Robert Walker

Followers

Following

Co-authors

Public Views

Interests

Uploads

Papers by Robert Walker

Evidence for involvement of human CYP3A in the 3‐hydroxylation of quinine

British Journal of Clinical Pharmacology, 2003

Aims Our previous studies using in vitro hepatic microsomal preparations suggested that the hepat... more Aims Our previous studies using in vitro hepatic microsomal preparations suggested that the hepatic metabolism of quinine to form the major metabolite 3-hydroxyquinine is most likely catalysed by human P450 3A (CYP3A). The present study was carried out to investigate the kinetics and to identify and further characterise the human liver CYP isoforms involved in the metabolism of quinine. Methods In vitro human microsomal techniques were employed. Results The mean apparent K m value for 3-hydroxyquinine formation was 83±19 (s.d.) mm, ranging from 57 mm to 123 mm in microsomes from ten human livers. There was a 6.7-fold variation in V max values (mean 547±416 pmol min −1 mg −1). Quinine 3-hydroxylation was inhibited by the specific CYP3A inhibitors, troleandomycin, midazolam and erythromycin. Inhibitors selective for CYP1A1/2, CYP2D6, CYP2E1, CYP2C9/10 or CYP2C19 had little or no effect on quinine 3-hydroxylation. Using microsomes from a panel of livers, significant correlations were found only between 3-hydroxyquinine activity and other CYP3A activities (caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1∞-hydroxylation and midazolam 4-hydroxylation) and immunoreactive CYP3A content. There were no statistically significant correlations with activities selective for CYP1A2, CYP2C9 and CYP2E1. Competitive inhibition of quinine 3-hydroxylation was observed with a substrate known to be specifically metabolized by human CYP3A, i.e. midazolam, with an apparent K i value of 11.0 mm. Conclusions The present results strongly indicate that the conversion of quinine to 3-hydroxyquinine is the major metabolic pathway in human liver in vitro and that the reaction is catalysed by CYP3A isoforms.

Download

The effect of spironolactone on cardiac and renal fibrosis following myocardial infarction in established hypertension in the transgenic Cyp1a1Ren2 rat

The renin-angiotensin-aldosterone axis plays a key role in mediating cardiac and kidney injury. M... more The renin-angiotensin-aldosterone axis plays a key role in mediating cardiac and kidney injury. Mineralocorticoid receptor antagonism has beneficial effects on cardiac dysfunction, but effects are less well quantified in the cardiorenal syndrome. This study investigated cardiac and kidney pathophysiology following permanent surgical ligation to induce myocardial infarction (MI) in hypertensive animals with or without mineralocorticoid receptor antagonism. Methods Hypertension was induced in adult male Cyp1a1Ren2 rats. Hypertensive animals underwent MI surgery (n = 6), and were then treated daily with spironolactone for 28 days with serial systolic blood pressure measurements, echocardiograms and collection of urine and serum biochemical data. They were compared to hypertensive animals (n = 4), hypertensive animals treated with spironolactone (n = 4), and hypertensive plus MI without spironolactone (n = 6). Cardiac and kidney tissue was examined for histological and immunohistochemical analysis. Results MI superimposed on hypertension resulted in an increase in interstitial cardiac fibrosis (p<0.001), renal cortical interstitial fibrosis (p<0.01) and glomerulosclerosis (p<0.01). Increased fibrosis was accompanied by myofibroblast and macrophage infiltration in the heart and the kidney. Spironolactone post-MI, diminished the progressive fibrosis (p<0.001) and inflammation (myofibroblasts (p<0.05); macrophages (p<0.01)) in both the heart and the kidney, despite persistently elevated SBP (182±19 mmHg). Despite the reduction in inflammation and fibrosis, spironolactone did not modify ejection fraction, proteinuria, or renal function when compared to untreated animals post MI.

Download

Predictors of Health Deterioration Among Older New Zealanders Undergoing Dialysis: A Three-Year Accelerated Longitudinal Cohort Study

Canadian Journal of Kidney Health and Disease

Background: Patient involvement in dialysis decision-making is crucial, yet little is known about... more Background: Patient involvement in dialysis decision-making is crucial, yet little is known about patient-reported outcomes over time on dialysis. Objective: To examine health-related outcomes over 24 and 36 months in an older cohort of dialysis patients. Design: The “Dialysis outcomes in those aged ≥65 years study” is a prospective longitudinal cohort study of New Zealanders with kidney failure. Setting: Three New Zealand nephrology units. Patients: Kidney failure (dialysis and predialysis) patients aged 65 or above. We have previously described outcomes after 12 months of dialysis therapy relative to baseline. Measurements: Patient-reported social and health factors using the SF-36, EQ-5D, and Kidney Symptom Score questionnaires. Methods: This article describes and compares characteristics of 120 older kidney failure patients according to whether they report “Same/better” or “Worse” health 24 and 36 months later, and identifies predictors of “worse health.” Modified Poisson regres...

Download

Experiences of New Zealand Haemodialysis Patients in Relation to Food and Nutrition Management: A Qualitative Study

Nutrients, 2021

People receiving haemodialysis have considerable and complex dietary and healthcare needs, includ... more People receiving haemodialysis have considerable and complex dietary and healthcare needs, including co-morbidities. A recent New Zealand study has shown that few patients on haemodialysis are able to meet nutritional requirements for haemodialysis. This study aims to describe the perspectives and experiences of dietary management among patients on haemodialysis in New Zealand. This exploratory qualitative study used in-depth semi-structured interviews. Purposive sampling was used to recruit participants from different ethnic groups. Forty interviews were conducted, audio-recorded and transcribed verbatim. An inductive approach was taken using thematic analysis. Forty participants were interviewed. Participants spoke of major disruption to their lives as a result of their chronic kidney disease and being on haemodialysis, including loss of employment, financial challenges, loss of independence, social isolation and increased reliance on extended family. Most had received adequate di...

Download

Transmission Electron Microscopy Tilt-Series Data from In-Situ Chondrocyte Primary Cilia

Data

The primary cilium has recently become the focus of intensive investigations into understanding t... more The primary cilium has recently become the focus of intensive investigations into understanding the physical structure and processes of eukaryotic cells. This paper describes two tilt-series image datasets, acquired by transmission electron microscopy, of in situ chick-embryo sternal-cartilage primary cilia. These data have been released under an open-access licence, and are well suited to tomographic reconstruction and modelling of the cilium.

Download

Myocardial global longitudinal strain: An early indicator of cardiac interstitial fibrosis modified by spironolactone, in a unique hypertensive rat model

PLOS ONE

Is global longitudinal strain (GLS) a more accurate non-invasive measure of histological myocardi... more Is global longitudinal strain (GLS) a more accurate non-invasive measure of histological myocardial fibrosis than left ventricular ejection fraction (LVEF) in a hypertensive rodent model. Background Hypertension results in left ventricular hypertrophy and cardiac dysfunction. Speckle-tracking echocardiography has emerged as a robust technique to evaluate cardiac function in humans compared with standard echocardiography. However, its use in animal studies is less clearly defined. Methods Cyp1a1Ren2 transgenic rats were randomly assigned to three groups; normotensive, untreated hypertensive or hypertensive with daily administration of spironolactone (human equivalent dose of 50 mg/day). Cardiac function and interstitial fibrosis development were monitored for three months. Results The lower limit of normal LVEF was calculated to be 75%. After three months hypertensive animals (196±21 mmHg systolic blood pressure (SBP)) showed increased cardiac fibrosis (8.8±3.2% compared with 2.4±0.7% % in normals), reduced LVEF (from 81±2% to 67±7%) and impaired myocardial GLS (from-17±2% to-11±2) (all p<0.001). Myocardial GLS demonstrated a stronger correlation with cardiac interstitial fibrosis (r 2 = 0.58, p<0.0001) than LVEF (r 2 = 0.37, p<0.006). Spironolactone significantly blunted SBP elevation (184±15, p<0.01), slowed the progression of cardiac fibrosis (4.9±1.4%, p<0.001), reduced the PLOS ONE |

Download

Renal Fibrosis mRNA Classifier: Validation in Experimental Lithium-Induced Interstitial Fibrosis in the Rat Kidney

PloS one, 2016

Accurate diagnosis of fibrosis is of paramount clinical importance. A human fibrosis classifier b... more Accurate diagnosis of fibrosis is of paramount clinical importance. A human fibrosis classifier based on metzincins and related genes (MARGS) was described previously. In this investigation, expression changes of MARGS genes were explored and evaluated to examine whether the MARGS-based algorithm has any diagnostic value in a rat model of lithium nephropathy. Male Wistar rats (n = 12) were divided into 2 groups (n = 6). One group was given a diet containing lithium (40 mmol/kg food for 7 days, followed by 60mmol/kg food for the rest of the experimental period), while a control group (n = 6) was fed a normal diet. After six months, animals were sacrificed and the renal cortex and medulla of both kidneys removed for analysis. Gene expression changes were analysed using 24 GeneChip® Affymetrix Rat Exon 1.0 ST arrays. Statistically relevant genes (p-value<0.05, fold change>1.5, t-test) were further examined. Matrix metalloproteinase-2 (MMP2), CD44, and nephroblastoma overexpressed...

Download

Spirituality in Renal Supportive Care: A Thematic Review

Healthcare, 2015

Chronic kidney disease is marked by a reduced life expectancy and a high symptom burden. For thos... more Chronic kidney disease is marked by a reduced life expectancy and a high symptom burden. For those who reach end-stage renal disease, the prognosis is poor, and this combined with the growing prevalence of the disease necessitates supportive and palliative care programmes that will address people's psychosocial, cultural and spiritual needs. While there is variation between countries, research reveals that many renal specialist nurses and doctors are reluctant to address spirituality, initiate end-of-life conversations or implement conservative treatment plans early. Yet, other studies indicate that the provision of palliative care services, which includes the spiritual dimension, can reduce symptom burden, assist patients in making advanced directives/plans and improve health-related quality of life. This review brings together the current literature related to renal supportive care and spirituality under the following sections and themes. The introduction and background sections situate spirituality in both healthcare generally and chronic kidney disease. Gaps in the provision of chronic kidney disease spiritual care are then considered, followed by a discussion of the palliative care model related to chronic kidney disease and spirituality. Chronic kidney disease spiritual needs and care approaches are discussed with reference to advanced care planning, hope, grief and relationships. A particular focus on quality of life is developed, with spirituality

Download

Spontaneous perinephric haemorrhage in an end-stage renal disease patient with multiple renal pseudoaneurysms

Nephrology (Carlton, Vic.), 2015

A 54-year-old man with end-stage renal disease (ESRD) secondary to presumed atypical haemolytic u... more A 54-year-old man with end-stage renal disease (ESRD) secondary to presumed atypical haemolytic uraemic syndrome (HUS) on long-term peritoneal dialysis presented with right-sided abdominal pain, haemodynamic instability and a sudden drop in haemoglobin from 11 g/dL to 5.3 g/dL. Medical history included hepatitis C with mild disease activity (alanine transaminase 8 U/L, hepatitis C virus RNA 859 658 iU/mL) and grade 1 hepatic fibrosis and a failed renal transplant due to presumed recurrent HUS. Computed tomography (CT) scan of the abdomen showed a right-sided perinephric haematoma. Renal angiography confirmed bleeding from one of multiple intra-renal pseudoaneurysms (Fig. 1) and he underwent successful angiographic embolization of the right kidney with subsequent rapid return of haemodynamic stability. He was discharged home on day 2 post-procedure. Follow-up angiography of the contralateral kidney failed to show any vascular abnormalities, but did have evidence of acquired cystic kidney disease. Spontaneous perinephric haemorrhage is an uncommon but recognized complication of chronic kidney disease (ESRD). We report a 54-year-old ESRD patient presenting with spontaneous perinephric haemorrhage from one of multiple intra-renal pseudoaneurysms. Classically, the condition is said to present as ‘Lenk’s triad’ of acute flank pain, tenderness and symptoms of internal bleeding. Confirmation of the diagnosis requires renal imaging, usually either via ultrasound or CT. In non-dialysis patients, most cases of spontaneous nontraumatic haemorrhage occur because of an underlying renal tumour, most commonly a renal cell carcinoma or angiomyolipoma. In dialysis patients who do not have an underlying tumour, haemorrhage usually relates to the development of acquired cystic renal disease. Renal pseudoaneurysms are arterially perfused haematomas contained within the renal parenchyma. They usually arise as a result of blunt renal trauma or following renal instrumentation. Spontaneous renal pseudoaneurysms are rare and often caused by underlying vascular disease or vasculitis (usually polyarteritis nodosa). Haemorrhage into a cyst can also occur in acquired cystic kidney disease. To our knowledge, this is the first reported case of multiple unilateral non-traumatic intraparenchymal renal pseudoaneurysms in a patient with chronic kidney disease leading to perinephric haemorrhage. The unilateral nature of the pseudoaneurysms is unusual. We postulate that the multiple unilateral renal pseudoaneurysms may represent localized hepatitis C related polyarteritis nodosa disease. This case highlights the importance of considering this diagnosis in dialysis patients presenting with Lenk’s triad and the need for prompt imaging to confirm diagnosis and expedite treatment. In addition, patients with conditions predisposing to vasculitis, for example, hepatitis C, may be more prone to developing pseudoaneurysms and complications thereof.

Fitness alters fluid regulatory but not behavioural responses to hypohydrated exercise

Physiology & Behavior, 2008

Dehydration is typical during prolonged exercise. Because training stimulates numerous adaptation... more Dehydration is typical during prolonged exercise. Because training stimulates numerous adaptations, some involving fluid regulation, it is conceivable that training involves adaptations to dehydration. This study tested the hypothesis that trained individuals have altered fluid regulatory, but not behavioural or perceptual responses to exercise when hypohydrated. Six trained (V.O2 peak: 65+/-8 mL kg(-1) min(-1)) and six untrained (V.O2 peak: 45+/-4 mL kg(-1) min(-1)) males cycled for 40 min at 70%V.O2 peak, once whilst euhydrated (EUH) and once whilst hypohydrated by ~2% body mass (HYPO), before a 40-min performance trial with euhydration (in EUH) or ad libitum drinking (in HYPO), in temperate conditions (24.3 degrees C, 50% rh). Baseline hydration was achieved by complete or partial rehydration from exercise+heat stress on the previous evening. Body mass was reduced (-1.8+/-0.1%) and plasma osmolality was increased (5+/-1 mosmol kg(-1)) similarly between fitness groups in HYPO compared to EUH (P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.05). During exercise, plasma [AVP] rose more in HYPO than EUH; the elevation was greater in the Untrained (4.1+/-1.7 vs. 2.0+/-0.8 pmol L(-1), P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.01) than Trained (1.4+/-0.6 vs. 1.1+/-0.5 pmol L(-1), P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.01; P=0.02). Increases in plasma [AVP] relative to osmolality were higher in Untrained than Trained (0.47+/-0.06 vs. 0.025+/-0.05 pmol mosmol(-1), P=0.03). Fitness groups had equivalent thirst ratings during fixed exercise but Trained were thirstier than Untrained when self regulating in HYPO (4.0+/-1.5 vs. 2.7+/-1.2; P=0.05); thus Trained tended to consume more fluid (1.20+/-0.16 vs. 0.88+/-0.16 L; P=0.19), but maintained similar hypohydration consistent with their greater sweat rate during HYPO. In conclusion, aerobic fitness attenuates the neuroendocrine ([AVP]) response to hypohydrated exercise, but not perceptual (thirst) or behavioural (ad libitum drinking) responses.

Effects of Early and Late Intervention with Epoetin on Left Ventricular Mass among Patients with Chronic Kidney Disease (Stage 3 or 4): Results of a Randomized Clinical Trial

Journal of the American Society of Nephrology, 2004

It is not known whether prevention of anemia among patients with chronic kidney disease would aff... more It is not known whether prevention of anemia among patients with chronic kidney disease would affect the development or progression of left ventricular (LV) hypertrophy. A randomized controlled trial was performed with 155 patients with chronic kidney disease (creatinine clearance, 15 to 50 ml/min), with entry hemoglobin concentrations ([Hb]) of 110 to 120 g/L (female patients) or 110 to 130 g/L (male patients). Patients were monitored for 2 yr or until they required dialysis; the patients were randomized to receive epoetin ␣ as necessary to maintain [Hb] between 120 and 130 g/L (group A) or between 90 and 100 g/L (group B). [Hb] increased for group A (from 112 Ϯ 9 to 121 Ϯ 14 g/L, mean Ϯ SD) and decreased for group B (from 112 Ϯ 8 to 108 Ϯ 13 g/L) (P Ͻ 0.001, group A versus group B). On an intent-to-treat analysis, the changes in LV mass index for the groups during the 2-yr period were not significantly different (2.5 Ϯ 20 g/m 2 for group A versus 4.5 Ϯ 20 g/m 2 for group B, P ϭ NS). There was no significant difference between the groups in 2-yr mean unadjusted systolic BP (141 Ϯ 14 versus 138 Ϯ 13 mmHg) or diastolic BP (80 Ϯ 6 versus 79 Ϯ 7 mmHg). The decline in renal function in 2 yr, as assessed with nuclear estimations of GFR, also did not differ significantly between the groups (8 Ϯ 9 versus 6 Ϯ 8 ml/min per 1.73 m 2). In conclusion, maintenance of [Hb] above 120 g/L, compared with 90 to 100 g/L, had similar effects on the LV mass index and did not clearly affect the development or progression of LV hypertrophy. The maintenance of [Hb] above 100 g/L for many patients in group B might have been attributable to the relative preservation of renal function. Chronic kidney disease (CKD) is widespread in the community, with a prevalence far exceeding previous estimates (1). Many studies examining mortality and morbidity rates among patients with CKD have identified high rates of cardiovascular

Download

Increasing home-based dialysis therapies to tackle dialysis burden around the world: A position statement on dialysis economics from the 2nd Congress of the International Society for Hemodialysis

Hemodialysis International, 2011

Download

Chronic interstitial fibrosis in the rat kidney induced by long-term (6-mo) exposure to lithium

AJP: Renal Physiology, 2013

There is a lack of suitable animal models that replicate the slowly progressive chronic interstit... more There is a lack of suitable animal models that replicate the slowly progressive chronic interstitial fibrosis that is characteristic of many human chronic nephropathies. We describe a chronic long-term (6-mo) model of lithium-induced renal fibrosis, with minimal active inflammation, which mimics chronic kidney interstitial fibrosis seen in the human kidney. Rats received lithium via their chow (60 mmol lithium/kg food) daily for 6 mo. No animals died during the exposure. Nephrogenic diabetes insipidus was established by 3 wk and persisted for the 6 mo. Following metabolic studies, the animals were killed at 1, 3, and 6 mo and the kidneys were processed for histological and immunohistochemical studies. Progressive interstitial fibrosis, characterized by increasing numbers of myofibroblasts, enhanced transforming growth factor-β1 expression and interstitial collagen deposition, and a minimal inflammatory cellular response was evident. Elucidation of the underlying mechanisms of injury...

Download

Sulfadiazine-induced crystal nephropathy: a new ‘old’ problem

Nephrology, 2015

With a greater awareness of toxoplasmosis infections, and increased prescribing of sulfadaizine, ... more With a greater awareness of toxoplasmosis infections, and increased prescribing of sulfadaizine, it is timely to remind colleagues of a largely forgotten clinical presentation. We present the case of crystal nephropathy secondary to sulfadiazine prescribed for retinal toxoplasmosis. A 60 year-old with left chorioretinal toxoplasmosis presented with 18 h of severe bilateral constant flank pain, nausea and acute kidney injury. He had no known renal disease. He had normal renal function prior to commencement of pyrimethamine 75 mg and sulfadiazine 1.5 g four times daily 6 days earlier. He was afebrile, blood pressure was 163/99 mmHg, and his abdominal examination revealed marked bilateral renal angle tenderness. His urine output was reduced. Initial plasma creatinine was 309 umol/L, and peaked at 530 umol/L, before rapidly improving following intervention. Urine microscopy showed many crystals, including dumbbell-shaped crystals (Fig. 1) with a positive Lignin test. Urinalysis showed no haematuria or proteinuria, pH 6 and <10 × 10 white cells/L. These urinary findings confirmed a diagnosis of sulfadiazine-induced crystal nephropathy. The patient was treated with intravenous sodium bicarbonate, 0.9% saline and frusemide to achieve a urine output over 100 mL/h and urine pH above 7.15. Following 3 days of treatment, the urine was devoid of crystals, and the lignin test was now negative, indicating resolving sulfadiazineinduced crystal nephropathy. One week later, his renal function had returned to normal.

Spironolactone mitigates, but does not reverse, the progression of renal fibrosis in a transgenic hypertensive rat

Physiological Reports

The pharmacokinetics of meropenem and piperacillin-tazobactam during sustained low efficiency haemodiafiltration (SLED-HDF)

European Journal of Clinical Pharmacology

Recruitment and participant baseline characteristics in the dialysis outcomes in those aged 65 years or older study

BMC Nephrology

Background: Despite an increasing number of older people commencing dialysis the impact of dialys... more Background: Despite an increasing number of older people commencing dialysis the impact of dialysis on their quality of life and survival, remains unclear. The Dialysis Outcomes in those aged over 65 years or older study is an accelerated prospective cohort longitudinal design study, designed to obtain sufficient health related quality of life data, linked to clinical data, to inform clinicians' and patients' decision-making with respect to end stage kidney disease (ESKD), outcomes, and options for management in New Zealand (NZ). Methods: The study has an accelerated prospective cohort longitudinal design, comprised of cross-sectional and longitudinal components. We report the baseline data on the 225 participants enrolled in the study. Dialysis duration was grouped in tertiles from less than one year (incident patients), 1-3 years and greater than 3 years. Health related quality of life data was obtained from self-reported questionnaires including KDQoL-36, EQ-5D-3 L, FACIT, WHODAS II, and the Personal Well-being Score. Results: The median age of the cohort was 71 years and two thirds were male. Three quarters of the participants were on dialysis at the baseline, with 42% of those on home dialysis (haemodialysis or peritoneal dialysis). Māori and Pacific people were over represented (20% Māori and 24% Pacific) in the sample, when compared to the general NZ population of the same age group (where 5% are Māori and 2% are Pacific). At baseline, there were no differences observed in sociodemographic, quality of life or health characteristics between the dialysis groups either by modality or duration of dialysis. Conclusions: We report the baseline characteristics of participants enrolled prospectively into a longitudinal cohort observational study examining health related quality of life factors with clinical characteristics on dialysis outcomes in a group of New Zealanders aged 65 years or older who are either on dialysis or have been educated about dialysis (BMC Nephrol 14:175, 2013). Subsequent publications are planned, analysing the prospective longitudinal data to identify key factors that determine both outcome and quality of life for individuals of this age group. Trial registration: ACTRN12611000024943.

Download

Sympathetic overactivity in dialysis patients-Underappreciated and clinically consequential

Seminars in dialysis, Jan 21, 2018

Cardiovascular morbidity and mortality remain frustratingly common in dialysis patients. A dearth... more Cardiovascular morbidity and mortality remain frustratingly common in dialysis patients. A dearth of established evidence-based treatment calls for alternative therapeutic avenues to be embraced. Sympathetic hyperactivity, predominantly due to afferent nerve signaling from the diseased native kidneys, has been established to be prognostic in the dialysis population for over 15 years. Despite this, tangible therapeutic interventions have, to date, been unsuccessful and the outlook for patients remains poor. This narrative review summarizes established experimental and clinical data, highlighting recent developments, and proposes why interventions to ameliorate sympathetic hyperactivity may well be beneficial for this high-risk population.

Breeding Characteristics and Dose-dependent Blood Pressure Responses of Transgenic Cyp1a1-Ren2 Rats

Comparative medicine, Jan 5, 2018

Hypertension is a leading risk factor for cardiovascular and chronic kidney disease. A new rodent... more Hypertension is a leading risk factor for cardiovascular and chronic kidney disease. A new rodent model (transgenic maleCyp1a1-Ren2 rats) provides reversible induction of hypertension through the addition of indole-3-carbinol (I3C) to the diet,without the need for surgical intervention, thus giving researchers control over both the onset of hypertension and its magnitude(I3C dose-dependency). We here report the breeding performance and productivity of Cyp1a1-Ren2 rats. Despite beingtransgenic, these animals proved to be efficient breeders. In addition to confirming inducible and reversible dose-dependenthypertension (by using I3C doses of 0.125%, 0.167%, and 0.25% [w/w] in the diet for 14 d, followed by normal chow for 4 d),we demonstrated that hypertension can be sustained chronically (14 wk) by continuous dosing with I3C (0.167% [w/w]) inthe diet. In chronically dosed male rats, systolic blood pressure continued to rise, from 173 ± 11 mm Hg after 1 mo to 196 ±19 mm Hg after 3 mo, ...

Medication Exposure and Health Outcomes in Older Patients with End-Stage Kidney Disease: A Prospective Study Undertaken in New Zealand

Drugs & aging, Jan 8, 2018

The impact of multiple medication exposure on health outcomes among older patients with end-stage... more The impact of multiple medication exposure on health outcomes among older patients with end-stage kidney disease (ESKD) is unknown. The objective of this study was to identify the impact of medicine exposure on hospitalisation rates and mortality in a prospective longitudinal observational study of older dialysis patients. Patient demographics, medication use, hospitalisation, mortality and co-morbidity data were collected through the prospective longitudinal cohort study DOS65 + (Dialysis Outcomes in those aged ≥ 65 years Study) (n = 225). Medication exposure was measured by the total number of individual medications and the number of predetermined 'medication groups'. Associations between medications prescribed at recruitment and health outcomes as measured by hospitalisation and mortality were assessed by univariate and multivariable regression analyses. Older ESKD patients were exposed to a median of ten (0-20) medications and eight (0-15) medication groups. Multivariate...

Robert Walker

Uploads

Papers by Robert Walker

Log In