BACKGROUND: Humans are exposed to uranium (U) in a variety of applications. Both animal and observational human studies support an associated U nephrotoxicity. Few statistical syntheses of the human data have been performed and these analyses are limited in the types of exposures considered.
OBJECTIVE: This study aims to evaluate the state of current evidence and to expand on existing meta-analyses by systematically evaluating kidney-associated causes of mortality in multiple U-exposed populations. This study also aims to evaluate the effect of U exposure on kidney function and biomarkers of kidney injury.
METHODS: The published and grey literature were systematically reviewed for studies that reported Standardized Mortality Ratios (SMR) for kidney cancer, chronic nephritis/nephrosis, all-cause mortality, diabetes, all circulatory/heart disease, and/or ischemic heart disease in U-exposed humans. Studies that reported kidney biomarker measures for U-exposed versus control subjects were identified separately.
RESULTS: 36 studies were included. The studies were parsed into subgroups based on setting of exposure. Analysis of kidney cancer and chronic nephritis/nephrosis mortality demonstrated an SMR of 0.93 (95CI: 0.82-1.05) and 0.82 (95CI: 0.70-0.96), respectively. The other clinical outcomes evaluated also demonstrated mortality deficits in exposed relative to unexposed individuals. Subgroup analyses demonstrated similar mortality deficits. Conversely, biomarker analyses suggested better kidney function in the controls, but none of these differences reached significance.
CONCLUSIONS: Given that most of the included mortality studies were conducted in occupational populations, the mortality deficits observed in our analyses were likely due to the healthy-worker effect. Additionally, our analyses of kidney biomarkers were severely limited by low precision due to a low number of available studies and small study-size. Future work needs to evaluate the progression of chronic and to end-stage kidney disease in community-based populations to better assess the full impact of prolonged chronic U exposure on kidney outcomes.

Chronic kidney disease (CKD) is a significant public health concern. Renal fibrosis is the final common pathway in the progression of kidney diseases, irrespective of the initial injury. Substantial evidence underscores the pivotal role of renal inflammation in the genesis of renal fibrosis. The presence of macrophages within normal renal tissue is significantly increased within diseased renal tissue, indicative of their crucial regulatory function in inflammation and fibrosis. Macrophages manifest a high degree of heterogeneity, exhibiting distinct phenotypic and functional traits in response to diverse stimuli within the local microenvironment in various types of kidney diseases. Broadly, macrophages are categorized into two principal groups: Classically activated, designated as M1 macrophages and alternatively activated, designated as M2 macrophages. A number of experimental models are widely used to study the underlying mechanisms driving renal inflammation and fibrosis progression. The present review delineated the phenotypic and functional attributes of macrophages present in diverse induced models, analyzing their disposition in relation to M1 and M2 polarization states.

Hypertension, a prevalent chronic ailment, has the potential to impair kidney function, and thereby resulting in hypertensive nephropathy. The escalating incidence of hypertensive nephropathy attributed to the aging population in urban areas, has emerged as a prominent cause of end-stage renal disease. Nevertheless, the intricate pathogenesis of hypertensive nephropathy poses considerable obstacles in terms of precise clinical diagnosis and treatment. This paper aims to consolidate the research findings on the pathogenesis of hypertensive nephropathy by focusing on the perspective of molecular biology.

Immunoglobulin A (IgA) vasculitis (IgAV, also known as Henoch-Schoenlein purpura, HSP) is the most common vasculitis of childhood. It usually presents with a simple, self-limiting disease course; however, a small subset of patients may develop kidney involvement (IgAV-N) which occurs 4-12 weeks after disease onset and is the biggest contributor to long-term morbidity. Treatment currently targets patients with established kidney involvement; however; there is a desire to work towards early prevention of inflammation during the window of opportunity between disease presentation and onset of significant nephritis. There are no clinical trials evaluating drugs which may prevent or halt the progression of nephritis in children with IgAV apart from the early use of corticosteroids which have no benefit. This article summarises the latest scientific evidence and clinical trials that support potential therapeutic targets for IgAV-N that are currently being developed based on the evolving understanding of the pathophysiology of IgAV-N. These span the mucosal immunity, B-cell and T-cell modulation, RAAS inhibition, and regulation of complement pathways, amongst others. Novel drugs that may be considered for use in early nephritis include TRF-budesonide; B-cell inhibiting agents including belimumab, telitacicept, blisibimod, VIS649, and BION-1301; B-cell depleting agents such as rituximab, ofatumumab, and bortezomib; sparsentan; angiotensin converting enzyme inhibitors (ACE-Is); and complement pathway inhibitors including avacopan, iptacopan, and narsoplimab. Further clinical trials, as well as pre-clinical scientific studies, are needed to identify mechanistic pathways as there may be an opportunity to prevent nephritis in this condition. Key Points • Kidney involvement is the main cause of long-term morbidity and mortality in IgA vasculitis despite the current treatment recommendations. • The evolving understanding of the pathophysiology of IgA vasculitis is allowing exploration of novel treatment options which target underlying immune pathways. • Novel treatments currently being trialled in IgA nephropathy may have benefit in IgA vasculitis due to the similarities in the underlying pathophysiology, such as TRF-budesonide, B-cell modulators, and complement inhibitors. • Further studies, including clinical trials of novel drugs, are urgently needed to improve the long-term outcomes for children with IgA vasculitis nephritis.

BACKGROUND: Henoch-Schönlein purpura (IgA vasculitis) is the most common childhood vasculitis, one of its complications is renal involvement. However, several treatment regimens have been proposed to improve renal function in the long term, but which drug regimen can be most effective is still controversial.
METHODS: This study was a systematic review. In order to find evidence related to the purpose of this study, databases including Google Scholar, Web of Science, ProQuest and Medline via PubMed, and Scopus were searched with the appropriate keywords. QUADAS-2 (a Quality Assessment tools for Diagnostic Accuracy Studies) checklist was also used to evaluate the quality of studies. Based on the keywords used in reviewing the information sources of scientific articles, in the first stage, 86 studies were included in the review. Taking into account characteristics such as lack of homogeneity with the objectives of the present study, finally, 11 studies were selected for analysis and final evaluation.
RESULTS: A total of 11 studies, including 722 patients in the age range of 5.5 to 9.9 years with HSP were included in the study. The follow-up period of the patients varied from 6 months to 16 years in terms of examining the treatment process. In terms of study type, 7 studies were conducted as prospective or retrospective (non-interventional) cohorts and 4 studies as randomized clinical trials. The treatment regimen of injectable methylprednisolone followed by oral prednisolone resulted in a long-term recovery of 79.2% (95% confidence interval between 0.66% and 88.2%); however, the need for additional immunosuppressive in two studies was mentioned as 38% and 46.1%, respectively. In the therapeutic regimen of oral methylprednisolone alone, a significant improvement in long-term renal function was achieved in comparison with placebo. Administration of injectable methylprednisolone followed by cyclosporine A had the highest effectiveness in terms of improving renal function in the long term.
CONCLUSIONS: Regimes based on the administration of prednisolone (either oral or injectable, either as a single drug or as a combination) lead to long-term improvement of renal function in patients with HSP, but the use of other immunosuppressive drugs such as cyclosporine A, of course, with optimizing the drug dose can lead to a significant improvement in the clinical performance.

COVID-19 usually presents with classic signs and symptoms, but it can involve multiple systems in atypical cases. SARS-CoV-2 has a complex interaction with the host immune system leading to atypical manifestations. In our case, a 32-year-old male patient presented with fatigue, sores on hands and feet, headache, productive cough with blood-tinged mucus, conjunctival hyperemia, purpuric rash on hands and feet, and splinter hemorrhages of fingernails for 2 weeks. The patient\'s SARS-CoV-2 antigen and PCR test were positive. Chest X-ray showed mixed density perihilar opacities in both lungs. Computed tomography of the chest showed extensive airspace opacities in both lungs, suggesting COVID-19 multifocal, multilobar pneumonitis. A renal biopsy indicated limited thrombotic microangiopathy and tubulointerstitial nephritis, for which he was started on steroids, and his renal functions gradually improved. He tested positive for C-ANCA during an immune workup. He was discharged with a steroid taper for nephritis. Once the taper reached less than 10 mg/day, he developed acute scleritis and a new pulmonary cavitary lesion of 6 cm. The biopsy via bronchoscopy revealed acute inflammatory cells with hemosiderin-laden macrophages. He was restarted on systemic steroids for scleritis after failing topical steroids, which incidentally also reduced the size of the cavitary lesion, indicating an immune component. Our case demonstrates the involvement of kidneys and vasculitis of the skin, sclera, and lungs by COVID-19. The patient\'s symptoms were not explained by any diseases other than COVID-19. Atypical cases of COVID-19 disease with multifocal systemic symptoms involving the skin, sclera, lungs, and kidneys should be high on differentials. Early recognition and intervention may decrease hospital stays and morbidity.

Acute focal bacterial nephritis (AFBN) is a kidney disease characterized by a localized bacterial infection that manifests as an inflammatory mass. Most children with AFBN have nonspecific symptoms including fever, vomiting, and abdominal discomfort, and some develop neurological symptoms such as meningeal irritation, unconsciousness, and seizures as their condition worsens. This was 2 cases of AFBN with central nervous system manifestations in children, and we analyzed its possible mechanisms of the clinical and radiographic features. We experience 2 very unusual cases of AFBN which were linked to central nervous system abnormalities. A 6-year-old boy with AFBN and clinically moderate ncephalitis/encephalopathy with a reversible splenial lesion (MERS) presented with neurological symptoms, including unconsciousness and convulsions. The second case involved an 8-year-old child with AFBN-associated acute encephalopathy who exhibited neurological symptoms, including unconsciousness. According to previous research, AFBN is linked to central nervous system impairment. As a result, when a clinician meets a patient with an inexplicable fever caused by a neurological condition, he should pay attention to this diagnosis of AFBN and follow it in the abdominal graph.

COVID-19 most related glomerular disease to date seems to be collapsing glomerulopathy, mostly in young Afroamerican patients with APOL1 gene risk alleles. However, in our population, predominant in elderly Caucasian patients, most biopsied pathology since the beginning of the pandemic has been IgA nephritis or Schönlein-Henoch purpura. Since the description of the first case of this entity after SARS-CoV-2 infection by our research group, three more cases have arisen, which are described in the following article. In contrast to the rest of IgA vasculitis cases reported, our patients presented more renal function deterioration and all of them required immunosupresive therapy. Moreover, some showed incomplete recovery of renal function. This case series strengthens the hypothesis that SARS-CoV-2 infection may be another trigger of this pathology.

Immune checkpoint inhibitors (ICI) have revolutionized the landscape of cancer treatment. Although several studies have shown that ICIs have a better safety profile than chemotherapy, some patients develop immune-related adverse events (irAEs), which require specialized and multidisciplinary management. Since ICI indications are rapidly increasing, it is crucial that clinicians involved in cancer care learn to identify irAEs and manage them properly. Here, we report a case series of 23 patients with severe irAEs requiring hospitalization over a period of 12 months and seize the opportunity to review and update different general features related to irAEs along with the management of the most frequent severe irAEs in our series.

Microscopic polyangiitis (MPA) is a systemic small-vessel vasculitis associated with anti-neutrophil cytoplasmic antibody (ANCA) and predominantly causes kidney and pulmonary injuries. Subarachnoid hemorrhage, a life-threatening manifestation of the central nervous system (CNS), rarely occurs in patients with ANCA-associated vasculitis (AAV). We report the case of a young man with spontaneous SAH recurrence and active nephritis. The patient was treated with a glucocorticoid pulse and intravenous cyclophosphamide (CTX) in combination with decreasing cerebral perfusion pressure and analgesic therapy. All the patients\' symptoms except the proteinuria resolved. We reviewed the clinical characteristics of 34 previously reported cases of SAH with AAV, comprising six cases of MPA, eight cases of granulomatosis with polyangiitis (GPA), and 19 cases of eosinophilic granulomatosis with polyangiitis (EGPA), and one case of unclassified AAV. All the cases showed features of active vasculitis. Concomitant nephritis and peripheral neuropathy were found in the MPA and EGPA cases with SAH, respectively. Renal and pulmonary manifestations were predominant in the patients with GPA and SAH. Ten patients had aneurysmal abnormalities, and six patients had cardiac abnormalities. Thirty-one patients were treated with glucocorticoids, and 18 patients received concurrent immunosuppressants. Patients with SAH had a mortality rate of 38.2%. The presence of cerebrovascular events or cardiac involvement in patients with AAV and SAH is associated with increased mortality of 64.3%. Our study indicates that SAH should be cautioned as a disease occurring in patients with AAV. Early diagnosis with aggressive immunosuppressive therapy can help improve the prognosis of patients with SAH.