RESUMEN

ABSTRACT: This case emphasizes the value of meticulous observation and regular follow-up of patients receiving rifampicin therapy. The prognosis for complete improvement in renal function in such cases was excellent, with prompt recognition and discontinuation of rifampicin. Teaching patients about these possible adverse effects and encouraging immediate reporting of signs and symptoms are likely to be beneficial because acute kidney injury can manifest itself very quickly after rifampicin is started. Even if renal failure can happen with any dose of rifampicin, primary physicians must have awareness about patients on intermittent or irregular therapy and those who have previously used this medication. It is challenging to determine the prevalence of adverse reactions to common antibiotics where a state- or country-wide reporting system is absent. Along with withdrawal of the causative agent patients were treated with corticosteroids (0.5-1 mg/kg/day) for an average period of 4-12 weeks showing significant recovery of renal function.

Asunto(s)

Antituberculosos , Nefritis Intersticial , Rifampin , Humanos , Nefritis Intersticial/inducido químicamente , Rifampin/efectos adversos , Rifampin/uso terapéutico , Antituberculosos/efectos adversos , Antituberculosos/uso terapéutico , Masculino , Granuloma/inducido químicamente , Granuloma/tratamiento farmacológico , Adulto , Femenino , Enfermedad Aguda

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BACKGROUND: Chronic kidney disease (CKD) is a significant clinical challenge in Sri Lanka. The present study presents histopathological diagnoses from native renal biopsies in Kandy District, 2011-2020. METHODS: Reports of 5,014 renal biopsies principally performed at Kandy Teaching Hospital over 2011-2020 were reviewed. After exclusions for post-kidney transplant biopsies (1,572) and those without evident pathology (347), 3,095 biopsies were included. The predominant histopathological entities were grouped and categorised according to diagnosis and stratified by age and sex. RESULTS: The main histopathological entities (all biopsies) were tubulointerstitial nephropathy (TIN) 25% (n = 760), glomerulonephritis (GN) 15% (467), lupus nephropathy 14% (429), focal segmental glomerular sclerosis (FSGS) 10% (297), and IgA nephropathy (IgAN) 8% (242). For adult women ≥ 15 years, the main histopathological entities were lupus nephropathy 24% (325), TIN 17% (228), and GN 16% (217). For adult men ≥ 15 years, the main histopathological entities were TIN 34% (449), GN 14% (180), and IgAN 10% (125). The proportion of TIN in the present study was higher than international studies of a similar size. CONCLUSION: This is the largest study of renal biopsies reported from Sri Lanka to date. TIN was the most common diagnosis in adults ≥ 15 years at 25%. Notable sex differences showed TIN was the most common histopathology in men (34%) but not in women (17%). No previously published similar study of this size has found TIN as the predominant diagnosis amongst renal biopsies in men. Further research is required into the possible causes of these observations in Sri Lanka. CLINICAL TRIAL NUMBER: Not applicable.

Asunto(s)

Riñón , Nefritis Intersticial , Humanos , Sri Lanka/epidemiología , Masculino , Adulto , Femenino , Biopsia , Nefritis Intersticial/patología , Nefritis Intersticial/epidemiología , Persona de Mediana Edad , Adulto Joven , Adolescente , Riñón/patología , Nefritis Lúpica/patología , Nefritis Lúpica/epidemiología , Glomerulonefritis por IGA/patología , Glomerulonefritis por IGA/epidemiología , Glomeruloesclerosis Focal y Segmentaria/patología , Glomeruloesclerosis Focal y Segmentaria/epidemiología , Niño , Glomerulonefritis/patología , Glomerulonefritis/epidemiología , Anciano , Factores Sexuales , Preescolar

RESUMEN

BACKGROUND: Acute kidney injury (AKI) has been well described as a complication of immune checkpoint inhibitor therapy. We present a series of patients, the majority with lung adenocarcinoma, who developed AKI while actively receiving immune checkpoint inhibitors. METHODS: This is a retrospectively analyzed clinical case series of six patients treated at City of Hope Comprehensive Cancer Center. Data were collected on gender, age, ethnicity, comorbidities, concomitant medications, type of malignancy, treatments, and renal function. All patients underwent renal biopsy for classification of the mechanism of AKI. Comprehensive genomic profiling (CGP) was performed on tumor tissue for all patients. RESULTS: Patterns of AKI included acute interstitial nephritis and acute tubular necrosis. Contributing factors included the use of concomitant medications known to contribute to AKI. All but two patients had full resolution of the AKI with the use of steroids. There were several mutations found on CGP that was notable including an Exon 20 insertion as well as multiple NF1 and TP53 mutations. There was high PD-L1 expression on tumor tissue noted in two out of six patients. In addition to AKI, a subset of patients had proteinuria with biopsies revealing corresponding glomerular lesions of minimal change disease and focal and segmental glomerulosclerosis. CONCLUSIONS: Our case series demonstrates that AKI from immune checkpoint inhibitors has a variable presentation that may require an individualized treatment approach. Further studies are needed to identify biomarkers that may help identify those at risk and guide the management of this condition.

Asunto(s)

Inhibidores de Puntos de Control Inmunológico , Neoplasias Pulmonares , Humanos , Masculino , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Anciano , Neoplasias Pulmonares/tratamiento farmacológico , Adenocarcinoma del Pulmón/tratamiento farmacológico , Adenocarcinoma del Pulmón/genética , Adenocarcinoma del Pulmón/patología , Lesión Renal Aguda/etiología , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/diagnóstico , Adulto , Nefritis Intersticial/diagnóstico , Nefritis Intersticial/patología , Nefritis Intersticial/inmunología

RESUMEN

Interstitial nephritis is the primary cause of mortality in IBV-infected chickens. Our previous research has demonstrated that Radix Isatidis polysaccharide (RIP) could alleviate this form of interstitial nephritis. To explore the mechanism, SPF chickens and chicken embryonic kidney cells (CEKs) were pre-treated with RIP and subsequently infected with QX-genotype IBV strain. Kidneys were sampled for transcriptomic and metabolomic analyses, and the cecum contents were collected for 16S rRNA gene sequencing. Results showed that pre-treatment with RIP led to a 50 % morbidity reduction in infected-chickens, along with decreased tissue lesion and viral load in the kidneys. Multi-omics analysis indicated three possible pathways (including antioxidant, anti-inflammatory and anti-apoptosis) which associated with RIP's efficacy against interstitial nephritis. Following further validation both in vivo and in vitro, the results showed that pre-treatment with RIP could activate the antioxidant transcription factor Nrf2, stimulate antioxidant enzyme expression, and consequently inhibit oxidative stress. Pre-treatment with RIP could also significantly reduce the expression of NLRP3 inflammasome and apoptosis-associated proteins (including Bax, Caspase-3, and Caspase-9). Additionally, RIP was also observed to promote the growth of beneficial bacteria in the intestine. Overall, pretreatment with RIP can alleviate QX-genotype IBV-induced interstitial nephritis via the Nrf2/NLRP3/Caspase-3 signaling pathway. This study lays the groundwork for the potential use of RIP in controlling avian infectious bronchitis (IB).

Asunto(s)

Caspasa 3 , Pollos , Virus de la Bronquitis Infecciosa , Factor 2 Relacionado con NF-E2 , Proteína con Dominio Pirina 3 de la Familia NLR , Nefritis Intersticial , Polisacáridos , Transducción de Señal , Animales , Virus de la Bronquitis Infecciosa/efectos de los fármacos , Virus de la Bronquitis Infecciosa/patogenicidad , Transducción de Señal/efectos de los fármacos , Polisacáridos/farmacología , Polisacáridos/química , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Nefritis Intersticial/tratamiento farmacológico , Nefritis Intersticial/virología , Caspasa 3/metabolismo , Caspasa 3/genética , Factor 2 Relacionado con NF-E2/metabolismo , Factor 2 Relacionado con NF-E2/genética , Enfermedades de las Aves de Corral/tratamiento farmacológico , Enfermedades de las Aves de Corral/virología , Infecciones por Coronavirus/tratamiento farmacológico , Infecciones por Coronavirus/virología , Infecciones por Coronavirus/veterinaria , Genotipo , Riñón/efectos de los fármacos , Riñón/patología

Asunto(s)

Antiinfecciosos Urinarios , Nefritis Intersticial , Nitrofurantoína , Humanos , Nefritis Intersticial/inducido químicamente , Nefritis Intersticial/patología , Nefritis Intersticial/diagnóstico , Nitrofurantoína/efectos adversos , Antiinfecciosos Urinarios/efectos adversos , Granuloma/inducido químicamente , Granuloma/patología , Granuloma/diagnóstico , Masculino , Cristalización , Riñón/patología , Riñón/efectos de los fármacos , Infecciones Urinarias/tratamiento farmacológico , Biopsia , Femenino , Persona de Mediana Edad

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

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

Asunto(s)

Lesión Renal Aguda , Antineoplásicos , Nefritis Intersticial , Humanos , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/epidemiología , Nefritis Intersticial/inducido químicamente , Nefritis Intersticial/epidemiología , Masculino , Femenino , Antineoplásicos/efectos adversos , Persona de Mediana Edad , Adulto , Anciano , Prevalencia , Bases de Datos Factuales , Farmacovigilancia

RESUMEN

BACKGROUND AND OBJECTIVES: In clinical practice, some patients are diagnosed with diabetic nephropathy (DN) combined with acute tubulointerstitial nephritis (ATIN) through renal biopsy. There is relatively little research on the treatment and prognosis of such patients, and no consensus exists on the use of glucocorticoid for treatment. Therefore, our study explores the progression of DN combined with ATIN and the renal outcomes after treatment with glucocorticoid. METHODS: This study retrospectively analyzed patients diagnosed with DN combined with ATIN through renal biopsy at our center from January 1, 2015, to December 31, 2021. We collected general patient information, laboratory indicators, renal pathology indicators, and the glucocorticoid usage after kidney biopsy. Follow-up data were collected from medical records. Statistical analysis methods included t-tests, non-parametric tests, and chi-square tests. Univariate and multivariate Cox regression analyses were used to evaluate the risk factors for renal endpoint events in patients. Statistical significance was defined as p-values < 0.05. RESULTS: In this study, a total of 67 patients were included. The subjects were divided into two groups based on whether they received glucocorticoid treatment: 33 patients in the steroid group and 34 in the non-steroid group. In the steroid group, 19 patients reached the renal endpoint event, which was significantly higher than in the non-steroid group (57.58% vs. 29.41%, p = 0.038). Univariate Cox regression analysis showed that serum creatinine (HR = 1.008, p < 0.001), albumin (HR = 0.919, p < 0.001), 24-h urinary protein (HR = 1.093, p = 0.002), hemoglobin (HR = 0.964, p = 0.001), triglycerides (HR = 1.12, p = 0.04), and the use of glucocorticoid (HR = 2.507, p = 0.019) were influencing factors for renal endpoint events in patients with DN combined with ATIN. Multivariate Cox regression analysis showed that albumin (HR = 0.863, p = 0.003) was an independent risk factor for renal endpoint events in patients with DN combined with ATIN. CONCLUSIONS: The use of glucocorticoid in treatment does not improve renal prognosis in patients with DN combined with ATIN. Lower levels of albumin are associated with a worse renal prognosis.

Asunto(s)

Nefropatías Diabéticas , Glucocorticoides , Nefritis Intersticial , Humanos , Estudios Retrospectivos , Masculino , Glucocorticoides/uso terapéutico , Glucocorticoides/administración & dosificación , Femenino , Nefritis Intersticial/tratamiento farmacológico , Persona de Mediana Edad , Pronóstico , Nefropatías Diabéticas/tratamiento farmacológico , Nefropatías Diabéticas/diagnóstico , Anciano , Adulto , Riñón/patología , Riñón/fisiopatología , Factores de Riesgo , Progresión de la Enfermedad , Biopsia , Modelos de Riesgos Proporcionales

RESUMEN

BACKGROUND: The advent of immune checkpoint inhibitors (ICIs) represented a significant breakthrough in cancer therapy. Recently, the combined use of atezolizumab and bevacizumab was approved as first-line treatment for unresectable hepatocellular carcinoma (HCC). Exposure to a novel and diverse spectrum of immune-related adverse events (irAEs) has increased with the growing utilization of ICIs, however, a comprehensive understanding surrounding newer agents is still lacking. The incidence of kidney toxicities is rare but rising, often underreported due to the lack of confirmatory biopsies. Here, we present a rare case of biopsy-proven acute interstitial nephritis (AIN) following atezolizumab-bevacizumab treatment of advanced unresectable HCC. CASE: An 84-year-old male with T4N0M0 hepatocellular carcinoma was admitted after cycle 5 of atezolizumab due to decreased urine output and dysuria with a serum creatine of 4.7 mg/dL compared to a baseline of 1.3 mg/dL. To confirm the diagnosis of possible intrinsic renal injury, an ultrasound-guided non-focal biopsy of the left kidney was performed, revealing AIN. Potential exacerbatory medications, such as proton-pump inhibitors, were discontinued. The patient was discharged on oral steroids with improvement in serum creatinine. Before completing the steroid taper, the patient developed pneumocystis pneumonia and eventually transitioned to hospice care. CONCLUSION: This case highlights the valuable role renal biopsy can play in accurately capturing irAEs and guiding appropriate management in the setting of ICI-induced AKI. It also exemplifies important considerations for steroid treatment of irAEs in the setting of comorbidities, such as diabetes.

Asunto(s)

Anticuerpos Monoclonales Humanizados , Bevacizumab , Carcinoma Hepatocelular , Neoplasias Hepáticas , Nefritis Intersticial , Humanos , Masculino , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/patología , Nefritis Intersticial/inducido químicamente , Nefritis Intersticial/diagnóstico , Nefritis Intersticial/patología , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/patología , Anticuerpos Monoclonales Humanizados/efectos adversos , Anticuerpos Monoclonales Humanizados/administración & dosificación , Anciano de 80 o más Años , Bevacizumab/efectos adversos , Bevacizumab/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biopsia , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Inhibidores de Puntos de Control Inmunológico/administración & dosificación

RESUMEN

Uncertainty exists regarding the association between diet and acute tubulointerstitial nephritis. Dietary factors served as exposures, including intake of alcohol, beef, non-oily fish, fresh fruit, oily fish, dried fruit, coffee, salad/raw vegetable, cereal, tea, water, salt, cooked vegetable, cheese, poultry, pork, Lamb/mutton, bread, and processed meat were extracted from the UK Biobank. Acute tubulointerstitial nephritis served as the outcome extracted from the FinnGen biobank. The 3 main methods of this analysis were weighted median, inverse-variance-weighted (IVW), and MR-Egger methods. The heterogeneity was measured employing Cochran Q test. The MR-PRESSO method was employed to identify possible outliers. The robustness of the IVW method was evaluated by employing the leave-one-out analysis. According to the IVW method, processed meat intake (OR = 0.485; P = .00152), non-oily fish intake (OR = 0.396; P = .0454), oily fish intake (OR = 0.612; P = .00161), and dried fruit intake (OR = 0.536; P = .00648) reduced the risk of acute tubulointerstitial nephritis. Other dietary factors were not shown to be causally related to acute tubulointerstitial nephritis. This study revealed that intake of processed meat, non-oily fish, oily fish, and dried fruit all decreased the risk of acute tubulointerstitial nephritis.

Asunto(s)

Dieta , Nefritis Intersticial , Humanos , Nefritis Intersticial/epidemiología , Dieta/estadística & datos numéricos , Dieta/efectos adversos , Masculino , Persona de Mediana Edad , Femenino , Factores de Riesgo , Reino Unido/epidemiología , Adulto , Anciano , Frutas

RESUMEN

BACKGROUND: Chronic kidney disease (CKD) patients are at a high risk of tuberculosis (TB), with a relative risk of developing active TB of 10%-25%. Similarly, glomerular disease increases the risk of TB due to diminished glomerular filtration rate, proteinuria, and immunosuppression use. Further, the first-line anti-TB drugs are associated with acute kidney injury (AKI) even in patients with normal kidney functions. METHODS: We retrospectively identified 10 patients hospitalized with unusual adverse effects of antituberculosis therapy (ATT) from 2013 to 2022. RESULTS: We found three cases of AKI caused by rifampicin: acute interstitial nephritis, crescentic glomerulonephritis, and heme pigment-induced acute tubular necrosis. We observed rifampicin-induced accelerated hypertension and thrombocytopenia in two patients on maintenance hemodialysis. Isoniazid caused pancreatitis and cerebellitis in two CKD patients, respectively. In a CKD patient, we detected acute gout secondary to pyrazinamide-induced reduced uric acid excretion. We also observed cases of drug rash with eosinophilia and systemic symptoms and hypercalcemia due to immune reconstitution inflammatory syndrome in patients with glomerular disease on ATT. Immediate discontinuation of the offending drug, along with specific and supportive management, led to a recovery in all cases. CONCLUSION: The adverse effects of ATT may be unusually severe and varied in kidney patients due to decreased renal elimination. Early recognition of these adverse effects and timely discontinuation of the offending drug is essential to limit morbidity and mortality.

Asunto(s)

Lesión Renal Aguda , Antituberculosos , Insuficiencia Renal Crónica , Humanos , Antituberculosos/efectos adversos , Antituberculosos/uso terapéutico , Masculino , Estudios Retrospectivos , Femenino , Persona de Mediana Edad , Lesión Renal Aguda/inducido químicamente , Anciano , Adulto , Insuficiencia Renal Crónica/complicaciones , Rifampin/efectos adversos , Rifampin/uso terapéutico , Isoniazida/efectos adversos , Isoniazida/uso terapéutico , Nefritis Intersticial/inducido químicamente , Tuberculosis/tratamiento farmacológico , Tuberculosis/complicaciones , Pirazinamida/efectos adversos , Pirazinamida/uso terapéutico , Glomerulonefritis/inducido químicamente , Síndrome Inflamatorio de Reconstitución Inmune

RESUMEN

We report a 67-year-old man who presented with poor dietary intake and fatigue. Laboratory tests showed leukopenia, antinuclear antibody (ANA) positivity, anti-dsDNA antibody (A-dsDNA) and anti-Smith antibody (anti-Sm) negativity, decreased C3 and C4, elevated serum immunoglobulin G (IgG), IgG4, and creatinine, and 1.25 g urinary protein at 24 hours. As his condition worsened, re-examination showed thrombocytopenia and A-dsDNA positivity, and renal biopsy pathology showed IgG4-related tubulointerstitial nephritis. The final diagnosis was IgG4-related disease (IgG4-RD) with systemic lupus erythematosus (SLE). His condition improved with glucocorticoid (GC) combined with hydroxychloroquine (HCQ) and mycophenolate mofetil (MMF) treatment. This case highlights that IgG4-RD and SLE may occur successively or co-exist and may convert into each other.

Asunto(s)

Enfermedad Relacionada con Inmunoglobulina G4 , Lupus Eritematoso Sistémico , Humanos , Masculino , Anciano , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/diagnóstico , Lupus Eritematoso Sistémico/inmunología , Lupus Eritematoso Sistémico/tratamiento farmacológico , Enfermedad Relacionada con Inmunoglobulina G4/diagnóstico , Enfermedad Relacionada con Inmunoglobulina G4/complicaciones , Enfermedad Relacionada con Inmunoglobulina G4/tratamiento farmacológico , Enfermedad Relacionada con Inmunoglobulina G4/inmunología , Glucocorticoides/uso terapéutico , Ácido Micofenólico/uso terapéutico , Inmunoglobulina G/sangre , Hidroxicloroquina/uso terapéutico , Inmunosupresores/uso terapéutico , Nefritis Intersticial/inmunología , Nefritis Intersticial/patología , Nefritis Intersticial/diagnóstico , Nefritis Intersticial/tratamiento farmacológico , Biopsia

Asunto(s)

Diquat , Humanos , Masculino , Diquat/envenenamiento , Herbicidas/envenenamiento , Adulto , Nefritis Intersticial/inducido químicamente , Lesión Renal Aguda/inducido químicamente , Femenino

Asunto(s)

Vacunas contra la COVID-19 , Nefritis Intersticial , Humanos , Enfermedad Aguda , COVID-19/prevención & control , COVID-19/complicaciones , Vacunas contra la COVID-19/efectos adversos , Nefritis Intersticial/inducido químicamente , Nefritis Intersticial/etiología , Vacunación/efectos adversos

RESUMEN

Background: Tubulointerstitial injury plays a pivotal role in the progression of diabetic kidney disease (DKD), yet the link between neutrophil extracellular traps (NETs) and diabetic tubulointerstitial injury is still unclear. Methods: We analyzed microarray data (GSE30122) from the Gene Expression Omnibus (GEO) database to identify differentially expressed genes (DEGs) associated with DKD's tubulointerstitial injury. Functional and pathway enrichment analyses were conducted to elucidate the involved biological processes (BP) and pathways. Weighted gene coexpression network analysis (WGCNA) identified modules associated with DKD. LASSO regression and random forest selected NET-related characteristic genes (NRGs) related to DKD tubulointerstitial injury. Results: Eight hundred ninety-eight DEGs were identified from the GSE30122 dataset. A significant module associated with diabetic tubulointerstitial injury overlapped with 15 NRGs. The hub genes, CASP1 and LYZ, were identified as potential biomarkers. Functional enrichment linked these genes with immune cell trafficking, metabolic alterations, and inflammatory responses. NRGs negatively correlated with glomerular filtration rate (GFR) in the Neph v5 database. Immunohistochemistry (IHC) validated increased NRGs in DKD tubulointerstitial injury. Conclusion: Our findings suggest that the CASP1 and LYZ genes may serve as potential diagnostic biomarkers for diabetic tubulointerstitial injury. Furthermore, NRGs involved in diabetic tubulointerstitial injury could emerge as prospective targets for the diagnosis and treatment of DKD.

Asunto(s)

Biomarcadores , Nefropatías Diabéticas , Humanos , Biomarcadores/metabolismo , Bases de Datos Genéticas , Nefropatías Diabéticas/genética , Nefropatías Diabéticas/diagnóstico , Nefropatías Diabéticas/metabolismo , Trampas Extracelulares/metabolismo , Perfilación de la Expresión Génica , Redes Reguladoras de Genes , Tasa de Filtración Glomerular , Nefritis Intersticial/genética , Nefritis Intersticial/diagnóstico

RESUMEN

INTRODUCTION: Immune checkpoint inhibitors (ICIs) induce acute interstitial nephritis (AIN) in 2-5% of patients, with a clearly higher incidence when they are combined with platinum derivatives. Unfortunately, suitable disease models and non-invasive biomarkers are lacking. To fill this gap in our understanding, we investigated the renal effects of cisplatin and anti-PD-L1 antibodies in mice, assessing PD-1 renal expression and cytokine levels in mice with AIN, and then we compared these findings with those in AIN-diagnosed cancer patients. METHODS: Twenty C57BL6J mice received 200 µg of anti-PD-L1 antibody and 5 mg/kg cisplatin intraperitoneally and were compared with those receiving cisplatin (n = 6), anti-PD-L1 (n = 7), or saline (n = 6). After 7 days, the mice were euthanized. Serum and urinary concentrations of TNFα, CXCL10, IL-6, and MCP-1 were measured by Luminex. The kidney sections were stained to determine PD-1 tissue expression. Thirty-nine cancer patients with AKI were enrolled (AIN n = 33, acute tubular necrosis (ATN) n = 6), urine MCP-1 (uMCP-1) was measured, and kidney sections were stained to assess PD-1 expression. RESULTS: Cisplatin and anti PD-L1 treatment led to 40% AIN development (p = 0.03) in mice, accompanied by elevated serum creatinine and uMCP1. AIN-diagnosed cancer patients also had higher uMCP1 levels than ATN-diagnosed patients, confirming our previous findings. Mice with AIN exhibited interstitial PD-1 staining and stronger glomerular PD-1 expression, especially with combination treatment. Conversely, human AIN patients only showed interstitial PD-1 positivity. CONCLUSIONS: Only mice receiving cisplatin and anti-PDL1 concomitantly developed AIN, accompanied with a more severe kidney injury. AIN induced by this drug combination was linked to elevated uMCP1, consistently with human AIN, suggesting that uMCP1 can be potentially used as an AIN biomarker.

Asunto(s)

Quimiocina CCL2 , Cisplatino , Inhibidores de Puntos de Control Inmunológico , Ratones Endogámicos C57BL , Nefritis Intersticial , Receptor de Muerte Celular Programada 1 , Animales , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Inhibidores de Puntos de Control Inmunológico/farmacología , Receptor de Muerte Celular Programada 1/metabolismo , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Nefritis Intersticial/orina , Nefritis Intersticial/patología , Nefritis Intersticial/inducido químicamente , Quimiocina CCL2/orina , Quimiocina CCL2/metabolismo , Cisplatino/efectos adversos , Humanos , Masculino , Femenino , Glomérulos Renales/patología , Glomérulos Renales/efectos de los fármacos , Antígeno B7-H1/metabolismo , Ratones , Persona de Mediana Edad , Anciano , Enfermedad Aguda

Asunto(s)

Humanos , Nefritis Intersticial , Dengue , Pacientes

RESUMEN

Infections can affect the kidney via different pathways. Urinary tract infections can directly involve the renal tissue by spreading along pre-existing canalicular structures. Such an ascending infection can manifest as a highly active and purulent or even abscessing interstitial nephritis or as a chronic-fibrosing process in recurrent pyelonephritis. Viral infections can also use the canalicular route as in polyomavirus nephropathy or spread via the blood stream in a hematogenous manner as in the case of cytomegalovirus or hantavirus infections. Likewise, bacterial infections can reach the kidney via the blood in the case of systemic infection. Another large group of nephropathies taking place as a sequel of infections includes infection-related glomerulonephritides (IRGN), which are mediated by a series of immunological mechanisms. These IRGN can be subdivided according to their temporal association with the infectious process, occurring either after the infection has healed (postinfectious) or accompanying the ongoing infectious process (parainfectious). The latter, in particular, is of increasing importance in the daily practice of nephropathologists, especially in older patients. A number of other glomerulonephritis forms, i.e., membranous or membranoproliferative forms, can occur as a consequence of infection. In addition, infections can trigger nephropathies, such as thrombotic microangiopathy. The present article gives an overview of morphologic changes in renal parenchyma that take place as a consequence of infectious processes, with particular focus on IRGN.

Asunto(s)

Glomerulonefritis , Humanos , Glomerulonefritis/patología , Glomerulonefritis/inmunología , Infecciones Urinarias/patología , Infecciones Urinarias/microbiología , Riñón/patología , Riñón/virología , Enfermedades Renales/patología , Enfermedades Renales/virología , Nefritis Intersticial/patología , Nefritis Intersticial/virología , Infecciones Bacterianas/patología , Infecciones Bacterianas/microbiología , Infecciones Bacterianas/inmunología

RESUMEN

BACKGROUND: Acute interstitial nephritis (AIN) is a complication of drugs that may cause permanent kidney injury. AIN has been reported in patients with inflammatory bowel disease (IBD) treated with the integrin inhibitor vedolizumab. Through systematic review of existing literature, we aimed to identify and describe cases of AIN in patients with IBD treated with vedolizumab. METHODS: We searched Medline, Embase, Cochrane, and Web of Science Core Collection between 1 January 2009 and 25 April 2023. The search yielded 1473 publications. Titles and abstracts were screened by two independent reviewers. Seventy publications were reviewed in full-text. Eight met the inclusion criteria. Clinical characteristics of AIN cases were extracted. Case causality assessment was performed according to two international adverse drug reaction probability assessment scales. Results were reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. RESULTS: Nine biopsy-confirmed cases of AIN were reported in six patients with ulcerative colitis and three with Crohn's disease. Mean age at AIN onset was 36 years (range = 19-58) and the majority of patients were females (n = 6/9). Time from vedolizumab treatment initiation to AIN onset spanned from hours to 12 months. Common symptoms were fever and malaise. Creatinine levels were elevated in all patients. Five patients sustained permanent kidney injury. CONCLUSION: Our findings suggest that vedolizumab, although rarely, could cause AIN in patients with IBD. Awareness of laboratory findings and symptoms consistent with AIN, along with monitoring of the kidney function, could be warranted in patients with IBD treated with vedolizumab.

Asunto(s)

Anticuerpos Monoclonales Humanizados , Fármacos Gastrointestinales , Enfermedades Inflamatorias del Intestino , Nefritis Intersticial , Humanos , Anticuerpos Monoclonales Humanizados/efectos adversos , Anticuerpos Monoclonales Humanizados/uso terapéutico , Nefritis Intersticial/inducido químicamente , Fármacos Gastrointestinales/efectos adversos , Fármacos Gastrointestinales/uso terapéutico , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Enfermedades Inflamatorias del Intestino/complicaciones , Colitis Ulcerosa/tratamiento farmacológico , Enfermedad Aguda

RESUMEN

Immune checkpoint inhibitors (ICIs) can provide survival benefits to cancer patients; however, they sometimes result in the development of renal immune-related adverse events (irAEs). Tubulointerstitial nephritis (TIN) is the most representative pathological feature of renal irAEs. However, the clinicopathological entity and underlying pathogenesis of ICI-induced TIN are unclear. Therefore, we compared the clinical and histological features of this condition with those of non-ICI drug-induced TIN. Age and C-reactive protein levels were significantly higher in ICI-induced TIN, but there were no significant differences in renal function. Immunophenotyping of ICI-induced TIN showed massive T cell and macrophage infiltration with fewer B cells, plasma cells, neutrophils, and eosinophils. Compared with those in non-ICI drug-induced TIN, CD4+ cell numbers were significantly lower in ICI-induced TIN but CD8+ cell numbers were not significantly different. However, CD8/CD3 and CD8/CD4 ratios were higher in ICI-induced TIN. Moreover, CD25+ and FOXP3+ cells, namely regulatory T cells, were less abundant in ICI-induced TIN. In conclusion, T cell, B cell, plasma cell, neutrophil, and eosinophil numbers proved useful for differentiating ICI-induced and non-ICI drug-induced TIN. Furthermore, the predominant distribution of CD8+ cells and low accumulation of regulatory T cells might be associated with ICI-induced TIN development.

Asunto(s)

Linfocitos T CD8-positivos , Inhibidores de Puntos de Control Inmunológico , Nefritis Intersticial , Linfocitos T Reguladores , Humanos , Nefritis Intersticial/inducido químicamente , Nefritis Intersticial/patología , Nefritis Intersticial/inmunología , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Masculino , Linfocitos T Reguladores/inmunología , Linfocitos T Reguladores/patología , Linfocitos T Reguladores/efectos de los fármacos , Femenino , Anciano , Linfocitos T CD8-positivos/patología , Linfocitos T CD8-positivos/inmunología , Persona de Mediana Edad , Adulto , Anciano de 80 o más Años