ORCID Profile
0000-0002-4561-0844
Current Organisation
Kolling Institute of Medical Research
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Publisher: Elsevier BV
Date: 05-2021
Publisher: MDPI AG
Date: 08-03-2023
Abstract: Onconephrology has emerged as a novel sub-specialty of nephrology dedicated to the intersection between the kidney and cancer. This intersection is broad and includes a number of important areas of focus, including concurrent chronic kidney disease (CKD) and cancer, acute kidney complications of cancer, and cancer-treatment-induced nephrotoxicity. The importance of onconephrology is even more evident when considering the global growth in the population of older adults, many of whom are living with some degree of frailty. Furthermore, a considerable proportion of older adults have CKD (some of whom eventually progress to kidney failure) and are at high risk of developing solid tumour and hematologic malignancies. Specific to kidney disease, the association between frailty status and kidney disease has been explored in depth, and tools to capture frailty can be used to guide the management and prognostication of older adults living with kidney failure. Whilst there is emerging data regarding the assessment and impact of frailty in onconephrology, there remains a relative paucity of knowledge within this topic. In this article, we evaluate the definition and operationalization of frailty and discuss the significance of frailty within onconephrology. We review evidence on current approaches to assessing frailty in onconephrology and discuss potential developments and future directions regarding the utilization of frailty in this patient population. A greater awareness of the intersections and interactions between frailty and onconephrology and further efforts to integrate frailty assessment in onconephrology to optimize the delivery of realistic and goal-directed management strategies for patients is needed.
Publisher: European Respiratory Society
Date: 15-09-2018
Publisher: European Respiratory Society
Date: 28-09-2019
Publisher: Cambridge Media
Date: 03-2022
Publisher: Baishideng Publishing Group Inc.
Date: 18-11-2021
Publisher: SAGE Publications
Date: 06-2020
Abstract: Ewing sarcoma usually develops in the second decade of life as a primary osseous malignancy. An extraskeletal primary source of this condition from the lung parenchyma is extremely uncommon. We report the case of a 33-year old man with primary Ewing sarcoma of the lung diagnosed upon postsurgical histological examination. Initially presenting with unilateral pleural effusion, our patient underwent various investigations before final diagnosis. This case report reviews the available literature of similarly reported cases and discusses the current developments on managing this rare and aggressive disease. As a supplementary learning point, this case reminds us always to consider unusual possibilities and seek further sub-specialist opinion when presented with unresolved clinical and radiological abnormalities that require further exploring beyond the primary line of investigations and treatment.
Publisher: MDPI AG
Date: 26-09-2022
Abstract: Global COVID-19 vaccination programs for children and adolescents have been developed with international clinical trial data confirming COVID-19 mRNA vaccine safety and efficacy for the pediatric population. The impact of COVID-19 vaccination in the kidneys is thought to be explained by a complex immune-mediated relationship between the two, although the pathophysiological mechanisms of how COVID-19 vaccination potentially induces kidney pathology are not presently well known. Whilst intrinsic kidney pathologies following COVID-19 vaccination have been reported in adults, such cases are only being recently reported with greater frequency in children and adolescents. Conforming to the PRISMA checklist, we conducted a systematic review of the current literature to provide an overview on the range of intrinsic kidney pathologies that have been reported following COVID-19 vaccination in children and adolescents. All English language research articles published on or before 30 June 2022 reporting new-onset or relapsed intrinsic kidney pathology in children or adolescents (≤18 years) following COVID-19 vaccination were selected for qualitative analysis. Out of 18 cases from the 13 published articles selected, there were 10 cases of IgA nephropathy (1 case of rapidly progressive glomerulonephritis requiring acute hemodialysis), 5 cases of minimal change disease (MCD), 1 case of concurrent MCD/tubulointerstitial nephritis (TIN) and 2 cases of TIN. There is no indication currently to avoid vaccination, unless specific circumstances exist, as the benefits of COVID-19 vaccination far outweigh its risks. Concluding the findings from our systematic review based on preliminary evidence, potential adverse effects to the kidney from COVID-19 vaccination affects a small number of children and adolescents among the many who have been vaccinated. There remains good reason at present to support vaccination of children and adolescents with a greater morbidity status, such as those living with preexisting chronic kidney disease. Close observation of all children and adolescents receiving COVID-19 vaccination is recommended, particularly in those with preceding intrinsic kidney pathology to identify risks of relapsed disease.
Publisher: Oxford University Press (OUP)
Date: 06-2023
DOI: 10.1093/NDT/GFAD063C_4146
Abstract: ANCA associated vasculitis (AAV) has a peak incidence in 65 -74 yr olds. As a result, it affects an ageing population who are vulnerable to co-morbidities, polypharmacy and frailty. Due to the high burden of morbidity and mortality in these patients, it is increasingly recognised that in idualised management is needed. Whilst current immunotherapies are effective, there remains caution in treating older patients due to the potential risks. Yet despite AAV being a condition that predominantly affects older people, few studies have looked specifically at the benefit of treating AAV in such age groups, or at frailty assessments tools to guide treatment. We aimed to evaluate treatment outcomes in older AAV patients, as well as frailty assessment tools to aid prognostication and management. A cohort study evaluating outcomes of induction immunosuppression in patients ≥75yrs was constructed from 2 centres, with subsequent meta-analysis of published data [1]. In addition, studies identifying frail patients, who may be at risk of adverse outcomes, were carried out using the quantitative tools Hospital Frailty Risk Score (HFRS) [2] and the Clinical Frailty Scale (CFS). Primary outcomes were mortality and end stage kidney disease (ESKD). The HFRS was calculated using hospital coding data from any hospital admissions between a patient's AAV diagnosis to 2yr follow up. Patients were categorized into low, intermediate and high HFRS groups. CFS scores at presentation were documented prospectively and then repeated a minimum of 6 weeks from diagnosis. A CFS score of ≥5 was used to categorise frailty. Differences in the scores were assessed and compared to clinical outcomes. Retrospective analysis of our AAV cohort aged ≥75 yrs demonstrated that induction immunosuppression was associated with a significant reduction in the 2yr mortality risk [HR 0.29 (95% CI 0.09–0.93)]. Following systematic review, with a study population of 290 patients, the pooled HR by meta-analysis confirmed a significant reduction in the risk of death with induction treatment [HR 0.31 (95% CI 0.16 - 0.57)]. Treated patients had a lower rate of ESKD, but this was not statistically significant [HR 0.71 (95% CI 0.15 – 3.35)]. Looking separately at frailty assessments, mortality and ESKD were assessed according to HFRS and CFS. Thirty-four patients with AAV aged ≥75 yrs were assessed using HFRS and categorised into the low (n = 18), intermediate (n = 13) and high (n = 3) HFRS groups. All patients in the high HFRS groups had ≥1 episodes of hospitalization after diagnosis of AAV. However, there was no difference in mortality or duration of hospitalisation between the 3 categories. Forty-one patients with AAV aged ≥65yrs were assessed using the CFS. The median CFS at diagnosis and follow-up was 4. There was no significant interval change in CFS (P = 0.16) suggesting that patients did not become frailer. Instead, there was a tendency towards improved frailty scores at reassessment (n = 17, 43%), with some patients going from a CFS of 6 (moderately frail) to 3 (managing well). There was no significant difference in ESKD between those categorised as frail and non-frail (P = 1.0), although crude mortality was higher among those initially categorised as frail (P = 0.03). Our research shows that older patients with AAV benefit from standard remission-induction therapy and those treated had favourable mortality outcomes compared to those who were not. Furthermore, frailty assessment tools do not correlate clearly with clinical outcomes. Whilst there is evidence to support the use of HFRS and CFS in a many diseases, its utility in determining frailty and potential susceptibility to adverse effects of therapy in patients with multifaceted, autoimmune inflammatory disease remains limited. Patients may present ‘frail’ as a result of significant disease burden, which has the potential to improve with appropriate treatment. We suggest that age alone and frailty at assessment should not be a limiting factor when considering treatment and prospective studies of this population are needed.
Publisher: Oxford University Press (OUP)
Date: 05-2022
Abstract: In iduals with end-stage kidney disease (ESKD) have a greater susceptibility towards coronavirus disease 2019 (COVID-19) infection compared to those without chronic kidney disease or ESKD, and these patients are more vulnerable to poor clinical outcomes. The introduction of COVID-19 vaccination programs displayed efficacy to improving clinical outcomes. A study based in the UK reported excellent humoral responses to the Pfizer BNT162b2 vaccine, but suboptimal responses to the Oxford AstraZeneca ChAdOx1-nCoV-19(AZD1222) vaccine amongst hemodialysis patients. High rate of humoral responses to two doses of the COVID-19 vaccination has been reported within small cohorts of peritoneal dialysis (PD) patients 3 to 8 weeks post vaccination, whilst one study confirmed maintenance of significant humoral responses 6 months post vaccination with the Pfizer BNT162b2 vaccine. Our study aimed at evaluating longer-term antibody responses—6 months after a two-dose regimen of the Pfizer BNT162b2 and Oxford AstraZeneca ChAdOx1-nCoV-19 (AZD1222) vaccines in patients receiving PD. This is a single-center observational study conducted for PD patients who were offered both doses of the COVID-19 vaccine [either Pfizer BNT162b2 or Oxford AstraZeneca ChAdOx1-nCoV-19(AZD1222)] since universal introduction of the vaccination program in our local area in December 2020. COVID-19 antibody testing was performed using the Siemens’ immunoassay targeting the spike protein S1 RBD (an index ≥ 1.0 was deemed as a positive result) between October and November 2021. Demographic and baseline clinical data were collected for each patient, and analysis focused on comparing the characteristics between PD patients with positive and negative COVID-19 antibody statuses. Statistical analysis was performed using SPSS version 24. Eighty-six patients were included in this study. The median age was 62 years (47–71) with a predominance of males (61.6%) and Caucasian ethnicity (75.6%). The majority of patients have hypertension (84.8%) with 38% having a history of cardiovascular disease and 34% being diabetic. Ten patients (11.6%) previously received a kidney transplant with 7 patients (8.2%) currently on immunosuppressive treatment, and 15 patients (17.4%) previously receiving such treatments. A total of 81 patients received both doses of the COVID-19 vaccine, of which 57 (70.4%) received Pfizer BNT162b2, 16 (19.7%) received Oxford AstraZeneca ChAdOx1-nCoV-19 (AZD1222) and the type of vaccine was unknown in 8 patients (9.9%). A total of 72 patients were COVID-19 antibody tested between October and November 2021 in which 68 (94.4%) had a positive antibody and 4 (5.6%) had a negative antibody test. The median time between first dose of the COVID-19 vaccination and antibody testing was 9 (8.6–9.5) months and the median time between second dose of the COVID-19 vaccination and antibody testing was 6.3 (5.8–6.7) months. Comparing the demographic and clinical characteristics between patients with positive and negative antibodies, a higher proportion of patients with history of receiving immunosuppression (currently or previously P = 0.004) had a negative antibody status despite receiving two doses of COVID-19 vaccination. There were no further significant differences observed. Full study results are presented in Tables 1 and 2. In our cohort of PD patients, detectable humoral response to COVID-19 vaccination was sustained 6 months following vaccination irrespective of the type of vaccination received. A higher proportion of patients with a history of receiving immunosuppression (current or past) had a poor antibody response following COVID-19 vaccinations, highlighting the importance of considering focused COVID-19 vaccination strategies in the context of immunosuppression.
Publisher: Elsevier BV
Date: 02-2022
Publisher: MDPI AG
Date: 29-10-2021
Abstract: Introduction: The introduction of COVID-19 vaccination programs has become an integral part of the major strategy to reduce COVID-19 numbers worldwide. New-onset and relapsed kidney histopathology have been reported following COVID-19 vaccination, sparking debate on whether there are causal associations. How these vaccines achieve an immune response to COVID-19 and the mechanism that this triggers kidney pathology remains unestablished. We describe the results of a systematic review for new-onset and relapsed kidney histopathology following COVID-19 vaccination. Methods: A systematic literature search of published data up until 31 August 2021 was completed through the Preferred Reporting Items for Systematic Reviews and Meta Analyses (PRISMA) guideline. Research articles reporting new onset or relapsed kidney histopathology in adult patients ( years) following COVID-19 vaccination were included for qualitative review. Only full-text articles published in the English language were selected for review. Results: Forty-eight cases from thirty-six articles were included in the qualitative synthesis of this systematic review. Minimal change disease (19 cases) was the most frequent pathology observed, followed by IgA nephropathy (14 cases) and vasculitis (10 cases). Other cases include relapse of membranous nephropathy, acute rejection of kidney transplant, relapse of IgG4 nephritis, new-onset renal thrombotic microangiopathy, and scleroderma renal crisis following COVID-19 vaccination. There was no mortality reported in any of the included cases. Patients in all but one case largely recovered and did not require long-term renal replacement therapy. Conclusion: This systematic review provides insight into the relationship between various kidney pathologies that may have followed COVID-19 vaccination. Despite these reported cases, the protective benefits offered by COVID-19 vaccination far outweigh its risks. It would be recommended to consider early biopsy to identify histopathology amongst patients presenting with symptoms relating to new-onset kidney disease following vaccination and to monitor symptoms for those with potential relapsed disease.
Publisher: MDPI AG
Date: 09-07-2022
DOI: 10.3390/IJMS23147610
Abstract: Chronic kidney disease (CKD) is a global health issue, affecting more than 10% of the worldwide population. The current approach for formal diagnosis and prognostication of CKD typically relies on non-invasive serum and urine biomarkers such as serum creatinine and albuminuria. However, histological evidence of tubulointerstitial fibrosis is the ‘gold standard’ marker of the likelihood of disease progression. The development of novel biomedical technologies to evaluate exfoliated kidney cells from urine for non-invasive diagnosis and prognostication of CKD presents opportunities to avoid kidney biopsy for the purpose of prognostication. Efforts to apply these technologies more widely in clinical practice are encouraged, given their potential as a cost-effective approach, and no risk of post-biopsy complications such as bleeding, pain and hospitalization. The identification of biomarkers in exfoliated kidney cells from urine via western blotting, enzyme-linked immunosorbent assay (ELISA), immunofluorescence techniques, measurement of cell and protein-specific messenger ribonucleic acid (mRNA)/micro-RNA and other techniques have been reported. Recent innovations such as multispectral autofluorescence imaging and single-cell RNA sequencing (scRNA-seq) have brought additional dimensions to the clinical application of exfoliated kidney cells from urine. In this review, we discuss the current evidence regarding the utility of exfoliated proximal tubule cells (PTC), podocytes, mesangial cells, extracellular vesicles and stem rogenitor cells as surrogate markers for the early diagnosis and prognostication of CKD. Future directions for development within this research area are also identified.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-10-2023
Publisher: Elsevier BV
Date: 03-2022
Publisher: Springer Science and Business Media LLC
Date: 08-03-2021
DOI: 10.1007/S11255-021-02798-7
Abstract: People living with chronic kidney disease (CKD) are at a higher risk of hip fracture with an associated increased mortality risk compared to in iduals without CKD. Our study aimed to evaluate the clinical assessment tools that best predict mortality risk following hip fracture for patients with CKD. Patients with CKD G3b-5D admitted to Lancashire Teaching Hospitals NHS Foundation Trust, U.K. between June 2013 and Dec 2019 were included. The association between CKD and post-fracture mortality risk was evaluated. All patients were assessed using tools that evaluated frailty status, co-morbidity, pre-operative risk, functional status and cardiopulmonary fitness. Receiver operating characteristic curve analyses were performed to determine the prognostic accuracy of the assessment tools for 30 day and 1 year mortality following hip fracture in patients with CKD. 397 patients fulfilled inclusion criteria with a mean age of 83.5 ± 9.2 years. Older age, female sex, intracapsular fracture and more severe CKD, co-morbidity and frailty status were all associated with an increased mortality risk. Patients with dialysis-dependent CKD and severe/very severe frailty had a hazard ratio for mortality of 2.55 (95% Cl 2.11–2.98) and 3.11 (95% Cl 2.47–3.93), respectively. The Clinical Frailty Scale demonstrated the best prognostic accuracy for both 30 day [Area Under the Curve (AUC) 0.91, 95% Cl 0.84–0.97] and 1 year mortality (AUC 0.93, 95% Cl 0.87–1.00). Patients with advanced CKD and severe frailty have a high mortality risk following hip fracture. The Clinical Frailty Scale is an excellent prognostic tool for mortality in this setting and could be easily incorporated into routine clinical practice.
Publisher: Wiley
Date: 03-2022
Publisher: MDPI AG
Date: 11-04-2023
DOI: 10.3390/BIOMEDICINES11041153
Abstract: The number of people living with chronic kidney disease (CKD) is growing as our global population continues to expand. With aging, diabetes, and cardiovascular disease being major harbingers of kidney disease, the number of people diagnosed with diabetic kidney disease (DKD) has grown concurrently. Poor clinical outcomes in DKD could be influenced by an array of factors—inadequate glycemic control, obesity, metabolic acidosis, anemia, cellular senescence, infection and inflammation, cognitive impairment, reduced physical exercise threshold, and, importantly, malnutrition contributing to protein-energy wasting, sarcopenia, and frailty. Amongst the various causes of malnutrition in DKD, the metabolic mechanisms of vitamin B (B1 (Thiamine), B2 (Riboflavin), B3 (Niacin/Nicotinamide), B5 (Pantothenic Acid), B6 (Pyridoxine), B8 (Biotin), B9 (Folate), and B12 (Cobalamin)) deficiency and its clinical impact has garnered greater scientific interest over the past decade. There remains extensive debate on the biochemical intricacies of vitamin B metabolic pathways and how their deficiencies may affect the development of CKD, diabetes, and subsequently DKD, and vice-versa. Our article provides a review of updated evidence on the biochemical and physiological properties of the vitamin B sub-forms in normal states, and how vitamin B deficiency and defects in their metabolic pathways may influence CKD/DKD pathophysiology, and in reverse how CKD/DKD progression may affect vitamin B metabolism. We hope our article increases awareness of vitamin B deficiency in DKD and the complex physiological associations that exist between vitamin B deficiency, diabetes, and CKD. Further research efforts are needed going forward to address the knowledge gaps on this topic.
Publisher: MDPI AG
Date: 16-03-2023
DOI: 10.3390/BIOMEDICINES11030926
Abstract: There is an increased incidence of elderly adults diagnosed with kidney failure as our global aging population continues to expand. Hence, the number of elderly adults indicated for kidney replacement therapy is also increasing simultaneously. Haemodialysis initiation is more commonly observed in comparison to kidney transplantation and peritoneal dialysis for the elderly. The onset of the coronavirus 2019 (COVID-19) pandemic brought new paradigms and insights for the care of this patient population. Elderly patients receiving haemodialysis have been identified as high-risk groups for poor COVID-19 outcomes. Age, immunosenescence, impaired response to COVID-19 vaccination, increased exposure to sources of COVID-19 infection and thrombotic risks during dialysis are key factors which demonstrated significant associations with COVID-19 incidence, severity and mortality for this patient group. Recent findings suggest that preventative measures such as regular screening and, if needed, isolation in COVID-19-positive cases, alongside the fulfillment of COVID-19 vaccination programs is an integral strategy to reduce the number of COVID-19 cases and consequential complications from COVID-19, particularly for high-risk groups such as elderly haemodialysis patients. The COVID-19 pandemic brought about the rapid development and repurposing of a number of medications to treat patients in the viral and inflammatory stages of their disease. However, elderly haemodialysis patients were grossly unrepresented in many of these trials. We review the evidence for contemporary treatments for COVID-19 in this population to provide clinicians with an up-to-date guide. We hope our article increases awareness on the associations and impact of COVID-19 for the elderly haemodialysis population, and encourage research efforts to address knowledge gaps in this topical area.
Publisher: Elsevier BV
Date: 11-2018
Publisher: Elsevier BV
Date: 10-2023
Publisher: BMJ Publishing Group Ltd and European League Against Rheumatism
Date: 06-2018
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 12-2019
Publisher: MDPI AG
Date: 24-01-2023
DOI: 10.3390/KIDNEYDIAL3010007
Abstract: Peritonitis is a common and potentially serious complication of peritoneal dialysis (PD). Common organisms include Staphylococcus Aureus, enterococci, and coagulase-negative staphylococcus. However, Stenotrophomonas maltophilia (S. maltophilia) is an uncommon cause of PD-related infection. We describe a series of three cases of S. maltophilia PD infection (two cases of PD peritonitis and one case of PD exit-site infection) that were identified over a seven-week period in a single centre. The cases were treated with antibiotics (the primary antibiotic being co-trimoxazole) for a mean duration of 30 ± 7.9 days. All of the patients required PD catheter removal due to treatment failure with antibiotics. Hospital admission was required in two of the cases and one case resulted in mortality, with the cause of death directly associated with complications from S. maltophilia infection. A multi-disciplinary team using root-cause analysis did not identify a common link between our cases but highlighted possible risk factors contributing to these presentations. Given the relative rarity of S. maltophilia, evidence on its management options remains limited. In this article, we draw upon our own experiences and examine the literature available from previously published case reports and series. These reports highlight S. maltophilia as a complex and challenging organism to treat. Our experience demonstrated the importance of early PD catheter removal in S. maltophilia PD infection, as this is likely more effective than prolonged antibiotic therapy and hence a safer management option, considering the resistant nature of S. maltophilia.
Publisher: Oxford University Press (OUP)
Date: 05-2022
Abstract: In iduals living with chronic kidney disease (CKD) are at greater risk of sustaining hip fractures compared with the general population. Following acute trauma, CKD patients are susceptible to lengthened hospitalization with their clinical condition exacerbated by frailty, co-morbidities and sarcopaenia. The most useful clinical assessment tools to predict lengthened in-hospital stays in patients with CKD following admission with hip fracture remain unestablished. Patients with CKD G3b-5 admitted from home to a tertiary centre hospital in North West UK with hip fracture between Jun 2013 and Jun 2020 were evaluated. Lengthened hospitalization is determined by & weeks of in-hospital stay in our analysis, given the average length of in-hospital stay is ∼14 days for the CKD population following hip fracture. Clinical assessment tools used in admission assessment for each patient included the Clinical Frailty Scale (CFS), Charlson's Co-morbidity Index (CCI), Chronic Kidney Disease Frailty Index Laboratory Score (CKD FI-LAB), Karnofsky's Performance Status Scale, Sernbo Score, Nottingham Hip Fracture Score, Estimated VO2 Peak, ASA Physical Status Classification System Score and the Abbreviated Mental Test Score. Receiver Operating Characteristic (ROC) curve analyses were performed to evaluate the ability of in idual clinical assessment tools to predict for & weeks of in-hospital stay in patients with CKD admitted following hip fracture. A total of 539 patients with CKDG3b-5 were admitted following hip fracture throughout the study period, of which 329 patients had & weeks of in-hospital stay. Within the cohort with & weeks of in-hospital stay, mean age was 84.4 ± 10.6 years. The female: male ratio was 1.6:1. Of those, 47 patients (14.3%) were on long-term dialysis. For this cohort, 30-day, 6-month and 1-year mortality were 6.7%, 14.9% and 43.2%, respectively. The odds ratio (OR) for 30-day {OR: 1.71, [95% confidence interval (95% CI) 1.04–2.39] P & .01}, 6-month (OR: 2.06, 95% CI 1.38–2.73 P & .01) and 1-year mortality (OR: 2.62, 95% CI 1.95–3.30 P & .01) was significantly higher in CKD patients with & 2 weeks of in-hospital stay following hip fracture compared with those who were discharged within the first 2 weeks of hospitalization. Area Under the Curve (AUC) values from ROC analyses for in idual clinical assessment tools are shown in Table 1. Frailty and co-morbidity clinical assessment tools (CFS, CCI and CKD FI-LAB) displayed the best predictive ability for lengthened in-hospital stays in patients living with CKD admitted following hip fracture. CKD patients with lengthened in-hospital stays following hip fracture have greater risks of acute in-hospital mortality and mortality over the short- to medium-term following discharge. Research initiatives should continue to evaluate multidisciplinary management strategies for the older CKD population following acute trauma. Reducing the length of hospitalization may improve survival outcomes and alleviate costs and public health burdens in the care of the older CKD population.
Publisher: MDPI AG
Date: 30-01-2023
Abstract: Merkel cell carcinoma (MCC) is an uncommon form of skin neoplasm with poor histological differentiation and an aggressive disease process, leading to high recurrence and mortality. There are multiple risk factors in which being in an immunocompromised state is a significant factor, and the discovery of Merkel cell polyomavirus (MCPyV) since 2008 has strengthened causal associations between MCC and immunosuppression. In iduals who have undergone kidney transplantation are therefore more susceptible to having MCC, secondary to post-transplant immunosuppression which plays a vital role in reducing the risk of transplant kidney rejection. Over recent years a rise in the incidence of MCC following kidney transplantation is noted, with increased reporting of such cases. Whilst localized MCC is observed, MCC metastasis to the lymphatic system, brain, bone, liver, lung, and heart has been previously observed in patients with transplanted kidneys. Kidney metastasis is less common and has been only reported in recent years with greater frequency. The management of aggressive, metastatic MCC has historically been palliative, and prognosis is poor. Recently, the use of immune checkpoint inhibitors for metastatic MCC in multi-center phase II clinical trials have shown promising survival outcomes and have been approved for use in countries such as the United States as a first-line treatment. In this review we will explore the potential pathophysiological processes of MCC manifesting post-kidney transplantation. We will then evaluate the epidemiology of MCC within the context of kidney transplantation, before discussing the various clinical presentations, diagnostic measures, surveillance strategies, and current treatment options as well as future directions to best manage MCC in kidney transplant recipients.
Publisher: MDPI AG
Date: 08-01-2022
DOI: 10.3390/URO2010001
Abstract: Urolithiasis has become more prevalent in recent years, given the rapid rise of the global geriatric population. Although factors such as ethnicity, dietary and fluid intake, co-morbidity status and age have been associated with increased incidence of urolithiasis, the links between frailty status and risks of developing urolithiasis are not yet known. In this commentary, we will explore the scale and significance of this relationship based on emerging evidence. We will review the plausible factors on how a more severe frailty status may be significantly associated with greater risks of developing urolithiasis. We will also discuss the strategies that may help to lower the incidence of urolithiasis in older and frail in iduals. We hope our article will bring greater awareness on this issue and motivate further research initiatives evaluating the relationship between frailty and urolithiasis, as well as holistic prevention strategies to lower the risks of developing urolithiasis within this vulnerable population.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-2023
Publisher: Oxford University Press (OUP)
Date: 08-12-2021
DOI: 10.1093/CKJ/SFAB253
Publisher: Oxford University Press (OUP)
Date: 07-10-2022
DOI: 10.1093/CKJ/SFAC220
Abstract: There is a rising demand for dialysis in the older population given the increased numbers of older adults living with chronic kidney disease (CKD) progressing to kidney failure. Home dialysis, i.e. peritoneal dialysis (PD) and home hemodialysis (HHD), has been available for decades, but more recently there has been a rapid increase in home dialysis utilization as patients and clinicians consider its practical and clinical advantages. For older adults, incident home dialysis utilization more than doubled and prevalent home dialysis growth nearly doubled over the past decade. Whilst its advantages and recent rise in popularity are evident, there are numerous barriers and challenges that are important to consider prior to initiating older adults on home dialysis. Some nephrology healthcare professionals do not view home dialysis as an option for older adults. Successful delivery of home dialysis for older adults may be made even more difficult by physical or cognitive limitations, concerns around dialysis adequacy, and treatment-related complications, as well as challenges relating to caregiver burnout and patient frailty that are unique to home dialysis and older adults. Ultimately, it would be important for clinicians, patients and their caregivers to define what constitutes a ‘successful therapy’ to ensure treatment goals are aligned towards each in idual's priorities of care, considering the complex challenges that surround an older adult receiving home dialysis. In this review, we evaluate some of the key challenges surrounding the delivery of home dialysis to older adults and propose potential solutions based on updated evidence to overcome these challenges.
Publisher: Baishideng Publishing Group Inc.
Date: 21-10-2022
Publisher: MDPI AG
Date: 19-08-2022
Abstract: Chronic kidney disease-associated pruritus (CKDaP) is an often under-diagnosed and under-recognized condition, despite its considerable prevalence within the chronic kidney disease (CKD) population. Universally accepted guidelines are also lacking. The true prevalence of CKDaP worldwide therefore remains unknown, although its negative impact on mortality and health-related quality of life outcomes is very clear. The pathophysiological mechanisms leading to the onset of CKDaP are only partly understood. CKDaP is currently believed to be caused by a multifactorial process, from local skin changes, metabolic alterations, the development of neuropathy and dysregulation of opioid pathways, and psychological factors. Much work has been carried out towards a more systematic and structured approach to clinical diagnosis. Various tools are now available to assess the severity of CKDaP. Many of these tools require greater validation before they can be incorporated into the guidelines and into routine clinical practice. Further efforts are also needed in order to increase the awareness of clinicians and patients so that they can identify the CKDaP signs and symptoms in a timely manner. Currently established treatment options for CKDaP focus on the prevention of xerosis via topical emollients, the optimization of dialysis management, early referral to kidney transplantation if appropriate, oral antihistamine, and a variety of neuropathic agents. Other novel treatment options include the following: topical analgesics, topical tacrolimus, cannabinoid-containing compounds, antidepressants, oral leukotrienes, opioids, and non-pharmacological alternative therapies (i.e., phototherapy, dietary supplements, acupuncture/acupressure). We provide an updated review on the evidence relating to the epidemiology, the pathophysiology, the clinical assessment and diagnosis, and the management of CKDaP.
Publisher: Elsevier BV
Date: 02-2021
Publisher: Oxford University Press (OUP)
Date: 19-10-2023
DOI: 10.1093/CKJ/SFAD270
Publisher: Elsevier BV
Date: 09-2023
Publisher: American Society of Nephrology (ASN)
Date: 04-2022
Publisher: Royal College of Surgeons of England
Date: 02-2019
Abstract: Although the mainstay of colorectal cancer treatment remains operative, a significant proportion of patients end up without surgery. This is because they are either deemed to have no oncological benefit from the resection (too much disease) or to be unfit for major surgery (too frail). The aim of this study was to assess the proportion and survival of these two groups among the totality of practice in a tertiary unit and to discuss the implications on the conceptual understanding of outcome measures. Data was collected over two study periods with the total duration of four years. Patient demographics, comorbidities, cancer staging and management pathways were all recorded. The primary endpoint was all-cause mortality. The total of 909 patients were examined. In the 29% who did not undergo resectional surgery, 6.5% had too little disease, 13.8% had too much disease, while 8.7% were deemed too frail. The highest two-year mortality was observed in the too much (83.2%) and too frail (75.9%) groups, whereas in patients with too little cancer the rate was 5.1%, and in those undergoing a resection it was 19.2% (P 0.001). The study has expectedly shown poor survival in the too much and too frail groups. We believe that understanding the prognosis in these subgroups is vital, as it informs complex decisions on whether to operate. Moreover, an overall reporting taking into account the proportion of these groups in an multidisciplinary team practice (the non-surgical index) is proposed to render in idual surgeon's mortality results meaningful as a comparative measure.
Publisher: Elsevier BV
Date: 02-2022
Publisher: Elsevier
Date: 2022
DOI: 10.1016/BS.VH.2022.01.011
Abstract: Chronic Kidney Disease (CKD) is an emerging public health issue with a fast-growing global prevalence. Impairment in vitamin B12 metabolism is considered a nontraditional risk factor of poor outcomes associated with CKD, and there is greater interest from the scientific community than ever before to explore the role and influence of vitamin B12 in CKD. Homocysteine metabolism forms an important component of the vitamin B12 metabolic pathway. Hyperhomocysteinemia is frequently observed in CKD and End-Stage Kidney Disease (ESKD), but its representation as a prognostic marker for CKD outcomes is still not fully clear. This chapter reviews the vitamin B12 and homocysteine metabolic pathways and their dysfunction in CKD states. Biochemical factors and the MTHFR genetic polymorphisms which disrupt vitamin B12 and homocysteine metabolism are explored. The mechanisms of homocysteine-mediated and vitamin B12-mediated tissue damage in CKD are discussed. This chapter reviews current perspective on definition and measurement of plasma vitamin B12 levels in the CKD population. Updated evidence investigating the prognostic role of vitamin B12 for CKD outcomes is presented. Findings from major clinical trials conducted relating to outcomes from multivitamin (including folic acid and vitamin B12) supplementation in nondialysis and dialysis-dependent CKD are highlighted. The prognostic value of vitamin B12 and effects of vitamin B12 supplementation in the context of kidney transplantation and acute kidney injury is also reviewed. Future research considerations are summarized based on evidence gaps in our knowledge base of this topic. Greater abundance of high-level evidence to guide an approach toward vitamin B12 measurement, monitoring and supplementation in CKD may contribute to improved clinical outcomes.
Publisher: Georg Thieme Verlag KG
Date: 25-03-1970
DOI: 10.1055/A-0808-4580
Publisher: Wiley
Date: 08-12-2022
DOI: 10.1111/SDI.13133
Abstract: Peritoneal dialysis (PD)‐associated peritonitis secondary to Ralstonia infection is very rare. Ralstonia pickettii is an organism that can grow in contaminated saline, water, chlorhexidine, and other medical products used in laboratories and the clinical setting. Infective endocarditis, prosthetic joint, and severe chest infections are previously reported with R. pickettii infection. We report a novel series of three cases diagnosed with PD‐associated peritonitis caused by R. pickettii , where the cases appeared consecutively to our unit during a span of 4 weeks. During the COVID‐19 pandemic, there were increased uses of non‐sterile gloves by clinical staff as a form of personal protective equipment throughout patient interaction and PD exchange, as recommended by local hospital policy for all staff attending to patient care. A multidisciplinary team root cause analysis of our cases suggested non‐sterile gloves being the likely source of environmental contamination, leading to PD‐associated peritonitis caused by R. pickettii in this scenario.
Publisher: MDPI AG
Date: 24-03-2022
Abstract: Background: The advancement of COVID-19 vaccination programs globally has been viewed as an integral strategy to reduce both the number of COVID-19 cases and consequential complications of COVID-19, particularly for high-risk patient groups. There are limited data on the antibody response and protection from disease infection and severity in patients requiring hemodialysis (HD) following COVID-19 vaccination during the Delta and Omicron variant predominance. We conducted a study aiming to evaluate humoral immunity derived from two different COVID-19 vaccines administered to our in-centre HD population and investigated the characteristics of breakthrough COVID-19 infections occurring post-vaccination within this population. Methods: This is a prospective observational study including patients receiving HD at Salford Royal Hospital. The first and second doses of COVID-19 vaccinations (Pfizer BioNTech BNT162b2 or Oxford AstraZeneca ChAdOx1 nCoV-19) were administered to this patient cohort since January 2021. The incidence of any breakthrough COVID-19 infections occurring in double vaccinated patients between 1 April 2021 and 15 January 2022 was recorded. Patients were screened weekly with nasal and pharyngeal nasopharyngeal swabs for real-time Reverse Transcription Polymerase Chain Reaction (rRT-PCR) for COVID-19, whilst SARS-CoV-2 antibody testing was performed alongside monthly routine HD bloods. Results: Four hundred eleven patients receiving HD were included in this study, of which 170 of 178 patients (95.5%) with available data on antibody status following two doses of the Pfizer BioNTech BNT162b2 vaccination had detectable antibody response, whilst this was the case for 97 of 101 patients (96.1%) who received two doses of the Oxford AstraZeneca ChAdOx1 nCoV-19 vaccine. For 12 seronegative patients who received a booster vaccine (third dose), nine seroconverted, while one remained negative and two were not tested. No statistically significant differences were observed with regards to antibody status between those receiving Pfizer BioNTech BNT162b2 and Oxford AstraZeneca ChAdOx1 nCoV-19 vaccines. Sixty-three of 353 patients with two doses of COVID-19 vaccination had breakthrough COVID-19 infection (40 during Delta and 23 during Omicron variant predominance). Of the 40 patients during the delta period, five were admitted into hospital and there were two reported deaths due to COVID-19-related illness. There were no COVID-19 associated hospitalizations or deaths during the Omicron variant predominance. Conclusions: The vast majority of HD patients who received two doses of the Pfizer BioNTech BNT162b2 or Oxford AstraZeneca ChAdOx1 nCoV-19 vaccinations developed detectable antibody responses. Our results support the value of booster vaccination with mRNA-based COVID-19 vaccine in HD patients and highlight the need for ongoing surveillance programmes with rRT-PCR and antibody testing for timely detection of positive cases.
Publisher: Elsevier BV
Date: 11-2018
Publisher: MDPI AG
Date: 26-06-2023
Abstract: Membranous nephropathy (MN) is the most prevalent cause of nephrotic syndrome amongst the non-diabetic adult population. A fifth of idiopathic nephrotic syndrome cases can be attributed to MN, rising to more than 40% in older patients over 60 years. Most MN cases are classified as being of a primary cause, where there is absence of a secondary disease process explaining its manifestation. Traditionally, the standard approach of diagnosing MN involves performing a kidney biopsy as histological evaluation offers not only conclusive evidence of the diagnosis but also provides valuable information regarding disease chronicity and the presence of any other kidney histopathological features. Nevertheless, kidney biopsy is an invasive procedure which poses risks for the patient including bleeding and pain and bears greater costs for the health system. The identification of the phospholipase A2 receptor (PLA2R) antigen in 2009 was a landmark discovery, one which has evolved our understanding of the disease processes in MN and subsequently our management approach of this condition. Antibodies against PLA2R (PLA2RAb) have since emerged as an attractive non-invasive test option to be applied for the diagnosis and prognostication of primary MN. However, much debate and unknowns remain about the accuracy and reliability of testing for PLA2RAb across various primary MN scenarios. We provide a review summarizing the historical journey of PLA2R in relation to its significance in primary MN and, more importantly, evidence emerging over the years which contemplated the role of PLA2RAb as a diagnostic and prognostic tool in primary MN.
Publisher: Oxford University Press (OUP)
Date: 05-2022
Abstract: Venous thrombosis (VT) is an established cause of increased morbidity and mortality amongst patients with nephrotic syndrome. Previous studies suggest primary membranous nephropathy (PMN) to be associated with the highest risk of developing VT amongst all nephrotic diseases. Antibodies to the phospholipase A2 receptor (anti-PLA2R) is identified as a pathogenic marker to the disease activity of PMN, and considered a strong prognostic marker toward disease progression and treatment response. Recent evidence cites the potential of anti-PLA2R as an independent risk factor of VT in PMN. Nevertheless, the pathophysiology of VT for anti-PLA2R + ve and –ve PMN is not fully known. Whether the common risk factors of VT remain as significant within the anti-PLA2R + ve and –ve PMN context is also not convincingly elucidated of yet. Our study aimed to evaluate and compare risk factors for VT in patients with anti-PLA2R + ve and –ve PMN. This is a retrospective analysis of patients diagnosed with PMN between October 2015 and September 2021. Patients included are age ≥18 years, have biopsy-diagnosed PMN and anti-PLA2R direct immunofluorescence assay testing following PMN diagnosis. Patients excluded were those with secondary causes of membranous nephropathy, history of previous immunosuppression, kidney transplantation before or following PMN diagnosis, or where iatrogenic causes such as major surgery or prolonged immobilization led to VT. Study patients were screened until 28 November 2021 for any VT event and were grouped between those with anti-PLA2R + ve and −ve test results. Demographic and clinical parameters from age, gender, presence of co-morbidities and common risk factors associated with increased risk of VT (hypertension, diabetes mellitus, atrial fibrillation, CHA2DS2-VASC ≥ 3, BMI & , malignant disease, hormonal treatment and contraceptive pill use), serum and urine biochemical test results at PMN diagnosis (albumin, 24-h proteinuria, proteinuria/albumin ratio, creatinine, eGFR, cholesterol, triglycerides and IgG) were collected. The comparison of demographic and clinical parameters for patients with and without VT in each of the anti-PLA2R + ve and –ve groups was conducted through chi-squared, t and Mann–Whitney U tests. Multivariate regression analysis determined the significance of association between each parameter and VT event occurrence. Seventy patients with PMN were included in this study, of which 39 patients are anti-PLA2R + ve and 31 patients are anti-PLA2R−ve. Eight patients (20.5%) had VT in the anti-PLA2R + ve group during follow-up whilst this was the case for four patients (12.9%) in the anti-PLA2R−ve group. In both groups, patients with VT were found to have higher serum cholesterol levels (P & 0.05). Lower serum albumin levels, and greater 24-h proteinuria and proteinuria/albumin ratio was observed in patients with VT within the anti-PLA2R−ve group (P & .05). Full results from the multivariate regression analysis are presented in Tables 1 and 2. Serum cholesterol is demonstrated to be significantly associated with VT in the anti-PLA2R + ve (OR 1.42, 95% confidence interval (CI) 1.12–1.72) and anti-PLA2R−ve groups (OR 1.45, 95% CI 1.15–1.76), respectively. Serum albumin (OR 0.72, 95% CI 0.49–0.96), 24-h proteinuria (OR 1.33, 95% CI 1.03–1.63) and proteinuria/albumin ratio (OR 1.32, 95% CI 1.04–1.59) are shown to be significantly associated with VT within the anti-PLA2R−ve group. There is supporting evidence that serum cholesterol, albumin and proteinuria may all present as important markers of risk prediction for VT in patients with PMN, though this will require further validation in prospective multi-center studies with larger patient s les. Close monitoring of these markers, and early intervention in response to hypercholesterolemia, hypoalbuminemia and proteinuria with consideration of anti-PLA2R status should ensue as part of primary prevention strategies to reduce VT incidence in the PMN population.
Publisher: Elsevier BV
Date: 04-2021
Publisher: Elsevier BV
Date: 04-2021
Publisher: Oxford University Press (OUP)
Date: 24-02-2022
DOI: 10.1093/CKJ/SFAC052
Publisher: Elsevier BV
Date: 10-2020
Publisher: Wiley
Date: 22-11-2023
Publisher: S. Karger AG
Date: 2022
DOI: 10.1159/000521162
Abstract: b i Background: /i /b Erythropoietin-stimulating agent (ESA) hyporesponsiveness is commonly observed in patients with anemia secondary to chronic kidney disease (CKD). Because of its complexity, a global consensus on how we should define ESA hyporesponsiveness remains unavailable. The reported prevalence and demographic information on ESA hyporesponsiveness within the CKD population are variable with no consensus definition. b i Summary: /i /b ESA hyporesponsiveness is defined as having no increase in hemoglobin concentration from baseline after the first month of treatment on appropriate weight-based dosing. The important factors associated with ESA hyporesponsiveness include absolute or functional iron deficiency, inflammation, and uremia. Hepcidin has been demonstrated to play an important role in this process. Mineral bone disease secondary to CKD and non-iron malnutrition among other factors are also associated with ESA hyporesponsiveness. There is continued debate toward determining a gold-standard treatment pathway to manage ESA hyporesponsiveness. The development of hypoxia-inducing factor-stabilizers brings new insights and opportunities in the management of ESA hyporesponsiveness. b i Key Message: /i /b Management of ESA hyporesponsiveness involves a comprehensive multidisciplinary team approach to address its risk factors. The progression of basic and clinical research on identifying risk factors and management of ESA hyporesponsiveness brings greater hope on finding solutions to eventually tackling one of the most difficult problems in the topic of anemia in CKD.
Publisher: Elsevier BV
Date: 05-2021
Publisher: Oxford University Press (OUP)
Date: 2022
DOI: 10.1093/RAP/RKAC078
Publisher: Dustri-Verlgag Dr. Karl Feistle
Date: 2022
DOI: 10.5414/CNCS110852
Publisher: S. Karger AG
Date: 2023
DOI: 10.1159/000531367
Abstract: b i Background: /i /b An aging population living with chronic kidney disease and progressing to kidney failure, subsequently receiving peritoneal dialysis (PD) is growing. A significant proportion of these patients are also living with multi-morbidities and some degree of frailty. Recent practice recommendations from the International Society of Peritoneal Dialysis advocate for high-quality, goal-directed PD prescription, and the Standardized Outcomes of Nephrology-PD initiative emphasized the need for an in idualized, goal-based care approach in all patients receiving PD treatment. In older patients, this approach to PD care is even more important. A frailty screening assessment, followed by a comprehensive geriatric assessment (CGA) prior to PD initiation and when dictated by change in relevant circumstances is paramount in tailoring PD care and prescription according to the needs, life goals, as well as clinical status of older patients with kidney failure. b i Summary: /i /b Our review aimed to summarize the different dimensions to be taken into account when delivering PD care to the older patient – from frailty screening and CGA in older patients receiving PD to employing a personalized, goal-directed PD prescription strategy, to preserving residual kidney function, optimizing blood pressure (BP) control, and managing anemia, to addressing symptom burden, to managing nutritional intake and promoting physical exercise, and to explore telehealth opportunities for the older PD population. b i Key Messages: /i /b What matters most to older PD patients may not be simply extending survival, but more importantly, to be living comfortably on PD treatment with minimal symptom burden in a home environment and to minimize treatment complications.
Publisher: S. Karger AG
Date: 21-09-2021
DOI: 10.1159/000518984
Abstract: Anti-glomerular basement membrane (anti-GBM) disease is a rare form of small-vessel vasculitis that typically causes rapidly progressive glomerulonephritis with or without alveolar haemorrhage. Previously, there has only been one reported case of tumour necrosis factor-α (TNF-α) antagonist-induced anti-GBM disease. Here, we describe the first reported case of etanercept-induced anti-GBM disease. A 55-year-old Caucasian man was referred to our tertiary specialist renal centre with a history of painless macroscopic haematuria. The patient has been receiving weekly etanercept injections over the past 12 months for psoriatic arthropathy. The serum immunology panel results highlighted a significantly raised anti-GBM titre (370.1 U). Etanercept was stopped, and the patient was empirically commenced on pulsed methylprednisolone, cyclophosphamide, and plasma exchange. A renal biopsy showed crescentic glomerulonephritis. Few days after admission, he tested positive for coronavirus disease 2019 (COVID-19), and a decision was made to withhold cyclophosphamide. There was further decline in renal function with hyperkalaemia for which he received 2 sessions of haemodialysis. He was restarted on cyclophosphamide upon discharge. The patient was switched to rituximab treatment afterwards as he developed leucopenia 2 weeks following the commencement of cyclophosphamide. The serum creatinine level continued to improve and remained dialysis-independent. In conclusion, with the increased use of etanercept and other TNF-α antagonists, the prescribing clinician must be aware of the rare but life-threatening drug-induced vasculitis. We recommend careful monitoring of renal indices with the use of this class of medications.
Publisher: BMJ
Date: 06-2015
Publisher: MDPI AG
Date: 14-03-2023
DOI: 10.3390/BIOMEDINFORMATICS3010017
Abstract: Digital information storage capacity and biomedical technology advancements in recent decades have stimulated the maturity and popularization of “big data” in medicine. The value of utilizing big data as a diagnostic and prognostic tool has continued to rise given its potential to provide accurate and insightful predictions of future health events and probable outcomes for in iduals and populations, which may aid early identification of disease and timely treatment interventions. Whilst the implementation of big data methods for this purpose is more well-established in specialties such as oncology, cardiology, ophthalmology, and dermatology, big data use in nephrology and specifically chronic kidney disease (CKD) remains relatively novel at present. Nevertheless, increased efforts in the application of big data in CKD have been observed over recent years, with aims to achieve a more personalized approach to treatment for in iduals and improved CKD screening strategies for the general population. Considering recent developments, we provide a focused perspective on the current state of big data and its application in CKD and nephrology, with hope that its ongoing evolution and revolution will gradually identify more solutions to improve strategies for CKD prevention and optimize the care of patients with CKD.
Publisher: American Medical Association (AMA)
Date: 03-10-2023
Publisher: Massachusetts Medical Society
Date: 19-07-2100
Publisher: Wiley
Date: 16-06-2021
DOI: 10.1111/HDI.12949
Abstract: An increasing demand for in‐center dialysis services has been largely driven by a rapid growth of the older population progressing to end‐stage kidney disease. Since the onset of the COVID‐19 pandemic, efforts to encourage home‐based dialysis options have increased due to risks of infective transmission for patients receiving hemodialysis in center‐based units. There are various practical and clinical advantages for patients receiving hemodialysis at home. However, the lack of caregiver support, cognitive and physical impairment, challenges of vascular access, and preparation and training for home hemodialysis (HHD) initiation may present as barriers to successful implementation of HHD in the older dialysis population. Assessment of an older patient's frailty status may help clinicians guide patients when making decisions about HHD. The development of an assisted HHD care delivery model and advancement of telehealth and technology in provision of HHD care may increase accessibility of HHD services for older patients. This review examines these factors and explores current unmet needs and barriers to increasing access, inclusion, and opportunities of HHD for the older dialysis population.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 07-2020
Publisher: MDPI AG
Date: 04-08-2022
DOI: 10.3390/KIDNEYDIAL2030040
Abstract: Anemia in chronic kidney disease (CKD) has become an important clinical issue with the increased prevalence of elderly patients living with CKD progressing to kidney failure. The causes of anemia in elderly in iduals tend to be multifactorial, exacerbated by the physiological effects of aging, frailty and declining kidney function. Erythropoiesis-stimulating agents (ESAs) are the conventional therapeutic option for anemia in CKD. However, ESA hyporesponsiveness is a commonly observed issue in clinical practice and an issue that is more challenging to resolve in elderly patients living with frailty, kidney disease, and multi-morbidities. Following the emergence of oral hypoxia-induced factor prolyl-hydroxylase inhibitors (HIF-PHI) in recent years, there is discussion on whether it is a solution to the conundrum of ESA hyporesponsiveness, as HIF-PHI treats anemia via an alternative physiological pathway. There remains uncertainty on the suitability of HIF-PHI use in elderly patients, given a lack of data on its safety over long-term follow-up for the elderly population. Further study is needed to provide answers, considering the clinical significance of this issue within a public-health scale.
Publisher: Oxford University Press (OUP)
Date: 22-04-2019
Publisher: MDPI AG
Date: 24-06-2023
Abstract: Amyloidosis is a complex disorder characterized by deposited insoluble fibrillar proteins which misfold into β-pleated sheets. The pathogenesis of amyloidosis can vary but can be the result of immune dysregulation that occurs from sustained high inflammatory states, often known as AA amyloidosis. Multi-organ involvement including hepatic, gastrointestinal, renal, cardiac and immunological pathological manifestations has been observed amongst in iduals presenting with amyloidosis. The recent global pandemic of severe acute respiratory syndrome coronavirus 2, also referred to as coronavirus 2019 (COVID-19), has been shown to be associated with multiple health complications, many of which are similar to those seen in amyloidosis. Though COVID-19 is recognized primarily as a respiratory disease, it has since been found to have a range of extra-pulmonary manifestations, many of which are observed in patients with amyloidosis. These include features of oxidative stress, chronic inflammation and thrombotic risks. It is well known that viral illnesses have been associated with the triggering of autoimmune conditions of which amyloidosis is no different. Over the recent months, reports of new-onset and relapsed disease following COVID-19 infection and vaccination have been published. Despite this, the exact pathophysiological associations of COVID-19 and amyloidosis remain unclear. We present a scoping review based on our systematic search of available evidence relating to amyloidosis, COVID-19 infection and COVID-19 vaccination, evaluating current perspectives and providing insight into knowledge gaps that still needs to be addressed going forward.
Publisher: Massachusetts Medical Society
Date: 25-02-2021
Publisher: AccScience Publishing
Date: 12-04-2023
DOI: 10.36922/AN.314
Abstract: Seizures are not uncommon in patients with chronic kidney disease (CKD), with an approximate incidence of roughly 10%. There are two primary groups: Patients who develop acute provoked seizures in the setting of CKD and patients with pre-existing epilepsy who then develop CKD. The recognition of potential etiology and management of seizures in this patient population may be challenging for clinicians, particularly non-neurologists. Standard antiepileptic drug (AED) treatment is indicated for those with pre-existing epilepsy. The prescription of AED in CKD population requires careful consideration, due to potentially altered pharmacokinetics. Clinicians frequently encounter challenges in the selection, loading, titration, and maintenance of AEDs. There are few internationally recognized consensus recommendations for AED prescription in CKD and dialysis. Non-AED management aims at addressing factors that may have provoked the seizure. In this article, we provide an in-depth review of the potential etiologies and pathophysiological pathways of provoked seizures in CKD. We discuss strategies, including non-AED treatment options, which aim to prevent, and/or manage provoked seizures in the setting of CKD. We discuss the AEDs used in contemporary clinical practice and how their metabolism is affected by CKD, concurrent AED prescriptions, and dialysis.
Publisher: Oxford University Press (OUP)
Date: 06-2023
DOI: 10.1093/NDT/GFAD063C_5507
Abstract: Hypertension is the second leading cause of chronic kidney disease (CKD) following diabetes and occurs in most patients with CKD. Finding an optimal treatment regime for hypertension remains challenging due to the complex bidirectional cause-and-effect relationship between hypertension and CKD, and hypertensive CKD patients may require treatment with multiple antihypertensive drugs. Database studies and practice guidelines have continued to demonstrate international variability in antihypertensive treatment practices. We analysed data from the Salford Kidney Study (SKS) database in relation to antihypertensive prescribing patterns amongst study patients. The SKS is an ongoing prospective study recruiting patients with CKD since the year 2002. Data including patient demographics, comorbidities, physical parameters, concurrent medications, and biochemical results are collected at baseline (study enrolment). All patients are followed up annually until they reach their endpoints [reaching end-stage kidney disease (ESKD), death, or discharge from follow-up] in idually, with updates in their medical records including a list of medications. We have used Cox regression analysis and Kaplan Meier charts to investigate the associations between Renin-Angiotensin-Aldosterone System inhibitor (RAASi) use and the number of antihypertensive agents (binary groups of ≤3 or & ), and clinical outcomes (ESKD and all-cause mortality). A total of 3230 patients recruited between October 2002 and December 2019 were included in this analysis. At baseline, the median age of the cohort was 67 years with a predominance of males (62%) and those of white ethnicity (96%). 90% had a history of hypertension and 32% were diabetic. The median blood pressure was 138/75 mmHg. Previous myocardial infarction was recorded in 15%, congestive cardiac failure in 17% and cerebrovascular disease in 7.7% of the patients. The median estimated glomerular filtration rate (eGFR) was 30 ml/min/1.73 m2 and the median urine protein creatinine ratio (uPCR) was 33 mg/mmol. RAASi agents (ACEi & ARB) (56%) were the most common antihypertensive medications to be prescribed, followed by diuretics (50%), calcium channel blockers (45%), and beta blockers (34%). The proportion of patients prescribed RAASi was associated with greater proteinuria (43 vs 33%, p& .001). CKD patients with preexisting cardiovascular comorbidities were more likely to be prescribed beta blockers (44 vs 27%, p& .001), diuretics (58 vs 39%, p& .001) and mineralocorticoid antagonists (6.4 vs 1.85%, p& .001). An increasing number of CKD patients were being prescribed ARBs over 24-month follow-up (34 vs 28%, p = 0.02). In a multivariable Cox-regression analysis, RAASi intake was not associated with reaching ESKD (HR 0.91 p = 0.49) but was associated with a significant survival benefit (HR 0.84 p = 0.001) (Figure 1). Use of a higher number of antihypertensive agents (i.e. & ) was associated with both greater mortality (HR 1.28 p = 0.02) and worse dialysis-free survival (HR 1.46 p = 0.007) (Figure 2). Antihypertensive prescribing patterns in the SKS were consistent with current guidelines in the U.K. (e.g. NICE guidance 2022), with RAASi being predominantly prescribed as the first-line antihypertensive agent. An overall survival benefit was noted with RAASi use, although there was no signal for reducing progression towards ESRD. Outcomes were poor in patients with resistant hypertension needing multiple antihypertensive agents. Considering existing variations between the U.K. and other international guidelines regarding antihypertensive treatment in CKD, continued research is indicated to bridge the gaps between these recommendations and optimise patient outcomes.
Publisher: MDPI AG
Date: 22-12-2021
Abstract: Introduction: COVID-19 infections resulting in pathological kidney manifestations have frequently been reported in adults since the onset of the global COVID-19 pandemic in December 2019. Gradually, there have been an increased number of COVID-19-associated intrinsic kidney pathologies in children and adolescents reported as well. The pathophysiological mechanisms between COVID-19 and the onset of kidney pathology are not fully known in children it remains a challenge to distinguish between intrinsic kidney pathologies that were caused directly by COVID-19 viral invasion, and cases which occurred as a result of multisystem inflammatory syndrome due to the infection. This challenge is made more difficult in children, due to the ethical limitations of performing kidney biopsies to reach a biopsy-proven diagnosis. Although previous systematic reviews have summarized the various pathological kidney manifestations that have occurred in adults following acute COVID-19 infection, such reviews have not yet been published for children and adolescents. We describe the results of a systematic review for intrinsic kidney pathology following COVID-19 infection in children and adolescents. Methods: A systematic literature search of published data up until 31 October was completed through the Preferred Reporting Items for Systematic Reviews and Meta Analyses (PRISMA) guidelines. Research articles reporting new-onset or relapsed intrinsic kidney pathology in children or adolescents (≤18 years) following acute COVID-19 infection were included for qualitative review. COVID-19 infection status was defined by a positive result from a RT-PCR, or nuclear antibody testing. Only full-text articles published in the English language were selected for review. Results: Twenty-nine cases from fifteen articles were included in the qualitative synthesis of this systematic review. Nephrotic syndrome, as an umbrella condition, appeared as the most frequently observed presentation (20 cases) with disease remission noted in all cases with steroid treatment. Other cases included numerous glomerulonephritides, such as acute necrotizing glomerulonephritis, MPO vasculitis and collapsing glomerulopathy, and thrombotic microangiopathies, such as aHUS. For patients with transplanted kidneys, T-cell-mediated rejection and mild tubular interstitial infiltration were noted following testing positive for COVID-19. There were no mortalities reported in any of the included cases, although two patients remained dialysis dependent at hospital discharge. Conclusion: This systematic review highlights the various intrinsic pathological kidney manifestations in children and adolescents as a result of acute COVID-19 infection. The clinical timeline and presentation of these cases support the mechanistic hypothesis between COVID-19 infection and the onset of intrinsic kidney pathologies within this context. The progressive introduction of vaccination programs for children and adolescents may hopefully reduce the severity of COVID-19-associated illnesses, and pathological kidney manifestations in this population.
Publisher: Wiley
Date: 29-03-2022
DOI: 10.1111/SDI.13079
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 12-2021
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Henry HL Wu.