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Background: BK-polyomavirus (BKpyV) nephropathy (BKVN) is associated with end-stage kidney disease in kidney and non-kidney solid organ transplantation, with no curative treatment. Case presentation: A 45-year-old woman with a past medical history of double lung transplantation subsequently developed end-stage kidney disease, of undetermined origin. One month after receiving a kidney transplant, a diagnosis of early BKVN was suspected, and in retrospect was a reasonable cause for the loss of her native kidneys. Minimisation of immunosuppression, achieved through extracorporeal photopheresis, allowed clearance of BKpyV and so prevented nephropathy. Both lung and kidney grafts had a satisfactory and stable function after one year of follow-up, with no rejection. Conclusions: Extracorporeal photopheresis may have facilitated minimisation of immunosuppression and BKpyV clearance without lung allograft rejection. [ABSTRACT FROM AUTHOR]

Background: The risk of developing and worsening chronic kidney disease (CKD) is associated with unhealthy dietary patterns. Food insecurity is defined by a limited or uncertain availability of nutritionally adequate and safe food; it is also associated with several chronic medical conditions. The aim of this systematic review is to investigate the current knowledge about the relationship between food insecurity and renal disease. Methods: We selected the pertinent publications by searching on the PubMed, Scopus, and the Web of Science databases, without any temporal limitations being imposed. The searching and selecting processes were carried out through pinpointed inclusion and exclusion criteria and in accordance with the Prisma statement. Results: Out of the 26,548 items that were first identified, only 9 studies were included in the systemic review. Eight out of the nine investigations were conducted in the US, and one was conducted in Iran. The studies evaluated the relationship between food insecurity and (i) kidney disease in children, (ii) kidney stones, (iii) CKD, (iv) cardiorenal syndrome, and (v) end stage renal disease (ESRD). In total, the different research groups enrolled 49,533 subjects, and food insecurity was reported to be a risk factor for hospitalization, kidney stones, CKD, ESRD, and mortality. Conclusions: The relationship between food insecurity and renal disease has been underestimated. Food insecurity is a serious risk factor for health problems in both wealthy and poor populations; however, the true prevalence of the condition is unknown. Healthcare professionals need to take action to prevent the dramatic effect of food insecurity on CKD and on other chronic clinical conditions. [ABSTRACT FROM AUTHOR]

With the coverage of COVID-19 vaccination, it has been possible to observe the potential side effects of SARS-CoV-2 vaccines, with the most common ones being fever, myalgia, headache, and fatigue. However, an association has been observed between new and recurrent kidney injuries, mainly glomerulonephritis and lupus nephritis associated with ANCA, with the Pfizer-BioNTech, Moderna, Sinovac, and AstraZeneca vaccines, although the relationship between them is not clear. We report a case of ANCA-related vasculitis and lupus glomerulonephritis after the second dose of the AstraZeneca vaccine. The elderly patient presented significant worsening of kidney function after immunosuppression and complications after a new onset COVID-19 infection that led to death. We provide a literature review about kidney damage related to ANCA vasculitis after COVID-19 vaccine, aiming for a better understanding of the pathophysiological mechanism of kidney injury, its presentation, and treatment. [ABSTRACT FROM AUTHOR]

IgG4-related disease (IgG4-RD) is an immune-mediated systemic fibroinflammatory condition characterized by serum IgG4 elevation and IgG4-positive plasma cell infiltration into various organs. It generally occurs in elderly males. Pediatric cases have been reported, albeit rarely, accordingly lack of recognition of such cases could delay therapeutic intervention leading to poorer outcomes. The present review is a descriptive review of all published case reports, cohort studies, and reviews of pediatric IgG4-RD listed in PubMed. Characteristics of pediatric IgG4-RD were clarified, including sex, organ involvement, serological and histological findings, and treatment. We assessed how many published cases met current classification and comprehensive diagnostic criteria. The characteristics of pediatricIgG4-RD differed from adult IgG4-RD in terms of sex and involved organs. There was no clear male dominance in numbers of cases, and surface organ involvement such as ophthalmic diseases were more common in the pediatric IgG4-RD. Organ involvement tended to be indolent and unilateral, causing difficulty in definitively diagnosing pediatric IgG4-RD. Only about 20% of published cases met IgG4-RD classification or comprehensive diagnostic criteria. Physicians should be careful in diagnosing pediatric IgG4-RD after excluding mimickers. International collaboration toward high-quality evidence to support diagnosis and treatment of pediatric IgG4-RD is advised. [ABSTRACT FROM AUTHOR]

In the context of the massive spread of coronavirus disease 2019 (COVID-19), the development of a COVID-19 vaccine is urgently needed. The Pfizer-BioNTech COVID-19 vaccine has been widely applied across global populations. Herein, we report a case of acute interstitial nephritis with acute kidney injury in a young healthy subject after administration of the COVID-19 vaccine. A 20-year-old man was admitted with abdominal discomfort and nausea. He had received the Pfizer-BioNTech COVID-19 vaccine 6 days before. At 9 days after vaccination, his kidney function was decreased, with serum creatinine levels of 1.8 mg/dL. Even with supportive care with hydration, his kidney function worsened, and he underwent a kidney biopsy. The pathology findings revealed diffuse interstitial infiltration of inflammatory cells, predominantly comprising lymphocytes, with preservation of the glomerulus. No abnormal findings were noted by immunofluorescence or electron microscopy. Based on a diagnosis of drug-related acute interstitial nephritis, we treated the patient with high-dose prednisolone. After administration of prednisolone, kidney function slowly improved. A close linkage between COVID-19 vaccination and acute interstitial nephritis should be considered in the clinic, despite the low incidence. [ABSTRACT FROM AUTHOR]

Background: Circular RNA RHOT1 (circRHOT1) plays crucial roles in tumorigenesis by competing with microRNAs. It is largely abundant in tumor cell-derived exosomes. Meanwhile, cancer-derived exosomes participate in diverse biological processes. However, the expression patterns and functions of exosomal circRHOT1 in breast cancer remain unknown. This study is aimed to investigate and elucidate the exosomal circRHOT1/miR-204-5p/PRMT5 axis in breast cancer. Methods: The exosomes derived from serum samples of breast cancer patients and breast cancer cell lines were characterized using transmission electron microscopy and Western blot. MTT, colony formation, wound healing, and transwell assays were utilized to analyze cell proliferation, migration, and invasion of breast cancer cells. Flow cytometry was used for apoptosis analysis. The bioinformatics method was employed to screen differentially expressed novel circRNAs and predict the microRNA targets of circRHOT1. Dual-luciferase reporter gene assays were performed to verify their direct interaction. Finally, Xenograft experiments were used to investigate the effect of exosomal circRHOT1 on tumor growth in vivo. Results: CircRHOT1 exhibited significantly high expression in exosomes derived from the serum of breast cancer patients and breast cancer cell lines, which suggested its potential diagnostic value. Breast cancer-derived exosomes promoted the cell proliferation, migration, invasion, and epithelial-mesenchymal transition of breast cancer cells while inhibiting apoptosis. However, exosomes with downregulated circRHOT1 inhibited the growth of co-cultured cells. Mechanistically, circRHOT1 acted as a sponge of miR-204-5p and promoted protein arginine methyltransferase 5 (PRMT5) expression. Moreover, miR-204-5p inhibitor and pcPRMT5 could reverse the tumor suppressive effects mediated by circRHOT1-knockdown. Furthermore, treatment with exosomes derived from breast cancer cells with circRHOT1 knockdown attenuated tumor growth in tumor-bearing nude mice, which was accompanied by a reduction in PRMT5 expression and an enhancement of miR-204-5p expression. Conclusion: The exosomal circRHOT1 may promote breast cancer progression by regulating the miR-204-5p/PRMT5 axis. The current study strengthens the role of circRHOT1, miR-204-5p, and PRMT5 in breast cancer development and provides a potential treatment strategy for breast cancer. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID-19) has spread considerably across the globe, affecting numerous children and adolescents besides adults. Despite its relatively lower incidence rates in children and adolescents than in adults, some infected children and adolescents exhibit a severe postinflammatory response known as multisystem inflammatory syndrome in children, followed by acute kidney injury, a common com plication. Meanwhile, few reports have been available regarding kidney complications such as idiopathic nephrotic syndrome and other glomerulopathies associated with COVID-19 infection and vaccination in children and adolescents. However, the morbidity and mortality of these complications are not exceptionally high; more importantly, causality has yet to be clearly established. Finally, vaccine hesitancy in these age groups should be addressed, considering the strong evidence of COVID-19 vaccine safety and efficacy. [ABSTRACT FROM AUTHOR]

Mesonephric remnants persist as an appendix of epididymis and paradidymis in efferent ductules in males and skene's glands and Gartner's ducts in females. The mesonephric remnant in the renal parenchyma is extremely rare and only a few cases have been reported in the literature. We present a case with a non-functioning atrophic left kidney. Histopathology showed variable-sized ducts filled with colloid-like material surrounded by collagenized stroma. The ureter showed hypertrophied muscle and a few ducts lined by flattened and a few by columnar epithelium resembling epididymis suggestive of mesonephric remnants. IHC for CD10, PAX 8, and GATA3 was positive. A diagnosis of congenital unilateral hypoplasia of kidneys and ureter with mesonephric remnants was given. [ABSTRACT FROM AUTHOR]

Background: The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been followed by many reports of the development and relapse of autoimmune diseases associated with SARS-CoV-2 vaccination. Some of these reports have involved relapse or onset of immunoglobulin A (IgA) nephropathy following SARS-CoV-2 vaccination. Here, we report on a patient with IgA nephropathy who presented with gross hematuria and rapidly progressive glomerulonephritis following SARS-CoV-2 vaccination. Case presentation: A 63-year-old male patient with a history of habitual tonsillitis underwent bilateral tonsillectomy. He had a history of alcoholic cirrhosis of the liver and microscopic hematuria and proteinuria were indicated during a health checkup 2 years before hospital admission. He developed hematuria after the SARS-CoV-2 vaccination, which led to rapidly progressive glomerulonephritis, for which he was hospitalized. A renal biopsy led to the diagnosis of IgA nephropathy. Although pulse steroid therapy during his condition resulted in hepatic encephalopathy, three courses combined with mizoribine improved his renal function. Conclusion: SARS-CoV-2 mRNA vaccines activate T cells, which are involved in the pathophysiology of IgA nephropathy. Therefore, this case suggests that the exacerbation of IgA nephropathy by the vaccine favors the vasculitis aspect of the disease. [ABSTRACT FROM AUTHOR]

Given the wide diversity of causes of hematuria, ranging from simple urinary tract infections with rapid recovery to severe glomerulonephritis with fast decline in kidney function, it is essential to recognize the underlying disease. The first objective of the assessment is to determine whether the cause of the hematuria is medically significant. The combination of hematuria with proteinuria, the presence of hypertension, or worsening kidney function can represent signs of progressive kidney disease. Differentiating the various causes of hematuria is often simple and obvious based on the clinical signs and gross appearance of the urine. However, in some instances, additional non-invasive investigations, such as ultrasound imaging, urinary red cell morphology, measurement of calcium and other solutes in the urine, evaluation of kidney function, and protein excretion, are needed to elucidate the nature of the hematuria. Taking a detailed family history can help in establishing the underlying cause in cases of familial hematuria. On the other hand, the decision to perform a kidney biopsy in children with asymptomatic hematuria remains a challenging issue for clinicians. Ultimately, the frequency of diagnosis of glomerular involvement causing hematuria may depend on the threshold for performing a kidney biopsy. The following review will focus on the diagnostics of hematuria, starting with difficulties regarding its definition, followed by various means to differentiate between urinary, glomerular, and other causes, and finally reviewing the most common diseases that, due to their frequency or their effect on kidney function, present a diagnostic challenge in everyday practice. [ABSTRACT FROM AUTHOR]

Background: Recent developments in mass spectrometry (MS) have revealed target antigens for membranous nephropathy (MN), including phospholipase A2 receptor and exostosin 1/exostosin 2 (EXT1/2). EXT1/2 are known antigens of autoimmune disease-related MN, especially membranous lupus nephritis. We describe the case of an elderly man who developed nephrotic syndrome followed by progressive renal dysfunction. Case presentation: A 78-year-old man presented with rapidly progressive renal dysfunction with proteinuria and hematuria. Three years previously, he had developed leg edema but did not receive any treatment. Laboratory tests showed elevated anti-nuclear antibody (Ab), anti-dsDNA Ab titer, and hypocomplementemia, indicating systemic lupus erythematous. Myeloperoxidase anti-neutrophil cytoplasmic Ab (ANCA) and anti-glomerular basement membrane (GBM) Ab were also detected. The renal pathologic findings were compatible with crescentic glomerulonephritis (GN), whereas non-crescentic glomeruli exhibited MN without remarkable endocapillary or mesangial proliferative change. Immunofluorescence microscopy revealed glomerular IgG, C3, and C1q deposition. All IgG subclasses were positive in glomeruli. Anti-PLA2R Ab in serum was negative. MS analysis was performed to detect the antigens of MN, and EXT1/2 was detected in glomeruli. Therefore, we reached a diagnosis of membranous lupus nephritis concurrent with both ANCA-associated vasculitis and anti-GBM-GN. The simultaneous occurrence of these three diseases is extremely rare. Conclusions: This is the first report of EXT1/2-related membranous lupus nephritis concurrent with ANCA-associated vasculitis and anti-GBM-GN. This case demonstrates the usefulness of MS in diagnosing complicated cases of MN. [ABSTRACT FROM AUTHOR]

Recent evidence has shown significant roles of mitochondria-derived vesicles (MDVs) in mitochondrial quality control (MQC) system. Under mild stress condition, MDVs are formed to carry the malfunctioned mitochondrial components, such as mitochondrial DNA (mtDNA), peptides, proteins and lipids, to be eliminated to restore normal mitochondrial structure and functions. Under severe oxidative stress condition, mitochondrial dynamics (fission/fusion) and mitophagy are predominantly activated to rescue mitochondrial structure and functions. Additionally, MDVs generation can be also triggered as the major MQC machinery to cope with unhealthy mitochondria when mitophagy is unsuccessful for eliminating the damaged mitochondria or mitochondrial fission/fusion fail to recover the mitochondrial structure and functions. This review summarizes the current knowledge on MDVs and discuss their roles in physiologic and pathophysiologic conditions. In addition, the potential clinical relevance of MDVs in therapeutics and diagnostics of kidney stone disease (KSD) are emphasized. [ABSTRACT FROM AUTHOR]

Background: Metastatic disease is the major cause of cancer-related deaths. Increasing evidence shows that primary tumor cells can promote metastasis by preparing the local microenvironment of distant organs, inducing the formation of the so-called "pre-metastatic niche". In recent years, several studies have highlighted that among the tumor-derived molecular components active in pre-metastatic niche formation, small extracellular vesicles (sEVs) play a crucial role. Regarding liver metastasis, the ability of tumor-derived sEVs to affect the activities of non-parenchymal cells such as Kupffer cells and hepatic stellate cells is well described, while the effects on hepatocytes, the most conspicuous and functionally relevant hepatic cellular component, remain unknown. Methods: sEVs isolated from SW480 and SW620 CRC cells and from clinical samples of CRC patients and healthy subjects were used to treat human healthy hepatocytes (THLE-2 cells). RT-qPCR, Western blot and confocal microscopy were applied to investigate the effects of this treatment. Results: Our study shows for the first time that TGFβ1-carrying CRC_sEVs impair the morphological and functional properties of healthy human hepatocytes by triggering their TGFβ1/SMAD-dependent EMT. These abilities of CRC_sEVs were further confirmed by evaluating the effects elicited on hepatocytes by sEVs isolated from plasma and biopsies from CRC patients. Conclusions: Since it is known that EMT of hepatocytes leads to the formation of a fibrotic environment, a well-known driver of metastasis, these results suggest that CRC_sEV-educated hepatocytes could have an active and until now neglected role during liver metastasis formation. [ABSTRACT FROM AUTHOR]

Immunoglobulin A (IgA) nephropathy is the most common type of glomerulonephritis worldwide characterized by excessive serum levels of glycosylated which triggers the generation of glycan-specific IgG and IgA autoantibodies. This pathological condition results in the formation of circulatory IgA immune complexes, which are essential for the development of glomerular inflammation, especially IgA nephropathy. The serum galactosylated IgA1, IgG, and IgA autoantibodies are suggested as the biomarkers of IgA nephropathy since IgA antibodies are early markers for disease activity too. Serum IgA antibodies emerged as the early COVID-19-specific antibody response about two days after initial symptoms of COVID-19 in comparison with IgG and IgM antibody concentrations, which appeared after five days. IgA nephropathy is frequently presented as microscopic or macroscopic hematuria and proteinuria with a male predominance. COVID-19 infection can include several organs aside from the lungs, such as kidneys through different mechanisms. It is demonstrated in most cases that short-lasting symptoms such as gross hematuria resolve either spontaneously or following a short course of steroids. This review summarized the reported cases of relapses or denovo reported cases of relapses or de-novo IgA nephropathy and IgA vasculitis following COVID-19 vaccination. [ABSTRACT FROM AUTHOR]

Background: Renal complications have previously been reported with various vaccinations, including those for influenza and hepatitis. On a similar note, a spectrum of nephrological complications, both de novo, and flare-ups, were reported after immunization with various coronavirus disease 2019 (COVID-19) vaccines, causing concerns among patients as well as physicians. Materials and Methods: A systematic search of the literature published on renal complications seen post-COVID-19 vaccination was performed up to April 2022 using electronic databases such as PubMed and Google Scholar. Result: Immunoglobulin A (IgA) nephropathy, minimal change disease, glomerulonephritis, acute kidney injury, nephrotic syndrome, and anti-neutrophil cytoplasmic antibody-associated vasculitis were some of the renal complications reported upon administration of COVID-19 vaccines. The causality and underlying pathogenic mechanisms linking these complications and COVID-19 vaccination remain unclear. Nonetheless, a temporal relationship has been established with dysregulated T-cell response, transient systemic pro-inflammatory cytokine response, molecular mimicry, delayed hypersensitivity reaction to the vaccine, and other mechanisms such as hyperresponsive IgA, dysregulation of neutrophil extracellular traps were hypothesized as the possible mechanisms linking renal complications and COVID-19 vaccination. Conclusion: This review emphasizes the need for rigorous surveillance and reporting of the adverse events following COVID-19 vaccination and explores the underlying mechanisms instigating these renal complications in individuals vaccinated against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). [ABSTRACT FROM AUTHOR]

The ongoing pandemic (also known as coronavirus disease-19; COVID-19) by a constantly emerging viral agent commonly referred as the severe acute respiratory syndrome corona virus 2 or SARS-CoV-2 has revealed unique pathological findings from infected human beings, and the postmortem observations. The list of disease symptoms, and postmortem observations is too long to mention; however, SARS-CoV-2 has brought with it a whole new clinical syndrome in "long haulers" including dyspnea, chest pain, tachycardia, brain fog, exercise intolerance, and extreme fatigue. We opine that further improvement in delivering effective treatment, and preventive strategies would be benefited from validated animal disease models. In this context, we designed a study, and show that a genetically engineered mouse expressing the human angiotensin converting enzyme 2; ACE-2 (the receptor used by SARS-CoV-2 agent to enter host cells) represents an excellent investigative resource in simulating important clinical features of the COVID-19. The ACE-2 mouse model (which is susceptible to SARS-CoV-2) when administered with a recombinant SARS-CoV-2 spike protein (SP) intranasally exhibited a profound cytokine storm capable of altering the physiological parameters including significant changes in cardiac function along with multi-organ damage that was further confirmed via histological findings. More importantly, visceral organs from SP treated mice revealed thrombotic blood clots as seen during postmortem examination. Thus, the ACE-2 engineered mouse appears to be a suitable model for studying intimate viral pathogenesis thus paving the way for identification, and characterization of appropriate prophylactics as well as therapeutics for COVID-19 management. [ABSTRACT FROM AUTHOR]

Testicular vasculitis (TV) develops when an organ is involved in systemic vasculitis. A 47-year-old man with eosinophilic granulomatosis with polyangiitis (EGPA) developed TV as the first clinical episode. The patient had bronchial asthma for 8 years and developed left testicular pain before developing arthralgia, abdominal involvement, and sensory polyneuropathy, which led to the diagnosis of EGPA. The induration of the affected testicle persisted even after initiating immunosuppressive therapy with corticosteroids and cyclophosphamide, raising concern for testicular neoplasm, while testicular pain and other symptoms resolved. The patient underwent inguinal orchiectomy, and a histology examination of the resected testicle revealed fibrinoid necrotizing vasculitis. Only three cases of biopsy-proven TV in patients with EGPA have been reported in our review of published English-language articles. Two of the three patients in the reviewed cases developed TV before being diagnosed with EGPA. Moreover, all patients underwent extirpation of the affected testicle, leading to a pathological diagnosis of TV. This report suggests that TV may develop and be the presenting condition in EGPA, although urogenital involvement is rare. [ABSTRACT FROM AUTHOR]

Infection-related glomerulonephritis is well recognized in patients with ongoing infections. It can be missed, however, if the infection is unusual or undetected. We present three cases where the renal biopsy findings prompted the identification or treatment of systemic infections. Case 1: A 84-year-old male presented with acute kidney injury (AKI) and IgA vasculitis on skin biopsy. A renal biopsy showed active glomerulonephritis with abundant neutrophils and predominantly mesangial immune complex deposits containing IgA. The findings prompted an infectious workup which was positive for COVID-19, suggesting exacerbation of IgA nephropathy by recent COVID-19 infection. Case 2: A 31-year-old female status post kidney transplant for granulomatosis with polyangiitis (GPA) had recent pregnancy with preterm delivery, disseminated herpes simplex virus (HSV) infection with HSV hepatitis, E. coli on urine culture, and AKI. A renal biopsy showed proliferative glomerulonephritis with subendothelial and mesangial immune complex deposits containing IgG and C3. The findings were most consistent with infection-related immune complex glomerulonephritis, most likely HSV-related. Case 3: A 78-year-old female presented with AKI, proteinuria, hematuria, and positive p-ANCA. Clinically, ANCA vasculitis was suspected, and renal biopsy did show focal, segmental, necrotizing glomerulonephritis. However, immunofluorescence and electron microscopy showed IgM-rich deposits in the mesangium. The unusual presentation prompted an infectious workup including a Bartonella antibody panel which showed very high titers, suggesting Bartonella endocarditis. Infection-related glomerulonephritis has a wide variety of presentations histologically and clinically. The three cases we present here emphasize the importance of recognizing these entities to help guide treatment and improve patient care. [ABSTRACT FROM AUTHOR]

Background: There are few reports on kidney complications after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) messenger RNA (mRNA) vaccination, especially in the pediatric population. We report a pediatric case diagnosed with crescentic glomerulonephritis (CrGN) after the second dose of the SARS-CoV-2 mRNA vaccine. Case-diagnosis/treatment: A 16-year-old girl was admitted due to dyspnea and headache approximately 6 weeks after receiving the second SARS-CoV-2 mRNA vaccine (Pfizer-BioNTech). She had previously experienced fever, nausea, vomiting, and dyspnea after the first vaccination, which persisted for a week. On admission, her blood pressure was 155/89 mmHg with a 7 kg weight gain in a month. She had microhematuria and proteinuria. Laboratory findings were as follows: blood urea nitrogen/creatinine, 66/9.57 mg/dL; and brain natriuretic peptide, 1,167 pg/mL. Anti-neutrophil cytoplasmic antibody (ANCA), anti-glomerular basement membrane (GBM) antibody, and antinuclear antibody findings were negative. Kidney doppler sonography revealed swelling and increased echogenicity of both kidneys with increased resistive index. Cardiac magnetic resonance imaging results showed early minimal fibrosis of myocarditis. We then started hemodialysis. Kidney biopsy showed diffuse extra capillary proliferative glomerulonephritis with diffuse crescent formation. We treated the patient with methylprednisolone pulse therapy with subsequent oral steroids and mycophenolate mofetil. Although dialysis was terminated, the patient remained in the chronic kidney disease stage. Conclusions: This is the first case of ANCA-negative CrGN after SARS-CoV-2 mRNA vaccination in the pediatric population. As children are increasingly vaccinated with SARS-CoV-2 mRNA vaccines, monitoring for kidney complications is warranted. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused significant economic and health damage worldwide. Rapid vaccination is one of the key strategies to curb severe illness and death due to SARS-CoV-2 infection. Hundreds of millions of people worldwide have received various COVID-19 vaccines, including mRNA vaccines, inactivated vaccines and adenovirus-vectored vaccines, but the side effects and efficacy of most vaccines have not been extensively studied. Recently, there have been increasing reports of immunoglobulin A nephropathy (IgAN) after COVID-19 vaccination, however, whether their relationship is causal or coincidental remains to be verified. Here, we summarize the latest clinical evidence of IgAN diagnosed by renal biopsy associated with the COVID-19 vaccine published by 10 July 2022 with the largest sample size, and propose a hypothesis for the pathogenesis between them. At the same time, the new opportunity presented by COVID-19 vaccine allows us to explore the mechanism of IgAN recurrence for the first time. Indeed, we recognize that large-scale COVID-19 vaccination has enormous benefits in preventing COVID-19 morbidity and mortality. The purpose of this review is to help guide the clinical assessment and management of IgA nephropathy post-COVID-19 vaccination and to enrich the 'multi-hit' theory of IgA nephropathy. [ABSTRACT FROM AUTHOR]

Background: Following the strong recommendation for coronavirus disease 2019 (COVID‑19) vaccination, many patients with medical comorbidities are being immunized. However, the safety of vaccination in patients with autoimmune diseases has not been well established. We report a new case of biopsy-proven IgA vasculitis with nephritis presenting as a nephrotic syndrome after mRNA COVID-19 vaccination in a patient with a history of leukocytoclastic vasculitis. Case presentation: A 76-year-old man with a history of cutaneous leukocytoclastic vasculitis presented with purpura in both lower limbs, followed by nephrotic syndrome after the second dose of BNT162b2 mRNA COVID-19 vaccination. Skin and renal biopsy revealed IgA vasculitis with nephritis. The patient's past medical history of leukocytoclastic vasculitis and features of chronicity in renal pathology suggest an acute exacerbation of preexisting IgA vasculitis after COVID-19 vaccination. After the steroid and renin-angiotensin system inhibitor use, purpura and acute kidney injury recovered within a month. Subnephrotic proteinuria with microscopic hematuria remained upon follow-up. Conclusion: Physicians should keep in mind the potential (re)activation of IgA vasculitis following mRNA COVID-19 vaccines. It is important to closely monitor COVID-19 vaccinated patients, particularly those with autoimmune diseases. [ABSTRACT FROM AUTHOR]

Purpose: Children with nephrotic syndrome may experience disease relapse or aggravation triggered by various viral infections. Limited studies on the clinical implications of the coronavirus disease 2019 (COVID-19) pandemic in children with nephrotic syndrome have been published worldwide. Therefore, this study aimed to investigate the effects of COVID-19 on the clinical course of nephrotic syndrome in children. Methods: The medical records of 59 patients with idiopathic nephrotic syndrome who visited our hospital between February and June 2022 were retrospectively analyzed. Results: Twenty of the total 59 patients with nephrotic syndrome were diagnosed with COVID-19 during the study period. The mean age at the time of the diagnosis of nephrotic syndrome and COVID-19 in all 20 patients was 4.6±3.5 and 8.9±3.9 years, respectively. Three patients (15%) were diagnosed with nephrotic syndrome relapse during COVID-19 and the relapse rate was similar to them without COVID-19 (20.5%, 8/39 patients). At the time of the COVID-19 diagnosis, fever (85%) and cough (40%) were the most common symptoms. After the diagnosis of COVID-19, all patients showed improvement with symptomatic treatment, including antipyretic analgesics and cold medicine. None of the critical patients required hospitalization or oral antiviral medications. Conclusions: Despite the use of immunosuppressants, the clinical manifestations of COVID-19 in children with nephrotic syndrome were not severe and are expected to be similar to that in the general population. The relapse rate of nephrotic syndrome in children with COVID-19 was also not different from them without COVID-19. [ABSTRACT FROM AUTHOR]

Background: Membranous nephropathy is an uncommon cause of nephrotic syndrome in pediatrics. Methods: We reviewed our kidney biopsy records for patients ≤ 20 years of age with membranous nephropathy without evidence of systemic lupus erythematosus within 6 months of biopsy (January 1995–September 2020). Staining for PLA2R, NELL1, THSD7A, SEMA3B, EXT2 (3 biopsies), and IgG-subclass were performed. Results: Sixteen children (≤ 12 years) and 25 adolescents (13–20 years) were identified. Four children and 15 adolescents showed autoantigen positivity: PLA2R+/SEMA3B- (13), SEMA3B+/PLA2R+ (2), SEMA3B+/PLA2R− (1), NELL1 (1), EXT2+ (2), and THSD7A (0). Co-morbidities associated with PLA2R positivity included IPEX syndrome, active hepatitis B, Von Hippel Lindau syndrome, solitary kidney, type 1 diabetes, hyperuricemia, pregnancy (1), obesity (3), type II diabetes, H. pylori, viral prodrome, and nephrolithiasis. The SEMA3B+/PLA2R− adolescent was pregnant, the NELL1+ adolescent was obese, and the two EXT2+ adolescents eventually met the clinical criteria for lupus (4, 9 years post-biopsy). Co-morbidities among the remaining 24 patients included remote hepatitis B (2), Down's syndrome, lysinuric protein intolerance, recurrent UTIs, hypothyroidism, pregnancy (3), and obesity (2). Follow-up data was available for 12 children and 16 adolescents. Of the 12 children, 6 achieved complete remission, 4 achieved partial remission, and 2 had no response to treatment (1 transplant). Of the 16 adolescents, 4 achieved complete remission, 4 achieved partial remission, and 8 had no response to treatment (3 transplants). A child with "full-house" immunofluorescence staining achieved spontaneous disease remission. Conclusion: Our non-lupus membranous nephropathy cohort represents one of the largest pediatric studies to date. A higher resolution version of the Graphical abstract is available as Supplementary information. [ABSTRACT FROM AUTHOR]

BACKGROUND: Exosomes and exosomal microRNAs have been implicated in tumor occurrence and metastasis. Our previous study showed that microRNA-761 (miR-761) is overexpressed in hepatocellular carcinoma (HCC) tissues and that its inhibition affects mitochondrial function and inhibits HCC metastasis. The mechanism by which exosomal miR-761 modulates the tumor microenvironment has not been elucidated. METHODS: Exosomal miR-761 was detected in six cell lines. Cell counting kit-8 (CCK-8) and transwell migration assays were performed to determine the function of exosomal miR-761 in HCC cells. The luciferase reporter assay was used to analyze miR-761 target genes in normal fibroblasts (NFs). The inhibitors AZD1480 and C188-9 were employed to determine the role of the Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway in the transformation of cancer-associated fibroblasts (CAFs). RESULTS: In this study, we characterized the mechanism by which miR-761 reprogrammed the tumor microenvironment. We found that HCC-derived exosomal miR-761 was taken up by NFs. Moreover, HCC exosomes affected the tumor microenvironment by activating NFs via suppressor of cytokine signaling 2 (SOCS2) and the JAK2/STAT3 signaling pathway. CONCLUSIONS: These results demonstrated that exosomal miR-761 modulated the tumor microenvironment via SOCS2/JAK2/STAT3 pathway-dependent activation of CAFs. Our findings may inspire new strategies for HCC prevention and therapy. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the clinical characteristics and outcomes of patients with nephropathy associated with POEMS syndrome who received novel agents in combination with dexamethasone therapy, and renal pathological changes based on repeat biopsy in some patients after these novel-agent-based therapies. Methods: The records of patients with nephropathy associated with POEMS syndrome in a single hospital from May 2017 to February 2021 were retrieved and studied in detail. All the patients received four cycles of initial novel-agent-based regimens such as bortezomib and dexamethasone (BD) or thalidomide plus dexamethasone (TD) or lenalidomide plus dexamethasone (RD) treatment. We further evaluated the pathological efficacy of these novel agents by repeat renal biopsy. Results: Twelve patients with an average age of 48.6 ± 8.3 years diagnosed with nephropathy associated with POEMS syndrome were enrolled in this study. The duration from disease onset to renal biopsy was 28(8.3 ~ 54.5) months. All patients achieved good clinical responses in different degree after four cycles of initial novel agents in combination with dexamethasone therapy. After the treatment with novel-agent-based regimens, the levels of proteinuria decreased in most patients and were negative in five patients. The levels of serum creatinine (SCr) decreased in ten patients. Serum M protein was negative in four patients and still positive in the other eight patients. The levels of serum vascular endothelial growth factor (VEGF) were detected in seven patients, which were all decreased. The levels of interleukin-6 (IL-6) were detected in eight patients, which were also decreased. Repeat biopsies were performed after four cycles of novel-agent-based therapies in four patients who were all treated with BD treatment. Mesangiolysis, mesangial cells proliferation, endothelial cells proliferation, subendothelial space widening and acute renal tubulointerstitial lesions improved, the chronic renal tubulointerstitial lesions were stable. Conclusions: Novel agents improved clinical manifestations in patients with nephropathy associated with POEMS syndrome. In addition, novel-agent-based regimens such as BD treatment improved renal pathological manifestations, which suggested that novel agents could improve renal prognosis of the patients from the perspective of renal pathology. [ABSTRACT FROM AUTHOR]

The lysosomal storage disease cystinosis is caused by mutations in CTNS, encoding the cystine transporter cystinosin, and in its severest form leads to proximal tubule dysfunction followed by kidney failure. Patients receive the drug-based therapy cysteamine from diagnosis. However, despite long-term treatment, cysteamine only slows the progression of end-stage renal disease. Preclinical testing in cystinotic rodents is required to evaluate new therapies; however, the current models are suboptimal. To solve this problem, we generated a new cystinotic rat model using CRISPR/Cas9-mediated gene editing to disrupt exon 3 of Ctns and measured various parameters over a 12-mo time course. Ctns-/- rats display hallmarks of cystinosis by 3-6 mo of age, as demonstrated by a failure to thrive, excessive thirst and urination, cystine accumulation in tissues, corneal cystine crystals, loss of LDL receptor-related protein 2 in proximal tubules, and immune cell infiltration. High levels of glucose, calcium, albumin, and protein were excreted at 6 mo of age, consistent with the onset of Fanconi syndrome, with a progressive diminution of urine urea and creatinine from 9 mo of age, indicative of chronic kidney disease. Kidney histology and immunohistochemistry showed proximal tubule atrophy and glomerular damage as well as classic "swan neck" lesions. Overall, Ctns-/- rats show a disease progression that more faithfully recapitulates nephropathic cystinosis than existing rodent models. The Ctns-/- rat provides an excellent new rodent model of nephropathic cystinosis that is ideally suited for conducting preclinical drug testing and is a powerful tool to advance cystinosis research. [ABSTRACT FROM AUTHOR]

Background & Aims: The BioNTech‐Pfizer vaccine is the only vaccine offered to children among all available vaccines. However, limited evidence is available about the clinical outcomes of COVID‐19 vaccines, especially among children and adolescents. This review offers a comprehensive and up‐to‐date overview of the BioNTech‐Pfizer vaccine's current information on children and adolescents. Methods: The review was conducted following the PRISMA guidelines; a comprehensive search was performed in PubMed, Scopus, MEDLINE, and EMBASE databases for research publications COVID‐19 published between December 2019 and October 2021. All studies reporting on the outcomes of vaccinating children in their respective institutes were included. Results: A total of 78 vaccinated children and adolescents from six studies were included. The majority of symptomatic vaccinated pediatrics were males (71%). The mean age was 15.6 years, and the BMI was 24.1. The most common clinical symptoms were found in chest pain (35%), fever (32%), and myalgia (17%). The most common cardiac symptom in the EKG results was ST elevation, and 35% of vaccinated pediatrics had elevated serum troponin. The hospitalization, including ICU admission, was lower than in unvaccinated groups. Statistically significant associations (p ≤ 0.05) were found in two symptoms (fever and headache) between the vaccinated and nonvaccinated pediatric groups. Conclusions: Although we found better outcomes in the vaccinated group versus the nonvaccinated pediatric group, more studies are still crucial to further understand the specific etiology underlying postvaccination, particularly myocarditis, psychological impact, and other cardiac clinical symptoms in children and adolescents after receiving the BioNTech‐Pfizer vaccine. [ABSTRACT FROM AUTHOR]

The microbial ecosystem within the bladder that can be measured within the urine, or urobiome, is an emerging field of study with little published data regarding children. However, investigations into urobiome research have the potential to significantly impact the understanding of the pathophysiology of genitourinary conditions, as well as potentially identify novel therapeutics. Therefore, both researchers and clinicians should be aware of pediatric urobiome research. The purpose of this review is to highlight the literature around urobiome research in urinary tract infections, nephrolithiasis, and neurogenic bladder; comment on pediatric-specific considerations when reading and interpreting the urobiome literature; and to identify new potential areas of research. [ABSTRACT FROM AUTHOR]

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination has become a major part of the strategy to reduce Coronavirus disease 2019 (COVID-19) numbers worldwide. To date, vaccinations based on several mechanisms have been used clinically, although relapse of existent glomerulonephritis presenting as gross hematuria, and occurrence of de novo glomerulonephritis have been reported.Case Presentation: We report the first sibling cases newly diagnosed as immunoglobulin A (IgA) nephropathy after the second dose of SARS-CoV-2 vaccination. 15- and 18-year-old men presented with gross hematuria following the second dose of SARS-CoV-2 vaccine (Pfizer, BNT162b2) received on the same day. Pathological findings of each kidney biopsy specimen were consistent with IgA nephropathy. Gross hematuria in both cases spontaneously recovered within several days.Conclusions: These cases indicate that SARS-CoV-2 vaccination might trigger de novo IgA nephropathy or stimulate its relapse, and also highlight the necessity of understanding the immunological responses to the novel mRNA vaccines in patients with kidney diseases. [ABSTRACT FROM AUTHOR]

The ocular manifestations of RA such as episcleritis and scleritis are important to consider in this patient, as the bilateral conjunctival injection observed in this patient may reflect an underlying systemic inflammatory process. Although the patient was at a low risk for developing ARF, as it is significantly less common in the US than underdeveloped countries, the presence of clinical carditis, polyarthralgia, fever of >=38.5°C, and significantly elevated markers of inflammation are sufficient to fulfill the 2015 Jones criteria for rheumatic fever and support the diagnosis of ARF in this patient. The angiographic findings suggestive of coronary vasculitis, and biopsy-proven vasculitis of small to medium-sized testicular arteries led to the specific diagnosis of PAN, which enabled the patient to receive the appropriate treatment for his underlying disease. [Extracted from the article]

Background Novel messenger RNA (mRNA)-based vaccines play an important role in current vaccination campaigns against SARS-CoV-2. They are highly efficacious and generally well tolerated. Vaccination in patients with immune-mediated kidney diseases is recommended. A number of cases with de novo or relapsing glomerulonephritis shortly after vaccine application have been reported, some of which presented with gross haematuria. Methods We collected 10 cases of macrohaematuria following mRNA-based severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination at our tertiary care institution and referring centres. Additionally, we pooled all 25 published cases from the literature with ours to analyse their clinical characteristics. Results Most macrohaematuria episodes (72.2%) began within 2 days after vaccination, the majority after the second dose. In some individuals, repeated episodes occurred after subsequent doses of the same vaccine. A total of 65.7% of patients never had macrohaematuria before. A total of 45.7% were known to suffer from immunoglobulin A nephropathy (IgAN); the rest had no prior renal diagnosis. IgAN was the most frequent new diagnosis, but anti-neutrophil cytoplasmic antibody-associated vasculitis and anti-glomerular basement membrane disease were also identified. Acute kidney injury (AKI) occurred in 28.6% of patients, with an increase in serum creatinine not meeting Kidney Disease: Improving Global Outcomes AKI criteria in 28.6%. Treatment ranged from conservative management, renin–angiotensin–aldosterone system inhibitors, steroids and cyclophosphamide to plasmapheresis. While renal outcomes were mainly favourable in isolated IgAN, they were poor in patients with additional or isolated small vessel vasculitis. Conclusion Awareness of gross haematuria after SARS-CoV-2 vaccination is important. Close follow-up and additional work up, particularly in individuals without known underlying kidney disease or worsening renal function, is essential. For patients with vaccine-associated macrohaematuria, an alternative vaccine class might be considered for subsequent vaccinations. [ABSTRACT FROM AUTHOR]

Backgrounds: Systemic amyloidosis is classified according to the deposited amyloid fibril protein (AFP), which determines its best therapeutic scheme. The most common type of AFP found are immunoglobulin light chains. The laser microdissection combined with mass spectrometry (LMD-MS) technique is a promising approach for precise typing of amyloidosis, however, the major difficulty in interpreting the MS data is how to accurately identify the precipitated AFP from background.Objectives: The objective of the present study is to establish a complete data interpretation procedure for LMD-MS based amyloidosis typing.Methods: Formalin-fixed paraffin-embedded specimens from patients with renal amyloidosis and non-amyloid nephropathies (including diabetic nephropathy, fibrillary glomerulonephritis, IgA nephropathy, lupus nephritis, membranous nephropathy, and normal tissue adjacent to tumors) were analyzed by LMD-MS. Forty-two specimens were used to train the data interpretation procedure, which was validated by another 50 validation specimens. Area under receiver operating curve (AUROC) analysis of amyloid accompanying proteins (AAPs, including apolipoprotein A-IV, apolipoprotein E and serum amyloid P-component) for discriminating amyloidosis from non-amyloid nephropathies was performed.Results: A stepwise data interpretation procedure that includes or excludes the types of amyloidosis group by group was established. The involvement of AFPs other than immunoglobulin was determined by P-score, as well as immunoglobulin light chain by variable of λ-κ, and immunoglobulin heavy chain by H-score. This achieved a total of 88% accuracy in 50 validation specimens. The AAPs showed significantly different expression levels between amyloidosis specimens and non-amyloid nephropathies. Each of the single AAP had a AUROC value more than 0.9 for diagnosis of amyloidosis from non-amyloid control, and the averaged level of the three AAPs showed the highest AUROC (0.966), which might be an alternative indicator for amyloidosis diagnosis.Conclusions: The proteomic data interpretation procedure for LMD-MS based amyloidosis typing was established successfully that has a high practicability in clinical application. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID‐19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has led to an unprecedented setback for global economy and health. Vaccination is one of the most effective interventions to substantially reduce severe disease and death due to SARS‐CoV‐2 infection. Vaccination programmes are being rolled out globally, but most of these vaccines have been approved without extensive studies on their side‐effects and efficacy. Recently, new‐onset autoimmune phenomena after COVID‐19 vaccination have been reported increasingly (e.g. immune thrombotic thrombocytopenia, autoimmune liver diseases, Guillain–Barré syndrome, IgA nephropathy, rheumatoid arthritis and systemic lupus erythematosus). Molecular mimicry, the production of particular autoantibodies and the role of certain vaccine adjuvants seem to be substantial contributors to autoimmune phenomena. However, whether the association between COVID‐19 vaccine and autoimmune manifestations is coincidental or causal remains to be elucidated. Here, we summarize the emerging evidence about autoimmune manifestations occurring in response to certain COVID‐19 vaccines. Although information pertaining to the risk of autoimmune disease as a consequence of vaccination is controversial, we merely propose our current understanding of autoimmune manifestations associated with COVID‐19 vaccine. In fact, we do not aim to disavow the overwhelming benefits of mass COVID‐19 vaccination in preventing COVID‐19 morbidity and mortality. These reports could help guide clinical assessment and management of autoimmune manifestations after COVID‐19 vaccination. [ABSTRACT FROM AUTHOR]

Background: Recent clinical reports indicate a correlation between gross hematuria after the coronavirus 2019 (COVID-19) vaccination in patients with glomerulonephritis, especially immunoglobulin A nephropathy (IgAN). Furthermore, healthcare workers in Japan were initially vaccinated with an mRNA vaccine from February 17, 2021, and some of them experienced gross hematuria after receiving the vaccination. Methods: We conducted a web-based survey of the councilor members of the Japanese Society of Nephrology (581 members, 382 facilities) to elucidate the relationship between gross hematuria and COVID-19 vaccination. Results: In the first survey, 27 cases (female: 22, 81.5%) of gross hematuria were reported after receiving a COVID-19 vaccination. Of them, 19 (70.4%) patients were already diagnosed with IgAN at the occurrence of gross hematuria. Proteinuria appeared in eight of the 14 (57.1%) cases with no proteinuria before vaccination and hematuria in five of the seven (71.4%) cases with no hematuria before vaccination. The second survey revealed that a renal biopsy was performed after vaccination in four cases, all of whom were diagnosed with IgAN. Only one case showed a slightly increased serum creatinine level, and no patients progressed to severe renal dysfunction. Conclusion: This study clarified the clinical features of gross hematuria after a COVID-19 vaccination. Because there was no obvious progression to severe renal dysfunction, safety of the COVID-19 vaccination is warranted at least in the protocol of inoculation twice. [ABSTRACT FROM AUTHOR]

Accumulation of misfolded proteins in the endoplasmic reticulum (ER) induces a well-orchestrated cellular response to reduce the protein burden within the ER. This unfolded protein response (UPR) is controlled primarily by three transmembrane proteins, IRE1α, ATF6, and PERK, the activity of which is controlled by BiP, the ER-resident Hsp70 protein. Binding of BiP to co-chaperones via their highly conserved J-domains stimulates the intrinsic ATPase activity of BiP, thereby providing the energy necessary for (re-)folding of proteins, or for targeting of misfolded proteins to the degradation pathway, processes specified and controlled by the respective co-chaperone. In this review, our aim is to elucidate the function of the co-chaperone ERDJ4, also known as MDG1, MDJ7, or DNAJB9. Knockout and knockin experiments clearly point to the central role of ERDJ4 in controlling lipogenesis and protein synthesis by promoting degradation of SREBP1c and the assembly of the protein complex mTORC2. Accumulating data reveal that ERDJ4 controls epithelial-to-mesenchymal transition, a central process during embryogenesis, in wound healing, and tumor development. Overexpression of ERdj4 has been shown to improve engraftment of transplanted human stem cells, possibly due to its ability to promote cellular survival in stressed cells. High ERDJ4-plasma levels are specific for fibrillary glomerulonephritis and serve as a diagnostic marker. As outlined in this review, the functions of ERDJ4 are manifold, depending on the cellular (patho-) physiological state, the cellular protein repertoire, and the subcellular localization of ERDJ4. [ABSTRACT FROM AUTHOR]

Background: Lymphovascular invasion (VI) is an established prognostic marker for many cancers including bladder cancer. There is a paucity of data regarding whether the prognostic significance of lymphatic invasion (LVI) differs from blood vessel invasion (BVI). The aim was to examine LVI and BVI separately using immunohistochemistry (IHC), and investigate their associations with clinicopathological characteristics and prognosis. A secondary aim was to compare the use of IHC with assessing VI on standard HAS (hematoxylin-azophloxine-saffron) sections without IHC. Methods: A retrospective, population –based series of 292 invasive bladder cancers treated with radical cystectomy (RC) with curative intent at Vestfold Hospital Trust, Norway were reviewed. Traditional histopathological markers and VI based on HAS sections were recorded. Dual staining using D2–40/CD31 antibodies was performed on one selected tumor block for each case. Results: The frequency of LVI and BVI was 32 and 28%, respectively. BVI was associated with features such as higher pathological stages, positive regional lymph nodes, bladder neck involvement and metastatic disease whereas LVI showed weaker or no associations. Both BVI and LVI independently predicted regional lymph node metastases, LVI being the slightly stronger factor. BVI, not LVI predicted higher pathological stages. BVI showed reduced recurrence free (RFS) and disease specific (DSS) survival in uni-and multivariable analyses, whereas LVI did not. On HAS sections, VI was found in 31% of the cases. By IHC, 51% were positive, corresponding to a 64% increased sensitivity in detecting VI. VI assessed without IHC was significantly associated with RFS and DSS in univariable but not multivariable analysis. Conclusions: Our findings indicate that BVI is strongly associated with more aggressive tumor features. BVI was an independent prognostic factor in contrast to LVI. Furthermore, IHC increases VI sensitivity compared to HAS. [ABSTRACT FROM AUTHOR]

Background: Urolithiasis is a multi-etiological disease resulting from a combination of environmental and genetic factors. One of the most challenging aspects of this disease is its high recurrence rate. For most patients, an in-depth metabolic evaluation may reveal the presence of urinary stones. The fact that different urinary stone-related compounds (USRCs) are measured by different methods renders the metabolic evaluation of urolithiasis quite tedious and complex.Methods: A three-channel ion chromatograph (IC) that automatically measures the concentration of common metabolic indicators of urolithiasis in urine (i.e., oxalate, citrate, uric acid, calcium, and magnesium) was developed to improve the efficiency. To validate its precision and specificity, standard curves were prepared using working solution of these indicators. 100 standard solutions of these indicators were measured with our new IC and three other ICs as the control instruments; analyte concentrations in 100 24-h urine samples from volunteers and 135 calculi patients were also measured.Results: All analytes had good linear relationships in concentration ranges of 0-10 mg/L. The precision experiments in the standard and urine samples showed that the measurement errors of the newly developed IC were all less than 5%. In urine, the recovery rate ranged from 99.6 to 100.4%, the coefficient of variation ranged from 1.39 to 2.99%, and the results matched between our newly developed IC and the control ICs. The results of the efficiency test showed that we can finish the analysis at the average number of 14 people per day with the new IC. While the average number in the control group is 3.85/day (p = 0.000).Conclusions: Overall, this multi-channel system significantly improves the efficiency of metabolic evaluation while retaining accuracy and precision. [ABSTRACT FROM AUTHOR]

Exostosin 1 and exostosin 2 (EXT1/EXT2) on glomerular basement membrane (GBM) were recently reported as novel putative antigens in secondary membranous nephropathy with autoimmune disease. However, the clinical significance of glomerular EXT1/EXT2 remains elusive in patients with lupus nephritis (LN). The immunofluorescence staining pattern of glomerular EXT1/EXT2 is also undetermined in membranous LN (MLN) or proliferative LN (PLN). We cross-sectionally analyzed patients with MLN (pure class V, n = 11) and PLN (class III, IV, and mixed class III/IV + V, n = 22) who underwent renal biopsies between 2010 and 2020 at Showa University Hospital. Glomerular EXT1/EXT2 expressions were evaluated by immunofluorescence. T-helper (Th) cell-related serum inflammatory cytokines were measured using enzyme-linked immunosorbent assay. The positivity for both EXT1/EXT2 was higher in patients with MLN than PLN (90.9% vs 63.6%, P = 0.212). MLN showed global and bright granular EXT1/EXT2 expressions along GBM, while PLN showed segmental and moderate expressions on GBM. Additionally, glomerular EXT1/EXT2 positivity was not associated with the degree of proteinuria or renal function in MLN and PLN patients, but the levels of serum anti-dsDNA antibody and circulating immune complexes were lower in patients with EXT1/EXT2-positive MLN than EXT1/EXT2-negative PLN. Moreover, serum complement levels and IL-4/IFN-γ ratios were elevated in EXT1/EXT2-positive MLN than EXT1/EXT2-negative PLN. Collectively, immunofluorescence staining for glomerular EXT1/EXT2 had characteristic patterns between MLN and PLN. Glomerular EXT1/EXT2 expressions tended to be high in Th2-dominant MLN patients without severe hypocomplementemia and elevated autoantibodies. Thus, EXT1/EXT2 might be involved in the unique developmental mechanism of MLN. [ABSTRACT FROM AUTHOR]

Neuroendocrine carcinomas (NECs) of the urinary bladder are very rare and can be observed in the context of mixed neuroendocrine/non-neuroendocrine neoplasms (MiNENs), most frequently in association with urothelial carcinoma. Small cell NECs are far more common than large cell NECs (LCNECs), which are exceedingly rare. We describe a primary MiNEN of the urinary bladder, composed of a LCNEC and of an adenocarcinoma, in which the neuroendocrine component reached complete pathological regression after neoadjuvant M-VAC chemotherapy, whereas the non-neuroendocrine component of the tumor progressed to metastatic disease. Compared to mixed neuroendocrine/non-neuroendocrine neoplasms described in the literature until now, this appears to be a unique case that expands the spectrum of neuroendocrine neoplasia of the urinary bladder. [ABSTRACT FROM AUTHOR]

There are unexplained geographical variations in the incidence of kidney cancer with the high rates reported in Baltic countries, as well as eastern and central Europe. Having access to a large and well-annotated collection of "tumor/non-tumor" pairs of kidney cancer patients from the Czech Republic, Romania, Serbia, UK, and Russia, we aimed to analyze the morphology of non-neoplastic renal tissue in nephrectomy specimens. By applying digital pathology, we performed a microscopic examination of 1012 frozen non-neoplastic kidney tissues from patients with renal cell carcinoma. Four components of renal parenchyma were evaluated and scored for the intensity of interstitial inflammation and fibrosis, tubular atrophy, glomerulosclerosis, and arterial wall thickening, globally called chronic renal parenchymal changes. Moderate or severe changes were observed in 54 (5.3%) of patients with predominance of occurrence in Romania (OR = 2.67, CI 1.07–6.67) and Serbia (OR = 4.37, CI 1.20–15.96) in reference to those from Russia. Further adjustment for comorbidities, tumor characteristics, and stage did not change risk estimates. In multinomial regression model, relative probability of non-glomerular changes was 5.22 times higher for Romania and Serbia compared to Russia. Our findings show that the frequency of chronic renal parenchymal changes, with the predominance of chronic interstitial nephritis pattern, in kidney cancer patients varies by country, significantly more frequent in countries located in central and southeastern Europe where the incidence of kidney cancer has been reported to be moderate to high. The observed association between these pathological features and living in certain geographic areas requires a larger population-based study to confirm this association on a large scale. [ABSTRACT FROM AUTHOR]