MR Perfusion Imaging for Kidney Disease.

Renal perfusion reflects overall function of a kidney. As an important indicator of kidney diseases, renal perfusion can be noninvasively measured by multiple methods of MR imaging, such as dynamic contrast-enhanced MR imaging, intravoxel incoherent motion analysis, and arterial spin labeling method. In this article we introduce the principle of the methods, review their recent technical improvements, and then focus on summarizing recent applications of the methods in assessing various renal diseases. By this review, we demonstrate the capability and clinical potential of the imaging methods, with the hope of accelerating their adoption to clinical practice.

Noscapine alleviates unilateral ureteral obstruction-induced inflammation and fibrosis by regulating the TGFß1/Smads signaling pathways.

Renal fibrosis is a common pathway leading to progressive renal function loss in various forms of chronic kidney disease. Many fibrogenic factors regulate renal fibrosis; two key players are post-injury inflammation and transforming growth factor-ß1 (TGF-ß1)-induced myofibroblast differentiation. Myofibroblast differentiation is tightly regulated by the microtubule polymerization. Noscapine, an antitussive plant alkaloid, is a potent microtubule-interfering agent previously identified as a potential anticancer compound. Here, we examined how noscapine affects renal fibrogenesis in an in vitro renal fibroblast model and an in vivo unilateral ureteral obstruction (UUO) model. UUO mice were intraperitoneally treated with noscapine at 1 day before UUO surgery and daily thereafter. At 7 days post-surgery, kidneys were collected for further analysis. To analyze whether noscapine inhibits downstream TGF-ß1-related signaling, we pre-incubated NRK-49F fibroblasts with noscapine and then performed TGF-ß1 stimulation. In UUO mice, noscapine attenuated extracellular matrix protein deposition and the expression levels of type I collagen, type IV collagen, α-smooth muscle actin, and fibronectin. In addition, noscapine decreased tubulointerstitial inflammation in UUO kidneys by reducing TLR2 expression, modulating NLRP3 inflammasome activation, reducing macrophage infiltration, and antagonizing the M2 macrophage phenotype. Furthermore, noscapine pre-incubation suppressed the TGF-ß1-induced fibroblast-myofibroblast transformation by downregulating the TGF-ß/Smads signaling pathways in NRK-49F cells. These results suggest that noscapine reduces tubulointerstitial inflammation and fibrosis in the kidneys of UUO mice and inhibits the fibroblast-myofibroblast transformation induced by TGF-ß1. Noscapine is an over-the-counter antitussive that has been used safely for several decades. Therefore, noscapine is an attractive therapeutic agent for inhibiting renal tubulointerstitial fibrosis.

Barriers to home dialysis and kidney transplantation for socially disadvantaged individuals.

PURPOSE OF REVIEW: People with kidney disease facing social disadvantage have multiple barriers to quality kidney care. The aim of this review is to summarize the patient, clinician, and system wide factors that impact access to quality kidney care and discuss potential solutions to improve outcomes for socially disadvantaged people with kidney disease. RECENT FINDINGS: Patient level factors such as poverty, insurance, and employment affect access to care, and low health literacy and kidney disease awareness can affect engagement with care. Clinician level factors include lack of early nephrology referral, limited education of clinicians in home dialysis and transplantation, and poor patient-physician communication. System-level factors such as lack of predialysis care and adequate health insurance can affect timely access to care. Neighborhood level socioeconomic factors, and lack of inclusion of these factors into public policy payment models, can affect ability to access care. Moreover, the effects of structural racism and discrimination nay negatively affect the kidney care experience for racially and ethnically minoritized individuals. SUMMARY: Patient, clinician, and system level factors affect access to and engagement in quality kidney care. Multilevel solutions are critical to achieving equitable care for all affected by kidney disease.

Mesenchymal stem cells overexpressing PBX1 alleviates haemorrhagic shock-induced kidney damage by inhibiting NF-κB activation.

Mesenchymal stem cells (MSCs) have favourable outcomes in the treatment of kidney diseases. Pre-B-cell leukaemia transcription factor 1 (PBX1) has been reported to be a regulator of self-renewal of stem cells. Whether PBX1 is beneficial to MSCs in the treatment of haemorrhagic shock (HS)-induced kidney damage is unknown. We overexpressed PBX1 in rat bone marrow-derived mesenchymal stem cells (rBMSCs) and human bone marrow-derived mesenchymal stem cells (hBMSCs) to treat rats with HS and hypoxia-treated human proximal tubule epithelial cells (HK-2), respectively. The results indicated that PBX1 enhanced the homing capacity of rBMSCs to kidney tissues and that treatment with rBMSCs overexpressing PBX1 improved the indicators of kidney function, alleviated structural damage to kidney tissues. Furthermore, administration with rBMSCs overexpressing PBX1 inhibited HS-induced NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome activation and the release of proinflammatory cytokines, and further attenuated apoptosis. We then determined whether NF-κB, an important factor in NLRP3 activation and the regulation of inflammation, participates in HS-induced kidney damage, and we found that rBMSCs overexpressing PBX1 inhibited NF-κB activation by decreasing the p-IκBα/IκBα and p-p65/p65 ratios and inhibiting the nuclear translocation and decreasing the DNA-binding capacity of NF-κB. hBMSCs overexpressing PBX1 also exhibited protective effects on HK-2 cells exposed to hypoxia, as shown by the increase in cell viability, the mitigation of apoptosis, the decrease in inflammation, and the inhibition of NF-κB and NLRP3 inflammasome activation. Our study demonstrates that MSCs overexpressing PBX1 ameliorates HS-induced kidney damage by inhibiting NF-κB pathway-mediated NLRP3 inflammasome activation and the inflammatory response.

Genetic testing in the evaluation of recipient candidates and living kidney donors.

PURPOSE OF REVIEW: The aim of this study is to provide an overview of the role of genetic testing in the evaluation of kidney transplant candidates and living donors who may be at risk for heritable kidney disease. We focus our discussion on monogenic diseases, excluding renal diseases that have complex polygenic influences. Adoption of new technologies such as next-generation sequencing (NGS) with comprehensive gene panels has greatly enabled access to genetic testing recently; yet transplant professionals rarely receive adequate training in clinical genetics. In addition to a broad discussion of genetic testing, we hope to illustrate the thought processes and resources used in clinical genetic evaluation of recipient candidates and donors. RECENT FINDINGS: Targeted renal genetic panels, whole exome and genome sequencing have greatly expanded our ability to test for pathogenic variants. Testing methods, analytic tools and the subsequent interpretation by the testing laboratory and treating physician impacts patient management and clinicians may lack the resources to practice in this new era of genomic medicine. SUMMARY: The expansion of genomics into transplant medicine can provide improved diagnosis in transplant candidates and potentially disease prediction in living donors. Transplant professionals need to be familiar with emerging trends, promises and limitations of NGS-based testing.

Therapeutic effect of hydrogen and its mechanisms in kidney disease treatment.

Hydrogen is a simple, colorless, and biologically active small molecule gas that can react with reactive oxygen species. Recent research suggests that hydrogen possesses several biological effects, including antioxidant, anti-inflammatory, and anti-apoptotic effects, while exhibiting an extremely high level of safety. Hydrogen application has shown promise in treating a range of acute and chronic diseases, both benign and malignant. Importantly, an increasing number of clinical studies on hydrogen have demonstrated its efficacy and safety in treating various diseases. This review highlights the beneficial effects of hydrogen in kidney diseases, summarizes potential mechanisms by which hydrogen may act in these diseases, and proposes several promising avenues for future research.

Perfil sociodemográfico e laboratorial dos pacientes submetidos à hemodiálise em um centro de referência do Estado do Ceará / Sociodemographic and laboratory profile of patients undergoing hemodialysis in a reference center in the State of Ceará / Perfil sociodemográfico y de laboratorio de dos pacientes sometidos a hemodiálisis en un centro de referencia del Estado de Ceará

A Doença Renal Crônica (DRC) é uma importante redução da função renal que causa alterações no metabolismo dos indivíduos. Para acompanhar a progressão da DRC e prevenir possíveis complicações, foi realizada uma pesquisa para avaliar o perfil sociodemográfico, bioquímico e hematológico de pacientes com Insuficiência Renal Crônica (IRC) submetidos a hemodiálise. Esta pesquisa foi quantitativa, descritiva e transversal de caráter retrospectivo, realizada por meio da análise de dados secundários contidos nos prontuários dos pacientes. A coleta de dados ocorreu no Centro de Hemodiálise da cidade de Russas, no Ceará. A amostra foi constituída por 161 pacientes com DRC, sendo 63,35% do sexo masculino e 85,71% pardos, com uma idade média de 54,39 anos. Desses, 63,97% tinham entre 2 e 10 anos de tratamento e 57,76% possuíam ensino fundamental incompleto. 19,25% residiam em Russas. Resultados: Após a hemodiálise, os resultados mostraram 44 mg/dL de Ureia, 48,44% dos pacientes com valores normais. A hemoglobina e hematócrito médios foram 11,8 g/dL e 33,7%, respectivamente, sendo que 63,35% tiveram valores reduzidos. 85,10% dos pacientes tiveram contagem de plaquetas normal, 72,04% níveis adequados de ferro e albumina, 52,79% tiveram níveis elevados de ferritina, 23,61% redução de transferrina e níveis lipídicos satisfatórios. 79,50% apresentaram níveis séricos de potássio dentro da normalidade, 12,42% de fósforo acima do normal, 85,09% de cálcio dentro dos valores normais, 39,13% de PTHi normais e 86,33% de glicose dentro dos valores considerados normais. Com base nos resultados, concluiu-se que todos os pacientes em tratamento hemodialítico apresentam diversas alterações em decorrência da DRC e do próprio processo de tratamento. Portanto, a realização de exames para avaliar ou monitorar possíveis complicações da IRC é essencial para criar estratégias e intervenções mais eficazes, que melhorem a assistência prestada a esses pacientes e, consequentemente, da qualidade e expectativa de vida dos mesmos.

Chronic Kidney Disease (CKD) is an important reduction in kidney function that causes changes in the metabolism of individuals. To monitor the progression of CKD and prevent possible complications, a survey was carried out to assess the sociodemographic, biochemical and hematological profile of patients with Chronic Renal Failure (CRF) undergoing hemodialysis. This research was quantitative, descriptive and cross-sectional with a retrospective character, carried out through the analysis of secondary data contained in the patients' medical records. Data collection took place at the Hemodialysis Center in the city of Russas, Ceará. The sample consisted of 161 patients with CKD, 63.35% male and 85.71% brown, with an average age of 54.39 years. Of these, 63.97% had between 2 and 10 years of treatment and 57.76% had incomplete primary education. 19.25% resided in Russas. Results: After hemodialysis, the results showed 44 mg/dL of Urea, 48.44% of patients with normal values. Average hemoglobin and hematocrit were 11.8 g/dL and 33.7%, respectively, with 63.35% having reduced values. 85.10% of the patients had normal platelet counts, 72.04% had adequate levels of iron and albumin, 52.79% had high levels of ferritin, 23.61% had reduced transferrin and satisfactory lipid levels. 79.50% had serum levels of potassium within the normal range, 12.42% of phosphorus above normal, 85.09% of calcium within normal values, 39.13% of PTHi normal and 86.33% of glucose within the values considered normal. Based on the results, it was concluded that all patients on hemodialysis have several changes due to CKD and the treatment process itself. Therefore, carrying out tests to assess or monitor possible complications of CRF is essential to create more effective strategies and interventions that improve the care provided to these patients and, consequently, their quality and life expectancy.

La Enfermedad Renal Crónica (ERC) es una reducción importante de la función renal que provoca cambios en el metabolismo de los individuos. Para monitorizar la evolución de la ERC y prevenir posibles complicaciones, se realizó una encuesta para evaluar el perfil sociodemográfico, bioquímico y hematológico de los pacientes con Insuficiencia Renal Crónica (IRC) en hemodiálisis. Esta investigación fue cuantitativa, descriptiva y transversal con carácter retrospectivo, realizada a través del análisis de datos secundarios contenidos en las historias clínicas de los pacientes. La recolección de datos ocurrió en el Centro de Hemodiálisis de la ciudad de Russas, Ceará. La muestra estuvo constituida por 161 pacientes con ERC, 63,35% del sexo masculino y 85,71% pardos, con una edad media de 54,39 años. De estos, 63,97% tenían entre 2 y 10 años de tratamiento y 57,76% tenían primaria incompleta. El 19,25% residía en Russas. Resultados: Posterior a la hemodiálisis los resultados arrojaron 44 mg/dL de Urea, 48,44% de los pacientes con valores normales. La hemoglobina y el hematocrito medios fueron 11,8 g/dl y 33,7 %, respectivamente, con un 63,35 % con valores reducidos. El 85,10% de los pacientes presentaba plaquetas normales, el 72,04% presentaba niveles adecuados de hierro y albúmina, el 52,79% presentaba niveles elevados de ferritina, el 23,61% presentaba transferrina reducida y niveles satisfactorios de lípidos. El 79,50% presentaba niveles séricos de potasio dentro de la normalidad, el 12,42% de fósforo por encima de lo normal, el 85,09% de calcio dentro de los valores normales, el 39,13% de PTHi normal y el 86,33% de glucosa dentro de los valores considerados normales. Con base en los resultados, se concluyó que todos los pacientes en hemodiálisis tienen varios cambios debido a la ERC y al propio proceso de tratamiento. Por tanto, la realización de pruebas para evaluar o monitorizar las posibles complicaciones de la IRC es fundamental para crear estrategias e intervenciones más eficaces que mejoren la atención a estos pacientes y, en consecuencia, su calidad y esperanza de vida.

ACT001 Alleviates chronic kidney injury induced by a high-fat diet in mice through the GPR43/AMPK pathway.

BACKGROUND: Roughly 10 -15% of global populace suffer from Chronic Kidney Disease(CKD). A major secondary disease that can progress to end-stage renal disease (ESRD) is obesity-associated kidney disease (ORG). Although clinical management strategies are currently available, morbidity and mortality rates are increasing. Thus, new solutions are needed. Intestinal permeability, systemic inflammation, and aberrant intestinal metabolites have all been linked to ORG. PURPOSE: ACT001 has anti-inflammatory, redox-regulatory and antitumour activities. The current study was designed to examine how ACT001 affects ORG and analyze the fundamental processes. METHODS: A high-fat diet (HFD) was used to generate ORG in female C57BL/6 J mice. ORG mice were divided into three groups at random: HFD, HFD + ACT001, HFD + polyphosphocholine (PPC). To assess renal and colonic damage, periodic acid-Schiff (PAS) and hematoxylin-eosin (HE) staining were used. Following that, renal inflammation, oxidative stress, lipid deposition, colonic inflammation, and intestinal permeability were evaluated by protein blotting, polymerase chain reaction (PCR), immunohistochemistry, and immunofluorescence staining. Lastly, the SCFAs content was assessed by gas chromatographymass spectrometry. RESULTS: Mice in the HFD group displayed more severe albuminuria, glomerular hypertrophy, renal oxidative damage, inflammation, and lipid accumulation than mice with the normal diet (ND) group, as well as lower levels of intestinal SCFA valproic acid, colonic inflammation, and tight junction protein downregulation. ACT001 treatment restores the content of valproic acid in intestinal SCFAs, promotes the binding of SCFAs to renal GPR43, activates the AMPK signalling pathway. Therefore, it promotes the Nrf2-Keap1 signalling pathway and inhibits the NF-κB signalling pathway. SCFAs, additionally, augment colonic GPR43 concentrations, diminishing NLRP3 inflammasome expression and restoring ZO-1 and occludin protein levels. CONCLUSION: This study is the first to look at ACT001's potential as a treatment for obesity-related kidney disease. Regulating GPR43 and AMPK signalling pathways, By controlling the GPR43 and AMPK signalling pathways, ACT001 improves colitis and the intestinal mucosal barrier, decreases renal lipid deposition, and suppresses inflammation and oxidative stress in the kidneys. According to this study, ACT001 could be a viable ORG therapy option.

Epidermal growth factor receptor activation is essential for kidney fibrosis development.

Fibrosis is the progressive accumulation of excess extracellular matrix and can cause organ failure. Fibrosis can affect nearly every organ including kidney and there is no specific treatment currently. Although Epidermal Growth Factor Receptor (EGFR) signaling pathway has been implicated in development of kidney fibrosis, underlying mechanisms by which EGFR itself mediates kidney fibrosis have not been elucidated. We find that EGFR expression increases in interstitial myofibroblasts in human and mouse fibrotic kidneys. Selective EGFR deletion in the fibroblast/pericyte population inhibits interstitial fibrosis in response to unilateral ureteral obstruction, ischemia or nephrotoxins. In vivo and in vitro studies and single-nucleus RNA sequencing analysis demonstrate that EGFR activation does not induce myofibroblast transformation but is necessary for the initial pericyte/fibroblast migration and proliferation prior to subsequent myofibroblast transformation by TGF-ß or other profibrotic factors. These findings may also provide insight into development of fibrosis in other organs and in other conditions.

Impact of Renal Replacement Therapy on Rejection among Liver Transplant Recipients.

Introduction: Renal dysfunction in liver transplant recipients is associated with an increased risk of morbidity and mortality, with an even higher risk among patients requiring renal replacement therapy. There is limited data evaluating rejection outcomes in patients requiring renal replacement therapy after liver transplant. Program evaluation aims: To evaluate the incidence of biopsy-proven acute rejection, recipient and graft survival, infection, renal dysfunction, and immunosuppression practices. Design: This was a single-center, retrospective, cohort study. To be eligible, patients were deceased donor liver transplant recipients ≥18 year of age transplanted between January 2017 and August 2019 who received steroid-only induction and tacrolimus as part of their initial immunosuppression regimen. Results: Recipients that required renal replacement therapy (N = 86) were compared to those who received no renal replacement therapy (N = 158). Biopsy-proven acute rejection at 1-year posttransplant was significantly higher among those requiring renal replacement therapy (36% vs 13%, P < .001). Patient survival at 12 months was 77% for those requiring renal replacement therapy and 94% for those not requiring renal replacement therapy (P < .001). Infection (HR 3.8, 95% CI 1.6-8.8; P < .001), but not rejection (HR 0.7, 95% CI 0.3-1.7; P = .5) was an independent predictor of mortality. The use of renal replacement therapy after liver transplant necessitated careful titration of immunosuppression to balance the detrimental risks of infection versus rejection in this high-risk population.

TLR2 mediates renal apoptosis in neonatal mice subjected experimentally to obstructive nephropathy.

Urinary tract obstruction during renal development leads to inflammation, tubular apoptosis, and interstitial fibrosis. Toll like receptors (TLRs) expressed on leukocytes, myofibroblasts and renal cells play a central role in acute inflammation. TLR2 is activated by endogenous danger signals in the kidney; its contribution to renal injury in early life is still a controversial topic. We analyzed TLR2 for a potential role in the neonatal mouse model of congenital obstructive nephropathy. Inborn obstructive nephropathies are a leading cause of end-stage kidney disease in children. Thus, newborn Tlr2-/- and wild type (WT) C57BL/6 mice were subjected to complete unilateral ureteral obstruction (UUO) or sham-operation on the 2nd day of life. The neonatal kidneys were harvested and analyzed at days 7 and 14 of life. Relative expression levels of TLR2, caspase-8, Bcl-2, Bax, GSDMD, GSDME, HMGB1, TNF, galectin-3, α-SMA, MMP-2, and TGF-ß proteins were quantified semi-quantitatively by immunoblot analyses. Tubular apoptosis, proliferation, macrophage- and T-cell infiltration, tubular atrophy, and interstitial fibrosis were analyzed immunohistochemically. Neonatal Tlr2-/- mice kidneys exhibited less tubular and interstitial apoptosis as compared to those of WT C57BL/6 mice after UUO. UUO induced neonatally did trigger pyroptosis in kidneys, however to similar degrees in Tlr2-/- and WT mice. Also, tubular atrophy, interstitial fibrosis, tubular proliferation, as well as macrophage and T-cell infiltration were unremarkable. We conclude that while TLR2 mediates apoptosis in the kidneys of neonatal mice subjected to UUO, leukocyte recruitment, interstitial fibrosis, and consequent neonatal obstructive nephropathy might lack a TLR2 involvement.

[Renal Side Effects of Novel Molecular Targeted Oncologic Agents].

The introduction of innovative therapies has changed the scenario of complications. The delay in the recognition of kidney adverse effects is partly due to the timing of the development of the kidney damage which occurs later than the observation period of registration studies, and partly to the exclusion of patients with known kidney impairment from registration trials. Renal disease has a significant impact on the management of cancer patients and often leads to discontinuation of therapy. Histological evaluations of kidney disorders induced by targeted/immunotherapy are very limited. Renal biopsy is critical for the management of renal toxicities and should be especially encouraged for patients showing adverse renal effects to novel cancer agents. We recently examined the histological features of patients treated with new cancer agents who underwent renal biopsy for new onset renal failure and/or urinary abnormalities. The cohort included 42 patients. The most frequently administered therapies were immunotherapy (54.8%) and anti-angiogenic treatments (45.2%). The most common adverse effect was tubular interstitial nephritis in the first group and thrombotic microangiopathy in the second one. Based on histological findings, definitive discontinuation of treatment could be restricted to a very limited number of patients. All of them had anti-VEGF-related TMA. Treatment discontinuation was unneeded in patients treated with ICIs. In patients treated with multidrug therapy, the histological findings made it possible to identify the weight of drug-related specific injury. Based on this data, renal biopsy should be considered in every cancer patient who develops urinary abnormalities or shows a worsening of renal function during treatment with immunotherapy or targeted therapy.

[Ten Years of Onconephrology].

Onconephrology is a subspecialty of Nephrology with the aim of fully dealing with the complex and bidirectional relationship between the tumor and the kidneys. In a world where Nephrologists still too often consider Oncological patients as "lost" and in which Oncologists are afraid to administer oncological therapies to patients with renal failure due to the absence of Literature data, Onconephrology was created with the aim of guaranteeing patients with renal disease the same treatment opportunities as the general population. Over the years this subspecialty has developed and more nephrologists, experts in the field, daily support oncologists in clinical-therapeutic decisions by dealing with cases of renal toxicity from oncological therapy, managing treatments in patients with renal failure and dealing with all those conditions associated with both oncological and renal pathology in terms of prevention and treatment. In this paper we will retrace the history of Onconephrology by analyzing what are the results achieved and what are the objectives for the future.

[Classification and Management of MGRS Related Diseases].

Monoclonal Gammopathies of Renal Significance (MGRS) are a complex group of disorders characterized by the production of aberrant monoclonal proteins that interact with kidney structures, causing tissue damage. Unlike neoplastic forms, kidney damage in MGRS does not correlate with clone mass or circulating monoclonal protein levels, conferring unique pre-neoplastic or non-neoplastic properties to the responsible clones. This manuscript explores the heterogeneity of monoclonal proteins involved, varying from full immunoglobulins to free light chains (FLC), and how they result in a spectrum of kidney lesions with differing prognoses. We also elaborate on diagnostic challenges, emphasizing the indispensable role of kidney biopsy, including advanced techniques like laser microdissection and mass spectrometry (LMD/MS) for deposit characterization, particularly in ambiguous or complex cases. Clinical management and treatment considerations, including the necessity for clone identification, are also discussed.

PREVALENCE OF RENAL DYSFUNCTION IN ACUTE STROKE PATIENTS AT ABAKALIKI NIGERIA: AN OBSERVATIONAL STUDY.

Introduction: Renal dysfunction is commonly seen in hospitalized stroke patients. It serves both as a risk factor for stroke and as a complication of stroke. Renal dysfunction is a poor prognostic factor for stroke and increases the risk of recurrence. Despite the above poor indices, there is a paucity of data on the prevalence of renal dysfunction in acute stroke patients in Nigeria. Objective: It is against this background that this study was conducted to identify the prevalence and pattern of renal dysfunction among acute stroke patients who were managed at a Federal Teaching Hospital in Abakaliki Nigeria. Methodology: This is a cross-sectional observational hospital-based study undertaken at the Emergency unit of the Alex Ekwueme Federal University Teaching Hospital Abakaliki, Nigeria from October 2021 to April 2022 (7-month period). Result: Amongst the 210 acute stroke patients enrolled in the study, 51 (24%) had renal dysfunction with no age and sex predilection. Haemorrhagic stroke, alteration in consciousness, and anaemia were significantly associated with renal dysfunction. Conclusion: The prevalence of renal dysfunction following acute stroke is high and there is a need for assessment of renal functions in every acute stroke patient and institute prompt multi-disciplinary treatment.

Mucosal-associated invariant T cells contribute to suppression of inflammatory myeloid cells in immune-mediated kidney disease.

Mucosal-associated invariant T (MAIT) cells have been implicated in various inflammatory diseases of barrier organs, but so far, their role in kidney disease is unclear. Here we report that MAIT cells that recognize their prototypical ligand, the vitamin B2 intermediate 5-OP-RU presented by MR1, reside in human and mouse kidneys. Single cell RNAseq analysis reveals several intrarenal MAIT subsets, and one, carrying the genetic fingerprint of tissue-resident MAIT17 cells, is activated and expanded in a murine model of crescentic glomerulonephritis (cGN). An equivalent subset is also present in kidney biopsies of patients with anti-neutrophil cytoplasmatic antibody (ANCA)-associated cGN. MAIT cell-deficient MR1 mice show aggravated disease, whereas B6-MAITCAST mice, harboring higher MAIT cell numbers, are protected from cGN. The expanded MAIT17 cells express anti-inflammatory mediators known to suppress cGN, such as CTLA-4, PD-1, and TGF-ß. Interactome analysis predicts CXCR6 - CXCL16-mediated cross-talk with renal mononuclear phagocytes, known to drive cGN progression. In line, we find that cGN is aggravated upon CXCL16 blockade. Finally, we present an optimized 5-OP-RU synthesis method which we apply to attenuating cGN in mice. In summary, we propose that CXCR6+ MAIT cells might play a protective role in cGN, implicating them as a potential target for anti-inflammatory therapies.

Autoantibodies from patients with kidney allograft vasculopathy stimulate a proinflammatory switch in endothelial cells and monocytes mediated via GPCR-directed PAR1-TNF-α signaling.

Non-HLA-directed regulatory autoantibodies (RABs) are known to target G-protein coupled receptors (GPCRs) and thereby contribute to kidney transplant vasculopathy and failure. However, the detailed underlying signaling mechanisms in human microvascular endothelial cells (HMECs) and immune cells need to be clarified in more detail. In this study, we compared the immune stimulatory effects and concomitant intracellular and extracellular signaling mechanisms of immunoglobulin G (IgG)-fractions from kidney transplant patients with allograft vasculopathy (KTx-IgG), to that from patients without vasculopathy, or matched healthy controls (Con-IgG). We found that KTx-IgG from patients with vasculopathy, but not KTx-IgG from patients without vasculopathy or Con-IgG, elicits HMEC activation and subsequent upregulation and secretion of tumor necrosis factor alpha (TNF-α) from HMECs, which was amplified in the presence of the protease-activated thrombin receptor 1 (PAR1) activator thrombin, but could be omitted by selectively blocking the PAR1 receptor. The amount and activity of the TNF-α secreted by HMECs stimulated with KTx-IgG from patients with vasculopathy was sufficient to induce subsequent THP-1 monocytic cell activation. Furthermore, AP-1/c-FOS, was identified as crucial transcription factor complex controlling the KTx-IgG-induced endothelial TNF-α synthesis, and mircoRNA-let-7f-5p as a regulatory element in modulating the underlying signaling cascade. In conclusion, exposure of HMECs to KTx-IgG from patients with allograft vasculopathy, but not KTx-IgG from patients without vasculopathy or healthy Con-IgG, triggers signaling through the PAR1-AP-1/c-FOS-miRNA-let7-axis, to control TNF-α gene transcription and TNF-α-induced monocyte activation. These observations offer a greater mechanistic understanding of endothelial cells and subsequent immune cell activation in the clinical setting of transplant vasculopathy that can eventually lead to transplant failure, irrespective of alloantigen-directed responses.

A pictorial review of genitourinary infections and inflammations.

Various infectious and inflammatory diseases affect the genitourinary system. This paper provides a review of multiple common and uncommon infectious and inflammatory conditions affecting the genitourinary system and some associated complications. These include acute infectious cystitis, emphysematous cystitis, acute pyelonephritis, emphysematous pyelonephritis, renal and perinephric abscesses, pyonephrosis, xanthogranulomatous pyelonephritis, epididymo-orchitis, vasitis, prostatitis, pelvic inflammatory disease, renal hydatid infection, renal tuberculosis, actinomycosis, Erdheim-Chester Disease, IgG4-Related Kidney Disease, urethritis and urethral strictures, ureteritis cystica, and genitourinary fistulas. Radiologists should be aware of these diseases' complications and management. Uncommon conditions must be considered when evaluating the genitourinary system.

Novel mutation in RPGRIP1L gene causing Joubert syndrome: A case report.

INTRODUCTION: Joubert syndrome is a rare disease of genetic origin with autosomal recessive inheritance and extreme genetic heterogeneity with more than 40 causative genes. Joubert syndrome 7 is caused by mutations in the RPGRIP1L gene. PATIENT CONCERNS: Our report describes a pediatric patient with clinical features compatible with JS type 7 such as hypotonia, developmental delay and aplasia of the cerebellar vermis. DIAGNOSIS: The clinical features and the MRI of the head and neck which showed alterations at the level of the posterior fossa, with absence of the vermis and horizontal disposition of the cerebellar peduncles, were compatible with Joubert syndrome. Whole exome sequencing detected the variants RPGRIP1L (NM_015272.2) c.697A > T (p. Lys233Ter) and RPGRIP1L (NM_015272.2) c.3545 del (p.Pro1182LeufsTer25). INTERVENTIONS: Resection was performed to correct the polydactyly. At age 2 years umbilical hernia, adenoid surgery and ventilatory tubes surgery were performed. Renal biopsy confirmed interstitial fibrosis and focally accentuated mild tubular atrophy with focal tubular hypertrophy, compatible with the clinical suspicion of Joubert syndrome. Congenital hip dislocation surgery was performed. The patient underwent surgery for correction of concomitant divergent strabismus and continued with glasses for astigmatism and hyperopia. OUTCOMES: Sanger sequencing confirmed the patient´s results and the father was found to be a carrier of RPGRIP1L (NM_015272.2) c.697A > T (p. Lys233Ter) and the mother and maternal grandmother as carriers of RPGRIP1L (NM_015272.2) c.3545del (p.Pro1182LeufsTer25). RPGRIP1L:c.3545del novel variant is a deletion which changes the reading frame, altering the RPGR1_C terminal domain and giving rise to an incomplete protein whose functions will be altered. CONCLUSION: This is the first genetically confirmed case of JS in Colombia, the first carrier of biallelic RPGRIP1L gene mutations with hip dislocation and incomplete glottic closure and the first report of the novel c.3545del likely pathogenic variant causing JS.