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Introduction: Kidney transplantation is the preferred modality of kidney replacement therapy for eligible patients with end-stage kidney disease (ESKD), given that it has been found to reduce mortality rates, improve quality of life, and is cost-effective compared to dialysis. Recent advancements in human leukocyte antigen (HLA) typing and donor-specific antibody (DSA) detection have helped to reduce the risk of rejection, but antibody-mediated rejection (AMR) can still occur without DSA. Previous studies suggest that rejection can be attributed to antibodies against Non-Human Leucocyte Antigens (non-HLAs). We aimed to acquire further understanding of the prevalence and distribution of non-HLA antibodies in our local population and attempt to correlate these findings with graft outcomes, as well as assess whether non-HLA antibodies can be utilized to determine graft impairment and dysfunction. Methods: We conducted a retrospective study involving kidney transplant recipients between January 2010 and December 2020. All included individuals were aged over 18 and underwent kidney-alone transplants; were ABO- and HLA-compatible; and were matched at A, B, and DR loci (mismatch 0:0:0). HLA testing was negative at the time of transplantation. The samples from both cases of early graft rejection and the control group were tested for non-HLA antibodies using One Lambda LABScreenTM, Autoantibody kit groups 1, 2, and 3, as well as the Immucor LIFECODES non-HLA autoantibody assay. Results: A total of 850 kidney transplant recipients were included, in which 12 patients experienced early graft rejection within the first month post transplant and 18 patients who did not experience graft rejection were selected as study controls. Our study reported no correlation between the total burden of non-HLA antibodies and early rejection, most likely as the result of a small sample size. Nevertheless, a sub-analysis revealed that specific high-frequency pre-transplant non-HLA antibodies such as GSTT, CXCL11, CXCL10, and HNR, detected by LIFECODES, were associated with rejection (Fisher's exact test with Bonferroni correction, p < 0.001). Most pre-transplant non-HLA antibody levels were reduced after transplantation, which was attributed to immunosuppression. Conclusion: The 'high frequency' non-HLA antibodies displayed an association with graft rejection, though the overall associations between the burden of non-HLA antibodies and rejection episodes remain inconclusive. Further work is needed to establish the rebound phenomenon of non-HLA antibodies, the development of de novo non-HLA antibodies in the long run, and their implications on graft survival.
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Introduction: Post-transplant malignancy is a significant cause of morbidity and mortality following kidney transplantation often emerging after medium- to long-term follow-up. To understand the risk factors for the development of de novo post-transplant malignancy (DPTM), this study aimed to assess the incidence, risk factors, and outcomes of DPTM at a single nephrology centre over two decades. Methods: This retrospective cohort study included 963 kidney transplant recipients who underwent kidney transplantation between January 2000 and December 2020 and followed up over a median follow-up of 7.1 years (IQR 3.9-11.4). Cox regression models were used to identify the significant risk factors of DPTM development, the association of DPTM with graft survival, and mortality with a functioning graft. Results: In total, 8.1% of transplant recipients developed DPTM, and the DPTM incidence rate was 14.7 per 100 patient-years. There was a higher mean age observed in the DPTM group (53 vs. 47 years, p < 0.001). The most affected organ systems were genitourinary (32.1%), gastrointestinal (24.4%), and lymphoproliferative (20.5%). Multivariate Cox analysis identified older age at transplant (aHR 9.51, 95%CI: 2.60-34.87, p < 0.001) and pre-existing glomerulonephritis (aHR 3.27, 95%CI: 1.10-9.77, p = 0.03) as significant risk factors for DPTM. Older age was significantly associated with poorer graft survival (aHR 8.71, 95%CI: 3.77-20.20, p < 0.001). When age was excluded from the multivariate Cox model, DPTM emerged as a significant risk factor for poor survival (aHR 1.76, 95%CI: 1.17-2.63, p = 0.006). Conclusion: These findings underscore the need for tailored screening, prevention, and management strategies to address DPTM in an aging and immunosuppressed kidney transplant population.
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Emerging evidence and perspectives have pointed towards the heart playing an important role in hepatorenal syndrome (HRS), outside of conventional understanding that liver cirrhosis is traditionally considered the sole origin of a cascade of pathophysiological mechanisms directly affecting the kidneys in this context. In the absence of established heart disease, cirrhotic cardiomyopathy may occur more frequently in those with liver cirrhosis and kidney disease. It is a specific form of cardiac dysfunction characterized by blunted contractile responsiveness to stress stimuli and altered diastolic relaxation with electrophysiological abnormalities. Despite the clinical description of these potential cardiac-related complications of the liver, the role of the heart has traditionally been an overlooked aspect of circulatory dysfunction in HRS. Yet from a physiological sense, temporality (prior onset) of cardiorenal interactions in HRS and positive effects stemming from portosystemic shunting demonstrated an important role of the heart in the development and progression of kidney dysfunction in cirrhotic patients. In this review, we discuss current concepts surrounding how the heart may influence the development and progression of HRS, and the role of systemic inflammation and endothelial dysfunction causing circulatory dysfunction within this setting. The temporality of heart and kidney dysfunction in HRS will be discussed. For a subgroup of patients who receive portosystemic shunting, the dynamics of cardiorenal interactions following treatment is reviewed. Continued research to determine the unknowns in this topic is anticipated, hopefully to further clarify the intricacies surrounding the liver-heart-kidney connection and improve strategies for management.
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Cardiomiopatias , Síndrome Hepatorrenal , Humanos , Cirrose Hepática/complicações , Coração , Cardiomiopatias/etiologia , Cardiomiopatias/terapia , Síndrome Hepatorrenal/etiologia , Síndrome Hepatorrenal/terapiaRESUMO
Clostridioides difficile (C. difficile) is a bacterial organism that typically infects the colon, which has had its homeostasis of healthy gut microbiota disrupted by antibiotics or other interventions. Patients with kidney transplantation are a group that are susceptible to C. difficile infection (CDI) and have poorer outcomes with CDI given that they conventionally require long-term immunosuppression to minimize their risk of graft rejection, weakening their responses to infection. Recognizing the risk factors and complex pathophysiological processes that exist between immunosuppression, dysbiosis, and CDI is important when making crucial clinical decisions surrounding the management of this vulnerable patient cohort. Despite the clinical importance of this topic, there are few studies that have evaluated CDI in the context of kidney transplant recipients and other solid organ transplant populations. The current recommendations on CDI management in kidney transplant and solid organ transplant recipients are mostly extrapolated from data relating to CDI management in the general population. We provide a narrative review that discusses the available evidence examining CDI in solid organ transplant recipients, with a particular focus on the kidney transplant recipient, from the epidemiology of CDI, clinical features and implications of CDI, potential risk factors of CDI, and, ultimately, prevention and management strategies for CDI, with the aim of providing areas for future research development in this topic area.
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Background: 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 individualized, 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. Summary: 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. Key Messages: 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.
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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.
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Glomerulonefrite Membranosa , Síndrome Nefrótica , Adulto , Idoso , Humanos , Autoanticorpos , Biópsia , Glomerulonefrite Membranosa/diagnóstico , Glomerulonefrite Membranosa/genética , Rim/patologia , Síndrome Nefrótica/patologia , Receptores da Fosfolipase A2 , Reprodutibilidade dos TestesRESUMO
Amyloidosis is a complex disorder characterized by deposited insoluble fibrillar proteins which misfold into ß-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 individuals 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.
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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.
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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 individual'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.
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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.
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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.