Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 698
Filtrar
1.
Medicine (Baltimore) ; 99(5): e18857, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32000387

RESUMO

RATIONALE: IgG4-related disease (IgG4-RD) is a slowly progressing inflammatory disease that can involve multiple organ systems. There is considerable overlap between IgG4-RDs and anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Herein, we present an unusual case of IgG4-associated tubulointerstitial nephritis (IgG4-TIN) and ANCA-associated glomerulonephritis (ANCA-GN) co-occurring with C3 glomerulonephritis (C3GN). PATIENT CONCERNS: A 72-year-old male was admitted to hospital because of fever and fatigue. He was diagnosed with elevated serum creatinine and IgG4 levels, and was positive for ANCA. DIAGNOSIS: Initially, the pathology supported a diagnosis of IgG4-TIN and ANCA-GN; however, further examination revealed he also had C3GN. INTERVENTIONS: The patient was treated with methylprednisolone and cyclophosphamide and received regular follow-up care. OUTCOMES: After treatment, the patient no longer exhibited fever or fatigue and had no complications. The seven-month follow-up showed downward trends in IgG4 and MPO-ANCA levels and stable 24-hour urine protein, serum creatinine levels. LESSONS: Anti-neutrophil cytoplasmic antibody-associated glomerulonephritis and IgG4-associated tubulointerstitial nephritis with C3glomerulonephritis rarely occur simultaneously. Laboratory analysis and pathology are both needed to ensure diagnostic accuracy. However, in this case, the three diseases overlapped to such a large extent that achieving a definitive diagnosis was particularly challenging. Timely and accurate diagnosis is crucial for selecting the best treatment course and optimizing patient outcome.


Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/diagnóstico , Glomerulonefrite/diagnóstico , Nefrite Intersticial/diagnóstico , Idoso , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/tratamento farmacológico , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/imunologia , Anticorpos Anticitoplasma de Neutrófilos/imunologia , Complemento C3/imunologia , Ciclofosfamida/uso terapêutico , Glomerulonefrite/tratamento farmacológico , Glomerulonefrite/imunologia , Glucocorticoides/uso terapêutico , Humanos , Imunoglobulina G/imunologia , Imunossupressores/uso terapêutico , Masculino , Metilprednisolona/uso terapêutico , Nefrite Intersticial/tratamento farmacológico , Nefrite Intersticial/imunologia
2.
Medicine (Baltimore) ; 98(48): e18178, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31770269

RESUMO

RATIONALE: Occasionally, tubulointerstitial lesions can be found in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). However, significantly isolated tubulointerstitial nephritis (TIN) with germinal centers is rare. PATIENT CONCERNS: A 17-year-old Chinese Han patient showed rapidly progressive glomerulonephritis, anuria, and serum creatinine of 19.4 mg/dL. DIAGNOSIS: He had positive ANCA targeting myeloperoxidase (55.0 RU/mL). The renal biopsy showed crescent formation in 100% of glomeruli. Of special note, the glomerular crescents were surrounded by granulomatous inflammation, extensive tubular destruction or disappearance, and massive interstitial infiltration. A diagnosis of AAV was thus made with the involved organ restricted to the kidney. INTERVENTIONS: The patient underwent 7 rounds of plasmapheresis, 3 pulses of methylprednisolone therapy (500 mg per pulse), and oral prednisolone (50 mg/d). Rituximab (500 mg) was used after the plasma exchange treatment. OUTCOMES: ANCA was negative, while anti-modified C-reactive protein (anti-mCRP) antibodies remained positive. The patient was dependent on hemodialysis. We found anti-mCRP antibody in the serum of the patient, with the major epitope on amino acids 35 to 47 of mCRP. LESSONS: We proposed that the anti-mCRP antibody might play an important role in this case of acute TIN in AAV.


Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos , Proteína C-Reativa/imunologia , Glucocorticoides/administração & dosagem , Nefrite Intersticial , Troca Plasmática/métodos , Plasmaferese/métodos , Rituximab/administração & dosagem , Adolescente , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/diagnóstico , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/imunologia , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/fisiopatologia , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/terapia , Anticorpos Anticitoplasma de Neutrófilos/sangue , Progressão da Doença , Centro Germinativo/patologia , Humanos , Fatores Imunológicos/administração & dosagem , Testes de Função Renal/métodos , Glomérulos Renais/patologia , Glomérulos Renais/fisiopatologia , Masculino , Nefrite Intersticial/diagnóstico , Nefrite Intersticial/imunologia , Nefrite Intersticial/fisiopatologia , Nefrite Intersticial/terapia , Resultado do Tratamento
3.
Transplant Proc ; 51(10): 3286-3292, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31732216

RESUMO

The 2017 Banff meeting provided specific criteria for the diagnosis of tubulointerstitial changes in chronic active T cell-mediated rejection (CATCR), with an emphasis on inflammation in areas of interstitial fibrosis and tubular atrophy, which was thought to reflect an ongoing T cell-mediated alloimmunity. CATCR is considered to occur as a consequence of persistent or recurrent acute T cell-mediated rejection. Acute T cell-mediated rejection is an acute cytotoxic T-cell reaction to HLA antigens on the donor kidneys and causes tubulitis, interstitial inflammation, and intimal arteries. However, unlike early T-cell transplant damage, CATCR can sometimes be difficult to diagnose because the subsequent chronic T-cell damage can become more complex from the accumulation of previous immune and nonimmune injuries. Furthermore, scoring inflammation in areas of interstitial fibrosis and tubular atrophy has potential problems because other diseases and not even native kidneys can have scattered inflammatory cells. Therefore, detailed insights on the pathogenesis of CATCR are indispensable for appropriate diagnosis and further treatment. In this study, the pathologic characteristics and possible factors involved in the interstitial lesions in both typical and complex cases of CATCR are discussed.


Assuntos
Rejeição de Enxerto/complicações , Transplante de Rim/efeitos adversos , Túbulos Renais/patologia , Rim/patologia , Nefrite Intersticial/patologia , Complicações Pós-Operatórias/patologia , Adulto , Idoso , Atrofia/imunologia , Atrofia/patologia , Feminino , Fibrose , Rejeição de Enxerto/imunologia , Antígenos HLA , Histocompatibilidade , Humanos , Inflamação , Masculino , Pessoa de Meia-Idade , Nefrite Intersticial/imunologia , Complicações Pós-Operatórias/imunologia
4.
Am J Physiol Renal Physiol ; 317(3): F658-F669, 2019 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-31364375

RESUMO

Progressive tubulointerstitial fibrosis may occur after acute kidney injury due to persistent inflammation. Purinergic signaling by 5'-ectonucleotidase, CD73, an enzyme that converts AMP to adenosine on the extracellular surface, can suppress inflammation. The role of CD73 in progressive kidney fibrosis has not been elucidated. We evaluated the effect of deletion of CD73 from kidney perivascular cells (including pericytes and/or fibroblasts of the Foxd1+ lineage) on fibrosis. Perivascular cell expression of CD73 was necessary to suppress inflammation and prevent kidney fibrosis in Foxd1CreCD73fl/fl mice evaluated 14 days after unilateral ischemia-reperfusion injury or folic acid treatment (250 mg/kg). Kidneys of Foxd1CreCD73fl/fl mice had greater collagen deposition, expression of proinflammatory markers (including various macrophage markers), and platelet-derived growth factor recepetor-ß immunoreactivity than CD73fl/fl mice. Kidney dysfunction and fibrosis were rescued by administration of soluble CD73 or by macrophage deletion. Isolated CD73-/- kidney pericytes displayed an activated phenotype (increased proliferation and α-smooth muscle actin mRNA expression) compared with wild-type controls. In conclusion, CD73 in perivascular cells may act to suppress myofibroblast transformation and influence macrophages to promote a wound healing response. These results suggest that the purinergic signaling pathway in the kidney interstitial microenvironment orchestrates perivascular cells and macrophages to suppress inflammation and prevent progressive fibrosis.


Assuntos
5'-Nucleotidase/metabolismo , Microambiente Celular , Fibroblastos/metabolismo , Rim/metabolismo , Macrófagos/metabolismo , Nefrite Intersticial/metabolismo , Pericitos/metabolismo , Traumatismo por Reperfusão/metabolismo , 5'-Nucleotidase/deficiência , 5'-Nucleotidase/genética , Actinas/metabolismo , Animais , Proliferação de Células , Células Cultivadas , Colágeno/metabolismo , Modelos Animais de Doenças , Fibroblastos/patologia , Fibrose , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/metabolismo , Proteínas Ligadas por GPI/deficiência , Proteínas Ligadas por GPI/genética , Proteínas Ligadas por GPI/metabolismo , Mediadores da Inflamação/metabolismo , Rim/imunologia , Rim/patologia , Macrófagos/patologia , Masculino , Camundongos da Linhagem 129 , Camundongos Endogâmicos C57BL , Camundongos Knockout , Nefrite Intersticial/genética , Nefrite Intersticial/imunologia , Nefrite Intersticial/patologia , Pericitos/patologia , Receptor beta de Fator de Crescimento Derivado de Plaquetas/metabolismo , Traumatismo por Reperfusão/genética , Traumatismo por Reperfusão/imunologia , Traumatismo por Reperfusão/patologia , Transdução de Sinais , Cicatrização
6.
Ren Fail ; 41(1): 657-661, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31296087

RESUMO

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.


Assuntos
Autoanticorpos/sangue , Proteína C-Reativa/imunologia , Rim/patologia , Nefrite Intersticial/imunologia , Idoso , Ciclofosfamida/uso terapêutico , Humanos , Imunoglobulina G/sangue , Masculino , Nefrite Intersticial/sangue , Nefrite Intersticial/tratamento farmacológico , Prednisona/uso terapêutico
7.
Am J Physiol Renal Physiol ; 317(3): F584-F592, 2019 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-31291122

RESUMO

Acute tubulointerstitial nephritis (ATIN) is a common cause of acute kidney injury characterized by inflammatory cells infiltrating in the interstitium. The present study aimed to explore noninvasive biomarkers that might indicate activity of pathological injuries and help direct treatment. Fifty-four patients with clinical-pathologically diagnosed ATIN from January 1, 2014, to June 30, 2016, at Peking University First Hospital were enrolled. Urine samples were collected on the morning of renal biopsy and assessed for urinary kidney injury molecule-1 (KIM-1) and urinary soluble C5b-9 (sC5b-9). Immunofluorescence staining for KIM-1 and C5b-9 was performed in biopsied kidney sections from ATIN cases. The clinical and pathological relevance of the two urinary biomarkers was analyzed. Both urinary KIM-1 and sC5b-9 values were significantly elevated in patients with ATIN compared with healthy controls. The urinary KIM-1 level positively correlated with urinary N-acetyl-ß-d-glucosaminidase (r = 0. 542, P = 0.001) and the pathological tubular injury score (r = 0.469, P < 0.001), whereas the urinary sC5b-9 level was related to pathological activity scores for tubular injury (r = 0.413, P = 0.002), interstitial inflammation (r = 0.388, P = 0.004), and treatment response (r = 0.564, P < 0.001). Urinary KIM-1 tended to have better diagnostic value for tubular injury than urinary sC5b-9, whereas only urinary sC5b-9 was able to demonstrate severe interstitial inflammation. A combination of urinary KIM-1 and sC5b-9 had an area under the receiver-operating characteristic curve of 0.864 (95% confidence interval: 0.766-0.963, P < 0.001, sensitivity: 75%, specificity: 88%) for acute tissue injury in ATIN. KIM-1 expression was markedly increased in renal tubular cells in both ATIN and acute tubular necrosis conditions, whereas a significant upregulation of C5b-9 was only detected in the tubular cells and interstitial cells in ATIN cases. Urinary KIM-1 is a specific biomarker for renal tubular injury in ATIN, whereas urinary sC5b-9 is valuable in demonstrating severe interstitial inflammation. The combination of these two biomarkers helps identify patients at an acute injury stage and, therefore, might facilitate clinical evaluation and guide immunosuppressive therapy.


Assuntos
Complexo de Ataque à Membrana do Sistema Complemento/urina , Receptor Celular 1 do Vírus da Hepatite A/análise , Nefrite Intersticial/diagnóstico , Nefrite Intersticial/urina , Adulto , Idoso , Biomarcadores/urina , Biópsia , Feminino , Imunofluorescência , Humanos , Rim/imunologia , Rim/patologia , Masculino , Pessoa de Meia-Idade , Nefrite Intersticial/imunologia , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos , Índice de Gravidade de Doença , Urinálise
9.
Arch Pathol Lab Med ; 143(10): 1212-1224, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31063013

RESUMO

CONTEXT.­: Light chain-associated acute tubulointerstitial nephritis (LC-ATIN) is a variant of light chain proximal tubulopathy (LCPT). It is characterized by interstitial inflammation with tubulitis and deposition of monoclonal light chains in the tubulointerstitium. LC-ATIN is a rather poorly recognized pattern of LCPT and not much is known about this entity. OBJECTIVE.­: To determine the clinicopathologic features of patients with LC-ATIN and investigate the proximal tubular injury and mechanism of interstitial inflammation in LC-ATIN. DESIGN.­: A total of 38 cases of LC-ATIN were identified from the archives of 5043 renal biopsy specimens. In all cases, routine light microscopic examination, immunofluorescence, and electron microscopic examination were performed. In selected cases, immunofluorescent staining of dendritic cells and immunohistochemical staining for 4 tubular injury markers-KIM-1, p53, bcl-2, and Ki-67-were performed. RESULTS.­: A characteristic finding in LC-ATIN cases was immunofluorescence staining of monoclonal light chains along tubular basement membranes in linear fashion and inside proximal tubular cells with a granular pattern. No monoclonal light chains were present in glomerular or vascular compartments confirmed with immunofluorescence, electron microscopy, and ultrastructural gold labeling. Ten of 15 LC-ATIN cases (67%) were concurrently positive for the 4 tubular injury markers. Dendritic cells were identified within the tubulointerstitium in the renal biopsy specimens, interacting with surrounding tubules with light-chain deposits and inflammatory cells. CONCLUSIONS.­: Significant proximal tubular injury occurs associated with LC-ATIN, and the monoclonal light chains accumulated in proximal tubular cells contribute to the injury. Dendritic cells are involved in the pathogenesis of interstitial inflammation in LC-ATIN.


Assuntos
Nefrite Intersticial/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/análise , Células Dendríticas/imunologia , Feminino , Imunofluorescência , Humanos , Imuno-Histoquímica , Inflamação/patologia , Túbulos Renais Proximais/imunologia , Túbulos Renais Proximais/patologia , Masculino , Microscopia Eletrônica , Pessoa de Meia-Idade , Nefrite Intersticial/imunologia
10.
Transplant Proc ; 51(5): 1472-1474, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31084921

RESUMO

INTRODUCTION: The immunosuppressant agents in kidney transplantation (KT) may lead to various complications such as opportunistic infections and malignancies. BK virus associated nephropathy is a significant complication following KT, and it can result in graft failure. BK virus causes tubulointerstitial nephritis, ureter stenosis, and even graft failure in KT recipients with impaired immune system. We described a 63-year-old woman, who was a hepatitis C carrier and on dialysis for 22 years before KT, who received cadaveric-donor KT 2 years previously. She reported decreasing urine output and general weakness. The serum creatinine level was slightly increased from 2.94 to 4.38 mg/dL. METHODS: Immunosuppressant medications including prednisolone, everolimus, cyclosporin, and mycophenolate sodium were continued as maintenance therapy post KT. Kidney biopsy was performed due to deterioration of graft function. RESULTS: The kidney biopsy showed consistent results with early-stage polyomavirus nephropathy, characterized by focal viral cytopathic changes with positive immunohistochemical signals and mesangial proliferative glomerulonephritis, immune-complex-mediated (Fig 1 and Fig 2). Negative C4d staining at peritubular capillary was reported. The dosage of mycophenolate sodium was tapered from 720 to 360 mg daily and that of everolimus increased from 0.5 to 1.0 mg daily due to BK viral infection with BK nephropathy. The serum creatinine level was 2.75 mg/dL after treatment. CONCLUSION: Early detection of BK nephropathy and decreasing immunosuppressant agents are the mainstay of treatment. Substituting leflunomide for mycophenolate sodium and increasing dosage of everolimus has been proposed to solve BK nephropathy. We presented that the use of leflunomide in such situation is in a timely manner.


Assuntos
Hospedeiro Imunocomprometido , Imunossupressores/efeitos adversos , Transplante de Rim , Infecções por Polyomavirus/imunologia , Infecções Tumorais por Vírus/imunologia , Vírus BK , Everolimo/uso terapêutico , Feminino , Humanos , Transplante de Rim/efeitos adversos , Leflunomida/uso terapêutico , Pessoa de Meia-Idade , Ácido Micofenólico/uso terapêutico , Nefrite Intersticial/imunologia , Nefrite Intersticial/virologia , Infecções Oportunistas/imunologia , Transplante Homólogo/efeitos adversos
11.
PLoS One ; 14(2): e0211915, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30779760

RESUMO

BACKGROUND: Tubulointerstitial nephritis (TIN) and uveitis syndrome (TINU) are likely to be autoimmune diseases. Based on previous studies, adults with isolated idiopathic uveitis have polymorphisms in interleukin 10 (IL-10) and tumor necrosis factor α (TNF-α) genes. We aimed to evaluate the presence of IL-10 and TNF-α polymorphisms in a nationwide cohort of pediatric TIN/TINU patients. METHODS: Single nucleotide polymorphisms in IL-10 (+434T/C, +504G/T, -1082G/A, -2849C/T) and in TNFα (-308G/A, -238G/A, -857C/T) genes were genotyped in 30 well-defined pediatric patients with idiopathic TIN/TINU syndrome. Control group frequencies for these SNPs were obtained from 393 independent Finnish subjects. RESULTS: The homozygous minor allele in IL-10 +434T (rs2222202) and IL-10+504G (rs3024490) was found in all patients with TIN or TINU syndrome while the frequency of these minor alleles in the control population was 44% and 23%, respectively (p <0.001). In IL-10 SNP -2849 (rs6703630) a significant difference was found with genotype TT in all patients (p = 0.004) and in subgroups with TINU syndrome (p = 0.017) and TINU syndrome with chronic uveitis (p = 0.01) compared to reference population. There were no statistical differences in any of the studied TNF-α genotypes between TIN/TINU patients and control population. CONCLUSIONS: A significant difference in the frequency of IL-10+434T and +504G alleles was found between TIN/TINU patients and control population. Genotype -2849TT was more frequently present in patients with TINU syndrome than in the reference subjects. Genetic variation in the inflammatory mediators may predispose to autoimmune nephritis and uveitis.


Assuntos
Alelos , Predisposição Genética para Doença , Interleucina-10/genética , Nefrite Intersticial/genética , Polimorfismo de Nucleotídeo Único , Uveíte/genética , Adolescente , Criança , Feminino , Genótipo , Humanos , Interleucina-10/imunologia , Masculino , Nefrite Intersticial/imunologia , Nefrite Intersticial/patologia , Uveíte/imunologia , Uveíte/patologia
12.
BMC Nephrol ; 20(1): 23, 2019 01 16.
Artigo em Inglês | MEDLINE | ID: mdl-30651091

RESUMO

BACKGROUND: Understanding the uncommon association of IgG4-related disease with other disorders is essential for the accurate diagnosis and effective treatment of patients. To the best of our knowledge, there have been only few reports of patients with IgG4-related kidney disease coexisting with metastasis of malignancy. Here, we report a rare case of simultaneous occurring IgG4-related tubulointerstitial nephritis and colon adenocarcinoma with hepatic metastasis. CASE PRESENTATION: A 71-year-old Chinese man presented with dysuria and was initially diagnosed as benign prostatic hyperplasia for one year. He was admitted to the hospital for surgery. After admission, the renal function tests revealed a rapid increase of serum creatinine from 291.0 µmol/L to 415 µmol/L. The hemoglobin level was 89 g/L. Fecal occult blood testing was positive. Urinalysis revealed mild proteinuria. The serum IgG4 level was 13.9 g/L. The abdominal imaging examination revealed multiple solid nodules in the liver. The gastrointestinal endoscopy combined with the biopsy revealed colon adenocarcinoma. Kidney biopsy showed massive IgG4-positive plasma cells and storiform fibrosis infiltration in the tubulointerstitial area, thus establishing the diagnosis of IgG4-related tubulointerstitial nephritis. Corticosteroid therapy was initiated, and subsequently, the renal function dramatically improved without the diminution of the liver nodules. The liver biopsy was performed and a diagnosis of metastatic colon adenocarcinoma was confirmed. CONCLUSIONS: We here reported a rare case of simultaneous occurring of IgG4-related tubulointerstitial nephritis, colon adenocarcinoma with hepatic metastasis. The case highlights the importance of screening for malignancy in patients with IgG4-related disease, and the nature of the mass in other organs of patients with coexisting IgG4-related disease and malignancy should be carefully checked.


Assuntos
Adenocarcinoma/complicações , Neoplasias do Colo/complicações , Imunoglobulina G/análise , Neoplasias Hepáticas/secundário , Nefrite Intersticial/complicações , Adenocarcinoma/diagnóstico , Adenocarcinoma/secundário , Idoso , Biópsia , Evolução Fatal , Humanos , Rim/patologia , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/diagnóstico , Masculino , Nefrite Intersticial/diagnóstico , Nefrite Intersticial/imunologia , Nefrite Intersticial/patologia , Plasmócitos/patologia
13.
CEN Case Rep ; 8(2): 119-124, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30637665

RESUMO

A 47-year-old man presented with severe hypokalemic paralysis and respiratory failure. A large amount of potassium was administered along with providing intensive care, and his condition improved. Hypokalemia was attributed to increased urinary potassium excretion. A kidney biopsy was performed to make a definitive histological diagnosis. It revealed acute tubulointerstitial nephritis (TIN). After the diagnosis, prednisolone was administered, and the TIN gradually improved. From the clinical course and laboratory findings, the TIN was presumed to be an autoimmune disorder. Further specific autoantibody tests were positive for anti-mitochondrial antibody (AMA), which has been gaining increasing attention in regard to TIN. In addition, all previous cases of TIN associated with AMA have affected females. The detailed pathogenetic mechanisms are as yet unclear and require further investigation.


Assuntos
Glucocorticoides/uso terapêutico , Hipopotassemia/etiologia , Mitocôndrias/imunologia , Nefrite Intersticial/diagnóstico , Nefrite Intersticial/patologia , Prednisolona/uso terapêutico , Doenças Autoimunes/complicações , Doenças Autoimunes/diagnóstico , Biópsia , Glucocorticoides/administração & dosagem , Humanos , Hipopotassemia/tratamento farmacológico , Rim/patologia , Masculino , Pessoa de Meia-Idade , Nefrite Intersticial/complicações , Nefrite Intersticial/imunologia , Paralisia , Prednisolona/administração & dosagem , Insuficiência Respiratória/diagnóstico , Resultado do Tratamento
14.
Kidney Int ; 95(2): 388-404, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30551896

RESUMO

Hypoxia promotes tubulointerstitial inflammation in the kidney. Although hypoxia inducible factor-1α (HIF-1α) is a master regulator of the response to hypoxia, the exact mechanisms through which HIF-1α modulates the induction of tubulointerstitial inflammation are still largely unclear. We demonstrated tubulointerstitial inflammation and increased tubular HIF-1α expression in murine models of ischemia/reperfusion injury and unilateral ureteral obstruction. Increased expression of HIF-1α in tubular epithelial cells was associated with selective shedding of microRNA-23a (miRNA-23a)-enriched exosomes in vivo and systemic inhibition of miRNA-23a prior to ischemia/reperfusion injury attenuated tubulointerstitial inflammation. In vitro, uptake of miRNA-23a-enriched exosomes by macrophages triggered their reprogramming into a pro-inflammatory state via suppression of the ubiquitin editor A20. To confirm the effect of miRNA-23a-containing exosomes on tubulointerstitial inflammation, we exposed tubular epithelial cells to hypoxic conditions to promote the release of miRNA-23a-containing exosomes. Injection of these miRNA-23a-enriched exosomes into uninjured renal parenchyma resulted in increased inflammatory infiltration in vivo. Taken together, our studies demonstrate that the HIF-1α-dependent release of miRNA-23a-enriched exosomes from hypoxic tubular epithelial cells activates macrophages to promote tubulointerstitial inflammation. Blockade of exosome-mediated miRNA-23a transfer between tubular epithelial cells and macrophages may serve as a novel therapeutic approach to ameliorate tubulointerstitial inflammation.


Assuntos
Células Epiteliais/imunologia , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Macrófagos/imunologia , MicroRNAs/metabolismo , Nefrite Intersticial/imunologia , Animais , Comunicação Celular/imunologia , Hipóxia Celular/genética , Hipóxia Celular/imunologia , Reprogramação Celular/genética , Reprogramação Celular/imunologia , Modelos Animais de Doenças , Células Epiteliais/citologia , Células Epiteliais/metabolismo , Exossomos/imunologia , Exossomos/metabolismo , Regulação da Expressão Gênica/imunologia , Humanos , Túbulos Renais/citologia , Túbulos Renais/imunologia , Macrófagos/metabolismo , Masculino , Camundongos , Nefrite Intersticial/patologia , Transdução de Sinais/genética , Transdução de Sinais/imunologia , Proteína 3 Induzida por Fator de Necrose Tumoral alfa/genética , Proteína 3 Induzida por Fator de Necrose Tumoral alfa/metabolismo
15.
Nephrol Dial Transplant ; 34(4): 711-717, 2019 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-30124906

RESUMO

BACKGROUND: Tubular basement membrane immune deposits (TBMID) has rarely been observed in renal allografts. It is usually found in BK virus nephropathy and immune complex glomerulonephritis; however, its significance is not well understood. We conducted a retrospective clinicopathological study on monoclonal immunoglobulin G (IgG) TBMID. METHODS: We studied 7177 renal allograft biopsy specimens obtained from Tokyo Women's Medical University from 2007 to 2015 and performed light microscopic, electron microscopic and immunofluorescence studies. RESULTS: Tubular basement membrane (TBM) deposits of IgG were found in 73 biopsies from 61 patients and the IgG subclass was obtained in 31 biopsies. There were no cases of monoclonal IgA or IgM TBMID. In total, 13 biopsies from 10 patients showed monoclonal IgG TBMID. Of these, seven showed monoclonal IgG1κ TBMID and one each showed monoclonal IgG2κ, IgG2λ and IgG3κ TBMID. Conversely, eight patients showed polyclonal IgG TBMID. In electron microscopy, large granular electron-dense deposits (EDDs) in the TBM were detected in all patients with monoclonal IgG1κ TBMID. EDDs were absent in TBM in patients with monoclonal IgG2κ, IgG2λ or IgG3κ TBMID. Progression of interstitial fibrosis and tubular atrophy (IFTA) was significantly higher in patients with monoclonal IgG1κ TBMID than in those with polyclonal IgG TBMID (P < 0.05). There were no significant differences in the other clinical parameters between monoclonal IgG1κ and polyclonal IgG TBMID. CONCLUSIONS: This is the first study of patients with monoclonal IgG TBMID in renal allografts. We found that monoclonal IgG1κ TBMID was associated with EDD formation in TBM and IFTA progression.


Assuntos
Anticorpos Monoclonais/imunologia , Membrana Basal/imunologia , Glomerulonefrite/imunologia , Imunoglobulina G/imunologia , Transplante de Rim/métodos , Nefrite Intersticial/imunologia , Adolescente , Adulto , Idoso , Aloenxertos , Anticorpos Monoclonais/metabolismo , Membrana Basal/metabolismo , Criança , Feminino , Glomerulonefrite/metabolismo , Glomerulonefrite/patologia , Humanos , Imunoglobulina G/metabolismo , Masculino , Pessoa de Meia-Idade , Nefrite Intersticial/metabolismo , Nefrite Intersticial/patologia , Prognóstico , Estudos Retrospectivos , Adulto Jovem
16.
Clin Exp Rheumatol ; 37(2): 279-285, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30183608

RESUMO

OBJECTIVES: Immunoglobulin G4 (IgG4)-related disease (IgG4-RD) is an immune-mediated fibroinflammatory disorder and is characterised by elevated serum IgG4 concentrations and dense lymphoplasmacytic infiltrate rich in IgG4+ plasma cells. IgG4-related tubulointerstitial nephritis (IgG4-TIN) is the most common manifestation of IgG4-related kidney disease (IgG4-RKD). We report four cases of kidney injury with concurrent IgG4-TIN and crescentic glomerulonephritis confirmed by renal pathology. METHODS: The medical charts of four patients were reviewed to collect clinical and laboratory data at the time of diagnosis, treatment and outcomes after 6-36 months. Two of them are cases of IgG4-TIN with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), and the other two cases are rare IgG4-TIN with antiglomerular basement membrane (anti-GBM) glomerulonephritis coexistent with ANCA-positive serum. RESULTS: Compared with IgG4-TIN, IgG4-TIN combined with AAV or anti-GBM glomerulonephritis is less associated with other organ injuries, and the clinical manifestations, treatment effects and prognosis were consistent with that of crescentic glomerulonephritis. CONCLUSIONS: IgG4-TIN concurrent with anti-GBM glomerulonephritis and positivity in serum has more severe clinical features and a worse renal prognosis than IgG4-TIN coexistent with AVV.


Assuntos
Anticorpos Anticitoplasma de Neutrófilos/metabolismo , Autoanticorpos/metabolismo , Glomerulonefrite/imunologia , Nefrite Intersticial/imunologia , Anticorpos Anticitoplasma de Neutrófilos/imunologia , Autoanticorpos/imunologia , Glomerulonefrite/metabolismo , Humanos , Imunoglobulina G/imunologia , Imunoglobulina G/metabolismo , Nefrite Intersticial/metabolismo
17.
Cell Death Dis ; 9(11): 1126, 2018 11 13.
Artigo em Inglês | MEDLINE | ID: mdl-30425237

RESUMO

Renal fibrosis, especially tubulointerstitial fibrosis, is the inevitable outcome of all progressive chronic kidney diseases (CKDs) and exerts a great health burden worldwide. For a long time, interests in renal fibrosis have been concentrated on fibroblasts and myofibroblasts. However, in recent years, growing numbers of studies have focused on the role of tubular epithelial cells (TECs). TECs, rather than a victim or bystander, are probably a neglected mediator in renal fibrosis, responding to a variety of injuries. The maladaptive repair mechanisms of TECs may be the key point in this process. In this review, we will focus on the role of TECs in tubulointerstitial fibrosis. We will follow the fate of a tubular cell and depict the intracellular changes after injury. We will then discuss how the repair mechanism of tubular cells becomes maladaptive, and we will finally discuss the intercellular crosstalk in the interstitium that ultimately proceeds tubulointerstitial fibrosis.


Assuntos
Células Epiteliais/patologia , Inflamassomos/imunologia , Túbulos Renais/patologia , Miofibroblastos/patologia , Nefrite Intersticial/patologia , Animais , Comunicação Celular/imunologia , Citocinas/genética , Citocinas/imunologia , Células Epiteliais/imunologia , Fibrose , Regulação da Expressão Gênica , Humanos , Inflamassomos/genética , Túbulos Renais/imunologia , Mitocôndrias/imunologia , Mitocôndrias/patologia , Monócitos/imunologia , Monócitos/patologia , Miofibroblastos/imunologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/imunologia , Nefrite Intersticial/genética , Nefrite Intersticial/imunologia , Transdução de Sinais
18.
Rheum Dis Clin North Am ; 44(4): 619-633, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30274627

RESUMO

Tubulointerstitial nephritis (TIN) is the second most common cause of acute intrinsic kidney injury after acute tubular necrosis. Although drug-induced forms of TIN represent the vast majority, rheumatic disease is another common cause and often underdiagnosed. Early diagnosis of acute interstitial nephritis and prompt withdrawal of the culprit medication or a correct treatment can avoid chronic damage and progressive chronic kidney disease. This review highlights the recent updates, clinical features, and treatment in TIN in autoimmune rheumatic disease.


Assuntos
Nefrite Intersticial , Insuficiência Renal Crônica , Doenças Reumáticas/complicações , Gerenciamento Clínico , Diagnóstico Precoce , Humanos , Nefrite Intersticial/diagnóstico , Nefrite Intersticial/etiologia , Nefrite Intersticial/imunologia , Nefrite Intersticial/terapia , Insuficiência Renal Crônica/etiologia , Insuficiência Renal Crônica/prevenção & controle
19.
Hum Pathol ; 81: 220-228, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30031099

RESUMO

Hypocomplementemia has been frequently reported in immunoglobulin G4-related kidney disease (IgG4-RKD). However, studies on the role of complement system in IgG4-RKD are lacking. A total of 40 429 renal biopsies from January 2010 to January 2018 were reexamined in the present study, and 17 patients were confirmed to meet the criteria of IgG4-RKD. According to the serum C3 levels, they were divided into 2 groups: the low-C3 group (C3 <0.8 g/L, n = 7) and the normal-C3 group (C3 ≥0.8 g/L, n = 10). Compared with the normal-C3-level group, the patients in the low-C3-level group had lower serum C4 concentrations (P = .025), higher serum IgG4 concentrations (P = .003), higher positive rates in rheumatoid factor (P = .033), more severe storiform fibrosis (P = .007) at diagnosis, and higher blood urea nitrogen levels at the latest test (P = .04). The serum levels of C3 were in negative correlation with the serum levels of IgG4 (P = .003), the levels of rheumatoid factor (P = .002), renal deposition of C1q (P = .028), storiform fibrosis (P < .001), scores of interstitial fibrosis (P = .015), the amount of renal IgG4-positive (IgG4+) plasma cells (P = .020), the ratios of IgG4+ plasma cells/CD138+ cells (P = .018), and the blood urea nitrogen concentrations at the last test (P = .023). Our study shows that IgG4-RKD is a relatively rare entity. Complement system may participate in the development of IgG4-RKD.


Assuntos
Ativação do Complemento , Proteínas do Sistema Complemento/imunologia , Glomerulonefrite Membranosa/imunologia , Doença Relacionada a Imunoglobulina G4/imunologia , Imunoglobulina G/imunologia , Rim/imunologia , Nefrite Intersticial/imunologia , Plasmócitos/imunologia , Adulto , Idoso , Biópsia , Ativação do Complemento/efeitos dos fármacos , Complemento C1q/imunologia , Complemento C3/imunologia , Complemento C4/imunologia , Feminino , Fibrose , Glomerulonefrite Membranosa/sangue , Glomerulonefrite Membranosa/diagnóstico , Glomerulonefrite Membranosa/tratamento farmacológico , Glucocorticoides/uso terapêutico , Humanos , Imunoglobulina G/sangue , Doença Relacionada a Imunoglobulina G4/sangue , Doença Relacionada a Imunoglobulina G4/diagnóstico , Doença Relacionada a Imunoglobulina G4/tratamento farmacológico , Imunossupressores/uso terapêutico , Rim/efeitos dos fármacos , Rim/patologia , Masculino , Pessoa de Meia-Idade , Nefrite Intersticial/sangue , Nefrite Intersticial/diagnóstico , Nefrite Intersticial/tratamento farmacológico , Plasmócitos/efeitos dos fármacos , Plasmócitos/patologia , Estudos Retrospectivos , Fator Reumatoide/sangue , Fator Reumatoide/imunologia , Fatores de Risco , Resultado do Tratamento
20.
Transpl Infect Dis ; 20(5): e12939, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29863293

RESUMO

Evolving BK polyomavirus-associated nephropathy (BKPyVAN) is characterized by tubulointerstitial inflammation that closely resembles acute T-cell-mediated allograft rejection if tubulitis is significant. The cellular composition of the inflammation varies during the course of BKPyVAN, and clusters of plasma cells may herald resolution of the infection. Less commonly, BKPyVAN can present with a predominance of histiocytes and granuloma formation. Granulomatous interstitial nephritis is uncommon in biopsies of either native or transplant kidneys. In both settings, this distinctive type of inflammatory response requires a systematic approach with careful clinicopathological assessment to determine its etiology. We present three patients with granulomatous BKPyVAN in the first year post-transplantation. These allograft biopsies at 4, 6, and 12 months post-transplant exemplify spontaneously resolving BKPyVAN, resolving infection after immunosuppression reduction, and early BKPyVAN, respectively. In immunosuppressed patients, BKPyVAN should be added to the relatively broad differential diagnosis of granulomatous tubulointerstitial nephritis.


Assuntos
Granuloma/patologia , Transplante de Rim/efeitos adversos , Nefrite Intersticial/patologia , Infecções por Polyomavirus/patologia , Infecções Tumorais por Vírus/patologia , Idoso , Vírus BK/isolamento & purificação , Biópsia , Feminino , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/prevenção & controle , Granuloma/imunologia , Granuloma/virologia , Humanos , Hospedeiro Imunocomprometido , Imunossupressão/efeitos adversos , Rim/patologia , Rim/virologia , Masculino , Pessoa de Meia-Idade , Nefrite Intersticial/imunologia , Nefrite Intersticial/virologia , Infecções por Polyomavirus/imunologia , Infecções por Polyomavirus/virologia , Infecções Tumorais por Vírus/imunologia , Infecções Tumorais por Vírus/virologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA