RESUMO
BACKGROUND: IgG4-related disease (IgG4-RD) often affects multiple organs and tissues, especially the kidneys, and is characterized by interstitial nephritis, obstructive nephropathy, and in rare cases glomerulopathy (including membranous nephropathy). CASE PRESENTATION: In this article, we report a patient with nephrotic syndrome as the only initial manifestation. Membranous nephropathy was confirmed by renal biopsy, but without any renal interstitial lesions. The nephrotic syndrome completely resolved after treatment with immunosuppressants but recurred after drug withdrawal, which was accompanied by acute kidney injury. Ultimately, IgG4-related interstitial nephritis with membranous nephropathy was confirmed by a second renal biopsy. After routine administration of steroids and cyclophosphamide, renal function returned to normal after 2 months, and nephrotic syndrome was ameliorated after 5 months. CONCLUSION: Special attention should be paid to this rare condition in the clinical setting. In patients with membranous nephropathy (MN) that is accompanied by multi-system damage, impaired renal function, elevated IgG4 levels (absolute or relative value), negative PLA2R, and/or renal interstitial plasma cell infiltration, the possibility of IgG4-related kidney disease (IgG4-RKD) should be carefully assessed.
Assuntos
Glomerulonefrite Membranosa/etiologia , Doença Relacionada a Imunoglobulina G4/complicações , Glomerulonefrite Membranosa/patologia , Humanos , Doença Relacionada a Imunoglobulina G4/diagnóstico , Masculino , Pessoa de Meia-IdadeRESUMO
Patients with both anti-glomerular basement membrane (anti-GBM) disease and Castleman disease have been rarely reported. In this study, we report 3 patients with this combination. They had immunologic features similar to patients with classic anti-GBM disease. Sera from the 3 patients recognized the noncollagenous (NC) domain of the α3 chain of type IV collagen (α3(IV)NC1) and its 2 major epitopes, EA and EB. All 4 immunogloblin G (IgG) subclasses against α3(IV)NC1 were detectable, with predominance of IgG1. In one patient with lymph node biopsy specimens available, sporadic plasma cells producing α3(IV)NC1-IgG were found, suggesting a causal relationship between the 2 diseases. One patient, who achieved remission with antibody clearance and normalization of serum creatinine and interleukin 6 concentrations after plasma exchange and 3 cycles of chemotherapy, experienced recurrence of anti-GBM antibodies and an increase in interleukin 6 concentration after chemotherapy discontinuation because of adverse effects, but both returned to normal after another cycle of chemotherapy. This clinical course and the pathologic findings support the hypothesis that the Castleman disease-associated tumor cells are the source of the anti-GBM autoantibodies.
Assuntos
Doença Antimembrana Basal Glomerular/epidemiologia , Doença Antimembrana Basal Glomerular/terapia , Autoantígenos/imunologia , Hiperplasia do Linfonodo Gigante/epidemiologia , Hiperplasia do Linfonodo Gigante/terapia , Adulto , Doença Antimembrana Basal Glomerular/imunologia , Doença Antimembrana Basal Glomerular/patologia , Biópsia por Agulha , Hiperplasia do Linfonodo Gigante/imunologia , Hiperplasia do Linfonodo Gigante/patologia , Colágeno Tipo IV/imunologia , Colágeno Tipo IV/metabolismo , Terapia Combinada , Comorbidade , Epitopos , Seguimentos , Hospitalização , Humanos , Imunoglobulina G/imunologia , Imuno-Histoquímica , Masculino , Metilprednisolona/uso terapêutico , Pessoa de Meia-Idade , Troca Plasmática/métodos , Pulsoterapia , Doenças Raras , Estudos de Amostragem , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
BACKGROUND: The aim of the study is to investigate the association between clinical and pathological features in a large cohort of Chinese patients with renal immunoglobulin light-chain amyloidosis (AL). METHODS: A series of 186 patients with renal AL amyloidosis diagnosed between 1990 and 2011 were retrospectively reviewed. The extent of amyloid deposition in glomeruli, blood vessels and tubulointerstitium were evaluated semiquantitatively. The renal amyloid load was defined by the sum of glomerular, vascular and interstitial deposits. The associations between the clinical manifestations and pathological features were analyzed. RESULTS: The extent of glomerular amyloid deposition was positively correlated with the level of proteinuria. Patients with codeposition of amyloid and immune complexes (ICs) in glomeruli had higher levels of proteinuria than those without ICs. Advanced glomerular amyloid deposition was an independent pathological factor associated with renal insufficiency at diagnosis. The degree of vascular amyloid (VA) deposition was positively correlated with cardiac involvement and hepatic involvement. Patients with AL-κ showed a higher prevalence of hepatic involvement and more severe VA deposition than patients with AL-λ. High renal amyloid load independently predicted the increased risk for overall death after adjusting for recognized confounders. CONCLUSIONS: The degree and localization of amyloid deposits in the kidney of AL patients were associated with the degree of proteinuria and renal insufficiency, as well as extrarenal organs involvement. There were some differences between AL-κ and AL -λ in clinical and pathological characteristics. The renal amyloid load was an independent predictor for overall mortality.
Assuntos
Amiloide/metabolismo , Amiloidose/patologia , Cadeias kappa de Imunoglobulina/metabolismo , Cadeias lambda de Imunoglobulina/metabolismo , Proteinúria/patologia , Amiloidose/complicações , Amiloidose/imunologia , Biomarcadores/metabolismo , China/epidemiologia , Feminino , Seguimentos , Taxa de Filtração Glomerular , Humanos , Técnicas Imunoenzimáticas , Cadeias kappa de Imunoglobulina/imunologia , Cadeias lambda de Imunoglobulina/imunologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Proteinúria/epidemiologia , Proteinúria/etiologia , Proteinúria/mortalidade , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
Lymphoblastic lymphoma is an uncommon subtype of lymphoid neoplasm in adults. Acute kidney injury at initial presentation due to lymphoblastic lymphoma infiltration of the kidneys has rarely been described. We report a 19-year-old woman who presented with acute kidney injury due to massive lymphomatous infiltration of the kidneys. The diagnosis of B-cell lymphoblastic lymphoma was established by immunohistochemical study of the biopsied kidney. The patient had an excellent response to the VDCLP protocol (vincristine, daunomycin, cyclophosphamide, asparaginase, and dexamethasone) with sustained remission. We recommend that lymphomatous infiltration be considered in patients presenting with unexplained acute kidney injury and enlarged kidneys.
Assuntos
Injúria Renal Aguda/diagnóstico , Rim/patologia , Linfoma de Células B/diagnóstico , Linfoma Imunoblástico de Células Grandes/diagnóstico , Injúria Renal Aguda/complicações , Injúria Renal Aguda/patologia , Movimento Celular/fisiologia , Diagnóstico Diferencial , Feminino , Humanos , Hipertrofia , Linfoma de Células B/complicações , Linfoma de Células B/patologia , Linfoma Imunoblástico de Células Grandes/complicações , Linfoma Imunoblástico de Células Grandes/patologia , Adulto JovemRESUMO
BACKGROUND: Aristolochic acid nephropathy (AAN) is a worldwide problem and one of the common causes of chronic kidney disease (CKD) in China. METHODS: Three hundred patients diagnosed as AAN from 1997 to 2006 were enrolled. Medical histories of Chinese herb ingestion, clinical-pathological features and risk factors for renal failure were recorded. Patients were followed up for 2-156 months. Factors involved in the prognosis of AAN were investigated. RESULTS: The 300 patients with AAN manifested three clinical subtypes, including acute kidney injury (acute AAN) in 13 patients, abrupt tubular dysfunction with normal serum creatinine (Scr) levels in seven cases and chronic tubulointerstitial nephropathy with decreased estimated glomerular filtration rate (eGFR) (chronic AAN) in 280 cases. The acute AAN cases had the highest aristolochic acid (AA)-I intake per day and developed progressive kidney failure during 1-7 years follow-up. The tubular dysfunction AAN patients had the lowest cumulative AA-I intake and were able to keep normal Scr levels during 2-8 years follow-up. The chronic AAN patients took the lowest AA-I dose per day but with the longest period and the highest cumulative dosage and exhibited a very large range of eGFR changing rate (from -21.6 to 5.2, median -3.5 mL/min/year). The cumulative AA-I intake (r = 0.330, P = 0.045) and the time course from the termination of AA medication to the start of follow-up (r = -0.430, P = 0.009) were found to be independent factors correlated with the decrease rate of eGFR in the chronic AAN patients. AA and the metabolites could be detected in a high frequency in patients who had stopped herbal medication for 1 year, which indicates a rather long washout time for these chemicals. CONCLUSIONS: AAN has variant phenotypes with distinct prognosis, which is determined by the variable AA medications. With better understanding of toxic and environmental causes for kidney injury, there would be a better chance to uncover the causal factors of cases of 'CKD without known causes' which is crucial for improving the disease outcomes.
Assuntos
Ácidos Aristolóquicos/efeitos adversos , Nefropatias/induzido quimicamente , Nefropatias/diagnóstico , Mutagênicos/efeitos adversos , Progressão da Doença , Feminino , Seguimentos , Humanos , Nefropatias/classificação , Masculino , Pessoa de Meia-Idade , Fenótipo , Prognóstico , Estudos Prospectivos , Fatores de RiscoRESUMO
BACKGROUND: Nephrotic syndrome is caused by a variety of glomerulopathy. The current study investigated the renal histopathological spectrum of patients with nephrotic syndrome who received a renal biopsy in our department within the last 15 years. METHODS: One thousand five hundred and twenty-three consecutive patients (≥14 years old at renal biopsy) with nephrotic syndrome were recruited. Patients were divided into four groups according to age at the time of renal biopsy. The renal histopathological spectrum was also compared between nephrotic-range proteinuria patients with and without hypoalbuminaemia. RESULTS: Among the 1523 patients, the most common cause of nephrotic syndrome was idiopathic membranous nephropathy (IMN) (20.7%), followed by minimal change disease (MCD) (20.4%). Among the patients aged 14-24, 25-44, 45-59 and ≥60 years, the most common cause of nephrotic syndrome was MCD (33.0%), lupus nephritis (LN) (23.0%), IMN (37.9%) and IMN (42.3%), respectively. Among the female patients aged 14-24 and 25-44 years, LN was the leading cause of nephrotic syndrome (35.8 and 36.2%, respectively). The proportion of patients with renal amyloidosis increased in parallel with patient age. The comparison between nephrotic patients with and without hypoalbuminaemia suggests that patients with MCD, LN or renal amyloidosis were more likely to develop hypoalbuminaemia. CONCLUSIONS: The renal histopathological spectrum of nephrotic syndrome differs between ages. MCD, LN and IMN were the main cause of nephrotic syndrome among younger patients, and IMN was the main cause of nephrotic syndrome among older patients. The proportion of patients with renal amyloidosis increased in parallel with patient age.
Assuntos
Rim/patologia , Síndrome Nefrótica/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , China , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto JovemRESUMO
BACKGROUND: The pathological characteristics of IgA nephropathy (IgAN) are highly variable. Urinary kidney injury molecule-1 (KIM-1) is a sensitive biomarker for proximal tubule injury. The aim of the study is to investigate the value of KIM-1 as a biomarker for assessing the renal injury in IgAN. METHODS: The levels of urinary KIM-1 in 202 patients with IgAN, 46 patients with other renal diseases as disease controls and 60 healthy blood donors as normal controls were measured. Correlations with clinical and histopathological features of patients with IgAN were evaluated. RESULTS: The levels of urinary KIM-1 were significantly higher in patients with IgAN than in normal controls (P < 0.001) and in patients with non-IgAN (P = 0.011). Urinary levels of KIM-1 in IgAN positively correlated with levels of serum creatinine and proteinuria and negatively with creatinine clearance. The more severe the tubulointerstitial injury was, the higher the levels of urinary KIM-1. Patients with severe mesangial proliferation, crescents formation or endocapillary proliferation had higher levels of urinary KIM-1 than those without. The levels of tubular KIM-1 expression in immunohistochemistry closely correlated with the levels of urinary KIM-1 (r = 0.553, P = 0.032). Renal survival was significantly worse in patients with elevated urinary KIM-1 (P = 0.020). CONCLUSION: Urinary KIM-1 may be a useful biomarker to evaluate kidney injury in IgAN.
Assuntos
Biomarcadores/urina , Glomerulonefrite por IGA/complicações , Necrose Tubular Aguda/urina , Glicoproteínas de Membrana/urina , Nefrite Intersticial/urina , Adulto , Estudos de Casos e Controles , Creatinina/sangue , Feminino , Glomerulonefrite por IGA/mortalidade , Receptor Celular 1 do Vírus da Hepatite A , Humanos , Testes de Função Renal , Necrose Tubular Aguda/etiologia , Necrose Tubular Aguda/mortalidade , Masculino , Nefrite Intersticial/etiologia , Nefrite Intersticial/mortalidade , Prognóstico , Proteinúria/mortalidade , Proteinúria/patologia , Proteinúria/urina , Receptores Virais , Taxa de SobrevidaRESUMO
OBJECTIVE: To examine the cellular components at different stages of the crescent formation in four most common types of human crescentic glomerulonephritis (CGN), including anti-GBM disease (GBM-CGN), crescentic IgA nephropathy (IgA-CGN), ANCA associated pauci-immune CGN (ANCA-CGN) and crescentic lupus glomerulonephritis (LN-CGN). METHODS: Renal biopsy specimens of patients with GBM-CGN (n = 10), IgA-CGN (n = 12), ANCA-CGN (n = 12), and LN-CGN (n = 11) were selected. Immunohistochemistry was adopted to identify the cellular components using different cell markers including cytokeratin (PEC), CD68 (macrophage), nestin (podocyte), podocalyxin (podocyte), CD3 (lymphocyte), CD15 (neutrophil) and PCNA. RESULTS: There were different subtypes of cell components identified during the formation of a cellular crescent in 4 different types of human CGN. Mainly of PEC 11.4 (0.0, 95.0)%, macrophage 8.0 (0.0, 35.0)% and podocyte 5.5 (0.0, 22.0)% and their constitutive percentages were different among various CGNs (P < 0.01). In all the CGNs studied, there were 50% of cells were negative to all the cell markers adopted for this expeiment. Podocalyxin positive cells 0.5 (0.0, 9.6)% were significantly less than nestin positive cells 5.5 (0.0, 22.0)% in all CGNs. PCNA positive cells were 44.7 (16.7, 83.3)% in the cellular crescent of all CGNs and co-localized with nestin (38/45 cases), CK (42/45 cases) or CD68 (24/45 cases). CONCLUSIONS: PEC, macrophage and podocyte might play important roles in the formation of crescents. The staining disparity of nestin and podocalyxin indicates that podocyte dedifferentiation may occur during the crescent formation. PEC, podocytes and macrophages may participate in the formation of crescent in common CGNs through active cellular proliferation.
Assuntos
Células Epiteliais/metabolismo , Glomerulonefrite/patologia , Macrófagos/metabolismo , Podócitos/metabolismo , Doença Antimembrana Basal Glomerular/metabolismo , Doença Antimembrana Basal Glomerular/patologia , Anticorpos Anticitoplasma de Neutrófilos/metabolismo , Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/metabolismo , Proliferação de Células , Células Epiteliais/patologia , Glomerulonefrite/classificação , Glomerulonefrite/metabolismo , Glomerulonefrite por IGA/metabolismo , Glomerulonefrite por IGA/patologia , Humanos , Proteínas de Filamentos Intermediários/metabolismo , Queratinas/metabolismo , Nefrite Lúpica/metabolismo , Nefrite Lúpica/patologia , Macrófagos/patologia , Proteínas do Tecido Nervoso/metabolismo , Nestina , Podócitos/patologia , Antígeno Nuclear de Célula em Proliferação/metabolismo , Sialoglicoproteínas/metabolismoRESUMO
The 2003 International Society of Nephrology/Renal Pathology Society (ISN/RPS) system for classifying patients with lupus nephritis was based on glomerular lesions exclusively, despite the fact that lupus nephritis affects all compartments of the kidney. Hence, we analyzed the tubulointerstitial lesions in patients with lupus nephritis within the different classes and subclasses of the 2003 ISN/RPS system. Among 313 patients from five centers in northern China with lupus nephritis, interstitial inflammatory cell infiltration, tubular atrophy, and interstitial fibrosis were severe in 170 patients with class IV, moderate in 55 with class III, and mild in 19 with class II and in 69 with class V disease, each with significance. The severity of tubulointerstitial lesions in classes IV-segmental and III was similar, whereas the score of interstitial inflammatory cell infiltration in patients with subclass IV-global was significantly higher than that in those with subclass IV-segmental. Interstitial fibrosis and tubular atrophy were each significantly more prominent in patients with both active and chronic lesions than in those with active lesions alone. The correlation coefficient ranged from 0.222 to 0.811 comparing glomerular and tubulointerstitial indices. In multivariate Cox hazard analysis of tubulointerstitial lesions, indices of interstitial infiltration, tubular atrophy, and interstitial fibrosis were confirmed as significant independent risk factors for renal outcome. Thus, we found that the 2003 ISN/RPS classification system of lupus nephritis, based on glomerular lesions, could also reflect related tubulointerstitial lesions. Hence, we suggest that the extent of tubulointerstitial lesions may be helpful in predicting renal outcome in patients with lupus nephritis.
Assuntos
Glomérulos Renais/patologia , Rim/patologia , Nefrite Lúpica/classificação , Nefrite Lúpica/patologia , China , Humanos , Análise Multivariada , Nefrologia/classificação , Fatores de Risco , SociedadesRESUMO
There are few clinicopathologic and outcome data on patients with crescentic lupus nephritis, therefore, we determined factors of the disease by retrospectively reviewing the records of 327 patients diagnosed with lupus nephritis. Of these, 152 cases were regrouped as class IV-G, including 33 patients with crescentic glomerulonephritis. Significantly, all patients with crescentic glomerulonephritis had acute kidney injury as compared with only about a quarter of the patients without the disease. On pathological evaluation, activity scores, chronicity indexes, relapse rates, and the frequency of positive serum anti-neutrophil cytoplasmic antibody (ANCA) were each significantly higher, whereas complete remission rates and renal outcomes, over a mean follow-up of 4 years, were significantly poorer in patients with crescentic glomerulonephritis. Our study shows that crescentic glomerulonephritis was not rare in patients with lupus nephritis and that their long-term outcome was poor. The precise role of ANCA in the pathologic course of crescentic lupus nephritis remains to be determined.
Assuntos
Rim/patologia , Nefrite Lúpica/patologia , Adolescente , Adulto , Anticorpos Anticitoplasma de Neutrófilos/sangue , Povo Asiático , China , Feminino , Glucocorticoides/uso terapêutico , Humanos , Imunossupressores/uso terapêutico , Nefrite Lúpica/tratamento farmacológico , Nefrite Lúpica/imunologia , Masculino , Pessoa de Meia-Idade , Prednisona/uso terapêutico , Indução de Remissão , Estudos Retrospectivos , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Primary glomerular disease (PGD) is the leading cause of end-stage renal disease (ESRD) in China. With the development of socioeconomic status of Chinese people in the last two decades, PGD in ESRD is intent to decrease. However, whether this affects the spectrum of PGD is not clear. The aim of the current study is to investigate the changing spectrum of PGD in China. METHODS: The records of 5398 consecutive native renal biopsies performed in adults (>or=14 years of age) in our centre between 1993 and 2007 were retrospectively analysed. The criteria for renal biopsy and pathologic diagnosis were kept unchanged. The patients were grouped according to a 5-year interval, 1993-97 (period 1), 1998-2002 (period 2) and 2003-07 (period 3). Then they were divided into four groups according to age for stratified analysis: 14-24 years, 25-44 years, 45-59 years and the elderly (>or=60 years). RESULTS: Three thousand, three hundred and thirty-one patients were diagnosed with PGD. PGD remained the most common renal disease, accounting for 65.9%, 57.7% and 63.2% in period 1, 2 and 3, respectively, without any significant difference. The proportion of elder patients increased significantly from 0% in 1993 to 9.1% in 2007 (P < 0.001). Within 1993-97, the leading PGD was IgA nephropathy (50.7%), followed by non-IgA MsPGN (19.9%), membranous nephropathy (MN) (13.3%) and minimal change disease (MCD) (6.3%), while within 2003-07, the most common PGD was still IgAN (58.2%), but followed by MN (14.3%), MCD (13.4%) and non-IgA MsPGN (7.0%). The age-adjusted frequency of IgAN and MCD increased significantly from period 1 to period 3 (P < 0.01 and P < 0.001, respectively), while that of non-IgA MsPGN, EnPGN and MPGN decreased significantly (P < 0.001, P < 0.01 and P < 0.05, respectively). There was no significant change in the age-adjusted frequency of FSGS, MN and CreGN during the study period. However, when patients were stratified by age, a sixfold increase in frequency of FSGS was identified in the 14- to 24-year group (P < 0.01). CONCLUSIONS: The spectrum of primary glomerulonephritis has changed within the last 15 years. The relative frequency of non-IgA MsPGN, EnPGN and MPGN decreased significantly, while that of MCD and IgA nephropathy increased significantly. The relative frequency of FSGS increased significantly in younger patients.
Assuntos
Falência Renal Crônica/epidemiologia , Falência Renal Crônica/patologia , Glomérulos Renais , Adolescente , Adulto , Distribuição por Idade , Idoso , China , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Distribuição por Sexo , Fatores Socioeconômicos , Fatores de Tempo , Adulto JovemRESUMO
BACKGROUND: It was reported that IgA nephropathy (IgAN) was the major cause of secondary malignant hypertension (MHT). However, the pathogenesis of MHT secondary to IgAN (IgAN-MHT) is unknown and its association with glomerular pathological phenotypes remains inconclusive. The present study aimed to investigate whether glomerular pathological phenotypes and anti-endothelial cell antibodies (AECA) were associated with the occurrence of IgAN-MHT. METHODS: The glomerular pathological phenotypes of 45 patients with IgAN-MHT were analysed using Haas' histologic grading system of IgAN. Sera were collected from 34 of the 45 patients with IgAN-MHT, 19 patients with primary MHT, 41 patients with non-MHT IgAN and 10 healthy volunteers. AECA of both IgG and IgA isotypes were detected by western blot analysis using human umbilical vein endothelial cell lysate as antigen. RESULTS: In the 45 patients with IgAN-MHT, 7 (15.56%), 5 (11.11%), 13 (28.89%), 9 (20%) and 11 (24.44%) patients were graded as Hass I, II, III, IV and V, respectively. Although the severity of non-ischaemic sclerosis, crescents and mesangial proliferation were significantly different between patients with different grades, the levels of blood pressure, SCr and proteinuria at presentation were comparable. Eleven and four protein bands of endothelial proteins could be blotted by AECA-IgG and AECA-IgA in sera from patients with IgAN-MHT. The prevalences of anti-121 kD AECA-IgG (15/34) and anti-92 kD AECA-IgA (10/34) in IgAN-MHT were significantly higher than that of primary MHT, non-MHT IgAN and normal controls, respectively. Patients with anti-92 kD AECA-IgA had more severe glomerular ischaemic sclerosis (6.25-92.86%, median 39.61%) than those without (0-91.67%, median 18.18%, P = 0.035). There was no significant difference in the prevalence of AECA between IgAN-MHT patients with different background glomerular lesions. Only one IgAN patient with MHT was found with both anti-121 kD AECA-IgG and anti-92 kD AECA-IgA. No particular manifestations were found. CONCLUSIONS: The occurrence of IgAN-MHT was not associated with the background glomerular pathological phenotypes of IgAN. AECA might play a role in the pathogenesis of IgAN-MHT.
Assuntos
Glomerulonefrite por IGA/complicações , Glomerulonefrite por IGA/patologia , Hipertensão Maligna/etiologia , Idoso , Autoanticorpos/sangue , Autoantígenos/isolamento & purificação , Estudos de Casos e Controles , Células Cultivadas , Células Endoteliais/imunologia , Feminino , Glomerulonefrite por IGA/classificação , Glomerulonefrite por IGA/imunologia , Humanos , Hipertensão Maligna/patologia , Hipertensão Maligna/fisiopatologia , Imunoglobulina A/sangue , Imunoglobulina G/sangue , Masculino , Pessoa de Meia-Idade , Fenótipo , PrognósticoRESUMO
AIM: Recent studies suggest that intrarenal arterial lesions are frequently observed in patients with immunoglobulin A nephropathy (IgAN). However, the mechanisms of the injury have not been elucidated. The level of serum von Willebrand factor (vWF) and the prevalence of anti-endothelial cell antibodies (AECA) were investigated in patients with IgAN with different intrarenal arterial lesions. METHODS: Sera from 28 patients with mild intrarenal arterial lesions (group 1) and 36 patients with severe intrarenal arterial lesions (group 2) were collected. Sera from 20 patients with idiopathic membranous nephropathy (group 3) and 50 healthy volunteers were also obtained as disease and normal controls, respectively. Serum vWF and AECA of both IgG and IgA isotype were detected. RESULTS: In comparison with normal controls, serum vWF was significantly higher in group 2 and group 3. Serum vWF was also significantly higher in group 2 than in group 1. Both IgG-AECA and IgA-AECA could be detected in three groups of patients. The prevalence of anti-87 kD IgG-AECA was greatest in patients in group 2. IgAN patients, especially those in group 2 with IgG-AECA or anti-87 kD IgG-AECA, had significantly higher serum creatinine and lower creatinine clearance than those without. No significant difference could be found for IgA-AECA. The level of serum vWF was higher in IgAN patients with IgG-AECA than that in patients without. CONCLUSION: Intrarenal arterial lesions are associated with endothelial cell damage in IgAN, and vWF is a useful serological biomarker of severe intrarenal arterial lesions. AECA, especially IgG-AECA, may play an important role in the pathogenesis of intrarenal arterial damage in IgAN.
Assuntos
Autoanticorpos/sangue , Células Endoteliais/imunologia , Glomerulonefrite por IGA , Imunoglobulina A/sangue , Imunoglobulina G/sangue , Artéria Renal/patologia , Fator de von Willebrand/análise , Adolescente , Adulto , Biomarcadores/sangue , Estudos de Casos e Controles , Células Cultivadas , Feminino , Glomerulonefrite por IGA/sangue , Glomerulonefrite por IGA/imunologia , Glomerulonefrite por IGA/patologia , Glomerulonefrite Membranosa/sangue , Glomerulonefrite Membranosa/imunologia , Glomerulonefrite Membranosa/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Regulação para Cima , Adulto JovemRESUMO
Focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD) have been suggested for the category of podocytopathies. An ultrastructural observation and immunogold labeling for cytoskeleton proteins of podocytes on 11 cases each of FSGS and MCD were performed. Compared to MCD, more severe ultrastructural alterations of podocyte were identified in FSGS, which were characterized by higher frequency of mat-like condensation of microfilaments in the foot process and the detachment of the foot process from glomerular basement membrane. The labeling of alpha-actinin of podocytes in FSGS was significantly higher than MCD, which suggested an abnormal expression of cytoskeleton protein of podocyte in FSGS. The present study demonstrated a much more severe podocyte injury at the ultrastructural level in FSGS than in MCD.
Assuntos
Proteínas do Citoesqueleto/análise , Glomerulosclerose Segmentar e Focal/metabolismo , Glomerulosclerose Segmentar e Focal/patologia , Nefrose Lipoide/metabolismo , Nefrose Lipoide/patologia , Podócitos/química , Podócitos/ultraestrutura , Citoesqueleto de Actina/ultraestrutura , Actinina/análise , HumanosRESUMO
OBJECTIVE: To study clinicopathological features and mechanism of renal injury in transplantation-associated thrombotic microangiopathy (TA-TMA). METHODS: The renal biopsies obtained from patients after hematopoietic cell transplantation or kidney transplantation were observed by immunofluorescence, light microscopy and electron microscopy (EM). RESULTS: The patients presented hypertension, massive proteinuria, intravascular haemolysis and renal insufficiency some time after transplantation. Various immunoglobulins and complements were negative in immunofluorescent staining. Light microscopy showed endothelial cell proliferation and swelling of glomerular capillary and small arteries, irregular thickened glomerular basement membrane and microthrombosis. EM revealed endothelial cell proliferation and swelling with thickened lamina rara interna of glomerular basement membrane. CONCLUSION: TA-TMA is a rare complication after organ or tissue transplantation. Kidney is often involved in TA-TMA with massive proteinuria, anemia and renal failure. Differential diagnosis should be made between TA-TMA and rejection or other renal diseases. Renal biopsy is a major method for accurate diagnosis. TA-TMA correlates to endothelial cell injury caused by viral infection and/or immunosuppressive drugs for anti-rejection.
Assuntos
Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Rim/efeitos adversos , Rim/patologia , Microangiopatias Trombóticas/etiologia , Microangiopatias Trombóticas/patologia , Biópsia por Agulha , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: The kidney is one of the organs affected in patients with propylthiouracil (PTU)-associated antineutrophil cytoplasmic antibody (ANCA)-positive vasculitis. We present a series of Chinese patients with renal involvement in PTU-associated ANCA-positive vasculitis and describe their clinical and pathological characteristics. METHODS: Clinical and pathological data from patients with PTU-associated ANCA-positive vasculitis with renal involvement, diagnosed in Peking University First Hospital, were collected and analyzed retrospectively. RESULTS: Nineteen patients with PTU-associated ANCA-positive vasculitis were treated at Peking University First Hospital between December 1999 and December 2005, and 15 of them had renal involvement. Of the 15 patients, 13 were female and 2 were male, with an average age of 26.3 +/- 11.8 years. All 15 patients were perinuclear ANCA positive with specificities to myeloperoxidase (15 of 15), cathepsin G (9 of 15), human leukocyte elastase (8 of 15), lactoferrin (7 of 15), azurocidin (5 of 15), and proteinase 3 (4 of 15). Duration of PTU administration was 43.0 +/- 31.2 months. All 15 patients had clinical markers of renal involvement, including hematuria (100%), proteinuria (100%), and renal function abnormality (47%). All 15 patients underwent percutaneous renal biopsy. Ten patients had necrotizing crescentic glomerulonephritis, and 7 of these 10 patients had immune complex deposition. Three patients had minimal involvement, 2 patients had immunoglobulin A nephropathy, and 2 patients had membranous nephropathy. PTU treatment was discontinued in all 15 patients. All except 2 patients with minimal renal involvement received immunosuppressive treatment. Eleven of 15 patients achieved complete clinical remission. CONCLUSION: Renal involvement in our case series of patients with PTU-associated ANCA-positive vasculitis was heterogeneous, and nearly half our patients had renal immune complex deposition.
Assuntos
Anticorpos Anticitoplasma de Neutrófilos/sangue , Doenças do Complexo Imune/induzido quimicamente , Nefropatias/induzido quimicamente , Propiltiouracila/efeitos adversos , Vasculite/induzido quimicamente , Vasculite/patologia , Adolescente , Adulto , Criança , Feminino , Humanos , Doenças do Complexo Imune/imunologia , Doenças do Complexo Imune/patologia , Imunossupressores/uso terapêutico , Rim/efeitos dos fármacos , Rim/imunologia , Rim/patologia , Nefropatias/imunologia , Nefropatias/patologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Vasculite/imunologiaRESUMO
BACKGROUND: The blood vessels of a transplanted organ are the interface between donor and recipient. The endothelium in the blood vessels is thought to be the major target for graft rejection. Endothelial cells of a transplanted organ can be of recipient origin after transplantation. In this study, we tested whether endothelial chimerism correlated with the graft rejection and cold ischemia. METHODS: We studied the biopsy samples from 34 renal transplants of female recipients who received the kidney from a male donor for the presence of endothelial cells of recipient origin. We examined the tissue sections of renal biopsy samples by fluorescence in situ hybridization (FISH) for the presence of endothelial cells containing two X chromosomes using a biotinylated Y chromosome probe and digoxigenin labelled X chromosome probe, and then analyzed the relationship between the endothelial cell chimerism and the rejection and cold ischemia. RESULTS: Endothelial chimerism was common and irrespective of rejections (P > 0.05). The cold ischemic time of chimerism group was longer than no chimerism group ((14.83 +/- 4.03) hours vs (11.27 +/- 3.87) hours, P < 0.05). CONCLUSIONS: There is no correlation between the percentage of recipient endothelial cells in vascular endothelial cells and the type of graft rejection. The endothelium damaged by ischemic injury might be repaired by the endothelial cells from the recipient.
Assuntos
Células Endoteliais/patologia , Hibridização in Situ Fluorescente , Transplante de Rim , Rim/patologia , Quimeras de Transplante , Animais , Biópsia , Feminino , Rejeição de Enxerto , Humanos , Masculino , Camundongos , Fatores de Tempo , Transplante HomólogoRESUMO
OBJECTIVE: To report the clinical and pathological characteristics of renal involvement in angiolymphoid hyperplasia with eosinophilia (ALHE). METHODS: Three cases of ALHE with renal involvement were diagnosed in our hospital. Routine pathological examination and immunohistochemical study of CD(31), CD(34) and F(8) of lymph node and renal biopsy specimens were performed and the clinical and pathological features were analysed. RESULTS: All three patients were male. Subcutaneous mass in the neck and head region accompanied with proteinuria and renal function impairment were the clinical characteristics of the three patients. Peripheral blood eosinophilia with elevated IgE level was detected in all the 3 patients. The level of serum immunoglobulins and complements were abnormal in 2 of them. They were sensitive to corticosteroid and cyclophosphamide therapy, but one case showed a recurrence after the withdrawal of immunosuppressive agents. Histopathological examination of lymph node and renal tissue showed a prominent proliferation of small vessels lined with hypertrophic epitheloid endothelial cells, which led to a narrowed or even closed vascular lumen. Diffuse infiltration of eosinophils, lymphocytes and plasma cells was identified around the hyperplastic vessels. With immunohistochemical study, CD(31), CD(34) and F(8) were positive in hyperplastic endothelial cells. Renal lesions were mainly distributed in tubulointerstitial area, while one case exhibited membranous nephropathy (stage I). CONCLUSION: ALHE with renal involvement is not rare in our country. The clinical and pathological characteristics of ALHE suggested that it might belong to an entity of angiolymphoid hyperplasia associated with allergic response.
Assuntos
Hiperplasia Angiolinfoide com Eosinofilia/patologia , Rim/patologia , Nefrite Intersticial/patologia , Antígenos CD34/análise , Biópsia por Agulha , Fator VIII/análise , Humanos , Imuno-Histoquímica , Rim/química , Linfonodos/química , Linfonodos/patologia , Masculino , Molécula-1 de Adesão Celular Endotelial a Plaquetas/análiseRESUMO
OBJECTIVE: To assess the significance of urinary podocyte and its possible implication as a marker of activity of lupus nephritis. METHODS: The presence of podocytes in urinary sediment was detected with immunochemical staining using anti-podocalyxin antibody. The correlation of the number of urinary podocytes with activity index of renal pathological lesions, hematuria, and proteinuria was analyzed respectively. The proliferating podocytes in renal biopsy tissue and urine from patients with class IV lupus nephritis were examined with double immunohistochemical staining. RESULTS: Thirty-one patients with lupus nephritis undergoing renal biopsy were enrolled into the study. Renal pathological findings of the patients could be classified into WHO class III (25.8%), class IV (64.5%) and class V (9.7%). 90% of the patients had positive urinary podocytes. The number of urinary podocytes was strongly and positively correlated with the severity of hematuria (r=0.639, P=0.000) and glomerular pathological activity index (r=0.487, P=0.014) in patients of class III and class IV. The amount of proteinuria was not correlated with pathological activity index, even though all the patients had proteinuria. Furthermore, the number of urinary podocytes, the severity of hematuria and the amount of proteinuria were all decreased after treatment with methyl prednisone, cyclophosphamide or mycophenolate mofetil. Interestingly, the urinary podocytes could disappear even before the remission of hematuria and proteinuria after treatment. Proliferative podocytes were observed both in biopsied kidney tissue and urinary sediments in patients of class IV. CONCLUSION: The presence and the number of urinary podocytes can be used as a valuable marker to grade the activity of lupus nephritis and to evaluate the efficacy of steroid therapy.
Assuntos
Glomérulos Renais/patologia , Nefrite Lúpica/patologia , Podócitos/citologia , Adulto , Contagem de Células , Feminino , Hematúria/patologia , Humanos , Imuno-Histoquímica , Rim/citologia , Nefrite Lúpica/urina , Masculino , Pessoa de Meia-Idade , Antígeno Nuclear de Célula em Proliferação/imunologia , Proteinúria/patologia , Sialoglicoproteínas/imunologia , Urina/citologiaRESUMO
OBJECTIVE: To study the clinical and pathological features of cryoglobulinemic glomerulonephritis. METHODS: The clinical and pathologic data from 8 cases with cryoglobulinemic glomerulonephritis, which were referred to Peking University First Hospital from 2002 to 2006, were reviewed. RESULTS: There were seven males and one female, with an average age of 48.6 +/- 13.6 years. Most of the patients were referred as primary glomerulonephritis and the mean interval from onset to diagnosis was 19 months. 5 cases showed positive result with blood cryoglobulin test as inferred from renal biopsy. At the time of diagnosis 5 cases (5/8) showed nephritic syndrome and 3 (3/8) progression of renal failure. Fifty percent of the patients died in 6 months during the two-year follow-up. The main pathological pattern was membranoproliferative glomerulonephritis (7/8) with glomerular subendothelial deposits and intraluminal thrombi. Four cases (4/8) were associated with lymphoproliferative disorders and only one case with HCV infection. CONCLUSION: Cryoglobulinemic glomerulonephritis was not rare. Most of the patients were diagnosed at a late stage with a poor prognosis in China. It should draw a special attention of the clinicians.