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INTRODUCTION: Patients with ADTKD-MUC1 have one allele producing normal mucin-1 (MUC1) and one allele producing mutant MUC1, which remains intracellular. We hypothesized that ADTKD-MUC1 patients, who have only 1 secretory-competent wild-type MUC1 allele, should exhibit decreased plasma mucin-1 (MUC1) levels. To test this hypothesis, we repurposed the serum CA15-3 assay used to measure MUC1 in breast cancer to measure plasma MUC1 levels in ADTKD-MUC1. METHODS: This cross-sectional study analyzed CA15-3 levels in a reference population of 6,850 individuals, in 85 individuals with ADTKD-MUC1, and in a control population including 135 individuals with ADTKD-UMOD and 114 healthy individuals. RESULTS: Plasma CA15-3 levels (mean ± standard deviation) were 8.6 ± 4.3 U/mL in individuals with ADTKD-MUC1 and 14.6 ± 5.6 U/mL in controls (p < 0.001). While there was a significant difference in mean CA15-3 levels, there was substantial overlap between the 2 groups. Plasma CA15-3 levels were <5 U/mL in 22% of ADTKD-MUC1 patients, in 0/249 controls, and in 1% of the reference population. Plasma CA15-3 levels were >20 U/mL in 1/85 ADTKD-MUC1 patients, in 18% of control individuals, and in 25% of the reference population. Segregation of plasma CA15-3 levels by the rs4072037 genotype did not significantly improve differentiation between affected and unaffected individuals. CA15-3 levels were minimally affected by gender and estimated glomerular filtration rate. DISCUSSION/CONCLUSIONS: Plasma CA15-3 levels in ADTKD-MUC1 patients are approximately 40% lower than levels in healthy individuals, though there is significant overlap between groups. Further investigations need to be performed to see if plasma CA15-3 levels would be useful in diagnosis, prognosis, or assessing response to new therapies in this disorder.
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Mucina-1/sangre , Nefritis Intersticial/sangre , Uromodulina/genética , Adulto , Anciano , Alelos , Biomarcadores/sangre , Estudios de Casos y Controles , Estudios Transversales , Femenino , Voluntarios Sanos , Humanos , Masculino , Persona de Mediana Edad , Mucina-1/genética , Mutación , Nefritis Intersticial/genética , PronósticoRESUMEN
BACKGROUND: Diffusion-weighted (DW) and blood oxygen level-dependent (BOLD) magnetic resonance imaging are classical sequences of functional MR, but the exploration in non-transplanted kidney disease is limited. OBJECTS: To analyze the characteristics of apparent diffusion coefficient (ADC) and R2* value using DW and BOLD imaging in tubulointerstitial nephritis (TIN). METHODS: Four acute TIN, thirteen chronic TIN patients, and four controls were enrolled. We used multiple gradient-echo sequences to acquire 12 T2*-weighted images to calculate the R2* map. DW imaging acquired ADC values by combining a single-shot spin-echo echo-planar imaging pulse sequence and the additional motion probing gradient pulses along the x,y, z-axes with two b values:0 and 200, as well as 0 and 800 s/mm2. ATIN patients performed DW and BOLD magnetic resonance at renal biopsy(T0) and the third month(T3). We assessed the pathological changes semiquantitatively, and conducted correlation analyses within functional MR, pathological and clinical indexes. RESULTS: In ATIN, ADCs were significantly lower(b was 0,200 s/mm2, 2.86 ± 0.19 vs. 3.39 ± 0.11, b was 0,800 s/mm2, 1.76 ± 0.12 vs. 2.16 ± 0.08, P < 0.05) than controls, showing an obvious remission at T3. Cortical and medullary R2* values (CR2*,MR2*) were decreased, significant difference was only observed in MR2*(T0 24.3 ± 2.1vs.T3 33.1 ± 4.1,P < 0.05). No relationship was found between functional MR and histopathological indexes.MR2* had a close relationship with eGFR (R = 0.682,P = 0.001) and serum creatinine(R = -0.502,P = 0.012). Patients with lower ADC when b was 0,200 s/mm2 showed more increase of ADC(R = -0.956,P = 0.044) and MR2*(R = -0.949,P = 0.05) after therapy. In CTIN group, lowered MR2* and MR2*/CR2* provided evidence of intrarenal ischemia. CTIN with advanced CKD (eGFR< 45) had significantly lower ADCb200 value. CONCLUSIONS: We observed the reduction and remission of ADC and R2* values in ATIN case series. ATIN patients had concurrently decreased ADCb800 and MR2*. The pseudo normalization of CR2* with persistently low MR2* in CTIN suggested intrarenal hypoxia.
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Imagen de Difusión por Resonancia Magnética/métodos , Nefritis Intersticial/sangre , Nefritis Intersticial/diagnóstico por imagen , Oxígeno/sangre , Humanos , Isquemia/diagnóstico , Riñón/irrigación sanguínea , Riñón/diagnóstico por imagen , Riñón/patología , Nefritis Intersticial/patología , Estudios ProspectivosRESUMEN
BACKGROUND: Acute interstitial nephritis (AIN) is an important and common cause of acute renal failure. There are no generally accepted guidelines for the treatment of AIN, due to the lack of prospective randomized trials. Since AIN is characterized by an enhanced immune response, immunosuppressive treatment could potentially improve prognosis by attenuating inflammation and subsequent fibrosis. Despite the limited evidence of effects of steroids and potential adverse effects, prednisolone is frequently used in the treatment of AIN and there is a strong need for clinical trials on the effects of immunosuppression, including steroids, in the treatment of AIN. We aimed to evaluate the effectiveness of prednisolone treatment in AIN, and hypothesized a positive effect of prednisolone treatment on renal function in AIN. METHODS: The study is a randomized, controlled, prospective, open label multicenter study, including incident adult patients with biopsy proven AIN. Patients will be randomized 1:1 to one of 2 treatment regimens: A. No prednisolone treatment (control group) and B. B) Oral prednisolone treatment staring with 60 mg daily tapered over 8 weeks. One hundred ten patients (55 in each group) are planned to be included and followed for 1 year. Primary outcome is renal function estimated by eGFR 3 months after inclusion. Secondary outcomes are renal function after 12 months and need for renal replacement therapy and quality of life after 3 and 12 months. In addition, with-in prednisolone group analysis are performed to estimate the importance of treatment delay. Exploratory analyses include analysis of biomarkers in urine and plasma and the evaluation of these biomarkers in relation to renal prognosis and re-evaluation of renal biopsies to identify possible renal prognostic factors. DISCUSSION: Strengths and possible limitations in the design are evaluated. The study will provide important information on the effects of prednisolone treatment in AIN and as well as prognostic information relevant for future use of biomarkers and histology. Ultimately, this would lead to improved and evidence based clinical guidelines for the treatment of AIN. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT04376216 (Retrospectively registered on May 6, 2020).
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Inmunosupresores/uso terapéutico , Nefritis Intersticial/tratamiento farmacológico , Prednisolona/uso terapéutico , Lesión Renal Aguda/etiología , Lesión Renal Aguda/prevención & control , Lesión Renal Aguda/terapia , Administración Oral , Creatinina/sangre , Tasa de Filtración Glomerular , Humanos , Nefritis Intersticial/sangre , Nefritis Intersticial/complicaciones , Estudios Prospectivos , Calidad de Vida , Inducción de Remisión , Terapia de Reemplazo RenalRESUMEN
Acute and chronic transplant rejections due to alloreactivity are essential contributors to graft loss. However, the strength of alloreactivity is biased by non-immunological factors such as ischemia reperfusion injury (IRI). Accordingly, protection from IRI could be favorable in terms of limiting graft rejection. Caveolin-1 (Cav-1) is part of the cell membrane and an important regulator of intracellular signaling. Cav-1 has been demonstrated to limit IRI and to promote the survival of a variety of cell types including renal cells under stress conditions. Accordingly, Cav-1 could also play a role in limiting anti-graft immune responses. Here, we evaluated a possible association between pre-transplant serum concentrations of Cav-1 and the occurrence of rejection during follow-up in a pilot study. Therefore, Cav-1-serum concentrations were analyzed in 91 patients at the time of kidney transplantation and compared to the incidence of acute and chronic rejection. Higher Cav-1 levels were associated with lower occurrence of acute cellular tubulointerstitial rejection episodes.
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Caveolina 1/sangre , Rechazo de Injerto/sangre , Trasplante de Riñón/efectos adversos , Nefritis Intersticial/sangre , Nefritis Intersticial/etiología , Adulto , Anciano , Biomarcadores , Femenino , Rechazo de Injerto/diagnóstico , Rechazo de Injerto/mortalidad , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Nefritis Intersticial/diagnóstico , Nefritis Intersticial/mortalidad , Periodo Perioperatorio , Pronóstico , Daño por Reperfusión/diagnóstico , Daño por Reperfusión/etiología , Daño por Reperfusión/metabolismoRESUMEN
Genes of UMOD, HNF1B, MUC1, REN and SEC61A1 were reported to be associated with autosomal dominant tubulointerstitial kidney disease (ADTKD). 48 probands and their family members (N = 27) were enrolled in this genetic screening study. A combination of methods was employed for comprehensive molecular analysis of both copy number variations (CNVs) and single nucleotide variants (SNVs). 35 probands were followed for years. The phenotype-genotype and genotype-outcome correlation were inferred from these datasets. In this cohort, 18 probands were diagnosed with ADTKD, according to Kidney Disease: Improving Global Outcomes (KDIGO) guideline. Moreover, 11 probands were diagnosed with ADTKD-UMOD, one with ADTKD-REN and one with ADTKD-HNF1B, based on molecularly confirmed pathogenic variants. The 11 UMOD variants were mainly located in codons 28 to 289 and half of the variants were found to change the cysteine amino acid. According to the follow-up data, suspected ADTKD individuals had a better prognosis compared to ADTKD individuals (p = 0.029). Individuals with a cysteine substitution in the UMOD gene appeared to have a better prognosis than individuals with other amino acid substitutions (p = 0.015).
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Pueblo Asiatico/genética , Genes Dominantes , Nefritis Intersticial/genética , Adulto , China , Estudios de Cohortes , Variaciones en el Número de Copia de ADN/genética , Femenino , Genotipo , Humanos , Estimación de Kaplan-Meier , Masculino , Mutación/genética , Nefritis Intersticial/sangre , Linaje , Fenotipo , Resultado del Tratamiento , Uromodulina/sangreRESUMEN
INTRODUCTION: Pembrolizumab is a monoclonal antibody approved for adult patients with advanced non-small-cell lung cancer (NSCLC). Although immune related adverse events are considered to be well tolerated, complications may occur and discontinuation of the treatment could be required. CASE REPORT: A 62-year old patient diagnosed with advanced non-small cell lung cancer experienced a decline in the renal function after seven cycles with pembrolizumab.Management & outcome: After ruling out other common causes of interstitial nephritis, pembrolizumab was attributed as a cause of interstitial nephritis. At first, toxicity was managed with corticosteroids and closely monitoring the patient, but finally pembrolizumab had to be discontinued due to the kidney function did not recover. DISCUSSION: Renal and urinary disorders were reported in <3% of patients treated with pembrolizumab, being interstitial nephritis the most reported toxicity. The kidney damage can be a complication to consider in patients receiving pembrolizumab. Early identification of an increase in serum creatinine levels may help with prevention by establishing an effective treatment, although it may not mean a total recovery of kidney function.
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Anticuerpos Monoclonales Humanizados/efectos adversos , Nefritis Intersticial/inducido químicamente , Nefritis Intersticial/diagnóstico por imagen , Anticuerpos Monoclonales/efectos adversos , Antineoplásicos Inmunológicos/efectos adversos , Carcinoma de Pulmón de Células no Pequeñas/sangre , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Humanos , Neoplasias Pulmonares/sangre , Neoplasias Pulmonares/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Nefritis Intersticial/sangreRESUMEN
BACKGROUND: A renal biopsy is needed to define active inflammatory infiltration and guide therapeutic management in drug-induced acute tubulointerstitial nephritis (D-ATIN). However, factors such as various contraindications, refusal of informed consent and limited technical support may stop the biopsy process. It is thus of great importance to explore approaches that could deduce probable pathologic changes. METHODS: A total of 81 biopsy-proven D-ATIN patients were enrolled from a prospective cohort of ATIN patients at Peking University First Hospital. The systemic inflammation score (SIS) was developed based on the CRP and ESR levels at biopsy, and patients were divided into high-SIS, median-SIS, and low-SIS groups. The demographic data, clinicopathologic features, and renal outcomes were compared. RESULTS: The SIS was positively correlated with inflammatory cell infiltration and was inversely correlated with interstitial fibrosis. The number of interstitial inflammatory cells increased significantly with increasing SISs. The proportions of neutrophils and plasma cells were the highest in the high-SIS group compared with the other two groups. Prednisone (30-40 mg/day) was prescribed in all patients. The high-SIS group tended to have more favorable renal restoration than the other two groups. By 12 months postbiopsy, a decreased eGFR (< 60 mL/min/1.73 m2) was observed in 66.7% of medium-SIS patients, 32.4% of high-SIS patients, and 30.4% of low-SIS patients. CONCLUSION: The SIS was positively correlated with active tubulointerstitial inflammation and therefore could help to aid therapeutic decisions in D-ATIN.
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Sedimentación Sanguínea , Proteína C-Reactiva/metabolismo , Nefritis Intersticial/sangre , Adulto , Biopsia , Femenino , Glucocorticoides/uso terapéutico , Humanos , Inflamación/complicaciones , Riñón/patología , Masculino , Persona de Mediana Edad , Nefritis Intersticial/inducido químicamente , Nefritis Intersticial/tratamiento farmacológico , Nefritis Intersticial/patología , Prednisona/uso terapéutico , Estudios ProspectivosRESUMEN
BACKGROUND: Glycosuria is one of the manifestations of acute tubulointerstitial nephritis (ATIN), but may also be observed in other renal diseases. In this study, we investigated the value of non-diabetic glycosuria as a diagnostic clue for ATIN. METHODS: We retrospectively reviewed the medical records of adult patients who underwent a kidney biopsy as an evaluation for serum creatinine > 1.4 mg/dL. Patients with proteinuria in the nephrotic range, diabetes mellitus, or transplanted kidney were excluded. The laboratory abnormalities suggestive of tubular injury were compared between 28 patients (14 men and 14 women, mean age 48.5 ± 14.1 years) with ATIN and 116 patients (76 men and 40 women, mean age 53.1 ± 15.0 years) with other diagnoses. RESULTS: In ATIN, glycosuria (≥ 1+ on dipstick; 68%) was more frequent than hypophosphatemia (18%), hypouricemia (18%), hypokalemia (18%), and tubular proteinuria (40%). In other diagnoses, glycosuria (≥ 1+) was detected in 7 (6%) patients; 6 of them had the histological diagnosis of antineutrophil cytoplasmic antibody-associated glomerulonephritis. The presence of glycosuria (≥ 1+) had 68% sensitivity and 94% specificity for ATIN, with the positive likelihood ratio of 11.24 and the negative likelihood ratio of 0.34. Pyuria and low total CO2 were equally and more sensitive (68% and 71%, respectively) than glycosuria (≥ 1+), but had no diagnostic value due to low specificities (58% and 60%, respectively). CONCLUSION: In non-diabetic, non-nephrotic patients undergoing a kidney biopsy for azotemia, 1+ or higher glycosuria, if present, was a good predictor of the diagnosis of ATIN.
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Azotemia/etiología , Glucosuria/etiología , Riñón/patología , Nefritis Intersticial/diagnóstico , Nefritis Intersticial/orina , Adulto , Anciano , Biopsia , Creatinina/sangre , Femenino , Humanos , Hipopotasemia/etiología , Masculino , Persona de Mediana Edad , Nefritis Intersticial/sangre , Nefritis Intersticial/patología , Proteinuria/etiología , Estudios Retrospectivos , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: The roles of asymptomatic hyperuricemia or uric acid (UA) crystals in CKD progression are unknown. Hypotheses to explain links between UA deposition and progression of CKD include that (1) asymptomatic hyperuricemia does not promote CKD progression unless UA crystallizes in the kidney; (2) UA crystal granulomas may form due to pre-existing CKD; and (3) proinflammatory granuloma-related M1-like macrophages may drive UA crystal-induced CKD progression. METHODS: MALDI-FTICR mass spectrometry, immunohistochemistry, 3D confocal microscopy, and flow cytometry were used to characterize a novel mouse model of hyperuricemia and chronic UA crystal nephropathy with granulomatous nephritis. Interventional studies probed the role of crystal-induced inflammation and macrophages in the pathology of progressive CKD. RESULTS: Asymptomatic hyperuricemia alone did not cause CKD or drive the progression of aristolochic acid I-induced CKD. Only hyperuricemia with UA crystalluria due to urinary acidification caused tubular obstruction, inflammation, and interstitial fibrosis. UA crystal granulomas surrounded by proinflammatory M1-like macrophages developed late in this process of chronic UA crystal nephropathy and contributed to the progression of pre-existing CKD. Suppressing M1-like macrophages with adenosine attenuated granulomatous nephritis and the progressive decline in GFR. In contrast, inhibiting the JAK/STAT inflammatory pathway with tofacitinib was not renoprotective. CONCLUSIONS: Asymptomatic hyperuricemia does not affect CKD progression unless UA crystallizes in the kidney. UA crystal granulomas develop late in chronic UA crystal nephropathy and contribute to CKD progression because UA crystals trigger M1-like macrophage-related interstitial inflammation and fibrosis. Targeting proinflammatory macrophages, but not JAK/STAT signaling, can attenuate granulomatous interstitial nephritis.
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Hiperuricemia/complicaciones , Hiperuricemia/patología , Nefritis Intersticial/etiología , Nefritis Intersticial/patología , Insuficiencia Renal Crónica/etiología , Insuficiencia Renal Crónica/patología , Animales , Enfermedades Asintomáticas , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Granuloma/etiología , Granuloma/metabolismo , Granuloma/patología , Hiperuricemia/metabolismo , Ratones , Nefritis Intersticial/sangre , Insuficiencia Renal Crónica/sangreRESUMEN
BACKGROUND: Hypomagnesemia in patients with congenital anomalies of the kidneys and urinary tract or autosomal dominant tubulointerstitial kidney disease is highly suggestive of HNF1B-associated disease. Intriguingly, the frequency of low serum Mg2+ (sMg) level varies and is lower in children than in adults with HNF1B mutations that could be partially due to application of inaccurate normal limit of sMg, irrespective of age and gender. We aimed to re-assess cross-sectionally and longitudinally the frequency of hypomagnesemia in HNF1B disease by using locally derived reference values of sMg. METHODS: Fourteen children with HNF1B-associated kidney disease were included. Control group comprising 110 subjects served to generate 2.5th percentiles of sMg as the lower limits of normal. RESULTS: In both controls and patients, sMg correlated with age, gender, and fractional excretion of Mg2+. In girls, sMg concentration was higher than in boys when analyzed in the entire age spectrum (p < 0.05). In HNF1B patients, mean sMg was lower than in controls as compared with respective gender- and age-specific interval (p < 0.001). Low sMg levels (< 0.7 mmol/l) were found in 21.4% of patients at diagnosis and 36.4% at last visit, which rose to 85.7% and 72.7% respectively when using the age- and gender-adjusted reference data. Similarly, in the longitudinal observation, 23% of sMg measurements were < 0.7 mmol/l versus 79.7% when applying respective references. CONCLUSIONS: Hypomagnesemia is underdiagnosed in children with HNF1B disease. sMg levels are age- and gender-dependent; thus, the use of appropriate reference data is crucial to hypomagnesemia in children.
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Factor Nuclear 1-beta del Hepatocito/genética , Magnesio/sangre , Nefritis Intersticial/sangre , Anomalías Urogenitales/sangre , Reflujo Vesicoureteral/sangre , Adolescente , Factores de Edad , Niño , Preescolar , Estudios Transversales , Análisis Mutacional de ADN , Femenino , Humanos , Riñón/metabolismo , Estudios Longitudinales , Masculino , Mutación , Nefritis Intersticial/diagnóstico , Nefritis Intersticial/genética , Valores de Referencia , Reabsorción Renal/genética , Estudios Retrospectivos , Factores Sexuales , Anomalías Urogenitales/diagnóstico , Anomalías Urogenitales/genética , Reflujo Vesicoureteral/diagnóstico , Reflujo Vesicoureteral/genéticaRESUMEN
IgG4-RD may affect several organs including kidneys. The kidney is involved in approximately 20% of patient with IgG4-RD. The most common intrinsic kidney disease is tubulointerstitial nephritis (IgG4-TIN). Retroperitoneal fibrosis (IgG4-RPF) may induce obstructive acute renal failure. More rarely, IgG4-RKD can manifest as a glomerular disease, in particular as a membranous nephropathy (MN). It mostly affects middle-aged to elderly men and causes acute or chronic renal dysfunction, multiple hypodense lesions on CT-Scan and various extra-renal lesions. Increased serum IgG4 and hypocomplementemia are the most important serological findings for the diagnosis of IgG4-RD and thus should be systematically assessed when IgG4-RKD is suspected. Specific diagnosis criteria for IgG4-TIN including interstitial infiltration of IgG4-positive plasma cells, storiform fibrosis and tubular basement membrane immune complex deposits have been proposed. Corticosteroids are effective and remain the first-line therapy but relapses or severe forms could respond to immunosuppressive therapy.
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Enfermedad Relacionada con Inmunoglobulina G4/complicaciones , Enfermedades Renales/etiología , Lesión Renal Aguda/sangre , Lesión Renal Aguda/etiología , Creatinina/sangre , Femenino , Glomerulonefritis Membranosa/sangre , Glomerulonefritis Membranosa/tratamiento farmacológico , Glomerulonefritis Membranosa/etiología , Glomerulonefritis Membranosa/patología , Humanos , Inmunoglobulina G/sangre , Enfermedad Relacionada con Inmunoglobulina G4/sangre , Enfermedad Relacionada con Inmunoglobulina G4/tratamiento farmacológico , Enfermedad Relacionada con Inmunoglobulina G4/patología , Riñón/diagnóstico por imagen , Enfermedades Renales/sangre , Enfermedades Renales/tratamiento farmacológico , Enfermedades Renales/patología , Masculino , Persona de Mediana Edad , Nefritis Intersticial/sangre , Nefritis Intersticial/tratamiento farmacológico , Nefritis Intersticial/etiología , Nefritis Intersticial/patología , Fibrosis Retroperitoneal/complicaciones , Fibrosis Retroperitoneal/tratamiento farmacológico , Fibrosis Retroperitoneal/patología , Esteroides/uso terapéuticoRESUMEN
OBJECTIVE: To investigate the incidence of tubulointerstitial injury in lupus nephritis (LN) and to examine clinicopathological factors that could indicate the presence of tubulointerstitial injury. METHODS: This study included 98 patients with LN. Clinical data and the pathological results of the initial renal biopsy were collected. RESULTS: The frequency of each tubulointerstitial injury parameter was over 50%, except for the interstitial edema, in the 98 patients investigated in this study. The most frequently detected tubulointerstitial injury parameter was tubular atrophy in this study. Neutrophil infiltration/karyorrhexis, wire loop lesion, and arteriosclerosis were observed frequently in patients with tubulointerstitial injuries. High serum creatinine and blood urea nitrogen (BUN) were observed more frequently in patients with tubulointerstitial injuries except tubular degeneration. The multivariable regression analysis showed a relationship between neutrophil infiltration/karyorrhexis and interstitial fibrosis/tubular degeneration, a relationship between wire loop lesion and tubulointerstitial inflammation/edema, and a relationship between arteriosclerosis and tubulointerstitial injuries (except interstitial edema). Patients with tubular degeneration had lower D-Dimer levels compared with those without. Patients with interstitial fibrosis had higher blood leukocyte counts than those without. The rate of low response to therapy was 13% among those without tubulointerstitial inflammation, but 35% in those with interstitial inflammation (P = 0.03). CONCLUSION: Acute and chronic renal tubulointerstitial lesions are often found along with glomerular and vascular lesions. Immune and vascular factors are probably involved in tubulointerstitial injuries. Tubulointerstitial inflammation may be the initiator of chronic renal injury and may predict response to therapy.Key Pointsâ¢To provide a theoretical basis for tubulointerstitial injury in LN.
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Inflamación/patología , Glomérulos Renales/patología , Nefritis Lúpica/patología , Nefritis Intersticial/patología , Adulto , Atrofia , Creatinina/sangre , Femenino , Fibrosis , Humanos , Nefritis Lúpica/sangre , Nefritis Lúpica/inmunología , Masculino , Persona de Mediana Edad , Nefritis Intersticial/sangre , Nefritis Intersticial/inmunología , Análisis de Regresión , Factores de Riesgo , Índice de Severidad de la Enfermedad , Adulto JovenRESUMEN
Drug-induced hypersensitivity syndrome (DIHS), also referred to as drug reaction with eosinophilia and systemic symptoms (DRESS), is a severe hypersensitivity drug reaction affecting the skin and multiple internal organ systems. We report a 47-year-old man with DIHS/DRESS and comorbidities (fulminant type 1 diabetes mellitus, valsartan-induced photosensitivity, vitiligo and acute interstitial nephritis). Although acute interstitial nephritis usually appears in the early phase, his is a rare case of acute interstitial nephritis more than 2 years after the onset of DIHS/DRESS.
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Síndrome de Hipersensibilidad a Medicamentos/complicaciones , Fatiga/tratamiento farmacológico , Nefritis Intersticial/diagnóstico , Acetaminofén/efectos adversos , Biopsia , Carbocisteína/efectos adversos , Claritromicina/efectos adversos , Creatinina/sangre , Síndrome de Hipersensibilidad a Medicamentos/tratamiento farmacológico , Síndrome de Hipersensibilidad a Medicamentos/patología , Quimioterapia Combinada/efectos adversos , Medicamentos Herbarios Chinos/efectos adversos , Humanos , Riñón/patología , Masculino , Persona de Mediana Edad , Muramidasa/efectos adversos , Nefritis Intersticial/sangre , Nefritis Intersticial/etiología , Nefritis Intersticial/patología , Prednisolona/uso terapéutico , Piel/patología , Factores de TiempoRESUMEN
BACKGROUND: Although most cases of tubulointerstitial nephritis in paraproteinemia are monoclonal light chain deposition-mediated, interstitial nephritis as neoplastic interstitial cell infiltration has rarely been described. On the other hand, lympho-plasma-cell-rich tubulointerstitial nephritis, in which the infiltrative cells are usually polytypic, is often evident in primary Sjögren's syndrome (pSS). Herein we present a rare case of pSS in a patient who had been diagnosed as having IgA kappa-type monoclonal gammopathy of undetermined significance (MGUS) and developed tubulointerstitial nephritis with monotypic (IgA kappa) lympho-plasmacytic infiltrates. CASE PRESENTATION: A 74-year-old Japanese woman with pSS who had been diagnosed as having IgA kappa-type MGUS developed progressive renal dysfunction. Renal biopsy revealed tubulointerstitial nephritis with abundant plasma cell-rich mononuclear cell infiltrates without atypia. Immunohistochemical staining for immunoglobulins and light chains showed that most infiltrates were positive for IgA and kappa. Most of the infiltrative cells were positive for CD38 and CD138, and cells positive for CD 19 and CD 45 were also widely evident. Electron microscopy and immunofluorescence studies revealed no apparent immunological deposits in the glomeruli and tubules. Bone marrow and whole-body radiological examinations revealed no findings suggestive of multiple myeloma or lymphoma. Renal function improved rapidly with prednisolone 40 mg daily and has been maintained at the same level on low-dose prednisolone and azathioprine for 18 months. CONCLUSION: Tubulointerstitial nephritis with monotypic cell infiltrates, without immunological deposits, is a quite rare histological picture in MGUS, and might be a unique renal manifestation in patients with pSS.
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Inmunoglobulina A/sangre , Linfocitos/metabolismo , Nefritis Intersticial/sangre , Paraproteinemias/sangre , Células Plasmáticas/metabolismo , Síndrome de Sjögren/sangre , Anciano , Femenino , Humanos , Nefritis Intersticial/complicaciones , Nefritis Intersticial/diagnóstico por imagen , Paraproteinemias/complicaciones , Paraproteinemias/diagnóstico por imagen , Síndrome de Sjögren/complicaciones , Síndrome de Sjögren/diagnóstico por imagenRESUMEN
Background: IgG4-related acute tubulointerstitial nephritis is a type of autoimmune-mediated interstitial nephritis. Recently, autoantibodies against modified C-reactive protein (mCRP) were found to play a pathogenic role in renal diseases through the formation of tubulointerstitial lesions. This is the first case report on the presence of mCRP autoantibodies in a patient with IgG4-associated acute tubulointerstitial nephritis. Case presentation: A 70-year-old man was admitted with renal dysfunction and a medical history of bile duct stenosis, an inflammatory pancreatic mass, hypertension, and diabetes. On admission, laboratory tests showed higher than normal levels of serum creatinine and IgG4 and lower than normal levels of complements 3 and 4. In addition, the mCRP autoantibody levels were elevated, and the findings of kidney biopsy revealed interstitial nephritis with rich plasma cells in the renal interstitium. The patient was administered prednisone and cyclophosphamide therapy, which resulted in a rapid improvement in renal function. Conclusion: IgG4-related autoimmune disease should be considered in the diagnosis of patients who have tubulointerstitial nephritis with multisystem involvement. Further, mCRP autoantibodies may be associated with IgG4-related tubulointerstitial nephritis and might be useful as a diagnostic marker of the disease.
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Autoanticuerpos/sangre , Proteína C-Reactiva/inmunología , Riñón/patología , Nefritis Intersticial/inmunología , Anciano , Ciclofosfamida/uso terapéutico , Humanos , Inmunoglobulina G/sangre , Masculino , Nefritis Intersticial/sangre , Nefritis Intersticial/tratamiento farmacológico , Prednisona/uso terapéuticoRESUMEN
Prolyl hydroxylase domain enzyme inhibitors (PHDIs) stabilize hypoxia-inducible factors (HIFs), and are protective in models of acute ischemic and inflammatory kidney disease. Whether PHDIs also confer protection in chronic inflammatory kidney disease models remains unknown. Here we investigated long-term effects of PHDI treatment in adenine-induced nephropathy as a model for chronic tubulointerstitial nephritis. After three weeks, renal dysfunction and tubulointerstitial damage, including proximal and distal tubular injury, tubular dilation and renal crystal deposition were significantly attenuated in PHDI-treated (the isoquinoline derivative ICA and Roxadustat) compared to vehicle-treated mice with adenine-induced nephropathy. Crystal-induced renal fibrosis was only partially diminished by treatment with ICA. Renoprotective effects of ICA treatment could not be attributed to changes in adenine metabolism or urinary excretion of the metabolite 2,8-dihydroxyadenine. ICA treatment reduced inflammatory infiltrates of F4/80+ mononuclear phagocytes in the kidneys and supported a regulatory, anti-inflammatory immune response. Furthermore, interstitial deposition of complement C1q was decreased in ICA-treated mice fed an adenine-enriched diet. Tubular cell-specific HIF-1α and myeloid cell-specific HIF-1α and HIF-2α expression were not required for the renoprotective effects of ICA. In contrast, depletion of mononuclear phagocytes with clodronate largely abolished the nephroprotective effects of PHD inhibition. Thus, our findings indicate novel and potent systemic anti-inflammatory properties of PHDIs that confer preservation of kidney function and structure in chronic tubulointerstitial inflammation and might counteract kidney disease progression.
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Nefritis Intersticial/tratamiento farmacológico , Fagocitos/efectos de los fármacos , Prolil Hidroxilasas/metabolismo , Inhibidores de Prolil-Hidroxilasa/farmacología , Insuficiencia Renal Crónica/prevención & control , Adenina/metabolismo , Adenina/toxicidad , Animales , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Ácido Clodrónico/farmacología , Complemento C1q/inmunología , Complemento C1q/metabolismo , Modelos Animales de Enfermedad , Glicina/análogos & derivados , Glicina/farmacología , Glicina/uso terapéutico , Humanos , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Isoquinolinas/farmacología , Isoquinolinas/uso terapéutico , Túbulos Renales/citología , Túbulos Renales/efectos de los fármacos , Túbulos Renales/inmunología , Túbulos Renales/patología , Masculino , Ratones , Ratones Transgénicos , Nefritis Intersticial/sangre , Nefritis Intersticial/inducido químicamente , Nefritis Intersticial/inmunología , Fagocitos/inmunología , Prolil Hidroxilasas/inmunología , Inhibidores de Prolil-Hidroxilasa/uso terapéutico , Sustancias Protectoras/farmacología , Sustancias Protectoras/uso terapéutico , Insuficiencia Renal Crónica/inmunologíaRESUMEN
INTRODUCTION: In sarcoidosis, renal involvement includes hypercalcemia-related nephrocalcinosis and granulomatous tubulointerstitial nephritis. Hypercalcemia is thought to be due to increased production of 1,25 dihydroxyvitamin D (1-25D), but 1-25D levels have not been evaluated in sarcoidosis patients with renal dysfunction. MATERIALS AND METHODS: We enrolled 9 sarcoidosis patients who underwent renal biopsy, and compared the serum 1-25D concentration and eGFR with those in 428 non-sarcoidosis patients who had renal dysfunction (stage 2 or higher CKD with an estimated glomerular filtration rate < 90). RESULTS: Serum calcium and 1-25D levels were significantly higher in the sarcoidosis patients than in the non-sarcoidosis patients (p < 0.01 and p = 0.01, respectively). There was a positive correlation between 1-25D and eGFR in the patients without sarcoidosis (r = 0.693; p < 0.01). As the renal function of sarcoidosis patients was improved by steroid therapy, the serum 1-25D and adjusted serum calcium levels decreased to near the median values in non-sarcoidosis patients. On renal biopsy, CD68 staining was positive for tissue macrophages in all 8 patients who had tubulointerstitial nephritis (with or without typical granulomas), while Von Kossa staining showed calcification of tubules near or inside granulomas in 6 of these 8 patients. CONCLUSION: While tissue macrophages promote development of tubulointerstitial nephritis and 1-25D overproduction in renal sarcoidosis, hypercalcemia secondary to elevation of 1-25D may be related to renal calcification and granuloma formation.
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24,25-Dihidroxivitamina D 3/sangre , Hipercalcemia/sangre , Enfermedades Renales/sangre , Sarcoidosis/sangre , Adulto , Anciano , Antígenos CD/análisis , Antígenos de Diferenciación Mielomonocítica/análisis , Biopsia , Calcio/sangre , Estudios de Cohortes , Femenino , Tasa de Filtración Glomerular , Humanos , Hipercalcemia/etiología , Riñón/patología , Enfermedades Renales/complicaciones , Enfermedades Renales/patología , Macrófagos/patología , Masculino , Persona de Mediana Edad , Nefritis Intersticial/sangre , Nefritis Intersticial/patología , Estudios Retrospectivos , Sarcoidosis/complicaciones , Sarcoidosis/tratamiento farmacológico , Esteroides/uso terapéutico , Adulto JovenRESUMEN
A 63-year-old man with pharyngeal cancer had been prescribed pilocarpine hydrochloride for xerostomia after concomitant chemoradiotherapy. After 6 months of taking pilocarpine hydrochloride, he was referred to our hospital due to gradually developing renal insufficiency. The patient underwent detailed urinalysis, blood chemistry analysis, immune-serology testing. A renal biopsy was also performed. He was diagnosed with chronic tubulointerstitial nephritis (TIN) caused by lymphocytic infiltration of the interstitium, tubular atrophy, and interstitial fibrotic changes. Infections, autoimmune diseases, and genetic factors were ruled out as causes of TIN; a drug-induced lymphocyte stimulation test confirmed that he had high stimulation index scores for pilocarpine hydrochloride and a normal range stimulation score for other supplements. These results indicated that the TIN could have been induced by pilocarpine hydrochloride. Drug discontinuation partly improved his renal function and tubule marker levels. To our knowledge, this is the first report of TIN following administration of pilocarpine hydrochloride. This finding could contribute to future treatment decisions for patients with TIN and those using pilocarpine hydrochloride.
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Agonistas Muscarínicos/efectos adversos , Nefritis Intersticial/inducido químicamente , Pilocarpina/efectos adversos , Insuficiencia Renal/etiología , Quimioradioterapia/métodos , Humanos , Masculino , Persona de Mediana Edad , Nefritis Intersticial/sangre , Nefritis Intersticial/patología , Nefritis Intersticial/orina , Neoplasias Faríngeas/complicaciones , Neoplasias Faríngeas/tratamiento farmacológico , Neoplasias Faríngeas/radioterapia , Privación de Tratamiento , Xerostomía/tratamiento farmacológico , Xerostomía/etiologíaRESUMEN
A 61-year-old man was diagnosed with sarcoidosis involving the lungs, eyes, parotid gland and extrathoracic lymph nodes complicated by chronic kidney injury and hypercalcemia. Kidney biopsy showed non-specific interstitial nephritis and nephrosclerosis. However, immunohistochemical staining of cell surface markers revealed a multinucleated giant macrophage surrounded by T-cells, suggesting granulomatous interstitial nephritis. Corticosteroid improved the kidney function, and reduced the serum levels of calcium and angiotensin-converting enzyme. Sarcoid nephropathy may be caused by the combination of several sarcoidosis-associated pathophysiological conditions and a comprehensive kidney examination should be performed to assess the type of injury when determining a treatment strategy.
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Nefritis Intersticial/etiología , Sarcoidosis/complicaciones , Biomarcadores/sangre , Biopsia , Calcio/sangre , Glucocorticoides/uso terapéutico , Humanos , Hipercalcemia/etiología , Riñón/patología , Masculino , Persona de Mediana Edad , Nefritis Intersticial/sangre , Nefritis Intersticial/tratamiento farmacológico , Nefritis Intersticial/patología , Nefroesclerosis/sangre , Nefroesclerosis/etiología , Nefroesclerosis/patología , Peptidil-Dipeptidasa A/sangre , Cintigrafía , Sarcoidosis/sangre , Sarcoidosis/tratamiento farmacológico , Sarcoidosis/patologíaRESUMEN
Corticosteroids may hasten recovery in drug-induced acute interstitial nephritis (DI-AIN). However, there is no consensus regarding the effectiveness of corticosteroid compared with non-corticosteroid therapy. We conducted a systematic review of the literature according to Preferred Reporting in Systematic Reviews and Meta-Analysis (PRISMA) guidelines using MEDLINE, EMBASE, CINAHL, Scopus and Web of Science from inception until November 2017 using predefined search terms. Studies that compared the effects of corticosteroid therapy versus non-corticosteroid therapy in the treatment of DI-AIN were included. Outcomes were change in serum creatinine, adverse drug reactions, need for renal replacement therapy (RRT) and death. Due to considerable heterogeneity, a meta-analysis was not performed. There were no randomised controlled trials. Eight retrospective studies met inclusion criteria, with 430 patients (300 received and 130 did not receive corticosteroid therapy) and a median age of 57 (range 29-75) and 58 (22-76) years respectively. When treatment details were reported, prednisone was commenced at 40-60 mg daily in five studies, and two studies commenced intravenous methylprednisolone 1 mg/kg with a treatment duration of 1.5-12 weeks. Non-corticosteroid therapy was poorly defined across all studies. Four studies showed no difference in serum creatinine between corticosteroid and comparator arms, while four studies found a benefit. Adverse drug reactions, need for RRT and deaths were infrequently reported. Risk of bias was high across all domains. The limited evidence does not support the use of corticosteroids in the treatment of DI-AIN. Larger, well-designed trials are needed to help guide clinical management of this condition.