Peritoneal dialysis-associated peritonitis presenting with Ralstonia pickettii infection: A novel series of three cases during the COVID-19 pandemic.

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.

Exfoliated Kidney Cells from Urine for Early Diagnosis and Prognostication of CKD: The Way of the Future?

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/progenitor cells as surrogate markers for the early diagnosis and prognostication of CKD. Future directions for development within this research area are also identified.

Patient safety and the role of the Helsinki Declaration on Patient Safety in Anaesthesiology: A European survey.

BACKGROUND: The Helsinki Declaration on Patient Safety was launched in 2010 by the European Society of Anaesthesiology and the European Board of Anaesthesiology. It is not clear how widely its vision and standards have been adopted. OBJECTIVE: To explore the role of the Helsinki Declaration in promoting and maintaining patient safety in European anaesthesiology. DESIGN: Online survey. SETTING: A total of 38 countries within Europe. PARTICIPANTS: Members of the European Society of Anaesthesiology who responded to an invitation to take part by electronic mail. MAIN OUTCOME MEASURES: Responses from a 16-item online survey to explore each member anaesthesiologist's understanding of the Declaration and compliance with its standards. RESULTS: We received 1589 responses (33.4% response rate), with members from all countries responding. The median [IQR] response rate of members was 20.5% [11.7 to 37.0] per country. There were many commonalities across Europe. There were very high levels of use of monitoring (pulse oximetry: 99.6%, blood pressure: 99.4%; ECG: 98.1% and capnography: 96.0%). Protocols and guidelines were also widely used, with those for pre-operative assessment, and difficult and failed intubation being particularly popular (mentioned by 93.4% and 88.9% of respondents, respectively). There was evidence of widespread use of the WHO Safe Surgery checklist, with only 93 respondents (6.0%) suggesting that they never used it. Annual reports of measures taken to improve patient safety, and of morbidity and mortality, were produced in the hospitals of 588 (37.3%) and 876 (55.7%) respondents, respectively. Around three-quarters of respondents, 1216, (78.7%) stated that their hospital used a critical incident reporting system. Respondents suggested that measures to promote implementation of the Declaration, such as a formal set of checklist items for day-to-day practice, publicity, translation and simulation training, would currently be more important than possible changes to its content. CONCLUSION: Many patient safety practices encouraged by the Declaration are well embedded in many European countries. The data have highlighted areas where there is still room for improvement.

Hepatocardiorenal syndrome in liver cirrhosis: Recognition of a new entity?

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.

Clostridioides difficile Infection in Kidney Transplant Recipients.

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.

Evaluating the Clinical Relevance of Antibodies against Non-Human Leukocyte Antigen in Kidney Transplantation.

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.

Incidence, Risk Factors, and Outcomes of De Novo Malignancy following Kidney Transplantation.

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.

Physiological Associations between Vitamin B Deficiency and Diabetic Kidney Disease.

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.

Home dialysis in older adults: challenges and solutions.

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.

The Role of PLA2R in Primary Membranous Nephropathy: Do We Still Need a Kidney Biopsy?

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.

COVID-19 in Elderly Patients Receiving Haemodialysis: A Current Review.

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.

Is It Time to Integrate Frailty Assessment in Onconephrology?

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.

Delivering Personalized, Goal-Directed Care to Older Patients Receiving Peritoneal Dialysis.

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.

COVID-19 Infection and Vaccination and Its Relation to Amyloidosis: What Do We Know Currently?

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.

Antihypertensive prescribing patterns in non-dialysis dependent chronic kidney disease: Findings from the Salford Kidney Study.

BACKGROUND: Hypertension is commonly observed in patients living with chronic kidney disease (CKD). Finding an optimal treatment regime remains challenging due to the complex bidirectional cause-and-effect relationship between hypertension and CKD. There remains variability in antihypertensive treatment practices. AIM: To analyze data from the Salford Kidney Study database in relation to antihypertensive prescribing patterns amongst CKD patients. METHODS: The Salford Kidney Study is an ongoing prospective study that has been recruiting CKD patients since 2002. All patients are followed up annually, and their medical records including the list of medications are updated until they reach study endpoints [starting on renal replacement therapy or reaching estimated glomerular filtration rate (eGFR) expressed as mL/min/1.73 m2 ≤ 10 mL/min/1.73 m2, or the last follow-up date, or data lock on December 31, 2021, or death]. Data on antihypertensive prescription practices in correspondence to baseline eGFR, urine albumin-creatinine ratio, primary CKD aetiology, and cardiovascular disease were evaluated. Associations between patients who were prescribed three or more antihypertensive agents and their clinical outcomes were studied by Cox regression analysis. Kaplan-Meier analysis demonstrated differences in survival probabilities. RESULTS: Three thousand two hundred and thirty non-dialysis-dependent CKD patients with data collected between October 2002 and December 2019 were included. The median age was 65 years. A greater proportion of patients were taking three or more antihypertensive agents with advancing CKD stages (53% of eGFR ≤ 15 mL/min/1.73 m2 vs 26% of eGFR ≥ 60 mL/min/1.73 m2, P < 0.001). An increased number of patients receiving more classes of antihypertensive agents was observed as the urine albumin-creatinine ratio category increased (category A3: 62% vs category A1: 40%, P < 0.001), with the upward trends particularly noticeable in the number of individuals prescribed renin angiotensin system blockers. The prescription of three or more antihypertensive agents was associated with all-cause mortality, independent of blood pressure control (hazard ratio: 1.15; 95% confidence interval: 1.04-1.27, P = 0.006). Kaplan-Meier analysis illustrated significant differences in survival outcomes between patients with three or more and those with less than three antihypertensive agents prescribed (log-rank, P < 0.001). CONCLUSION: Antihypertensive prescribing patterns in the Salford Kidney Study based on CKD stage were consistent with expectations from the current United Kingdom National Institute of Health and Care Excellence guideline algorithm. Outcomes were poorer in patients with poor blood pressure control despite being on multiple antihypertensive agents. Continued research is required to bridge remaining variations in hypertension treatment practices worldwide.

Erythropoietin-Stimulating Agent Hyporesponsiveness in Patients Living with Chronic Kidney Disease.

Background: 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. Summary: 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. Key Message: 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.

Vitamin B12 and chronic kidney disease.

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.

Intrinsic Kidney Pathology in Children and Adolescents Following COVID-19 Vaccination: A Systematic Review.

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.