ORCID Profile
0000-0002-3520-3225
Current Organisation
John Hunter Hospital
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Publisher: Wiley
Date: 04-2021
DOI: 10.1111/IMJ.14774
Publisher: American Physiological Society
Date: 08-2015
DOI: 10.1152/AJPREGU.00526.2014
Abstract: Vitamin D deficiency (VDD) is widespread in the general population. Iodinated (IC) or gadolinium-based contrast media (Gd) may decrease renal function in high-risk patients. This study tested the hypothesis that VDD is a predisposing factor for IC- or Gd-induced nephrotoxicity. To this end, male Wistar rats were fed standard (SD) or vitamin D-free diet for 30 days. IC (diatrizoate), Gd (gadoterate meglumine), or 0.9% saline was then administered intravenously and six groups were obtained as the following: SD plus 0.9% saline (Sham-SD), SD plus IC (SD+IC), SD plus Gd (SD+Gd), vitamin D-free diet for 30 days plus 0.9% saline (Sham-VDD 30 ), vitamin D-free diet for 30 days plus IC (VDD 30 +IC), and vitamin D-free diet for 30 days plus Gd (VDD 30 +Gd). Renal hemodynamics, redox status, histological, and immunoblot analysis were evaluated 48 h after contrast media (CM) or vehicle infusion. VDD rats showed lower levels of total serum 25-hydroxyvitamin D [25(OH)D], similar plasma calcium and phosphorus concentration, and higher renal renin and angiotensinogen protein expression compared with rats fed SD. IC or Gd infusion did not affect inulin clearance-based estimated glomerular filtration rate (GFR) in rats fed SD but significantly decreased GFR in rats fed vitamin D-free diet. Both CM increased renal angiotensinogen, and the interaction between VDD and CM triggered lower renal endothelial nitric oxide synthase abundance and higher renal thiobarbituric acid reactive substances-to-glutathione ratio (an index of oxidative stress) on VDD 30 +IC and VDD 30 +Gd groups. Conversely, worsening of renal function was not accompanied by abnormalities on kidney structure. Additionally, rats on a VDD for 60 days displayed a greater fall in GFR after CM administration. Collectively, our findings suggest that VDD is a potential risk factor for IC- or Gd-induced nephrotoxicity most likely due to imbalance in intrarenal vasoactive substances and oxidative stress.
Publisher: Wiley
Date: 07-02-2020
DOI: 10.1111/NEP.13696
Abstract: Bile cast nephropathy (BCN) is an underdiagnosed cause of acute kidney injury (AKI). The precise pathogenesis of bilirubin tubular toxicity remains unknown. The aim of this study is to explore the cellular and molecular pathophysiology of human BCN. Paraffin-embedded sections of renal biopsy tissue from a BCN patient were stained by immunohistochemistry (IHC) for oxidative stress (4-hydroxynonenal), immune cell subpopulations, including dendritic cells (CD1c), macrophages (CD68) and T cells (CD3), and inflammasome activation by staining for active-caspase-1 and the inflammasome adaptor protein, ASC (apoptosis-associated speck-like protein containing a caspase activation and recruitment domain). Quantitative analyses of IHC staining were compared to healthy renal cortical tissue. We identified yellow to brown granular casts within the BCN case, consistent with the presence of bile pigment. The presence of bile pigment was associated with strong tubular 4-hydroxynonenal staining intensity, a marker of oxidative stress. Diffuse tubulointerstitial inflammatory cell infiltrate was detected, with elevated CD1c, CD68 and CD3 staining. Foci of inflammasome activity were co-localized with this intense immune cell infiltration, with increased active-caspase-1 and ASC staining. Our findings are the first to suggest that bile casts may lead to oxidative stress and trigger the inflammasome signalling cascade, leading to interstitial inflammation and driving AKI pathobiology. SUMMARY AT A GLANCE The report suggests that bile casts may lead to oxidative stress and trigger the inflammasome signalling cascade, leading to interstitial inflammation and driving bile cast nephropathy pathobiology.
Publisher: MDPI AG
Date: 27-11-2020
DOI: 10.3390/APP10238462
Abstract: Vitamin D (VD) is a steroid hormone classically known for its key role in maintaining calcium homeostasis in the body. VD also has important immunomodulatory functions. This review explores evidence for a role of VD in attenuating the activation of the nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasome. Dysregulated and inappropriate NLRP3 inflammasome activation occurs in a range of human diseases, including autoinflammatory disorders, metabolic disorders, and infections. VD appears to mediate its effects by binding of the VD receptor (VDR) to the sensor protein NLRP3, inhibiting deubiquitination and downstream inflammasome assembly. Some early clinical evidence suggests improved outcomes in inflammasome-mediated disorders when VD-deficient patients are treated with supplementation therapy.
Publisher: Springer Science and Business Media LLC
Date: 12-2021
DOI: 10.1186/S12882-021-02607-4
Abstract: Tolvaptan is the only available disease-modifying treatment for autosomal dominant polycystic kidney disease (ADPKD). Prior to October 2020 access to tolvaptan in Australia was restricted by a controlled monitoring and distribution program called IMADJIN®. Focusing on hepatic safety, the IMADJIN® program collected real-world data on patients with ADPKD. A retrospective, secondary data analysis of the IMADJIN® dataset was undertaken to determine the time to all-cause discontinuation of tolvaptan in Australia. Demographic and treatment data from 17 September 2018 to 30 September 2020 were extracted from the IMADJIN® dataset. Treatment persistence was analyzed using Kaplan-Meier methods, and Cox’s proportional hazard models were used to analyze differences in treatment persistence by age, sex and location. Four hundred seventy-nine patients with ADPKD were included in the analysis. After a median follow-up of 12.0 months (95% confidence interval [CI] 2.6, 23.4), the Kaplan-Meier estimation of 12-month persistence was 76.7% (95% CI 72.2, 80.5%). 114 (23.8%) patients discontinued treatment sex, state, and remoteness did not significantly affect treatment persistence. Patients in the youngest tertile were more likely to discontinue compared to older ages ( p = 0.049). Reasons for discontinuation included: aquaretic tolerability (4.2%), hepatic adverse events (abnormal liver function tests) (2.1%), disease progression (1.5%), and acute kidney injury (0.2%). Patients with a lack of aquaretic tolerance had shorter time to discontinuation. Hepatic toxicity events were initially observed 3 months after tolvaptan initiation and were less prevalent over time. Persistence to tolvaptan in the real-world IMADJIN® dataset was 76%. Discontinuation due to hepatic events was low. Prescribers should take extra care when initiating treatment in younger patients as they are more likely to discontinue tolvaptan compared to older in iduals. Nevertheless, the precise reason for this observation remains to be elucidated.
Publisher: Public Library of Science (PLoS)
Date: 11-07-2019
Publisher: Wiley
Date: 02-09-2020
Publisher: Wiley
Date: 13-04-2017
Publisher: John Wiley & Sons, Ltd
Date: 31-01-2013
Publisher: MDPI AG
Date: 23-04-2019
DOI: 10.3390/IJMS20081997
Abstract: Pigment nephropathy is an acute decline in renal function following the deposition of endogenous haem-containing proteins in the kidneys. Haem pigments such as myoglobin and haemoglobin are filtered by glomeruli and absorbed by the proximal tubules. They cause renal vasoconstriction, tubular obstruction, increased oxidative stress and inflammation. Haem is associated with inflammation in sterile and infectious conditions, contributing to the pathogenesis of many disorders such as rhabdomyolysis and haemolytic diseases. In fact, haem appears to be a signalling molecule that is able to activate the inflammasome pathway. Recent studies highlight a pathogenic function for haem in triggering inflammatory responses through the activation of the nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasome. Among the inflammasome multiprotein complexes, the NLRP3 inflammasome has been the most widely characterized as a trigger of inflammatory caspases and the maturation of interleukin-18 and -1β. In the present review, we discuss the latest evidence on the importance of inflammasome-mediated inflammation in pigment nephropathy. Finally, we highlight the potential role of inflammasome inhibitors in the prophylaxis and treatment of pigment nephropathy.
Publisher: Elsevier BV
Date: 12-2016
DOI: 10.1016/J.FREERADBIOMED.2016.10.012
Abstract: Acute kidney injury (AKI) is the most severe complication of rhabdomyolysis. Allopurinol (Allo), a xanthine oxidase inhibitor, has been in the spotlight in the last decade due to new therapeutic applications related to its potent antioxidant effect. The aim of this study was to evaluate the efficacy of Allo in the prevention and treatment of rhabdomyolysis-associated AKI. Male Wistar rats were ided into five groups: saline control group prophylactic Allo (300mg/L of drinking water, 7 days) glycerol (50%, 5ml/kg, IM) prophylactic Allo + glycerol and therapeutic Allo (50mg/Kg, IV, 30min after glycerol injection) + glycerol. Glycerol-injected rats showed markedly reduced glomerular filtration rate associated with renal vasoconstriction, renal tubular damage, increased oxidative stress, apoptosis and inflammation. Allo ameliorated all these alterations. We found 8-isoprostane-PGF Allo treatment attenuates renal dysfunction in a model of rhabdomyolysis-associated AKI by reducing oxidative stress (systemic, renal and muscular), apoptosis and inflammation. This may represent a new therapeutic approach for rhabdomyolysis-associated AKI - a new use for an old and widely available medication.
Publisher: Elsevier BV
Date: 11-2020
Publisher: Elsevier BV
Date: 10-2012
DOI: 10.1016/J.TRANSPROCEED.2012.07.010
Abstract: Conversion to sirolimus (SRL)-based immunosuppression in renal transplant recipients is an alternative for chronic allograft dysfunction (CAD), cancer and viral infections. We sought to analyze the indications for and safety and efficacy of conversion to SRL among renal transplant patients. We examined a retrospective cohort, using medical records of renal transplant recipients >18 years old who had their immunosuppressive regimen converted to a SRL-based treatment. Data analysis included the indication for conversion, time posttransplant, as well as urine protein and serum creatinine at conversion and 6 months thereafter. The end points included death, graft loss and/or discontinuation of SRL. We included 112 patients in this series who had indications for conversion: fungal, polyomavirus, or cytomegalovirus infection (n = 32), CAD (n = 30), cancer (n = 21), immunologic (n = 3), and other reasons (n = 26). Changes in immunosuppression were performed at 41 ± 57 months posttransplant or later in cancer patients. SRL was discontinued in 9 patients owing to adverse events such as edema, proteinuria, mucositis, or pneumonitis. Graft loss was observed in 19 patients, and death in 6. In 87 patients with functioning grafts, protein/creatinine ratios increased from 0.28 ± 0.03 (conversion) to 0.63 ± 0.09 (after 6 months P < .001). Serum creatinine decreased from 2.24 ± 0.13 (conversion) to 1.89 ± 0.75 mg/dL (after 6 months P < .001). Graft survival was 88% at 1 and 80% at 3 years after conversion. In, SRL was well tolerated conversion to SRL improved graft function with a slight increase in proteinuria.
Publisher: MDPI AG
Date: 18-07-2018
DOI: 10.20944/PREPRINTS201807.0320.V1
Abstract: Vitamin D (VD) is a pro-hormone essential for life in higher animals. It is present in few types of foods and is produced endogenously in the skin by a photochemical reaction. The final step of VD activation occurs in the kidneys involving a second hydroxylation reaction to generate the biologically active metabolite 1,25(OH)2-VD. Extrarenal 1& alpha -hydroxylation has also been described to have an important role in autocrine and paracrine signaling. Vitamin D deficiency (VDD) has been in the spotlight as a major public health-care issue with an estimated prevalence of more than a billion people worldwide. Among in iduals with chronic kidney disease (CKD), VDD prevalence has been reported to be as high as 80%. Classically VD plays a pivotal role in calcium and phosphorus homeostasis. Nevertheless, there is a growing body of evidence supporting the importance of VD in many vital nonskeletal biological processes such as endothelial function, renin-angiotensin-aldosterone system modulation, redox balance and innate and adaptive immunity. In in iduals with CKD, VDD has been associated with albuminuria, faster progression of kidney disease and increased all-cause mortality. Recent guidelines support VD supplementation in CKD based on extrapolation from cohorts conducted in the general population. In this review, we discuss new insights on the multifactorial pathophysiology of VDD in CKD as well as how it may negatively modulate different organs and systems. We also critically review the latest evidence and controversies of VD monitoring and supplementation in CKD patients.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 12-2022
DOI: 10.2215/CJN.08090722
Abstract: Climate change is the biggest global health threat of the twenty-first century. Health care itself is a significant contributor to greenhouse gas emissions, and dialysis programs contribute disproportionately. Nephrology societies have called for increased recognition and action to minimize the environmental effect of dialysis care, but little data exist regarding environmental sustainability practices within dialysis facilities worldwide. This survey reports a baseline of environmental sustainability practices of dialysis facilities in Australia and New Zealand. An online survey was used to collect data regarding key areas of environmental sustainability practices within dialysis facilities between November 2019 and December 2020. An invitation to complete the survey was sent to the heads of all dialysis facilities in Australia and New Zealand. Responses were received from 132 dialysis facilities, representing 33% (122 of 365) of dialysis services within Australia and New Zealand. Most responses were from public satellite facilities (53 of 132 40%), in-center dialysis facilities (33 of 132 25%), and co-located dialysis and home therapies facilities (28 of 132 21%). Opportunities for improvement in environmental sustainability practices were identified in three domains. ( 1 ) Culture. A minority of facilities reported having an environmental sustainability strategy in place (44 of 132 33%) or undertaking sustainability audits (27 of 132 20%). Only 7% (nine of 132) reported the inclusion of environmental training in staff induction programs. ( 2 ) Building design, infrastructure, and energy use. Few facilities reported the use of renewable energy (18 of 132 14%), reclaiming reverse osmosis reject water (16 of 126 13%), or the use of motion-sensor light switches (58 of 131 44%). ( 3 ) Operations. A minority of facilities reported waste management education (47 of 131 36%), auditing waste generation (23 of 132 17%), or that environmental sustainability was considered in procurement decisions (33 of 132 25%). Environmental sustainability is not currently prioritized in clinical practice, building design and infrastructure, or management systems in Australian and New Zealand dialysis facilities responding to this survey.
Publisher: MDPI AG
Date: 17-08-2018
Abstract: Vitamin D (VD) is a pro-hormone essential for life in higher animals. It is present in few types of foods and is produced endogenously in the skin by a photochemical reaction. The final step of VD activation occurs in the kidneys involving a second hydroxylation reaction to generate the biologically active metabolite 1,25(OH)2-VD. Extrarenal 1α-hydroxylation has also been described to have an important role in autocrine and paracrine signaling. Vitamin D deficiency (VDD) has been in the spotlight as a major public healthcare issue with an estimated prevalence of more than a billion people worldwide. Among in iduals with chronic kidney disease (CKD), VDD prevalence has been reported to be as high as 80%. Classically, VD plays a pivotal role in calcium and phosphorus homeostasis. Nevertheless, there is a growing body of evidence supporting the importance of VD in many vital non-skeletal biological processes such as endothelial function, renin-angiotensin-aldosterone system modulation, redox balance and innate and adaptive immunity. In in iduals with CKD, VDD has been associated with albuminuria, faster progression of kidney disease and increased all-cause mortality. Recent guidelines support VD supplementation in CKD based on extrapolation from cohorts conducted in the general population. In this review, we discuss new insights on the multifactorial pathophysiology of VDD in CKD as well as how it may negatively modulate different organs and systems. We also critically review the latest evidence and controversies of VD monitoring and supplementation in CKD patients.
Publisher: Public Library of Science (PLoS)
Date: 20-11-2017
Publisher: John Wiley & Sons, Ltd
Date: 04-08-2010
Publisher: Springer Science and Business Media LLC
Date: 08-2020
DOI: 10.1186/S12882-020-01983-7
Abstract: Renal biopsy is often required to obtain information for diagnosis, management and prognosis of kidney disease that can be broadly classified into acute kidney injury (AKI) and chronic kidney disease (CKD). The most common conditions identified on renal biopsy are glomerulonephritis and tubulo-interstitial disorders. There is a paucity of information on management strategies and therapeutic outcomes in AKI and CKD patients. A renal biopsy registry will provide information on biopsy-proven kidney disorders to improve disease understanding and tracking, healthcare planning, patient care and outcomes. A registry of patients, that includes biopsy-proven kidney disease, was established through the collaboration of nephrologists from Queensland Hospital and Health Services and pathologists from Pathology Queensland services. The registry is in keeping with directions of the Advancing Kidney Care 2026 Collaborative, established in September 2018 as a Queensland Health initiative. Phase 1 of the registry entailed retrospective acquisition of data from all adult native kidney biopsies performed in Queensland, Australia, from 2002 to 2018. Data were also linked with the existing CKD.QLD patient registry. From 2019 onwards, phase 2 of the registry involves prospective collection of all incident consenting patients referred to Queensland public hospitals and having a renal biopsy. Annual reports on patient outcomes will be generated and disseminated. Establishment of the Queensland Renal Biopsy Registry (QRBR) aims to provide a profile of patients with biopsy-proven kidney disease that will lead to better understanding of clinico-pathological association and facilitate future research. It is expected to improve patient care and outcomes.
Publisher: Wiley
Date: 25-06-2013
DOI: 10.1111/JCH.12154
Publisher: Wiley
Date: 08-2017
Abstract: Radiological insertion of Tenckhoff catheters can be an alternative option for peritoneal dialysis access creation, as compared to surgical catheter insertion. This study will review the outcomes and complications of radiological Tenckhoff catheter insertion in a metropolitan renal service and compare costs between surgical and radiological insertion. Data were collected prospectively for all patients who had a Tenckhoff catheter insertion for peritoneal dialysis (PD) under radiological guidance at our hospital from May 2014 to November 2016. The type of catheter used and complications, including peri-catheter leak, exit site infection and peritonitis were reviewed. Follow-up data were also collected at points 3, 6 and 12 months from catheter insertion. Costing data were obtained from Queensland Health Electronic Reporting System (QHERS) data, average staff salaries and consumable contract price lists. In the 30-month evaluation period, 70 catheters were inserted. Two patients had an unsuccessful procedure due to the presence of abdominal adhesions. Seven patients had an episode of peri-catheter leak, and four patients had an exit site infection following catheter insertion. Peritonitis was observed in nine patients during the study period. The majority of patients (90%) remained on peritoneal dialysis at 3-month follow-up. The average costs of surgical and radiological insertion were noted to be AUD$7788.34 and AUD$1597.35, respectively. Radiological Tenckhoff catheter insertion for peritoneal dialysis appears to be an attractive and cost-effective option given less waiting periods for the procedure, the relatively low cost of insertion and comparable rates of complications.
Publisher: Elsevier BV
Date: 09-2018
Publisher: Public Library of Science (PLoS)
Date: 02-2018
Publisher: Universidade de Sao Paulo, Agencia USP de Gestao da Informacao Academica (AGUIA)
Publisher: Informa UK Limited
Date: 15-11-2016
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 08-2021
Abstract: The incidence of bleeding complications after percutaneous kidney biopsies is low. Female sex may be associated with a greater risk for bleeding complications after percutaneous kidney biopsies. This association and the plausible mechanisms require further evaluation in prospective study
Publisher: Oxford University Press (OUP)
Date: 09-12-2014
DOI: 10.1093/JAC/DKU483
Abstract: To evaluate the occurrence of systemic and renal abnormalities in the offspring of Wistar rats exposed to tenofovir disoproxil fumarate (DF) during pregnancy. Female Wistar rats received a standard diet, with or without addition of tenofovir DF (100 mg/kg diet), 1 week before mating and during pregnancy. Offspring from the tenofovir DF group were placed with an untreated foster mother during breastfeeding and compared with offspring from rats maintained on a standard diet during mating and pregnancy (control). Control and tenofovir DF were followed up at 3 and 6 months of age. Monthly body weight and systolic blood pressure (SBP), glomerular counts, renal function, biochemical parameters, angiotensin II, renal renin angiotensin aldosterone system (RAAS) and renal sodium transporters were analysed. Tenofovir DF offspring showed lower birth weight compared with the control group. After the third month, growth among the tenofovir DF group experienced a rapid catch-up. SBP increased progressively after the second month of age in the tenofovir DF group. Nephron number did not differ between the groups however, the tenofovir DF group showed glomerular structural changes. Plasma aldosterone was higher in the tenofovir DF group, associated with a significant increase in renal expression of RAAS. The tenofovir DF rats showed up-regulation of renal sodium transporters and consequently lower urinary sodium excretion. This is the first demonstration using an experimental model that maternal exposure to tenofovir DF during gestation results in overactivation of RAAS, up-regulation of renal sodium transporters and hypertension in the offspring.
Publisher: MDPI AG
Date: 24-06-2017
DOI: 10.3390/NU9070651
Publisher: International Joint Conferences on Artificial Intelligence Organization
Date: 07-2020
Abstract: In order to improve the performance of Bayesian optimisation, we develop a modified Gaussian process upper confidence bound (GP-UCB) acquisition function. This is done by s ling the exploration-exploitation trade-off parameter from a distribution. We prove that this allows the expected trade-off parameter to be altered to better suit the problem without compromising a bound on the function's Bayesian regret. We also provide results showing that our method achieves better performance than GP-UCB in a range of real-world and synthetic problems.
Publisher: MDPI AG
Date: 18-04-2019
DOI: 10.20944/PREPRINTS201904.0208.V1
Abstract: Pigment nephropathy is an acute decline in renal function following the deposition of endogenous haem-containing proteins in the kidneys. Haem pigments such as myoglobin and haemoglobin are filtered by glomeruli and absorbed by the proximal tubules. They cause renal vasoconstriction, tubular obstruction, increased oxidative stress and inflammation. Haem is associated with inflammation in sterile and infectious conditions, contributing to the pathogenesis of many disorders such as rhabdomyolysis and haemolytic diseases. In fact, haem appears to be a signaling molecule that is able to activate the inflammasome pathway. Recent studies highlight a pathogenic function for haem in triggering inflammatory responses through the activation of the nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasome. Among the inflammasome multiprotein complexes, the NLRP3 inflammasome has been the most widely characterized as a trigger of inflammatory caspases and the maturation of interleukin-18 and -1& beta . In the present review, we discuss the latest evidence on the importance of inflammasome-mediated inflammation in pigment nephropathy. Finally, we highlight the potential role of inflammasome inhibitors in the prophylaxis and treatment of pigment nephropathy.
No related grants have been discovered for Pedro Henrique Franca Gois.