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Abstract Background Minimal Change Disease (MCD) and Focal Segmental Glomerulosclerosis (FSGS) are a spectrum of disease causing the nephrotic syndrome (NS), characterised by proteinuria with debilitating oedema, as well as a high risk of venous thromboembolic disease and infection. Untreated, 50–60% patients with FSGS progress to end stage kidney disease after 5 years. These diseases respond to immunosuppression with high dose glucocorticoids, but 75% will relapse as the glucocorticoids are withdrawn, leading to significant morbidity associated with prolonged use. In children, the B cell depleting monoclonal antibody rituximab reduces relapse risk, but this drug has not been tested in randomised controlled trial in adults. Methods 130–150 adults with new or relapsing MCD/FSGS, from UK Renal Units, are being randomised to receive either rituximab (two 1 g infusions two weeks apart) or placebo. Partipicipants are recruited when they present with nephrosis, and all are treated with glucocorticoids as per KDIGO guidelines. Once in remission, prednisolone is withdrawn according to a pre-specified regimen. If in remission at 6 months, participants receive a further dose of trial drug. If they relapse, they are unblinded, and if they have received placebo, they are offered open label rituximab with protocolised prednisolone as in the main phase of the trial. The primary end point is time from remission to relapse. A number of secondary endpoints will be assessed including the effect of rituximab on: (1) NHS and societal resource use and hence cost: (2) safety: (3) other measures of efficacy, such as achievement of partial and complete remission of NS and the preservation of renal function: (4) health status of participant. Trial Registration TURING received ethical approval on 14 Jun 2019 - REC reference: 19/LO/0738. It is registered on EudraCT, with ID number: 2018-004611-50, with a start date of 2019-06-14.

Abstract This study aims to figure out the worldwide prevalence of anticancer therapy-associated acute kidney injury (AKI) and tubulointerstitial nephritis (TIN) and the relative risk of each cancer drug. We conducted an analysis of VigiBase, the World Health Organization pharmacovigilance database, 1967–2023 via disproportionate Bayesian reporting method. We further categorized the anticancer drugs into four groups: cytotoxic therapy, hormone therapy, immunotherapy, and targeted therapy. Reporting odds ratio (ROR) and information component (IC) compares observed and expected values to investigate the associations of each category of anticancer drugs with AKI and TIN. We identified 32,722 and 2056 reports (male, n = 17,829 and 1,293) of anticancer therapy-associated AKI and TIN, respectively, among 4,592,036 reports of all-drug caused AKI and TIN. There has been a significant increase in reports since 2010, primarily due to increased reports of targeted therapy and immunotherapy. Immunotherapy exhibited a significant association with both AKI (ROR: 8.92; IC0.25: 3.06) and TIN (21.74; 4.24), followed by cytotoxic therapy (7.14; 2.68), targeted therapy (5.83; 2.40), and hormone therapy (2.59; 1.24) for AKI, and by cytotoxic therapy (2.60; 1.21) and targeted therapy (1.54; 0.61) for TIN. AKI and TIN were more prevalent among individuals under 45 years of age, with a female preponderance for AKI and males for TIN. These events were reported in close temporal relationship after initiation of the respective drug (16.53 days for AKI and 27.97 days for TIN), and exhibited a high fatality rate, with 23.6% for AKI and 16.3% for TIN. These findings underscore that kidney-related adverse drug reactions are of prognostic significance and strategies to mitigate such side effects are required to optimize anticancer therapy.

Posttransplant malignancies are an important complication of solid organ transplantation. Kidney transplant recipients are at particularly high risk of cancer development. The most relevant risk factors of carcinogenesis are the use of immunosuppressive agents and oncogenic viral infections. Additionally, immune dysregulation caused by these factors may predispose to various types of organ damage. Paraneoplastic glomerular diseases are one of the most interesting and understudied cancer manifestations. The appropriate diagnosis of paraneoplastic glomerular damage can be challenging in kidney transplant recipients, due to factors inherent to concomitant medication and common comorbidities. Recent advances in the field of molecular and clinical nephrology led to a significant improvement in our understanding of glomerular diseases and their more targeted treatment. On the other hand, introduction of novel anticancer drugs tremendously increased patients’ survival, at the cost of kidney-related side effects. Our review aims to provide insights into diagnosis and treatment of paraneoplastic glomerular diseases, with a special attention to kidney transplant recipients.

Kidney transplantation significantly improves the survival of patients with end-stage kidney disease (ESKD) compared to other forms of kidney replacement therapy. However, kidney transplant recipients’ outcomes are not fully satisfactory due to increased risk of cardiovascular diseases, infections, and malignancies. Immune-related complications remain the biggest challenge in the management of kidney graft recipients. Despite the broad spectrum of immunosuppressive agents available and more detailed methods used to monitor their effectiveness, chronic allograft nephropathy remains the most common cause of kidney graft rejection. The kynurenine (KYN) pathway is the main route of tryptophan (Trp) degradation, resulting in the production of a plethora of substances with ambiguous properties. Conversion of Trp to KYN by the enzyme indoleamine 2,3-dioxygenase (IDO) is the rate-limiting step determining the formation of the next agents from the KYN pathway. IDO activity, as well as the production of subsequent metabolites of the pathway, is highly dependent on the balance between pro- and anti-inflammatory conditions. Moreover, KYN pathway products themselves possess immunomodulating properties, e.g., modify the activity of IDO and control other immune-related processes. KYN metabolites were widely studied in neurological disorders but recently gained the attention of researchers in the context of immune-mediated diseases. Evidence that this route of Trp degradation may represent a peripheral tolerogenic pathway with significant implications for transplantation further fueled this interest. Our review aimed to present recent knowledge about the role of the KYN pathway in the pathogenesis, diagnosis, monitoring, and treatment of kidney transplant recipients’ complications.

Abstract Little is known about the prevalence of chronic kidney disease (CKD) during the coronavirus disease 2019 (COVID-19) pandemic. We aimed to investigate the long-term trends in CKD prevalence from South Korea including the early pandemic. We used data from 108,152 Korean adults from 2007 to 2020 obtained from a representative longitudinal serial study. We defined CKD as a condition when the participant’s estimated glomerular filtration rate was

IntroductionPatients with immune-mediated glomerular diseases are considered at high risk for severe COVID-19 outcomes. However, conclusive evidence for this patient population is scarce.MethodsWe created a global registry and retrospectively collected clinical data of patients with COVID-19 and a previously diagnosed immune-mediated glomerular disease to characterize specific risk factors for severe COVID-19 outcomes.ResultsFifty-nine patients with a history of immune-mediated glomerular diseases were diagnosed with COVID-19 between 01.03.2020 and 31.08.2021. Over a mean follow-up period of 24.79 ± 18.89 days, ten patients (16.9%) developed acute kidney injury. Overall, 44.1% of patients were managed in an outpatient setting and therefore considered as having “non-severe” COVID-19, while 55.9% of patients had severe COVID-19 requiring hospitalization including worse outcomes. Comparing both groups, patients with severe COVID-19 were significantly older (53.55 ± 17.91 versus 39.77 ± 14.95 years, p = .003), had lower serum albumin levels at presentation (3.00 ± 0.80 g/dL versus 3.99 ± 0.68 g/dL, p = .016) and had a higher risk of developing acute kidney injury (27% versus 4%, p = .018). Male sex (p

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Abstract On October 2020, the US Food and Drug Administration (FDA) approved remdesivir as the first drug for the treatment of coronavirus disease 2019 (COVID‐19), increasing remdesivir prescriptions worldwide. However, potential cardiovascular (CV) toxicities associated with remdesivir remain unknown. We aimed to characterize the CV adverse drug reactions (ADRs) associated with remdesivir using VigiBase, an individual case safety report database of the World Health Organization (WHO). Disproportionality analyses of CV‐ADRs associated with remdesivir were performed using reported odds ratios and information components. We conducted in vitro experiments using cardiomyocytes derived from human pluripotent stem cell cardiomyocytes (hPSC‐CMs) to confirm cardiotoxicity of remdesivir. To distinguish drug‐induced CV‐ADRs from COVID‐19 effects, we restricted analyses to patients with COVID‐19 and found that, after adjusting for multiple confounders, cardiac arrest (adjusted odds ratio [aOR]: 1.88, 95% confidence interval [CI]: 1.08–3.29), bradycardia (aOR: 2.09, 95% CI: 1.24–3.53), and hypotension (aOR: 1.67, 95% CI: 1.03–2.73) were associated with remdesivir. In vitro data demonstrated that remdesivir reduced the cell viability of hPSC‐CMs in time‐ and dose‐dependent manners. Physicians should be aware of potential CV consequences following remdesivir use and implement adequate CV monitoring to maintain a tolerable safety margin.

We report a case of a patient double-seropositive for anti-glomerular basement membrane (anti-GBM) and anti-neutrophil cytoplasmic antibodies (ANCA) who reported retrosternal chest pain during a regular hemodialysis session associated with ST-segment depression in electrocardiogram and an increase of serum high-sensitivity troponin T. Urgent coronary angiography excluded obstructive coronary artery disease, suggesting the diagnosis of ischemia with non-obstructive coronary arteries. This case illustrates an unusual presentation of cardiovascular involvement in a patient with double-positive ANCA/anti-GBM disease, emphasizing the possible relevance of coronary microvascular dysfunction and the need for close cardiovascular follow-up in this patient population.

The publication of genetic epidemiology meta-analyses has increased rapidly, but it has been suggested that many of the statistically significant results are false positive. In addition, most such meta-analyses have been redundant, duplicate, and erroneous, leading to research waste. In addition, since most claimed candidate gene associations were false-positives, correctly interpreting the published results is important. In this review, we emphasize the importance of interpreting the results of genetic epidemiology meta-analyses using Bayesian statistics and gene network analysis, which could be applied in other diseases.

Membranous nephropathy (MN) is the most common cause of primary nephrotic syndrome among adults. The identification of phospholipase A2 receptor (PLA2R) as target antigen in most patients changed the management of MN dramatically, and provided a rationale for B-cell depleting agents such as rituximab. The efficacy of rituximab in inducing remission has been investigated in several studies, including 3 randomized controlled trials, in which complete and partial remission of proteinuria was achieved in approximately two-thirds of treated patients. Due to its favorable safety profile, rituximab is now considered a first-line treatment option for MN, especially in patients at moderate and high risk of deterioration in kidney function. However, questions remain about how to best use rituximab, including the optimal dosing regimen, a potential need for maintenance therapy, and assessment of long-term safety and efficacy outcomes. In this review, we provide an overview of the current literature and discuss both strengths and limitations of “the new standard.”

The human nasal microbiome is characterized by biodiversity and undergoes changes during the span of life. In granulomatosis with polyangiitis (GPA), the persistent nasal colonization by Staphylococcus aureus (S. aureus) assessed by culture-based detection methods has been associated with increased relapse frequency. Different research groups have characterized the nasal microbiome in patients with GPA and found that patients have a distinct nasal microbiome compared to controls, but the reported results between studies differed. In order to increase comparability, there is a need to standardize patient selection, sample preparation, and analytical methodology; particularly as low biomass samples like those obtained by nasal swabbing are impacted by reagent contamination. Optimization in obtaining a sample and processing with the inclusion of critical controls is needed for consistent comparative studies. Ongoing studies will analyze the nasal microbiome in GPA in a longitudinal way and the results will inform whether or not targeted antimicrobial management in a clinical trial should be pursued or not. This review focuses on the proposed role of S. aureus in GPA, the (healthy) nasal microbiome, findings in the first pilot studies in GPA, and will discuss future strategies.

Objective: Since the outbreak of the coronavirus disease 2019 (COVID-19) in December of 2019 in China, estimating the pandemic’s case fatality rate (CFR) has been the focus and interest of many stakeholders. In this manuscript, we prove that the method of using the cumulative CFR is static and does not reflect the trend according to the daily change per unit of time. Methods: A proportion meta-analysis was carried out on the CFR in every country reporting COVID-19 cases. Based on these results, we performed a meta-analysis for a global COVID-19 CFR. Each analysis was performed using two different calculations of CFR: according to the calendar date and according to the days since the outbreak of the first confirmed case. We thus explored an innovative and original calculation of CFR, concurrently based on the date of the first confirmed case as well as on a daily basis. Results: For the first time, we showed that using meta-analyses according to the calendar date and days since the outbreak of the first confirmed case, were different. Conclusion: We propose that a CFR according to days since the outbreak of the first confirmed case might be a better predictor of the current CFR of COVID-19 and its kinetics.

Background: Coronavirus Disease 2019 (COVID-19) is characterized by an unpredictable disease course, ranging from asymptomatic to severe, life-threatening infections. Asymptomatic COVID-19 infections have been described, and the aim of this systematic review was to summarise their presentation forms. Methods: We searched PubMed® and Google® (1 December 2019 to 29 March 2020) and extracted age, laboratory findings, and computed tomography (CT) scans. Pooled incidence rates of clinical characteristics were analyzed using random-effect models. Results: In total, 506 patients from 34 studies (68 single cases and 438 from case-series) with an asymptomatic course were identified. Patients with normal radiology were younger (19.59 ± 17.17 years) than patients with abnormal radiology (39.14 ± 26.70 years) (p-value = 0.013). Despite being asymptomatic, CT investigations revealed abnormalities in 62.2% of the cases; ground-glass opacities were most frequently observed (43.09% by meta-analysis). Most studies reported normal laboratory findings (61.74% by meta-analysis). Conclusions: More than half of the patients without any symptoms present with CT abnormalities. Asymptomatic patients may be contagious and thus a potential source of transmission of COVID-19.

Objectives: To assess the association of public interest in coronavirus infections with the actual number of infected cases for selected countries across the globe. Methods: We performed a Google TrendsTM search for “Coronavirus” and compared Relative Search Volumes (RSV) indices to the number of reported COVID-19 cases by the European Center for Disease Control (ECDC) using time-lag correlation analysis. Results: Worldwide public interest in Coronavirus reached its first peak end of January when numbers of newly infected patients started to increase exponentially in China. The worldwide Google TrendsTM index reached its peak on the 12th of March 2020 at a time when numbers of infected patients started to increase in Europe and COVID-19 was declared a pandemic. At this time the general interest in China but also the Republic of Korea has already been significantly decreased as compared to end of January. Correlations between RSV indices and number of new COVID-19 cases were observed across all investigated countries with highest correlations observed with a time lag of −11.5 days, i.e. highest interest in coronavirus observed 11.5 days before the peak of newly infected cases. This pattern was very consistent across European countries but also holds true for the US. In Brazil and Australia, highest correlations were observed with a time lag of −7 days. In Egypt the highest correlation is given with a time lag of 0, potentially indicating that in this country, numbers of newly infected patients will increase exponentially within the course of April. Conclusions: Public interest indicated by RSV indices can help to monitor the progression of an outbreak such as the current COVID-19 pandemic. Public interest is on average highest 11.5 days before the peak of newly infected cases.

IgA vasculitis, formerly known as Henoch-Schönlein purpura, is a systemic IgA-mediated vasculitis of the small vessels commonly seen in children. The natural history of IgA vasculitis is generally self-limiting; however, one-third of patients experience symptom recurrence and a refractory course. This systematic review examined the use of dapsone in refractory IgA vasculitis cases. A literature search of PubMed databases retrieved 13 articles published until June 14, 2018. The most common clinical feature was a palpable rash (100% of patients), followed by joint pain (69.2%). Treatment response within 1–2 days was observed in 6 of 26 patients (23.1%) versus within 3–7 days in 17 patients (65.4%). Relapse after treatment discontinuation was reported in 17 patients (65.4%) but not in 3 patients (11.5 %). Four of the 26 patients (15.4%) reported adverse effects of dapsone including arthralgia (7.7%), rash (7.7%), and dapsone hypersensitivity syndrome (3.8%). Our findings suggest that dapsone may affect refractory IgA vasculitis. Multicenter randomized placebo-controlled trials are necessary to determine the standard dosage of dapsone at initial or tapering of treatment in IgA vasculitis patients and evaluate whether dapsone has a significant benefit versus steroids or other medications.

Chronic nasal carriage of Staphylococcus aureus (SA) has been shown to be significantly higher in GPA patients when compared to healthy subjects, as well as being associated with increased endonasal activity and disease relapse. The aim of this study was to investigate SA involvement in GPA by applying a network-based analysis (NBA) approach to publicly available nasal transcriptomic data. Using these data, our NBA pipeline generated a proteinase 3 (PR3) positive ANCA associated vasculitis (AAV) disease network integrating differentially expressed genes, dysregulated transcription factors (TFs), disease-specific genes derived from GWAS studies, drug–target and protein–protein interactions. The PR3+ AAV disease network captured genes previously reported to be dysregulated in AAV associated. A subnetwork focussing on interactions between SA virulence factors and enriched biological processes revealed potential mechanisms for SA’s involvement in PR3+ AAV. Immunosuppressant treatment reduced differential expression and absolute TF activities in this subnetwork for patients with inactive nasal disease but not active nasal disease symptoms at the time of sampling. The disease network generated identified the key molecular signatures and highlighted the associated biological processes in PR3+ AAV and revealed potential mechanisms for SA to affect these processes.

Abstract Background Pregnancy is rare in women on hemodialysis. Recommendations for the treatment of secondary hyperparathyroidism (sHPT) and preservation of bone health in pregnant dialysis patients are lacking. Case presentation We present the case of a young woman with end-stage kidney disease (ESKD) due to lupus nephritis, who developed multiple brown tumors while on hemodialysis during her second pregnancy. During her first pregnancy sHPT was well controlled and no skeletal complications occurred. Before the second pregnancy she developed severe sHPT. During pregnancy, dialysis time was increased to 24 h per week, the patient was given oral calcitriol, and the dialysate calcium concentration was set at 1.5 mmol/l. In week 20 the patient complained about bone pain in her left hip. Magnetic resonance imaging revealed a cystic lesion compatible with a brown tumor. The baby was delivered in the 36th week by cesarean section. Further assessment identified multiple brown tumors of her skeleton, including the acetabulum, tibia, ribs, skull, thoracic spine and thumb. She required multiple orthopedic surgeries. Three months after pregnancy, etelcalcetide was started, which brought about a gradual improvement in her sHPT. Conclusions This case demonstrates that the combination of pregnancy and severe sHPT in dialysis patients can have deleterious consequences for bone health.

Background Ultra-endurance cyclists regularly report various extents of bodily decline during long-distance bicycle rides, including potential kidney function-related symptoms such as swelling of body parts and urine changes. This study aimed to assess the prevalence of these symptoms in a representative cohort of ultra-endurance cyclists and shed light on potential predictors related to the ride, the rider and the rider’s behavior. Methods Between November 26 and December 14, 2020, 1350 people participated in an online survey investigating potential kidney-related symptoms of ultra-distance cycling. Frequency and severity of edema-like (“swelling”) symptoms and perceived changes in urine output, concentration and quality were associated with ride-related factors, demographic parameters and rider behavior-related variables. Results A total of 919 participants met the predefined inclusion criteria. The majority (N = 603, 65.6%) stated that they suffered from at least one potential kidney function-related symptom, out of which 498 (54.2%) stated one or more edema-like (“swelling”) symptoms. In correlational and multiple regression analyses, female sex, intake of analgesics and drinking strategies correlated with swelling symptoms. Further analyses indicated that drinking due to thirst and/or drinking adapted to ambient sweating and temperature negatively correlated with swelling symptoms, whereas “drinking as much as possible” enhanced these. Intake of analgesics was moderately positively correlated with swelling symptoms. Conclusions According to our survey, edema-like symptoms occur in the majority of ultra-distance cyclists and female sex, drinking strategy and intake of analgesic drugs are major predictors thereof. Studies are needed to investigate the underlying pathophysiological processes of such symptoms.

Years of standing still have ended, and the field of nephrology has seen a plethora of clinical trials, changing the therapeutic landscape of chronic kidney disease (CKD) and immune-mediated kidney disease management [...]

ObjectiveTo characterize the incidence, type, and risk factors of severe infections (SI) in patients with autoimmune kidney diseases treated with rituximab (RTX).MethodsWe conducted a multicenter retrospective cohort study of adult patients with immune-related kidney diseases treated with at least one course of RTX between 2015 and 2019. As a part of the ABCDE Registry, detailed data on RTX application and SI were collected. SI were defined by Common Terminology Criteria for Adverse Events v5.0 as infectious complications grade 3 and above. Patients were dichotomized between “nephrotic” and “nephritic” indications. The primary outcome was the incidence of SI within 12 months after the first RTX application.ResultsA total of 144 patients were included. Twenty-five patients (17.4%) presented with SI, mostly within the first 3 months after RTX administration. Most patients in the nephritic group had ANCA-associated vasculitis, while membranous nephropathy was the leading entity in the nephrotic group. Respiratory infections were the leading SI (n= 10, 40%), followed by urinary tract (n=3, 12%) and gastrointestinal infections (n=2, 8%). On multivariable analysis, body mass index (BMI, 24.6 kg/m2versus 26.9 kg/m2, HR: 0.88; 95%CI: 0.79-0.99; p=0.039) and baseline creatinine (HR: 1.25; 95%CI: 1.04-1.49; p=0.017) were significantly associated with SI. All patients in the nephritic group (n=19; 100%) who experienced a SI received oral glucocorticoid (GC) treatment at the time of infection. Hypogammaglobulinemia was frequent (58.5%) but not associated with SI.ConclusionsAfter RTX administration, impaired kidney function and lower BMI are independent risk factors for SI. Patients with nephritic glomerular diseases having concomitant GC treatment might be at higher risk of developing SI.

BackgroundLiver transplantation (LT) is the only curative treatment for end-stage liver disease. Less than 10% of global transplantation needs are met worldwide, and the need for LT is still increasing. The death rates on the waiting list remain too high. ObjectiveIt is, therefore, critical to raise awareness among the public and health care providers and in turn increasingly acquire donors. MethodsWe performed a Google Trends search using the search terms liver transplantation and liver transplant on October 15, 2020. On the basis of the resulting monthly data, the annual average Google Trends indices were calculated for the years 2004 to 2018. We not only investigated the trend worldwide but also used data from the United Network for Organ Sharing (UNOS), Spain, and Eurotransplant. Using pairwise Spearman correlations, Google Trends indices were examined over time and compared with the total number of liver transplants retrieved from the respective official websites of UNOS, the Organización Nacional de Trasplantes, and Eurotransplant. ResultsFrom 2004 to 2018, there was a significant decrease in the worldwide Google Trends index from 78.2 in 2004 to 20.5 in 2018 (–71.2%). This trend was more evident in UNOS than in the Eurotransplant group. In the same period, the number of transplanted livers increased worldwide. The waiting list mortality rate was 31% for Eurotransplant and 29% for UNOS. However, in Spain, where there are excellent awareness programs, the Google Trends index remained stable over the years with comparable, increasing LT numbers but a significantly lower waiting list mortality (15%). ConclusionsPublic awareness in LT has decreased significantly over the past two decades. Therefore, novel awareness programs should be initialized.

The most effective method of limiting the coronavirus disease pandemic of 2019 (COVID-19) is vaccination. For the determination of the comparative efficacy and safety of COVID-19 vaccines and their platforms during the pre-Delta era, a systematic review and network meta-analysis was conducted. The MEDLINE, Embase, and MedRxiv databases were searched, and the gray literature was manually searched up to 8 July 2021. The review includes the phase II and III randomized controlled trials (RCTs) that assessed the efficacy, immunogenicity, and safety of the COVID-19 vaccines. The network meta-analysis used a Bayesian model and used the surface under the cumulative ranking to rank the comparisons between the vaccines. All included studies were quality appraised according to their design, and the heterogeneity of the analyses was assessed using I2. In terms of vaccine efficacy, the mRNA-1273 vaccine ranked the highest, and the CoronaVac vaccine ranked the lowest. The mRNA-1273 ranked the highest for neutralizing antibody responses to live SARS-CoV-2. The WIV04 vaccine was associated with the lowest incidence of both local and systemic adverse reactions. All studies except one had a low to moderate risk of bias. The mRNA platform vaccines showed higher efficacy and more adverse reactions than the other vaccines.

BackgroundThe use of social big data is an important emerging concern in public health. Internet search volumes are useful data that can sensitively detect trends of the public's attention during a pandemic outbreak situation. ObjectiveOur study aimed to analyze the public’s interest in COVID-19 proliferation, identify the correlation between the proliferation of COVID-19 and interest in immunity and products that have been reported to confer an enhancement of immunity, and suggest measures for interventions that should be implemented from a health and medical point of view. MethodsTo assess the level of public interest in infectious diseases during the initial days of the COVID-19 outbreak, we extracted Google search data from January 20, 2020, onward and compared them to data from March 15, 2020, which was approximately 2 months after the COVID-19 outbreak began. In order to determine whether the public became interested in the immune system, we selected coronavirus, immune, and vitamin as our final search terms. ResultsThe increase in the cumulative number of confirmed COVID-19 cases that occurred after January 20, 2020, had a strong positive correlation with the search volumes for the terms coronavirus (R=0.786; P

Contrast-associated acute kidney injury (CA-AKI) is a major concern when iodinated contrast material is administered, especially in patients at risk. Efforts have been undertaken to understand the detrimental effects of contrast media (CM). With the use of low-osmolar or iso-osmolar CM the incidence of CA-AKI has steadily decreased within the past decade; however, especially in the pediatric population information is scarce. Incidence rates have been reported to range between 0% to 18.75%, particularly depending on indication, selection of population (i.e. preexisting co-morbidities), and definition of AKI. Different biomarkers have been proposed, but confirmatory studies are either lacking or have contributed to their lack of diagnostic power. Proteomic approaches have been employed and may pave the way to such discovery. Prevention strategies have been tested and proposed, but the recently published AMACING and PRESERVE trials have shown that commonly used strategies (such as systematic hydration or administration of N-acetylcysteine) have no role in the prevention of CA-AKI. We propose that thoughtful assessment of one’s fluid state is the most appropriate approach and depending on the hydration status diuretics or fluid administration should be provided to achieve an euvolemic state ahead of contrast exposure.

Abstract Background Ear, nose and throat involvement in granulomatosis with polyangiitis (GPA) is frequently the initial disease manifestation. Previous investigations have observed a higher prevalence of Staphylococcus aureus in patients with GPA, and chronic nasal carriage has been linked with an increased risk of disease relapse. In this cross-sectional study, we investigated changes in the nasal microbiota including a detailed analysis of Staphylococcus spp. by shotgun metagenomics in patients with active and inactive granulomatosis with polyangiitis (GPA). Shotgun metagenomic sequence data were also used to identify protein-encoding genes within the SEED database, and the abundance of proteins then correlated with the presence of bacterial species on an annotated heatmap. Results The presence of S. aureus in the nose as assessed by culture was more frequently detected in patients with active GPA (66.7%) compared with inactive GPA (34.1%). Beta diversity analysis of nasal microbiota by bacterial 16S rRNA profiling revealed a different composition between GPA patients and healthy controls (P = 0.039). Beta diversity analysis of shotgun metagenomic sequence data for Staphylococcus spp. revealed a different composition between active GPA patients and healthy controls and disease controls (P = 0.0007 and P = 0.0023, respectively), and between healthy controls and inactive GPA patients and household controls (P = 0.0168 and P = 0.0168, respectively). Patients with active GPA had a higher abundance of S. aureus, mirroring the culture data, while healthy controls had a higher abundance of S. epidermidis. Staphylococcus pseudintermedius, generally assumed to be a pathogen of cats and dogs, showed an abundance of 13% among the Staphylococcus spp. in our cohort. During long-term follow-up of patients with inactive GPA at baseline, a higher S. aureus abundance was not associated with an increased relapse risk. Functional analyses identified ten SEED protein subsystems that differed between the groups. Most significant associations were related to chorismate synthesis and involved in the vitamin B12 pathway. Conclusion Our data revealed a distinct dysbiosis of the nasal microbiota in GPA patients compared with disease and healthy controls. Metagenomic sequencing demonstrated that this dysbiosis in active GPA patients is manifested by increased abundance of S. aureus and a depletion of S. epidermidis, further demonstrating the antagonist relationships between these species. SEED functional protein subsystem analysis identified an association between the unique bacterial nasal microbiota clusters seen mainly in GPA patients and an elevated abundance of genes associated with chorismate synthesis and vitamin B12 pathways. Further studies are required to further elucidate the relationship between the biosynthesis genes and the associated bacterial species.

Aging is a major driver for chronic kidney disease (CKD) and the counterbalancing of aging processes holds promise to positively impact disease development and progression.In this study we generated a signature of renal age-associated genes (RAAGs) based on six different data sources including transcriptomics data as well as data extracted from scientific literature and dedicated databases. Protein abundance in renal tissue of the 634 identified RAAGs was studied next to the analysis of affected molecular pathways. RAAG expression profiles were furthermore analysed in a cohort of 63 CKD patients with available follow-up data to determine association with CKD progression. 23 RAAGs were identified showing concordant regulation in renal aging and CKD progression. This set was used as input to computationally screen for compounds with the potential of reversing the RAAG/CKD signature on the transcriptional level. Among the top-ranked drugs we identified atorvastatin, captopril, valsartan, and rosiglitazone, which are widely used in clinical practice for the treatment of patients with renal and cardiovascular diseases. Their positive impact on the RAAG/CKD signature could be validated in an in-vitro model of renal aging.In summary, we have (i) consolidated a set of RAAGs, (ii) determined a subset of RAAGs with concordant regulation in CKD progression, and (iii) identified a set of compounds capable of reversing the proposed RAAG/CKD signature. Keywords: Renal aging, Chronic kidney disease progression, Computational compound screening, Drug repurposing, Anti-aging

Introduction. The soluble urokinase-type plasminogen activator receptor (suPAR) has been found to be elevated in primary focal segmental glomerulosclerosis (pFSGS). However, its usefulness as a biomarker for FSGS remains controversial. We conducted a meta-analysis aiming at investigating the significance of suPAR in diagnosing pFSGS. Methods. Electronic databases (PubMed and EMBASE) were searched to identify studies comparing suPAR levels in FSGS patients and controls, from the earliest available date to May 1, 2018. A random-effects model with standardized mean difference (SMD) was used for meta-analyses. Risk of bias was assessed using the Newcastle-Ottawa quality assessment scale. Results. A total of 187 articles were screened, and the final analysis included 13 articles. In comparison to healthy controls, serum suPAR levels were significantly increased in pFSGS patients (SMD, 1.07, 95% confidence interval (CI) 0.65 to 1.48; participants=814; studies=9, I2=85%). Higher suPAR levels were also found in patients with pFSGS compared to those with minimal change disease (SMD 0.53, 95% CI 0.22 to 0.84). Of note, such a difference was not found in pediatric groups (SMD 0.42, 95% CI -0.13 to 0.96) while it was more evidently noted in adult patients (SMD 1.32, 95% CI 0.90 to 1.74). Serum suPAR levels did not differ between pFSGS patients in remission compared to those in active proteinuric state (SMD 0.29, 95% CI -0.30 to 0.88). Comparison with membranous nephropathy and IgA nephropathy showed no significant difference. Conclusions. Our meta-analysis demonstrated that, in comparison to both healthy controls and controls with minimal change disease, suPAR levels were significantly higher in adult patients with pFSGS. suPAR levels did not differ between pFSGS patients during the initial period of diagnosis and those in remission.

Idiopathic nephrotic syndrome (INS) in children is characterized by massive proteinuria and hypoalbuminemia. Minimal change nephrotic syndrome (MCNS) is the most common form of INS in children. The pathogenesis of MCNS still remains unclear, however, several hypotheses have been recently proposed. For several decades, MCNS has been considered a T-cell disorder, which causes the impairment of the glomerular filtration barrier with the release of different circulating factors. Increased levels of several cytokines are also suggested. Recently, a "two-hit" theory was proposed that included the induction of CD80 (B7-1) and regulatory T-cell (Treg) dysfunction, with or without impaired autoregulatory functions of the podocyte. In contrast to the well-established involvement of T cells, the role of B cells has not been clearly identified. However, B-cell biology has recently gained more attention, because rituximab (a monoclonal antibody directed against CD20-bearing cells) demonstrated a very good therapeutic response in the treatment of childhood and adult MCNS. Here, we discuss recent insights into the pathogenesis of MCNS in children.

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis is an autoimmune disorder which affects small- and, to a lesser degree, medium-sized vessels. ANCA-associated vasculitis encompasses three disease phenotypes: granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA). This classification is largely based on clinical presentations and has several limitations. Recent research provided evidence that genetic background, risk of relapse, prognosis, and co-morbidities are more closely related to the ANCA serotype, proteinase 3 (PR3)-ANCA and myeloperoxidase (MPO)-ANCA, compared to the disease phenotypes GPA or MPA. This finding has been extended to the investigation of biomarkers predicting disease activity, which again more closely relate to the ANCA serotype. Discoveries related to the immunopathogenesis translated into clinical practice as targeted therapies are on the rise. This review will summarize the current understanding of the immunopathogenesis of ANCA-associated vasculitis and the interplay between ANCA serotype and proposed disease biomarkers and illustrate how the extending knowledge of the immunopathogenesis will likely translate into development of a personalized medicine approach in the management of ANCA-associated vasculitis.

Background and objectives: Characterization of pediatric coronavirus disease 2019 (COVID-19) is necessary to control the pandemic, as asymptomatic or mildly infected children may act as carriers. To date, there are limited reports describing differences in clinical, laboratory, and radiological characteristics between asymptomatic and symptomatic infection, and between younger and older pediatric patients. The objective of this study is to compare characteristics among: (1) asymptomatic versus symptomatic and (2) less than 10 versus greater or equal to 10 years old pediatric COVID-19 patients. Materials and Methods: We searched for all terms related to pediatric COVID-19 in electronic databases (Embase, Medline, PubMed, and Web of Science) for articles from January 2020. This protocol followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Results: Eligible study designs included case reports and series, while we excluded comments/letters, reviews, and literature not written in English. Initially, 817 articles were identified. Forty-three articles encompassing 158 confirmed pediatric COVID-19 cases were included in the final analyses. Lymphocytosis and high CRP were associated with symptomatic infection. Abnormal chest CT more accurately detected asymptomatic COVID-19 in older patients than in younger ones, but clinical characteristics were similar between older and younger patients. Conclusions: Chest CT scan findings are untrustworthy in younger children with COVID-19 as compared with clinical findings, or significant differences in findings between asymptomatic to symptomatic children. Further studies evaluating pediatric COVID-19 could contribute to potential therapeutic interventions and preventive strategies to limit spreading.

Eosinophilic esophagitis (EoE) is a relatively new condition described as an allergic-mediated disease of the esophagus. Clinically, it is characterized by dysphagia, food impaction, and reflux-like symptoms. Multiple genome-wide association studies (GWAS) have been conducted to identify genetic loci associated with EoE. The integration of numerous studies investigating the genetic polymorphisms in EoE and the Mendelian diseases associated with EoE are discussed to provide insights into the genetic risk of EoE, notably focusing on CCL26 and CAPN14. We focus on the genetic loci investigated thus far, and their classification according to whether the function near the loci is known. The pathophysiology of EoE is described by separately presenting the known function of each cell and molecule, with the major contributors being eosinophils, Th2 cells, thymic stromal lymphopoietin (TSLP), transforming growth factor (TGF)-β1, and interleukin (IL)-13. This review aims to provide detailed descriptions of the genetics and the comprehensive pathophysiology of EoE.

This study aimed to verify noteworthy findings between genetic risk factors and autism spectrum disorder (ASD) by employing the false positive report probability (FPRP) and the Bayesian false-discovery probability (BFDP). PubMed and the Genome-Wide Association Studies (GWAS) catalog were searched from inception to 1 August, 2019. We included meta-analyses on genetic factors of ASD of any study design. Overall, twenty-seven meta-analyses articles from literature searches, and four manually added articles from the GWAS catalog were re-analyzed. This showed that five of 31 comparisons for meta-analyses of observational studies, 40 out of 203 comparisons for the GWAS meta-analyses, and 18 out of 20 comparisons for the GWAS catalog, respectively, had noteworthy estimations under both Bayesian approaches. In this study, we found noteworthy genetic comparisons highly related to an increased risk of ASD. Multiple genetic comparisons were shown to be associated with ASD risk; however, genuine associations should be carefully verified and understood.

Sarcopenia refers to a decrease in skeletal muscle mass and function. Because sarcopenia affects mortality, and causes significant disability, the clinical importance of sarcopenia is emerging. At first, sarcopenia was recognized as an age-related disease but, recently, it has been reported to be prevalent also in younger patients with autoimmune diseases. Specifically, the association of sarcopenia and autoimmune diseases such as rheumatoid arthritis has been studied in detail. Although the pathogenesis of sarcopenia in autoimmune diseases has not been elucidated, chronic inflammation is believed to contribute to sarcopenia, and moreover the pathogenesis seems to be different depending on the respective underlying disease. The definition of sarcopenia differs among studies, which limits direct comparisons. Therefore, in this review, we cover various definitions of sarcopenia used in previous studies and highlight the prevalence of sarcopenia in diverse autoimmune diseases including rheumatoid arthritis, spondyloarthritis, systemic sclerosis, inflammatory bowel disease, and autoimmune diabetes. In addition, we cover the pathogenesis and treatment of sarcopenia in autoimmune and rheumatic diseases. This review provides a comprehensive understanding of sarcopenia in various autoimmune diseases and highlights the need for a consistent definition of sarcopenia.

Background and objective: Despite medical advances, we are facing the unprecedented disaster of the coronavirus disease 2019 (COVID-19) pandemic without available treatments and effective vaccines. As the COVID-19 pandemic has approached its culmination, desperate efforts have been made to seek proper treatments and response strategies, and the number of clinical trials has been rapidly increasing. In this time of the pandemic, it is believed that learning lessons from it would be meaningful in preparing for future pandemics. Thus, this study aims at providing a comprehensive landscape of COVID-19 related clinical trials based on the ClinicalTrials.gov database. Materials and methods: Up to 30 March 2020, we identified a total of 147 eligible clinical trials and reviewed the overview of the studies. Results: Until then, the most clinical trials were set up in China. Treatment approaches are the most frequent purpose of the registered studies. Chloroquine, interferon, and antiviral agents such as remdesivir, lopinavir, and ritonavir are agents under investigation in these trials. Conclusions: In this study, we introduced the promising therapeutic options that many researchers and clinicians are interested in, and to address the hidden issues behind clinical trials in this COVID-19 pandemic.

Focal segmental glomerulosclerosis (FSGS) is one of the primary glomerular disorders in both children and adults which can progress to end-stage renal failure. Although there are genetic and secondary causes, circulating factors have also been regarded as an important factor in the pathogenesis of FSGS, because about 40% of the patients with FSGS have recurrence after renal transplantation. Soluble urokinase-type plasminogen activator receptor (suPAR) is a soluble form of uPAR, which is a membrane-bound protein linked to GPI in various immunologically active cells, including podocytes. It has recently been suggested as a potential circulating factor in FSGS by in vitro podocyte experiments, in vivo mice models, and human studies. However, there have also been controversies on this issue, because subsequent studies showed conflicting results. suPAR levels were also increased in patients with other glomerular diseases and were inversely correlated with estimated glomerular filtration rate. Nevertheless, there has been no balanced review on this issue. In this review, we compare the conflicting data on the involvement of suPAR in the pathogenesis of FSGS and shed light on interpretation by taking into account many points and the potential variables and confounders influencing serum suPAR levels.

A better understanding of the pathophysiology of autoimmune disorders is desired to allow tailored interventions. Despite increased scientific interest a direct pathogenic factor in autoimmune renal disease has been described only in a minority like membranous nephropathy or ANCA-associated vasculitis. Nonetheless the initial step leading to the formation of these antibodies is still obscure. In this review we will focus on the possible role of microbial factors in this context. Staphylococcus aureus may be a direct pathogenetic factor in granulomatosis with polyangiitis (GPA). Chronic bacterial colonization or chronic infections of the upper respiratory tract have been proposed as trigger of IgA vasculitis and IgA nephropathy. Interventions to remove major lymphoid organs, such as tonsillectomy, have shown conflicting results but may be an option in IgA vasculitis. Interestingly no clear clinical benefit despite similar local colonization with bacterial strains has been detected in patients with IgA nephropathy. In systemic lupus erythematosus injection of bacterial lipopolysaccharide induced progressive lupus nephritis in mouse models. The aim of this review is to discuss and summarize the knowledge of microbial antigens in autoimmune renal disease. Novel methods may provide insight into the involvement of microbial antigens in the onset, progression, and prognosis of autoimmune kidney disorders.