RESUMEN

The utility of Rituximab (RTX) for IgA vasculitis nephritis (IgAVN) is not well established. Up to now, we analysed the largest samples of IgAVN patients treated by RTX with a total of 41 retrieved subjects up to December 29, 2023 in the present systematic review. We assessed the clinical profiles, efficacy, and safety of RTX treatments. The present review showed that the renal function tended to be stabilized (P = 1.000) and urinalysis tended to normalize after RTX treatment with no serious adverse events reported. Moreover, 40% (16/40) of patients was freed use of glucocorticoid after RTX administration (P < 0.001). The remission rate was 92.7% (38/41) and complete remission rate was 46.3% (19/41) in IgAVN patients. Interestingly, 76.9% (10/13) of IgAVN child patients achieved complete remission when compared with 32.1% (9/28) of adult patients (P = 0.017). In summary, our results support the benefit of RTX therapy in IgAVN patients, especially children subjects.

Asunto(s)

Rituximab , Humanos , Rituximab/uso terapéutico , Resultado del Tratamiento , Masculino , Adulto , Femenino , Factores Inmunológicos/uso terapéutico , Niño , Glomerulonefritis por IGA/tratamiento farmacológico , Inducción de Remisión , Vasculitis por IgA/tratamiento farmacológico , Nefritis/tratamiento farmacológico , Persona de Mediana Edad , Vasculitis/tratamiento farmacológico

RESUMEN

ABSTRACT: Quercetin is known for its antihypertensive effects. However, its role on hypertensive renal injury has not been fully elucidated. In this study, hematoxylin and eosin staining, terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining, and Annexin V staining were used to assess the pathological changes and cell apoptosis in the renal tissues of angiotensin II (Ang II)-infused mice and Ang II-stimulated renal tubular epithelial cell line (NRK-52E). A variety of technologies, including network pharmacology, RNA-sequencing, immunohistochemistry, and Western blotting, were performed to investigate its underlying mechanisms. Network pharmacology analysis identified multiple potential candidate targets (including TP53, Bcl-2, and Bax) and enriched signaling pathways (including apoptosis and p53 signaling pathway). Quercetin treatment significantly alleviated the pathological changes in renal tissues of Ang II-infused mice and reversed 464 differentially expressed transcripts, as well as enriched several signaling pathways, including those related apoptosis and p53 pathway. Furthermore, quercetin treatment significantly inhibited the cell apoptosis in renal tissues of Ang II-infused mice and Ang II-stimulated NRK-52E cells. In addition, quercetin treatment inhibited the upregulation of p53, Bax, cleaved-caspase-9, and cleaved-caspase-3 protein expression and the downregulation of Bcl-2 protein expression in both renal tissue of Ang II-infused mice and Ang II-stimulated NRK-52E cells. Moreover, the molecular docking results indicated a potential binding interaction between quercetin and TP53. Quercetin treatment significantly attenuated hypertensive renal injury and cell apoptosis in renal tissues of Ang II-infused mice and Ang II-stimulated NRK-52E cells and by targeting p53 may be one of the potential underlying mechanisms.

Asunto(s)

Angiotensina II , Antihipertensivos , Apoptosis , Modelos Animales de Enfermedad , Ratones Endogámicos C57BL , Farmacología en Red , Quercetina , Transducción de Señal , Proteína p53 Supresora de Tumor , Quercetina/farmacología , Animales , Apoptosis/efectos de los fármacos , Línea Celular , Masculino , Transducción de Señal/efectos de los fármacos , Antihipertensivos/farmacología , Ratas , Proteína p53 Supresora de Tumor/metabolismo , Proteína p53 Supresora de Tumor/genética , Redes Reguladoras de Genes/efectos de los fármacos , Proteínas Reguladoras de la Apoptosis/metabolismo , Proteínas Reguladoras de la Apoptosis/genética , Riñón/patología , Riñón/efectos de los fármacos , Riñón/metabolismo , RNA-Seq , Regulación de la Expresión Génica/efectos de los fármacos , Ratones , Presión Sanguínea/efectos de los fármacos , Hipertensión Renal/metabolismo , Hipertensión Renal/tratamiento farmacológico , Hipertensión Renal/patología , Nefritis

RESUMEN

PURPOSE: To define the clinical and histological characteristics of nephritis in patients with X-linked agammaglobulinemia (XLA) and their immunological profiles. METHODS: The clinical, immunological, and histological findings of nine patients with XLA and nephritis were retrospectively analyzed. RESULTS: Based on kidney histological findings, patients with XLA and nephritis could be divided into two groups, viz., chronic glomerulonephritis (CGN) and tubulointerstitial nephritis (TIN). The two groups showed different immunological profiles. Patients in the CGN group exhibited an atypical immunological profile of XLA, with pathogenic leaky B cells producing immunoglobulins that may play a role in forming immune complexes and causing immune-mediated glomerulonephritis. In contrast, patients in the TIN group exhibited a typical immunological profile of XLA, suggesting that antibody-independent/other BTK-dependent mechanisms, or immunoglobulin replacement therapy (IgRT)-related immune/nonimmune-mediated nephrotoxicity causes TIN. CONCLUSION: Nephritis occurring in patients with XLA could have links between their renal pathology and immunological status. Careful observation is recommended to detect kidney pathology in patients with XLA on IgRT.

Asunto(s)

Agammaglobulinemia , Enfermedades Genéticas Ligadas al Cromosoma X , Fenotipo , Humanos , Agammaglobulinemia/inmunología , Agammaglobulinemia/diagnóstico , Agammaglobulinemia/genética , Enfermedades Genéticas Ligadas al Cromosoma X/inmunología , Enfermedades Genéticas Ligadas al Cromosoma X/genética , Enfermedades Genéticas Ligadas al Cromosoma X/diagnóstico , Enfermedades Genéticas Ligadas al Cromosoma X/complicaciones , Masculino , Adolescente , Niño , Adulto , Estudios Retrospectivos , Preescolar , Adulto Joven , Agammaglobulinemia Tirosina Quinasa/genética , Nefritis Intersticial/inmunología , Nefritis Intersticial/diagnóstico , Riñón/patología , Riñón/inmunología , Linfocitos B/inmunología , Femenino , Glomerulonefritis/inmunología , Glomerulonefritis/diagnóstico , Nefritis/inmunología , Nefritis/diagnóstico , Nefritis/etiología

RESUMEN

INTRODUCTION: Vitexin is a natural flavonoid compound extracted from Vitex leaves or seeds, exhibiting various pharmacological activities including anticancer, antihypertensive, anti-inflammatory, and spasmolytic effects. However, its protective effects on hypertensive nephropathy (HN) and the underlying mechanisms remain unclear. METHODS: Spontaneous hypertension rats were fed a high-sugar and high-fat diet for 8 weeks to induce the disease HN model. From the 5th week, the rats were administered vitexin via gavage. Blood pressure was measured biweekly using the tail-cuff method. Histopathological changes were assessed using HE staining, and biochemical analyses were performed to evaluate the effects of vitexin on HN rats. The underlying mechanisms of vitexin treatment were investigated through western blotting. RESULTS: The data demonstrated that vitexin significantly lowered systolic, diastolic, and mean arterial pressures and ameliorated histopathological changes in HN rats. Biochemical analyses revealed that vitexin reduced the levels of creatinine (Cr), blood urea nitrogen (BUN), total cholesterol (TC), triglycerides (TG), total protein (TP), low-density lipoprotein cholesterol (LDL-C), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), malondialdehyde (MDA), and advanced glycation end products (AGEs), while increasing the levels of albumin (ALB) and superoxide dismutase (SOD). Western blotting results indicated that vitexin treatment decreased the expression of TNF-α, IL-6, and nuclear factor kappa-B (NF-κB), while increasing the expression of SOD. CONCLUSION: The findings of this study suggest that vitexin exerts protective effects against HN, providing pharmacological evidence for its potential use in HN treatment.

Asunto(s)

Apigenina , Hipertensión Renal , Animales , Apigenina/farmacología , Apigenina/uso terapéutico , Ratas , Hipertensión Renal/tratamiento farmacológico , Hipertensión Renal/patología , Masculino , Ratas Endogámicas SHR , Nefritis/tratamiento farmacológico , Nefritis/prevención & control , Nefritis/patología , Presión Sanguínea/efectos de los fármacos , FN-kappa B/metabolismo

RESUMEN

BACKGROUND: Hypertensive nephropathy (HN) is one of the main causes of end-stage renal disease (ESRD), leading to serious morbidity and mortality in hypertensive patients. However, existing treatment for hypertensive nephropathy are still very limited. It has been demonstrated that aerobic exercise has beneficial effects on the treatment of hypertension. However, the underlying mechanisms of exercise in HN remain unclear. METHODS: The spontaneously hypertensive rats (SHR) were trained for 8 weeks on a treadmill with different exercise prescriptions. We detected the effects of moderate intensity continuous training (MICT) and high intensity interval training (HIIT) on inflammatory response, renal function, and renal fibrosis in SHR. We further investigated the relationship between TLR4 and the NLRC4 inflammasome in vitro HN model. RESULTS: MICT improved renal fibrosis and renal injury, attenuating the inflammatory response by inhibiting TLR4/NF-κB pathway and the activation of NLRC4 inflammasome. However, these changes were not observed in the HIIT group. Additionally, repression of TLR4/NF-κB pathway by TAK-242 inhibited activation of NLRC4 inflammasome and alleviated the fibrosis in Ang II-induced HK-2 cells. CONCLUSION: MICT ameliorated renal damage, inflammatory response, and renal fibrosis via repressing TLR4/NF-κB pathway and the activation of NLRC4 inflammasome. This study might provide new references for exercise prescriptions of hypertension.

Asunto(s)

Proteínas de Unión al Calcio , Inflamasomas , FN-kappa B , Nefritis , Ratas Endogámicas SHR , Transducción de Señal , Receptor Toll-Like 4 , Animales , Receptor Toll-Like 4/metabolismo , FN-kappa B/metabolismo , Inflamasomas/metabolismo , Ratas , Proteínas de Unión al Calcio/metabolismo , Masculino , Nefritis/metabolismo , Nefritis/patología , Hipertensión Renal/metabolismo , Hipertensión Renal/patología , Fibrosis , Regulación hacia Abajo , Humanos , Terapia por Ejercicio/métodos , Riñón/patología , Riñón/metabolismo

RESUMEN

Immune-mediated nephritis is a leading cause of acute kidney injury and chronic kidney disease. While the role of B cells and antibodies has been extensively investigated in the past, the advent of immune-checkpoint inhibitors has led to a reappraisal of the role of T cells in renal immunology. However, it remains elusive how T cells with specificity for renal autoantigens are activated and participate in immune-mediated nephritis. Here, we followed the fate and function of pathogen-activated autoreactive CD8 T cells that are specific for a renal autoantigen. We demonstrate that recently activated splenic CD8 T cells developed a hybrid phenotype in the context of renal autoantigen cross-presentation, combining hallmarks of activation and T cell dysfunction. While circulating memory T cells rapidly disappeared, tissue-resident memory T cells emerged and persisted within the kidney, orchestrating immune-mediated nephritis. Notably, T cells infiltrating kidneys of patients with interstitial nephritis also expressed key markers of tissue residency. This study unveils how a tissue-specific immune response can dissociate from its systemic counterpart driving a compartmentalized immune response in the kidneys of mice and man. Consequently, targeting tissue-resident memory T cells emerges as a promising strategy to control immune-mediated kidney disease.

Asunto(s)

Autoantígenos , Linfocitos T CD8-positivos , Riñón , Células T de Memoria , Ratones Endogámicos C57BL , Animales , Autoantígenos/inmunología , Células T de Memoria/inmunología , Humanos , Ratones , Linfocitos T CD8-positivos/inmunología , Riñón/inmunología , Riñón/patología , Memoria Inmunológica , Nefritis/inmunología , Tolerancia Inmunológica , Masculino , Activación de Linfocitos/inmunología , Femenino

RESUMEN

OBJECTIVE: The objective of this meta-analysis was to compare the efficacy and safety between glucocorticoids combined with mycophenolate mofetil (MMF) versus glucocorticoids combined with cyclophosphamide (CTX) for henoch schonlein purpura nephritis (HSPN) in children. METHODS: Databases including PubMed, EMbase, the Cochrane Library, China National Knowledge Infrastructure, and Wanfang database were searched from the inception to April 5th, 2024. Eligible studies comparing glucocorticoids combined with MMF versus glucocorticoids combined with CTX for HSPN in children were included. Data were analyzed using Review Manager Version 5.3. RESULTS: Ten studies were included in the meta-analysis. Six randomized controlled trials (RCTs) and 4 non-randomized studies involving 675 patients were identified. Compared with CTX therapeutic schedule, MMF therapeutic schedule had a higher complete remission (CR) within the 6 months (OR 1.61, 95%CI 1.16-2.22, P = .004) and CR within the 12 months (OR 1.73, 95%CI 1.00-2.97, P = .05). However, there was no significant difference between MMF and CTX therapeutic schedule concerning total remission (TR) within the 6 months (OR 1.54, 95%CI 0.82-2.92, P = .18) and TR within the 12 months (OR 2.08, 95%CI 0.86-5.01, P = .10). In addition, incidences of gastrointestinal discomfort (OR 0.33, 95%CI 0.19-0.56, P < .0001), liver function injury (OR 0.28, 95%CI 0.09-0.87, P = .03), myelosuppression (OR 0.15, 95%CI 0.06-0.41, P = .0001), alopecia (OR 0.25, 95%CI 0.07-0.91, P = .03) in MMF therapeutic schedule were all lower than CTX therapeutic schedule. There was no statistically significant difference between the 2 therapeutic schedules concerning infection (OR 0.90, 95%CI 0.50-1.61, P = .72), rash (OR 0.38, 95%CI 0.07-2.04, P = .26). CONCLUSION: Glucocorticoids combined with MMF had a higher CR and lower incidence of adverse effects compared with glucocorticoids combined with CTX in the treatment of HSPN in children.

Asunto(s)

Ciclofosfamida , Quimioterapia Combinada , Vasculitis por IgA , Inmunosupresores , Ácido Micofenólico , Nefritis , Humanos , Vasculitis por IgA/tratamiento farmacológico , Vasculitis por IgA/complicaciones , Ciclofosfamida/uso terapéutico , Ciclofosfamida/efectos adversos , Ácido Micofenólico/uso terapéutico , Ácido Micofenólico/efectos adversos , Niño , Inmunosupresores/uso terapéutico , Inmunosupresores/efectos adversos , Inmunosupresores/administración & dosificación , Nefritis/tratamiento farmacológico , Glucocorticoides/uso terapéutico , Glucocorticoides/administración & dosificación , Glucocorticoides/efectos adversos , Resultado del Tratamiento , Ensayos Clínicos Controlados Aleatorios como Asunto , Preescolar

RESUMEN

In 67Ga-citrate scintigraphy (Ga-S), visual assessment is used by evaluating renal-uptake comparison with liver and spine and is simple and objective. We adopted the standardized uptake value (SUV) for 67Ga-citrate and proposed two quantitative indices, active nephritis volume (ANV) and total nephritis uptake (TNU). This study clarified the utility of new Ga-S-based quantitative indices in nephritis management. Before SUV measurement, the Becquerel calibration factor of 67Ga-citrate was obtained using a phantom experiment. Seventy patients who underwent SPECT/CT imaging were studied. SUV, ANV, and TNU were calculated using a quantitative analysis software for bone SPECT. SUVmean, ANV, and TNU were analyzed using the (1) threshold method (set 40%) and constant-value method for (2) vertebral SUVmax, and (3) vertebral SUVmean. ROC analysis was used to evaluate SUV, ANV, and TNU diagnostic abilities to distinguish nephritis presence and absence as well as interstitial nephritis (IN) and non-IN. The area under the curve (AUC) for nephritis presence or absence had a good value (0.80) for SUVmean (1), ANV (3), and TNU (3). The AUC for differentiation between IN and non-IN groups had a good value (0.80) for SUVmean (1). Thus, the new Ga-S-based quantitative indices were useful to evaluate nephritis and distinguish IN and non-IN.

Asunto(s)

Radioisótopos de Galio , Galio , Humanos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Adulto , Nefritis/diagnóstico por imagen , Citratos , Curva ROC , Anciano de 80 o más Años , Radiofármacos , Tomografía Computarizada por Tomografía Computarizada de Emisión de Fotón Único/métodos

RESUMEN

Hypertension affects a large number of individuals globally and is a common cause of nephropathy, stroke, ischaemic heart disease and other vascular diseases. While many anti-hypertensive medications are used safely and effectively in clinic practice, controlling hypertensive complications solely by reducing blood pressure (BP) can be challenging. α-Mangostin, a xanthone molecule extracted from the pericarp of Garcinia mangostana L., has shown various beneficial effects such as anti-tumor, anti-hyperuricemia, and anti-inflammatory properties. However, the effects of α-Mangostin on hypertension remain unknown. In this study, we observed that α-Mangostin significantly decreased systolic and diastolic blood pressure in spontaneously hypertensive rats (SHR), possibly through the down-regulation of angiotensin II (Ang II). We also identified early markers of hypertensive nephropathy, including urinary N-acetyl-ß-D-glucosaminidase (NAG) and ß2-microglobulin (ß2-MG), which were reduced by α-Mangostin treatment. Mechanistic studies suggested that α-Mangostin may inhibit renal tubular epithelial-to-mesenchymal transformation (EMT) by down-regulating the TGF-ß signaling pathway, thus potentially offering a new therapeutic approach for hypertension and hypertensive nephropathy.

Asunto(s)

Angiotensina II , Presión Sanguínea , Transición Epitelial-Mesenquimal , Hipertensión , Xantonas , Animales , Humanos , Masculino , Ratas , Angiotensina II/metabolismo , Antihipertensivos/farmacología , Antihipertensivos/uso terapéutico , Presión Sanguínea/efectos de los fármacos , Línea Celular , Transición Epitelial-Mesenquimal/efectos de los fármacos , Fibrosis/tratamiento farmacológico , Garcinia mangostana/química , Hipertensión/tratamiento farmacológico , Hipertensión/patología , Hipertensión Renal/tratamiento farmacológico , Hipertensión Renal/patología , Nefritis , Ratas Endogámicas SHR , Transducción de Señal/efectos de los fármacos , Xantonas/farmacología , Xantonas/uso terapéutico

RESUMEN

A man in his early 30s presented with sudden-onset respiratory distress, haemoptysis and reduced urine output. He was in volume overload with a blood pressure recording of 240/180 mm Hg. Pulmonary renal syndrome was suspected and he was initiated on plasmapheresis, followed by steroid pulse therapy. Chest radiography and the presence of fragmented red cells on the peripheral smear were unexplained. These were later explained by hypertensive nephropathy and thrombotic microangiopathy changes on renal biopsy. His respiratory and haematological parameters improved with blood pressure control. Malignant hypertension closely resembles pulmonary renal syndrome, which must be remembered in order to avoid plasmapheresis and high-dose immunosuppressive therapy.

Asunto(s)

Hipertensión Maligna , Humanos , Masculino , Hipertensión Maligna/complicaciones , Hipertensión Maligna/diagnóstico , Adulto , Nefritis/complicaciones , Nefritis/etiología , Diagnóstico Diferencial , Hemoptisis/etiología , Hemoptisis/diagnóstico , Hemoptisis/terapia , Hipertensión Renal

RESUMEN

BACKROUND: Complement activation may facilitate hypertension through its effects on immune responses. The anaphylatoxin C5a, a major inflammatory effector, binds to the C5a receptors 1 and 2 (C5aR1, C5aR2). We have recently shown that C5aR1-/- mice have reduced hypertensive renal injury. The role of C5aR2 in hypertension is unknown. METHODS: For examination of C5aR2 expression on infiltrating and resident renal cells a tandem dye Tomato-C5aR2 knock-in reporter mouse was used. Human C5aR2 expression was analyzed in a single-cell RNAseq data set from the kidneys of hypertensive patients. Finally, we examined the effect of angiotensin II-induced hypertension in C5aR2-deficient mice. RESULTS: Flow cytometric analysis of leukocytes isolated from kidneys of the reporter mice showed that dendritic cells are the major C5aR2-expressing population (34%) followed by monocyte/macrophages (30%) and neutrophils (14%). Using confocal microscopy C5aR2 was not detected in resident renal or cardiac cells. In the human kidney, C5aR2 was also mainly found in monocytes, macrophages, and dendritic cells with a significantly higher expression in hypertension (P < 0.05). Unilateral nephrectomy was performed followed by infusion of Ang II (0.75 ng/g/min) and a high salt diet in wildtype (n = 18) and C5aR2-deficient mice (n = 14). Blood pressure, renal injury (albuminuria, glomerular filtration rate, glomerular and tubulointerstitial injury, inflammation), and cardiac injury (cardiac fibrosis, heart weight, gene expression) did not differ between hypertensive wildtype and C5aR2-/- mice. CONCLUSIONS: In summary, C5aR2 is mainly expressed in myeloid cells in the kidney in mice and humans but its deficiency has no effect on Ang II-induced hypertensive injury.

Asunto(s)

Angiotensina II , Hipertensión , Riñón , Receptor de Anafilatoxina C5a , Animales , Receptor de Anafilatoxina C5a/metabolismo , Receptor de Anafilatoxina C5a/genética , Hipertensión/metabolismo , Hipertensión/fisiopatología , Humanos , Riñón/patología , Riñón/metabolismo , Riñón/inmunología , Masculino , Ratones Noqueados , Modelos Animales de Enfermedad , Ratones Endogámicos C57BL , Ratones , Presión Sanguínea , Enfermedades Renales/metabolismo , Enfermedades Renales/patología , Enfermedades Renales/inducido químicamente , Hipertensión Renal , Nefritis

RESUMEN

BACKGROUND: Autologous mesenchymal stem cells (MSCs) have emerged as a therapeutic option for many diseases. Hypertensive kidney disease (HKD) might impair MSCs' reparative ability by altering the biomolecular properties, but the characteristics of this impairment are unclear. In our previous pre-clinical studies, we found hypoxic preconditioning (HPC) enhanced angiogenesis and suppressed senescence gene expression. Thus, we hypothesize that HPC would improve human MSCs by enhancing their functionality and angiogenesis, creating an anti-inflammatory and anti-senescence environment. METHODS: MSC samples (n = 12 each) were collected from the abdominal fat of healthy kidney donors (HC), hypertensive patients (HTN), and patients with hypertensive kidney disease (HKD). MSCs were harvested and cultured in Normoxic (20% O2) or Hypoxic (1% O2) conditions. MSC functionality was measured by proliferation assays and cytokine released in conditioned media. Senescence was evaluated by senescence-associated beta-galactosidase (SA-beta-gal) activity. Additionally, transcriptome analysis using RNA-sequencing and quantitative PCR (qPCR) were performed. RESULTS: At baseline, normoxic HTN-MSCs had higher proliferation capacity compared to HC. However, HPC augmented proliferation in HC. HPC did not affect the release of pro-angiogenic protein VEGF, but increased EGF in HC-MSC, and decreased HGF in HC and HKD MSCs. Under HPC, SA-ß-gal activity tended to decrease, particularly in HC group. HPC upregulated mostly the pro-angiogenic and inflammatory genes in HC and HKD and a few senescence genes in HKD. CONCLUSIONS: HPC has a more favorable functional effect on HC- than on HKD-MSC, reflected in increased proliferation and EGF release, and modest decrease in senescence, whereas it has little effect on HTN or HKD MSCs.

Asunto(s)

Hipoxia de la Célula , Proliferación Celular , Células Madre Mesenquimatosas , Células Madre Mesenquimatosas/metabolismo , Células Madre Mesenquimatosas/citología , Humanos , Hipertensión Renal/metabolismo , Hipertensión Renal/patología , Senescencia Celular , Masculino , Femenino , Persona de Mediana Edad , Células Cultivadas , Nefritis

RESUMEN

We report a case of adenovirus nephritis (ADVN) in a kidney transplant recipient (KTR) occurring within 8 days post-transplantation. The patient, a 35-year-old male, displayed systemic symptoms, high-grade fever, and acute kidney injury (AKI) without signs of hemorrhagic cystitis (HC). Extensive diagnostic workup revealed widespread necrotizing granulomatous inflammation in the allograft, leading to the identification of adenovirus (ADV) via histopathology and polymerase chain reaction (PCR) testing. The source of ADV transmission remained uncertain, raising questions about the potential donor-derived infection. Unlike typical ADVN cases, the patient exhibited no hematuria or urinary symptoms. The case underscores the atypical presentation of ADVN in KTRs, challenging the conventional understanding of its timeline, transmission routes, and associated clinical features. We discuss the diagnostic challenges, histological findings, and management strategies for ADVN, emphasizing the importance of considering this entity in KTRs with unexplained fever and AKI, even in the absence of classical urinary symptoms or hematuria.

Asunto(s)

Cistitis , Trasplante de Riñón , Humanos , Masculino , Trasplante de Riñón/efectos adversos , Adulto , Cistitis/virología , Nefritis/virología , Infecciones por Adenoviridae , Hemorragia/etiología , Cistitis Hemorrágica

RESUMEN

Chronic kidney disease (CKD) is an emerging cause for morbidity and mortality worldwide. Acute kidney injury (AKI) can transition to CKD and finally to end-stage renal disease (ESRD). Targeted treatment is still unavailable. NF-κB signaling is associated with CKD and activated by B cell activating factor (BAFF) via BAFF-R binding. In turn, renal tubular epithelial cells (TECs) are critical for the progression of fibrosis and producing BAFF. Therefore, the direct involvement of the BAFF/BAFF-R system to the pathogenesis of CKD is conceivable. We performed non-accelerated nephrotoxic serum nephritis (NTN) as the CKD model in BAFF KO (B6.129S2-Tnfsf13btm1Msc/J), BAFF-R KO (B6(Cg)-Tnfrsf13ctm1Mass/J) and wildtype (C57BL/6J) mice to analyze the BAFF/BAFF-R system in anti-glomerular basement membrane (GBM) disease using high throughput RNA sequencing. We found that BAFF signaling is directly involved in the upregulation of collagen III as BAFF ko mice showed a reduced expression. However, these effects were not mediated via BAFF-R. We identified several upregulated genes that could explain the effects of BAFF in chronic kidney injury such as Txnip, Gpx3, Igfbp7, Ccn2, Kap, Umod and Ren1. Thus, we conclude that targeted treatment with anti-BAFF drugs such as belimumab may reduce chronic kidney damage. Furthermore, upregulated genes may be useful prognostic CKD biomarkers.

Asunto(s)

Factor Activador de Células B , Receptor del Factor Activador de Células B , Nefritis , Transcriptoma , Animales , Masculino , Ratones , Factor Activador de Células B/genética , Factor Activador de Células B/metabolismo , Receptor del Factor Activador de Células B/metabolismo , Receptor del Factor Activador de Células B/genética , Modelos Animales de Enfermedad , Perfilación de la Expresión Génica , Ratones Endogámicos C57BL , Ratones Noqueados , Nefritis/metabolismo , Nefritis/genética , Nefritis/patología , Insuficiencia Renal Crónica/metabolismo , Insuficiencia Renal Crónica/genética , Insuficiencia Renal Crónica/patología , Transducción de Señal

RESUMEN

Glycyrrhizin (GL) has immunoregulatory effects on various inflammatory diseases including hepatitis and nephritis. However, the mechanisms underlying the anti-inflammatory effect of GL on renal inflammation are not fully understood. Hepatorenal syndrome (HRS) is a functional acute renal impairment that occurs in severe liver disease, and we found that kidney injury also occurs in Con A-induced experimental hepatitis in mice. We previously found that GL can alleviate Con A-induced hepatitis by regulating the expression of IL-25 in the liver. We wanted to investigate whether GL can alleviate Con A-induced nephritis by regulating IL-25. IL-25 regulates inflammation by modulating type 2 immune responses, but the mechanism by which IL-25 affects kidney disease remains unclear. In this study, we found that the administration of GL enhanced the expression of IL-25 in renal tissues; the latter promoted the generation of type 2 macrophages (M2), which inhibited inflammation in the kidney caused by Con A challenge. IL-25 promoted the secretion of the inhibitory cytokine IL-10 by macrophages but inhibited the expression of the inflammatory cytokine IL-1ß by macrophages. Moreover, IL-25 downregulated the Con A-mediated expression of Toll-like receptor (TLR) 4 on macrophages. By comparing the roles of TLR2 and TLR4, we found that TLR4 is required for the immunoregulatory effect of IL-25 on macrophages. Our data revealed that GL has anti-inflammatory effects on Con A-induced kidney injury and that the GL/IL-25/M2 axis participates in the anti-inflammatory process. This study suggested that GL is a potential therapeutic for protecting against acute kidney injury.

Asunto(s)

Modelos Animales de Enfermedad , Ácido Glicirrínico , Síndrome Hepatorrenal , Interleucinas , Riñón , Macrófagos , Animales , Ratones , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Ácido Glicirrínico/farmacología , Ácido Glicirrínico/uso terapéutico , Síndrome Hepatorrenal/inducido químicamente , Síndrome Hepatorrenal/tratamiento farmacológico , Síndrome Hepatorrenal/metabolismo , Inflamación/metabolismo , Interleucina-10/metabolismo , Interleucina-1beta/metabolismo , Interleucinas/metabolismo , Riñón/patología , Riñón/metabolismo , Macrófagos/metabolismo , Macrófagos/efectos de los fármacos , Ratones Endogámicos C57BL , Nefritis/tratamiento farmacológico , Nefritis/metabolismo , Nefritis/etiología , Nefritis/prevención & control , Transducción de Señal/efectos de los fármacos , Receptor Toll-Like 2/metabolismo , Receptor Toll-Like 4/metabolismo , Concanavalina A , Hepatitis , Enfermedad Hepática Inducida por Sustancias y Drogas/complicaciones , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo

RESUMEN

Heart failure (HF) constitutes a major determinant of outcome in chronic kidney disease (CKD) patients. The main pattern of HF in CKD patients is preserved ejection fraction (HFpEF), and left ventricular diastolic dysfunction (LVDD) is a frequent pathophysiological mechanism and specific preclinical manifestation of HFpEF. Therefore, exploring and intervention of the factors associated with risk for LVDD is of great importance in reducing the morbidity and mortality of cardiovascular disease (CVD) complications in CKD patients. We designed this retrospective cross-sectional study to collect clinical and echocardiographic data from 339 nondialysis CKD patients without obvious symptoms of HF to analyze the proportion of asymptomatic left ventricular diastolic dysfunction (ALVDD) and its related factors associated with risk by multivariate logistic regression analysis. Among the 339 nondialysis CKD patients, 92.04% had ALVDD. With the progression of CKD stage, the proportion of ALVDD gradually increased. The multivariate logistic regression analysis revealed that increased age (OR 1.237; 95% confidence interval (CI) 1.108-1.381, per year), diabetic nephropathy (DN) and hypertensive nephropathy (HTN) (OR 25.000; 95% CI 1.355-48.645, DN and HTN vs chronic interstitial nephritis), progression of CKD stage (OR 2.785; 95% CI 1.228-6.315, per stage), increased mean arterial pressure (OR 1.154; 95% CI 1.051-1.268, per mmHg), increased urinary protein (OR 2.825; 95% CI 1.484-5.405, per g/24 h), and low blood calcium (OR 0.072; 95% CI 0.006-0.859, per mmol/L) were factors associated with risk for ALVDD in nondialysis CKD patients after adjusting for other confounding factors. Therefore, dynamic monitoring of these factors associated with risk, timely diagnosis and treatment of ALVDD can delay the progression to symptomatic HF, which is of great importance for reducing CVD mortality, and improving the prognosis and quality of life in CKD patients.

Asunto(s)

Insuficiencia Renal Crónica , Disfunción Ventricular Izquierda , Humanos , Femenino , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Estudios Transversales , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/fisiopatología , Disfunción Ventricular Izquierda/etiología , Disfunción Ventricular Izquierda/fisiopatología , Anciano , Medición de Riesgo , Progresión de la Enfermedad , Factores de Riesgo , Ecocardiografía , Hipertensión/complicaciones , Modelos Logísticos , Nefropatías Diabéticas/complicaciones , Nefropatías Diabéticas/fisiopatología , Diástole , Volumen Sistólico , Enfermedades Asintomáticas , Hipertensión Renal , Nefritis

RESUMEN

BACKGROUND: The appropriate duration of antimicrobial therapy for febrile urinary tract infection (fUTI) in children has not been established. This study examined the optimal duration of treatment for fUTI in children. METHODS: We created a protocol that used fever duration to determine the duration of antibiotic administration. Transvenous antibiotics were administered until 3 days after resolution of fever, followed by oral antibiotics for 1 week. Diagnosis of fUTI was based on a fever of 37.5°C or higher and a quantitative culture of catheterized urine yielded a bacteria count of ≥5 × 104. Acute focal bacterial nephritis (AFBN) and pyelonephritis (PN) were diagnosed on the basis of contrast-enhanced computed tomography (eCT) findings. We retrospectively reviewed treatment outcomes. RESULTS: Of the 78 patients treated according to our protocol, data from 58 were analyzed-49 children (30 boys) had PN and nine (three boys) had AFBN. Blood test results showed that patients with AFBN had significantly higher white blood cell counts and C-reactive protein levels than did those with PN; however, urinary findings and causative bacteria did not differ between groups. Time to resolution of fever and duration of intravenous antibiotic administration were significantly longer in patients with AFBN than in those with PN. However, average duration of AFBN treatment was 14.2 days, which was shorter than the previously reported administration period of 3 weeks. No recurrence was observed in AFBN patients. CONCLUSIONS: A protocol that used fever duration to determine the duration of antimicrobial treatment was useful. Invasive examinations, such as eCT, were not required.

Asunto(s)

Antibacterianos , Fiebre , Pielonefritis , Infecciones Urinarias , Humanos , Infecciones Urinarias/microbiología , Infecciones Urinarias/terapia , Infecciones Urinarias/tratamiento farmacológico , Infecciones Urinarias/diagnóstico , Masculino , Femenino , Fiebre/etiología , Fiebre/terapia , Antibacterianos/administración & dosificación , Antibacterianos/uso terapéutico , Estudios Retrospectivos , Preescolar , Factores de Tiempo , Pielonefritis/terapia , Pielonefritis/microbiología , Pielonefritis/tratamiento farmacológico , Lactante , Niño , Resultado del Tratamiento , Tomografía Computarizada por Rayos X , Proteína C-Reactiva/análisis , Nefritis/microbiología , Nefritis/terapia , Administración Oral , Enfermedad Aguda , Duración de la Terapia , Recuento de Leucocitos , Administración Intravenosa , Protocolos Clínicos

RESUMEN

Background: Renal impairments commonly occur as a complication of autoimmune connective tissue diseases (CTDs). Therefore, early nephritis prediction is vital for patient outcomes. Growth Arrest-Specific Protein 6 (GAS6) was found to be upregulated in many types of inflammatory renal disease, including diabetic nephropathy.Aim: To evaluate GAS6 as a predictor of renal impairment in adults with systemic sclerosis (SSc) and children with systemic lupus Erythematosus (SLE).Methods: The study included 60 patients with SSc and 40 children with SLE. The serum level of GAS6 was measured using the ELISA technique. In adults with SSc, total proteins in 24-h urine concentration of >300 mg/24 h indicated renal inflammation, while in children with SLE, nephritis was diagnosed by abnormal renal pathology.Results: In SSc patients, GAS6 significantly increased in patients with proteinuria. GAS6 is an independent predictor of nephritis with an odds ratio (OR) of 1.06 and a 95% confidence interval (CI) of 1.0-1.1. at cutoff 12.2 ng/mL GAS6 predicted proteinuria with sensitivity 86.7% (95% CI: 59.5% to 98.3%), specificity 57.8% (95% CI: 42.1% to 72.3%), positive predictive value 40.6% (95% CI: 31.5% to 50.4%), negative predictive value 92.9% (95% CI: 77.7% to 97.73%), and accuracy 65.0% (95% CI: 51.6% to 76.9%). In SLE patients, Serum GAS6 did not differ significantly between children with and without lupus nephritis.Conclusion: GAS6 is an independent predictor of nephritis in patients with SSc. However, there is no association between GAS6 and nephritis in juvenile patients with SLE.

Asunto(s)

Biomarcadores , Péptidos y Proteínas de Señalización Intercelular , Lupus Eritematoso Sistémico , Nefritis Lúpica , Esclerodermia Sistémica , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , Biomarcadores/sangre , Ensayo de Inmunoadsorción Enzimática , Péptidos y Proteínas de Señalización Intercelular/sangre , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/sangre , Nefritis Lúpica/sangre , Nefritis Lúpica/orina , Nefritis Lúpica/diagnóstico , Nefritis/etiología , Nefritis/sangre , Nefritis/orina , Nefritis/diagnóstico , Valor Predictivo de las Pruebas , Proteinuria/etiología , Esclerodermia Sistémica/complicaciones , Esclerodermia Sistémica/sangre , Anciano

Asunto(s)

Antibacterianos , Nefritis , Humanos , Niño , Enfermedad Aguda , Antibacterianos/uso terapéutico , Nefritis/diagnóstico , Nefritis/tratamiento farmacológico , Infecciones Bacterianas/diagnóstico , Infecciones Bacterianas/tratamiento farmacológico , Imagen por Resonancia Magnética , Ultrasonografía , Riñón/patología , Riñón/diagnóstico por imagen , Pielonefritis/diagnóstico , Pielonefritis/tratamiento farmacológico , Pielonefritis/terapia , Tomografía Computarizada por Rayos X , Preescolar , Interleucina-6/sangre

RESUMEN

Henoch-Schonlein purpura nephritis (HSPN) is a systemic vascular inflammatory disease. Huanglian Decoction (HLD) ameliorates renal injury in nephritis; however, the mechanism of action of HLD on HSPN has not been investigated. This study aimed to investigate the protective mechanism of HLD treatment in HSPN. The effects of HLD on HSPN biochemical indices, kidney injury and NF-κB/NLRP3 signaling pathway were analyzed by biochemical analysis, ELISA, HE and PAS staining, immunohistochemistry, immunofluorescence, and Western Blot. In addition, the effects of HLD on HSPN cells were analyzed. We found that HLD treatment significantly reduced renal tissue damage, decreased the levels of IL-17, IL-18, TNF-α, and IL-1ß, and increased the levels of TP and ALB in HSPN mice. It also inhibited the deposition of IgA, IgG, and C3 in kidney tissues and significantly decreased the expression of IκBα, p-IκBα, NLRP3, caspase-1, and IL-1ß in kidney tissues and cells. In addition, PMA treatment inhibited the above-mentioned effects of HLD. These results suggested that HLD attenuates renal injury, IgA deposition, and inflammation in HSPN mice and its mechanism of action may be related to the inhibition of the NF-κB/NLRP3 pathway.

Asunto(s)

Medicamentos Herbarios Chinos , Vasculitis por IgA , Nefritis , Animales , Ratones , Vasculitis por IgA/tratamiento farmacológico , FN-kappa B , Inhibidor NF-kappaB alfa , Proteína con Dominio Pirina 3 de la Familia NLR , Riñón , Nefritis/tratamiento farmacológico , Inmunoglobulina A , Transducción de Señal