiological Response Heterogeneity Is of Prognostic Significance in Metastatic Renal Cell Carcinoma Treated with Vascular Endothelial Growth Factor-targeted Therapy.

Eur Urol Focus 2020 09 6;6(5):999-1005. Epub 2019 Feb 6.

Barts Cancer Institute, CRUK Experimental Cancer Medicine Centre, London, UK; Department of Oncology, Royal Free NHS Foundation Trust, London, UK. Electronic address:

Background: Response evaluation criteria in solid tumours (RECIST) is widely used to assess tumour response but is limited by not considering disease site or radiological heterogeneity (RH).

Objective: To determine whether RH or disease site has prognostic significance in patients with metastatic clear-cell renal cell carcinoma (ccRCC).

Design, Setting, And Participants: A retrospective analysis was conducted of a second-line phase II study in patients with metastatic ccRCC (NCT00942877), evaluating 138 patients with 458 baseline lesions.

Intervention: The phase II trial assessed vascular endothelial growth factor-targeted therapy±Src inhibition.

Outcome Measurements And Statistical Analysis: RH at week 8 was assessed within individual patients with two or more lesions to predict overall survival (OS) using Kaplan-Meier method and Cox regression model. We defined a high heterogeneous response as occurring when one or more lesion underwent a ≥10% reduction and one or more lesion underwent a ≥10% increase in size. Disease progression was defined by RECIST 1.1 criteria.

Results And Limitations: In patients with a complete/partial response or stable disease by RECIST 1.1 and two or more lesions at week 8, those with a high heterogeneous response had a shorter OS compared to those with a homogeneous response (hazard ratio [HR] 2.01; 95% confidence interval [CI]: 1.39-2.92; p<0.001). Response by disease site at week 8 did not affect OS. At disease progression, one or more new lesion was associated with worse survival compared with >20% increase in sum of target lesion diameters only (HR 2.12; 95% CI: 1.43-3.14; p<0.001). Limitations include retrospective study design.

Conclusions: RH and the development of new lesions may predict survival in metastatic ccRCC. Further prospective studies are required.

Patient Summary: We looked at individual metastases in patients with kidney cancer and showed that a variable response to treatment and the appearance of new metastases may be associated with worse survival. Further studies are required to confirm these findings.
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http://dx.doi.org/10.1016/j.euf.2019.01.010DOI Listing
September 2020

Low dialysate sodium levels for chronic haemodialysis.

Cochrane Database Syst Rev 2019 01 16;1:CD011204. Epub 2019 Jan 16.

Department of Medicine, Counties Manukau Health, Orakau Rd, Auckland, New Zealand.

Background: Cardiovascular (CV) disease is the leading cause of death in dialysis patients, and strongly associated with fluid overload and hypertension. It is plausible that low dialysate [Na+] may decrease total body sodium content, thereby reducing fluid overload and hypertension, and ultimately reducing CV morbidity and mortality.

Objectives: This review evaluated harms and benefits of using a low (< 138 mM) dialysate [Na+] for maintenance haemodialysis (HD) patients.

Search Methods: We searched the Cochrane Kidney and Transplant Register of Studies up to 7 August 2018 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov.

Selection Criteria: Randomised controlled trials (RCTs), both parallel and cross-over, of low (< 138 mM) versus neutral (138 to 140 mM) or high (> 140 mM) dialysate [Na+] for maintenance HD patients were included.

Data Collection And Analysis: Two investigators independently screened studies for inclusion and extracted data. Statistical analyses were performed using random effects models, and results expressed as risk ratios (RR) for dichotomous outcomes, and mean differences (MD) or standardised MD (SMD) for continuous outcomes, with 95% confidence intervals (CI). Confidence in the evidence was assessed using GRADE.

Main Results: We included 12 studies randomising 310 patients, with data available for 266 patients after dropout. All but one study evaluated a fixed concentration of low dialysate [Na+], and one profiled dialysate [Na+]. Three studies were parallel group, and the remaining nine cross-over. Of the latter, only two used a washout between intervention and control periods. Most studies were short-term with a median (interquartile range) follow-up of 3 (3, 8.5) weeks. Two were of a single HD session, and two of a single week's HD. Half of the studies were conducted prior to 2000, and five reported use of obsolete HD practices. Risks of bias in the included studies were often high or unclear, lowering confidence in the results.Compared to neutral or high dialysate [Na+], low dialysate [Na+] had the following effects on "efficacy" endpoints: reduced interdialytic weight gain (10 studies: MD -0.35 kg, 95% CI -0.18 to -0.51; high certainty evidence); probably reduced predialysis mean arterial blood pressure (BP) (4 studies: MD -3.58 mmHg, 95% CI -5.46 to -1.69; moderate certainty evidence); probably reduced postdialysis mean arterial BP (MAP) (4 studies: MD -3.26 mmHg, 95% CI -1.70 to -4.82; moderate certainty evidence); probably reduced predialysis serum [Na+] (7 studies: MD -1.69 mM, 95% CI -2.36 to -1.02; moderate certainty evidence); may have reduced antihypertensive medication (2 studies: SMD -0.67 SD, 95% CI -1.07 to -0.28; low certainty evidence). Compared to neutral or high dialysate [Na+], low dialysate [Na+] had the following effects on "safety" endpoints: probably increased intradialytic hypotension events (9 studies: RR 1.56, 95% 1.17 to 2.07; moderate certainty evidence); probably increased intradialytic cramps (6 studies: RR 1.77, 95% 1.15 to 2.73; moderate certainty evidence).Compared to neutral or high dialysate [Na+], low dialysate [Na+] may make little or no difference to: intradialytic BP (2 studies: MD for systolic BP -3.99 mmHg, 95% CI -17.96 to 9.99; diastolic BP 1.33 mmHg, 95% CI -6.29 to 8.95; low certainty evidence); interdialytic BP (2 studies:, MD for systolic BP 0.17 mmHg, 95% CI -5.42 to 5.08; diastolic BP -2.00 mmHg, 95% CI -4.84 to 0.84; low certainty evidence); dietary salt intake (2 studies: MD -0.21g/d, 95% CI -0.48 to 0.06; low certainty evidence).Due to very low quality of evidence, it is uncertain whether low dialysate [Na+] changed extracellular fluid status, venous tone, arterial vascular resistance, left ventricular mass or volumes, thirst or fatigue. Studies did not examine cardiovascular or all-cause mortality, cardiovascular events, or hospitalisation.

Authors' Conclusions: It is likely that low dialysate [Na+] reduces intradialytic weight gain and BP, which are effects directionally associated with improved outcomes. However, the intervention probably also increases intradialytic hypotension and reduces serum [Na+], effects that are associated with increased mortality risk. The effect of the intervention on overall patient health and well-being is unknown. Further evidence is needed in the form of longer-term studies in contemporary settings, evaluating end-organ effects in small-scale mechanistic studies using optimal methods, and clinical outcomes in large-scale multicentre RCTs.
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http://dx.doi.org/10.1002/14651858.CD011204.pub2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6353061PMC
January 2019

Update: Rationale and design of the Sodium Lowering In Dialysate (SoLID) trial: a randomised controlled trial of low versus standard dialysate sodium concentration during hemodialysis for regression of left ventricular mass.

BMC Nephrol 2015 Aug 1;16:120. Epub 2015 Aug 1.

Auckland Clinical School, Faculty of Medical and Health Sciences, University of Auckland, Private Bag 93311, Otahuhu, Auckland, 1640, New Zealand.

After the publication of our paper Dunlop et al. "Rationale and design of the Sodium Lowering In Dialysate (SoLID) trial: a randomised controlled trial of low versus standard dialysate sodium concentration during hemodialysis for regression of left ventricular mass", we became aware of further data correlating left ventricular (LV) mass index at baseline and their corresponding mass at 12 months, using cardiac magnetic resonance imaging (MRI) in patients on hemodialysis. The original published sample size for the SoLID trial of 118 was a conservative estimate, calculated using analysis of covariance and a within person Pearson's correlation for LV mass index of 0.75. New data communicated to the SoLID trial group has resulted in re-calcuation of the sample size, based upon a within person Pearson's correlation of 0.8 but otherwise unchanged assumptions. As a result, the SoLID trial will now recruit 96 participants.
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http://dx.doi.org/10.1186/s12882-015-0080-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4528362PMC
August 2015

Providencia rettgeri peritonitis in a patient on peritoneal dialysis with perforated appendicitis.

Perit Dial Int 2014 Jul-Aug;34(5):569-70

Department of Renal Medicine, Counties Manukau District Health Board, Auckland, New Zealand Faculty of Medical and Health Sciences, University of Auckland, Auckland, New ZealandDepartment of Renal Medicine, Counties Manukau District Health Board, Auckland, New Zealand Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4114679PMC
http://dx.doi.org/10.1177/089686081403400501DOI Listing
May 2015

Rationale and design of the Myocardial Microinjury and Cardiac Remodeling Extension Study in the Sodium Lowering in Dialysate trial (Mac-SoLID study).

BMC Nephrol 2014 Jul 21;15:120. Epub 2014 Jul 21.

Faculty of Medical and Health Sciences, University of Auckland, Private Bag 93311, Otahuhu, Auckland 1640, New Zealand.

Background: The Sodium Lowering in Dialysate (SoLID) trial is an ongoing a multi-center, prospective, randomised, single-blind (assessor), controlled, parallel assignment clinical trial, enrolling 96 home and self-care hemodialysis (HD) patients from 7 centers in New Zealand. The trial will evaluate the hypothesis that lower dialysate [Na+] during HD results in lower left ventricular (LV) mass. Since it's inception, observational evidence has suggested increased mortality risk with lower dialysate [Na+], possibly due to exacerbation of intra-dialytic hypotension and subsequent myocardial micro-injury. The Myocardial Micro-injury and Cardiac Remodeling Extension Study in the Sodium Lowering In Dialysate Trial (Mac-SoLID study) aims to determine whether lower dialysate [Na+] results in (i) increased levels of high-sensitivity Troponin T (hsTnT), a well-established marker of intra-dialytic myocardial micro-injury in HD populations, and (ii) increased fixed LV segmental wall motion abnormalities, a marker of recurrent myocardial stunning and micro-injury, and (iii) detrimental changes in LV geometry due to maladaptive homeostatic mechanisms.

Methods/design: The SoLID trial and the Mac-SoLID study are funded by the Health Research Council of New Zealand. Key exclusion criteria: patients who dialyse > 3.5 times per week, pre-dialysis serum sodium <135 mM, and maintenance haemodiafiltration. In addition, some medical conditions, treatments or participation in other dialysis trials that contraindicate the study intervention or confound its effects, will be exclusion criteria. The intervention and control groups will receive dialysate sodium 135 mM and 140 mM respectively, for 12 months. The primary outcome measure for the Mac-SOLID study is repeated measures of [hsTnT] at 0, 3, 6, 9, and 12 months. The secondary outcomes will be assessed using cardiac magnetic resonance imaging (MRI), and comprise LV segmental wall motion abnormality scores, LV mass to volume ratio and patterns of LV remodeling at 0 and 12 months.

Discussion: The Mac-SoLID study enhances and complements the SoLID trial. It tests whether potential gains in cardiovascular health (reduced LV mass) which low dialysate [Na+] is expected to deliver, are counteracted by deterioration in cardiovascular health through alternative mechanisms, namely repeated LV stunning and micro-injury.

Trial Registration: Australian and New Zealand Clinical Trials Registry number: ACTRN12611000975998.
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http://dx.doi.org/10.1186/1471-2369-15-120DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4114800PMC
July 2014

Treatment resistant gastric antral vascular ectasia in a patient undergoing haemodialysis.

J Ren Care 2014 Dec 25;40(4):263-5. Epub 2014 Jun 25.

Department of Renal Medicine, Middlemore Hospital, South Auckland, Papatoetoe, New Zealand.

Gastric antral vascular ectasia (GAVE) is an important cause of upper gastrointestinal bleeding and has a high prevalence in patients with renal insufficiency. We report the first documented case of a 52-year-old patient on haemodialysis with GAVE refractory to repeated endoscopic argon plasma coagulation (APC) therapy and highlight the difficulties in its management. We recognise the need for further studies to investigate the optimal management of this condition and suggest alternative treatment strategies to be considered in patients with APC refractory GAVE, such as endoscopic band ligation and changing dialysis modality.
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http://dx.doi.org/10.1111/jorc.12077DOI Listing
December 2014

Rationale and design of the Sodium Lowering In Dialysate (SoLID) trial: a randomised controlled trial of low versus standard dialysate sodium concentration during hemodialysis for regression of left ventricular mass.

BMC Nephrol 2013 Jul 15;14:149. Epub 2013 Jul 15.

South Auckland Clinical School, Faculty of Medical and Health Sciences, University of Auckland, Private Bag 93311, Otahuhu, Auckland 1640, New Zealand.

Background: The current literature recognises that left ventricular hypertrophy makes a key contribution to the high rate of premature cardiovascular mortality in dialysis patients. Determining how we might intervene to ameliorate left ventricular hypertrophy in dialysis populations has become a research priority. Reducing sodium exposure through lower dialysate sodium may be a promising intervention in this regard. However there is clinical equipoise around this intervention because the benefit has not yet been demonstrated in a robust prospective clinical trial, and several observational studies have suggested sodium lowering interventions may be deleterious in some dialysis patients.

Methods/design: The Sodium Lowering in Dialysate (SoLID) study is funded by the Health Research Council of New Zealand. It is a multi-centre, prospective, randomised, single-blind (outcomes assessor), controlled parallel assignment 3-year clinical trial. The SoLID study is designed to study what impact low dialysate sodium has upon cardiovascular risk in dialysis patients. The study intends to enrol 118 home hemodialysis patients from 6 sites in New Zealand over 24 months and follow up each participant over 12 months. Key exclusion criteria are: patients who dialyse more frequently than 3.5 times per week, pre-dialysis serum sodium of <135 mM, and maintenance hemodiafiltration. In addition, some medical conditions, treatments or participation in other dialysis trials, which contraindicate the SoLID study intervention or confound its effects, will be exclusion criteria. The intervention and control groups will be dialysed using dialysate sodium 135 mM and 140 mM respectively, for 12 months. The primary outcome measure is left ventricular mass index, as measured by cardiac magnetic resonance imaging, after 12 months of intervention. Eleven or more secondary outcomes will be studied in an attempt to better understand the physiologic and clinical mechanisms by which lower dialysate sodium alters the primary end point.

Discussion: The SoLID study is designed to clarify the effect of low dialysate sodium upon the cardiovascular outcomes of dialysis patients. The study results will provide much needed information about the efficacy of a cost effective, economically sustainable solution to a condition which is curtailing the lives of so many dialysis patients.

Trial Registration: Australian and New Zealand Clinical Trials Registry number: ACTRN12611000975998.
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http://dx.doi.org/10.1186/1471-2369-14-149DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3720185PMC
July 2013

Independent community house hemodialysis as a novel dialysis setting: an observational cohort study.

Am J Kidney Dis 2013 Apr 7;61(4):598-607. Epub 2012 Dec 7.

Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand.

Background: There is revived interest in home hemodialysis (HD), which is spurred by cost containment and experience indicating lower mortality risk compared with facility HD and peritoneal dialysis (PD). Social barriers to home HD include disruptions to the home environment, interference with family life, overburdening of support networks, and fear of social isolation. A submodality of home HD, in which patients from urban settings undertake independent HD in unstaffed nonmedical community-based home-like settings, is described in this study. The survival of patients treated in this manner is compared with that of those using conventional home HD.

Study Design: An observational cohort study using the Australia and New Zealand Dialysis and Transplant Registry.

Setting & Participants: All adult patients starting renal replacement therapy in New Zealand since March 31, 2000, followed up through December 31, 2010.

Predictor: The main predictor was time-varying dialysis modality (home HD, facility HD, PD, and community house HD), adjusting for the confounding effects of patient demographics and time-varying comorbid conditions.

Outcome: Patient mortality.

Results: 4,709 patients with 12,883 patient-years of follow-up (5,591, PD; 1,532, home HD; 5,647, facility HD; and 113, community house HD) were analyzed. Community house HD patients were younger, healthier, and more likely to be Pacific people than those using other modalities, including home HD. Relative to home HD, adjusted mortality HRs were 2.18 (95% CI, 1.78-2.67) for facility HD, 2.17 (95% CI, 1.77-2.66) for PD, and 1.48 (95% CI, 0.64-3.40) for community house HD.

Limitations: Small number of patients receiving community house HD, possible residual confounding from the limited collection of comorbid conditions (eg, no collection of cognitive or motor impairment), and absence of socioeconomic, medication, and biochemical data in analyses.

Conclusions: Within limits, this study shows community house HD to be both safe and effective. Community house HD provides an option to improve the uptake of home HD.
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http://dx.doi.org/10.1053/j.ajkd.2012.10.020DOI Listing
April 2013

Are dialysate sodium levels too high?

Semin Dial 2012 May 9;25(3):277-83. Epub 2012 Apr 9.

Universal lower dialysate [Na+] is often advocated as a means of improving the dire cardiovascular plight of our dialysis patients. However, there is evidence associating lower dialysate [Na+] and increased morbidity and mortality especially in frailer patients, probably as a result of more frequent intra-dialytic hypotension. In this editorial, we summarize arguments for and against lower dialysate [Na+], and provide recommendations around selecting the most appropriate dialysate [Na+] for specific clinical subsets that may benefit from manipulation of salt and water balance. The lack of overall clarity on relative benefits and risks of lower dialysate [Na+] does not support the case for empirical "across the board" change, and experimental testing in clinical trials is required to determine safe and effective use.
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http://dx.doi.org/10.1111/j.1525-139X.2012.01072.xDOI Listing
May 2012

Major spontaneous renal haemorrhage as an unusual complication of systemic amyloidosis.

J Ren Care 2011 Jun;37(2):72-4

Renal Department, Salford Royal NHS Foundation Trust, Salford, UK.

We report the case of a patient with systemic amyloidosis who developed a life-threatening spontaneous haemorrhage from an amyloid kidney. A review of the literature suggests that this is a rare complication of renal amyloidosis. However, the grossly abnormal renal angiography observed in our patient has previously been described in the literature. Therefore, spontaneous renal haemorrhage should be considered a risk in any systemic amyloid patient, especially in the differential diagnosis for those patients with the condition who present with an acute abdomen.
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http://dx.doi.org/10.1111/j.1755-6686.2011.00214.xDOI Listing
June 2011
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