RESUMO
BACKGROUND: Bisphosphonates are administered to post-transplantation patients with mineral and bone disorders; however, the association between bisphosphonate therapy and long-term renal graft survival remains unclear. METHODS: This nested case-control study investigated the effects of bisphosphonates on long-term graft outcomes after kidney transplantation. We enrolled 3836 kidney transplant recipients treated from April 1979 to June 2016 and matched patients with graft failure to those without (controls). Annual post-transplant bone mineral density assessments were performed and recipients with osteopenia or osteoporosis received bisphosphonate therapy. The associations between bisphosphonate use and long-term graft outcomes and graft survival were analyzed using conditional logistic regression and landmark analyses, respectively. RESULTS: A landmark analysis demonstrated that death-censored graft survival was significantly higher in bisphosphonate users than in non-users in the entire cohort (log-rank test, P < 0.001). In the nested case-control matched cohort, bisphosphonate users had a significantly reduced risk of graft failure than did non-users (odds ratio = 0.38; 95% confidence interval 0.30-0.48). Bisphosphonate use, increased cumulative duration of bisphosphonate use >1 year and increased cumulative bisphosphonate dose above the first quartile were associated with a reduced risk of graft failure, after adjustments. CONCLUSIONS: Bisphosphonates may improve long-term graft survival in kidney transplant recipients.
Assuntos
Doenças Ósseas Metabólicas/tratamento farmacológico , Difosfonatos/uso terapêutico , Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto , Transplante de Rim/efeitos adversos , Osteoporose/tratamento farmacológico , Adulto , Densidade Óssea/efeitos dos fármacos , Conservadores da Densidade Óssea/uso terapêutico , Doenças Ósseas Metabólicas/etiologia , Doenças Ósseas Metabólicas/patologia , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Rejeição de Enxerto/etiologia , Rejeição de Enxerto/patologia , Humanos , Masculino , Osteoporose/etiologia , Osteoporose/patologia , Taxa de Sobrevida , TransplantadosRESUMO
The aim of this study was to clarify the nature and clinical significance of glomerular subepithelial microparticles (SMPs), located between the basal surface of the podocytes and the glomerular basement membrane. Ultrastructural morphology of 79 renal biopsy samples (obtained from 25 native and 54 transplanted kidneys), showing SMPs in the last 3 years, was reevaluated with regard to the podocyte changes and clinical condition of the patients. One hundred and nine SMPs were identified, with 32.9% of the samples having two or more per glomerulus. Overall, they were most frequently located in the open capillary loops (55%). However, in the native kidney samples with mesangial deposits, 64.3% of SMPs were present in the mesangium-bound areas. Each vesicle ranged from 46.9 to 87.1 nm, and vesicles were admixed with curved strands in larger SMPs. Diffuse effacement of the foot processes and condensation of the actin filaments were present in 56.0% and 62.4% of the samples, respectively. SMPs were associated with hematuria, proteinuria of ≥ 1 gm, and immune complex deposition in the patients with native kidneys, whereas they were related to hyperglycemia and elevated serum creatinine levels in the patients with renal allografts. Patients with native and transplanted kidneys most commonly presented with IgA nephropathy and allograft rejection, respectively. Finding SMPs in the renal biopsy samples is not rare and they may act as a footprint of podocyte injury caused by diverse etiologies. Considering their size, podocyte exosomes could be a possible source of SMPs.
Assuntos
Glomerulonefrite por IGA , Podócitos , Membrana Basal Glomerular , Mesângio Glomerular , Humanos , ProteinúriaRESUMO
We aimed to determine the relative contribution of each complement (C3 and C4d) deposition to the progression of IgA nephropathy (IgAN). We enrolled a total of 380 patients with biopsy-confirmed IgAN. Mesangial deposition of C3(<2+ vs. ≥2+) and C4d(positive vs. negative) was evaluated by immunofluorescence staining and immunohistochemistry, respectively. Study endpoint was the composite of a 30% decline in eGFR or ESRD. The risk of reaching the primary outcome was significantly higher in patients having C3 ≥ 2+ and C4d(+) than in corresponding counterparts. Adding C3 deposition to clinical data acquired at kidney biopsy modestly increased the area under the receiver-operating characteristic curve, net reclassification improvement, and integrated discrimination improvement (IDI); adding C4d increased IDI only. In conclusion, mesangial C3 and C4d deposition was an independent risk factor for progression of IgAN. C3 showed better predictability than C4d, suggesting that lectin pathway alone has limited clinical prognostic value.
Assuntos
Complemento C3/imunologia , Complemento C4/imunologia , Glomerulonefrite por IGA/imunologia , Adulto , Feminino , Taxa de Filtração Glomerular , Glomerulonefrite por IGA/patologia , Glomerulonefrite por IGA/fisiopatologia , Humanos , Rim/imunologia , Rim/patologia , Rim/fisiopatologia , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Adulto JovemRESUMO
BACKGROUND: Complement activation has been highlighted in immunoglobulin (Ig) A nephropathy pathogenesis. However, whether the complement system can affect the downstream phenotype of IgA nephropathy remains unknown. Herein, we investigated the association of mesangial C3 deposition with the Oxford classification and their joint effects on worsening kidney function. METHODS: We investigated 453 patients with biopsy-proven IgA nephropathy. C3 deposition was defined as an immunofluorescence intensity of C3 ≥2+ within the mesangium. The subjects were classified according to the combination of C3 deposition and Oxford classification lesions. The primary endpoint was a composite of ≥30% decline in the estimated glomerular filtration rate or an increase in proteinuria ≥3.5 g/g during follow-up. RESULTS: Among the Oxford classification lesions, mesangial hypercellularity (M1), segmental glomerulosclerosis (S1) and tubulointerstitial fibrosis (T1-2) and crescentic lesion significantly correlated with C3 deposition. During a median follow-up of 33.0 months, the primary endpoint occurred more in patients with M1, S1, T1-2 and mesangial C3 deposition than in those without. In individual multivariable-adjusted Cox analyses, the presence of M1, S1, T1-2 and C3 deposition was significantly associated with higher risk of reaching primary endpoint. In the combined analyses of C3 deposition and the Oxford classification lesions, the hazard ratios for the composite outcome were significantly higher in the presence of C3/M1, C3/S1 and C3/crescent than in the presence of each lesion alone. CONCLUSIONS: Complement deposition can strengthen the significance of the Oxford classification, and the presence of both components portends a poorer prognosis in IgA nephropathy.
Assuntos
Biomarcadores/análise , Complemento C3/análise , Fibrose/diagnóstico , Taxa de Filtração Glomerular , Glomerulonefrite por IGA/patologia , Proteinúria/diagnóstico , Adulto , Feminino , Fibrose/etiologia , Fibrose/metabolismo , Glomerulonefrite por IGA/classificação , Glomerulonefrite por IGA/complicações , Humanos , Masculino , Prognóstico , Proteinúria/etiologia , Proteinúria/metabolismo , Estudos RetrospectivosRESUMO
BACKGROUND: Despite the obvious survival benefit compared to that among waitlist patients, outcomes of positive crossmatch kidney transplantation (KT) are generally inferior to those of human leukocyte antigen (HLA)-compatible KT. This study aimed to compare the outcomes of positive complement-dependent cytotoxicity (CDC) crossmatch (CDC + FC+) and positive flow cytometric crossmatch (CDC-FC+) with those of HLA-compatible KT (CDC-FC-) after successful desensitization. METHODS: We retrospectively analyzed 330 eligible patients who underwent KTs between June 2011 and August 2017: CDC-FC- (n = 274), CDC-FC+ (n = 39), and CDC + FC+ (n = 17). Desensitization protocol targeting donor-specific antibody (DSA) involved plasmapheresis, intravenous immunoglobulin (IVIG), and rituximab with/without bortezomib for positive-crossmatch KT. RESULTS: Death-censored graft survival and patient survival were not different among the three groups. The median estimated glomerular filtration rate was significantly lower in the CDC + FC+ group than in the compatible group at 6 months (P < 0.001) and 2 years (P = 0.020). Biopsy-proven rejection within 1 year of CDC-FC-, CDC-FC+, and CDC + FC+ were 15.3, 28.2, and 47.0%, respectively. Urinary tract infections (P < 0.001), Pneumocystis jirovecii pneumonia (P < 0.001), and cytomegalovirus viremia (P < 0.001) were more frequent in CDC-FC+ and CDC + FC+ than in CDC-FC-. CONCLUSIONS: This study showed that similar graft and patient survival was achieved in CDC-FC+ and CDC + FC+ KT compared with CDC-FC- through DSA-targeted desensitization despite the higher incidence of rejection and infection than that in compatible KT.
Assuntos
Complemento C1q/metabolismo , Citometria de Fluxo/métodos , Sobrevivência de Enxerto/fisiologia , Antígenos HLA/sangue , Teste de Histocompatibilidade/métodos , Transplante de Rim/métodos , Adulto , Feminino , Seguimentos , Teste de Histocompatibilidade/mortalidade , Humanos , Transplante de Rim/mortalidade , Doadores Vivos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxa de Sobrevida/tendências , Transplantados , Resultado do TratamentoRESUMO
BACKGROUND: Mutations in the AarF domain containing kinase 4 gene (ADCK4), one of the novel genes causing steroid-resistant nephrotic syndrome (SRNS), usually manifest as isolated adolescent-onset focal segmental glomerulosclerosis (FSGS). ADCK4 interacts with components of the coenzyme Q10 (CoQ10) biosynthesis pathway. METHODS: The incidence and phenotypes of patients with ADCK4 mutations were investigated in a cohort of Korean pediatric patients with SRNS. RESULTS: Among the 53 patients enrolled in the study the incidence of ADCK4-associated FSGS was 7.5% (n = 4) in children aged 5 years and older with multidrug-resistant FSGS. Two additional patients were included for phenotype analyses, one detected by family screening and the other with cyclosporine-responsive FSGS. These six patients presented proteinuria without overt nephrotic syndrome at a median age of 110 (range 60-153) months, of whom five progressed to end-stage renal disease within a median period of 46 (range 36-79) months after onset. Renal biopsies revealed mitochondrial abnormalities in podocytes and tubular cells of all patients. Notably, all patients showed accompanying medullary nephrocalcinosis. None of the patients showed other extrarenal manifestations. CONCLUSIONS: ADCK4 mutations should be considered in older children presenting with steroid resistant FSGS. An early diagnosis of ADCK4 mutations is essential because the condition is treatable with CoQ10 supplementation at an early stage. The association with medullary nephrocalcinosis may be an additional diagnostic indicator.
Assuntos
Glomerulosclerose Segmentar e Focal/epidemiologia , Falência Renal Crônica/epidemiologia , Nefrocalcinose/epidemiologia , Síndrome Nefrótica/congênito , Proteínas Quinases/genética , Criança , Progressão da Doença , Feminino , Estudos de Associação Genética , Glomerulosclerose Segmentar e Focal/genética , Glomerulosclerose Segmentar e Focal/patologia , Humanos , Incidência , Falência Renal Crônica/genética , Coreia (Geográfico)/epidemiologia , Masculino , Mutação , Nefrocalcinose/genética , Nefrocalcinose/patologia , Síndrome Nefrótica/epidemiologia , Síndrome Nefrótica/genética , Síndrome Nefrótica/patologiaRESUMO
AIMS: ABO-incompatible (ABOi) kidney transplantation (KT) is being increasingly performed to overcome donor shortages. However, debate persists regarding the post-transplant outcomes of ABOi KT vs. that of ABO-compatible (ABOc) KT. METHODS: A total 454 recipients who underwent living-donor KT (LDKT) between June 2010 and July 2014 at Severance Hospital (Seoul) were retrospectively reviewed. 100 ABOi and 354 ABOc KTs were compared. Recipients with a pretransplant positive crossmatch to their donors, pretransplant donor-specific anti-HLA antibody (DSA), or high panel reactive antibody (PRA ≥ 50%) were excluded from both the ABOi and ABOc KT groups. Finally, the authors compared the transplant outcomes of 95 of these ABOi KTs and 121 ABOc KTs performed over the same period. RESULTS: No significant difference in incidence of biopsy-proven acute rejection was observed between the ABOi and ABOc KT groups (p = 0.230), and group glomerular filtration rate of ABOi KT was comparable to that of ABOc KT (p > 0.05 at all time points). 3-year death-censored graft survival rates were similar (96.8 vs. 96.6%, respectively; p = 0.801). However, the incidences of postoperative bleeding, cytomegalovirus infection, fungal infection, and serious infection rates were significantly higher after ABOi KT. CONCLUSIONS: In this study, graft renal function and survival after ABOi KT were excellent, and the incidence of acute rejection was similar to that of ABOc KT. However, efforts are needed to reduce hemorrhagic and infectious complications after ABOi KT. ABOi KT can be a good strategy to overcome ABO antibody barriers and relieve donor shortage.â©.
Assuntos
Sistema ABO de Grupos Sanguíneos/imunologia , Incompatibilidade de Grupos Sanguíneos/imunologia , Transplante de Rim , Doadores Vivos , Adulto , Feminino , Rejeição de Enxerto/epidemiologia , Sobrevivência de Enxerto , Humanos , Incidência , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
BACKGROUND: Little information is currently available on the development of tubulointerstitial lesions in children with Henoch-Schönlein nephritis (HSN). To identify the impact of the development of tubulointerstitial changes in HSN, we retrospectively analyzed renal biopsies obtained from children with HSN. METHODS: Twenty-eight children with HSN from whom serial renal biopsies had been obtained before and after immunosuppressive therapy were enrolled in the study. The patients were divided into two groups according to the observed change in tubulointerstitial lesion development: group I (n = 15), with stable or improved tubulointerstitial lesions, and group II (n = 13), with worsened tubulointerstitial lesions. Group II patients had longer duration of proteinuria than group I patients (3.7 ± 3.7 years vs. 1.7 ± 1.7 years, p = 0.052). RESULTS: The change in serum albumin level was negatively correlated with the change in tubulointerstitial scores before and after treatment (γ = -0.444, p = 0.018). Group II patients showed a significant decrease in immunoglobulin G (IgG) and IgA deposits after treatment (p = 0.039 and 0.003, respectively), while group II patients did not (p = 0.458 and 0.506, respectively). CONCLUSIONS: Although the International Study of Kidney Disease in Children classification of HSN does not include tubulointerstitial lesions, they can progress during treatment and could have significant clinical implications in association with the duration of proteinuria.
Assuntos
Vasculite por IgA/tratamento farmacológico , Vasculite por IgA/patologia , Imunossupressores/uso terapêutico , Rim/patologia , Nefrite Intersticial/tratamento farmacológico , Nefrite Intersticial/patologia , Biópsia , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Vasculite por IgA/sangue , Vasculite por IgA/imunologia , Imunoglobulina G/imunologia , Imunoglobulina G/metabolismo , Masculino , Nefrite Intersticial/sangue , Nefrite Intersticial/imunologia , Proteinúria/urina , Estudos Retrospectivos , Albumina Sérica/análiseRESUMO
BACKGROUND: CD44 is a marker of activated parietal epithelial cells (PECs), and is expressed in glomerular visceral epithelial cells (VECs) during development of segmental sclerosis. We explored the significance of glomerular epithelial CD44 expression in relation to segmental sclerosis in patients with mild IgA nephropathy (IgAN). METHODS: A total of 126 cases of IgAN were divided into three groups based on glomerular morphology: normal (group A, n = 30), mild mesangial proliferation without segmental sclerosis or synechia (SS) (group B, n = 31), or mild mesangial proliferation with SS (group C, n = 65). The number of CD44-expressing PECs and VECs was counted in each glomerulus and expressed as the mean number per case. RESULTS: CD44 staining was positive in VECs in 59.5 %, in PECs in 79.4 % and in both cell types in 56.3 % of cases. The number of CD44+ PECs or VECs was significantly higher in group C than in groups A or B. Cases with >1 CD44+ cell (PECs and VECs) per glomerulus were associated with increased urine protein/creatinine ratio (UPCr) at last follow-up. The presence of >1 CD44+ VEC/glomerulus was associated with increased UPCr and serum creatinine levels, and decreased estimated glomerular filtration rate (eGFR) even in the absence of SS at the time of biopsy. CONCLUSION: CD44 was expressed in PECs and VECs in association with SS in IgAN. Increased CD44 expression in VECs is a sign of active glomerular injury and dysfunction in these patients.
Assuntos
Glomerulonefrite por IGA/complicações , Glomerulosclerose Segmentar e Focal/etiologia , Receptores de Hialuronatos/análise , Glomérulos Renais/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Células Epiteliais/imunologia , Feminino , Taxa de Filtração Glomerular , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Podocytic infolding glomerulopathy (PIG) is a rare glomerular abnormality involving glomerular basement membrane (GBM) bubbling viewable by light microscopy, extensive invagination of the podocytic cytoplasm, and the presence of microstructures viewable by electron microscopy. PIG was proposed as a new disease entity in 2008. However, cases have been reported exclusively in Japan and no case reports outside Japan have been published. Here, we report a case of PIG in a 44-year-old Korean female. The patient showed mild proteinuria without renal functional impairment or other systemic diseases. Glomeruli were normocellular, but GBMs were diffusely and mildly thickened and showed a bubbly appearance with periodic acid methenamine silver (PAMS) staining. Immunofluorescence microscopy showed minimal mesangial IgM deposition, but staining was negative for IgG, IgA, C3, C4, C1q, and fibrinogen. Electron microscopy showed diffuse distribution of microtubules and microspherules within thickened GBM (620-1180 nm). Additional serologic tests revealed positive antinuclear antibodies, but other autoimmune markers were normal or negative. The patient was treated with steroids for three months, after which proteinuria decreased to the normal range.
Assuntos
Nefropatias , Adulto , Feminino , Membrana Basal Glomerular , Humanos , Microscopia Eletrônica , Microesferas , PodócitosRESUMO
C3 glomerulonephritis (C3GN) is a recently described, rare glomerular disease characterized by predominant or sole glomerular C3 deposits. Morphologic features of C3GN are similar to those of dense deposit disease (DDD); however, ribbon-like intramembranous electron-dense deposits are absent in the former. We report a case of de novo C3GN in a renal allograft with morphologic transformation to DDD. A 6-year-old boy presented with congenital left renal agenesis and right ureteropelvic junction obstruction. The patient underwent pyeloplasty but experienced recurrent urinary tract infections. At the age of 22 years, he received a renal allograft from a living related donor. C3GN was diagnosed after 1 year of transplantation; initial histology showed minimal mesangiopathy and this progressed to mesangial proliferation and membranoproliferative features over the next 7 years. Serum creatinine levels were stabilized with anti-rejection treatments for combating repeated episodes of acute rejection; however, glomerular and tubular band-like electron-dense deposits became evident.
Assuntos
Complemento C3/análise , Glomerulonefrite Membranoproliferativa/imunologia , Glomérulos Renais/imunologia , Transplante de Rim/efeitos adversos , Aloenxertos , Biópsia , Progressão da Doença , Imunofluorescência , Glomerulonefrite Membranoproliferativa/patologia , Humanos , Imunossupressores/uso terapêutico , Glomérulos Renais/ultraestrutura , Transplante de Rim/métodos , Doadores Vivos , Masculino , Microscopia Eletrônica , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome (OMIM 304790) is a rare hereditary disorder of the immune regulatory system caused by FOXP3 mutations. The clinical features of this syndrome include a wide spectrum of severe autoimmune diseases and renal involvement, mostly due to tubulointerstitial diseases, in some patients. Glomerulopathy of membranous nephropathy (MN) and minimal change nephrotic syndrome (MCNS), however, have also been reported. We encountered two children with IPEX syndrome from the same family. Interestingly, they had different glomerular lesions: one had MN and the other had MCNS. Herein we describe the cases of these siblings and review the possible mechanisms for the development of two different renal lesions.
Assuntos
Diabetes Mellitus Tipo 1/congênito , Diarreia/diagnóstico , Doenças Genéticas Ligadas ao Cromossomo X/diagnóstico , Glomerulonefrite Membranosa/diagnóstico , Doenças do Sistema Imunitário/congênito , Rim/patologia , Nefrose Lipoide/diagnóstico , Pré-Escolar , Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 1/genética , Diarreia/genética , Fatores de Transcrição Forkhead/genética , Doenças Genéticas Ligadas ao Cromossomo X/genética , Glomerulonefrite Membranosa/genética , Humanos , Doenças do Sistema Imunitário/diagnóstico , Doenças do Sistema Imunitário/genética , Recém-Nascido , Masculino , Mutação , Nefrose Lipoide/genética , IrmãosRESUMO
BACKGROUND: To date, there has been much controversy about the role of crescentic lesion as a significant prognostic factor in immunoglobulin A nephropathy (IgAN). This study evaluated whether crescentic lesions predict adverse renal outcomes in IgAN patients. METHODS: A total of 430 patients with biopsy-proven IgAN between January 2000 and December 2009 were included. Histological variables of the Oxford classification (Oxford-MEST) and the presence of crescents were assessed. The primary endpoint was a 50% decline in estimated glomerular filtration rate. RESULTS: Of the 430 patients, 81 (18.8%) had a crescentic lesion. During a mean follow-up of 61 months, the primary outcome occurred in 19 (23.5%) patients with crescents compared with 40 (11.5%) patients without crescents (P=0.01). A Kaplan-Meier plot showed that the 10-year renal survival rate was significantly lower in patients with crescents than patients without crescents (P=0.01). However, in a multivariable Cox analysis which included clinical factors and the Oxford-MEST, crescents were not significantly associated with an increased risk of developing the primary outcome [hazard ratio: 0.71, 95% confidence interval (CI) 0.36-1.41, P=0.33]. Furthermore, adding crescents to the Oxford-MEST did not improve the discriminative ability for the prediction of renal outcomes [c-statistic: 0.86 (0.81-0.91) vs. 0.86 (0.80-0.91), P=0.21]. CONCLUSION: Crescentic lesion was not an independent prognostic factor, suggesting that crescents have limited value in predicting renal outcomes of IgAN.
Assuntos
Taxa de Filtração Glomerular , Glomerulonefrite por IGA/patologia , Rim/patologia , Adulto , Idoso , Biópsia , Feminino , Seguimentos , Glomerulonefrite por IGA/complicações , Glomerulonefrite por IGA/fisiopatologia , Humanos , Incidência , Estimativa de Kaplan-Meier , Rim/fisiopatologia , Falência Renal Crônica/epidemiologia , Falência Renal Crônica/etiologia , Falência Renal Crônica/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , República da Coreia/epidemiologia , Estudos Retrospectivos , Taxa de Sobrevida/tendências , Fatores de Tempo , Adulto JovemRESUMO
BACKGROUND: Many studies have shown that clinical characteristics and outcomes differ depending on pathologic variants of focal segmental glomerulosclerosis (FSGS). However, these are not well defined in Asian populations. METHODS: This retrospective study evaluated clinical features and outcomes of pathologic FSGS variants in 111 adult patients between January 2004 and December 2012. Primary outcome was the composite of doubling of baseline serum creatinine concentrations (D-SCr) or onset of end-stage renal disease (ESRD). Secondary outcome included complete (CR) or partial remission (PR). RESULTS: There were 70 (63.1%), 20 (18.0%), 17 (15.3%), 3 (2.7%), and 1 (0.9%) patients with not-otherwise specified (NOS), tip, perihilar, cellular, and collapsing variants, respectively. At presentation, nephrotic-range proteinuria occurred more commonly in tip lesion than in other variants. The overall 5-year renal survival rate was 76.8%. During a median follow-up of 34.5 months, only 1 (5.0%) patient with a tip lesion reached the composite end point compared to 2 (11.8%) and 12 (17.1%) patients in perihilar and NOS variants, but this difference was not statistically significant in an adjusted Cox model. However, tip lesion was associated with a significantly increased probability of achieving CR (P = 0.044). CONCLUSION: Similar to other populations, Korean adult patients with FSGS have distinct clinical features with the exception of a rare frequency of cellular and collapsing variants. Although pathologic variants were not associated with overall outcome, the tip variant exhibited favorable outcome in terms of achieving remission. Further studies are required to delineate long-term outcome and response to treatment of the pathologic variants.
Assuntos
Povo Asiático , Creatinina/sangue , Glomerulosclerose Segmentar e Focal/etnologia , Glomerulosclerose Segmentar e Focal/patologia , Idade de Início , Biomarcadores/sangue , Comorbidade , Feminino , Glomerulosclerose Segmentar e Focal/sangue , Glomerulosclerose Segmentar e Focal/diagnóstico , Glomerulosclerose Segmentar e Focal/terapia , Humanos , Incidência , Falência Renal Crônica/diagnóstico , Falência Renal Crônica/etnologia , Falência Renal Crônica/prevenção & controle , Masculino , Pessoa de Meia-Idade , Proteinúria/epidemiologia , República da Coreia/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida , Resultado do TratamentoRESUMO
This study was designed to evaluate whether sirolimus (SRL) conversion effectively improves renal function and histopathology in calcineurin inhibitor (CNI)-treated renal recipients with mild to moderate renal insufficiency. SRL conversion from CNI was performed in patients who underwent kidney transplantation from 6 months to 5 yr prior to screening. Forty-five patients were enrolled. The effect of SRL conversion on graft function was evaluated, and protocol biopsies were performed preconversion and 1 yr after conversion. Overall graft function after SRL conversion gradually improved, and the improvement in renal function was closely associated with the shorter duration of CNI exposure. When we divided the patients by the duration of CNI exposure, the patients with less than 1 yr of CNI exposure demonstrated significant improvement, but patients with a greater than 1 yr CNI exposure did not exhibit significant improvement. In contrast, protocol biopsies demonstrated no significant improvements in the modified "ah" score or other Banff scores after SRL conversion. Furthermore, the duration of CNI treatment prior to SRL conversion was not associated with histological findings 1 yr after SRL conversion. SRL conversion improved graft function in renal recipients with mild to moderate renal insufficiency, but this effect is not accompanied by histological improvement.
Assuntos
Inibidores de Calcineurina/administração & dosagem , Rejeição de Enxerto/etiologia , Rejeição de Enxerto/prevenção & controle , Transplante de Rim/métodos , Insuficiência Renal/terapia , Sirolimo/administração & dosagem , Adulto , Sinergismo Farmacológico , Feminino , Sobrevivência de Enxerto/efeitos dos fármacos , Humanos , Imunossupressores , Transplante de Rim/efeitos adversos , Masculino , Insuficiência Renal/diagnóstico , República da Coreia , Índice de Gravidade de Doença , Tolerância ao Transplante/efeitos dos fármacos , Resultado do TratamentoRESUMO
The purpose of this study was to investigate the clinical, laboratory, and pathologic characteristics of dense deposit disease (DDD) in Korean children and to determine whether these characteristics differ between Korean and American children with DDD. In 2010, we sent a structured protocol about DDD to pediatric nephrologists throughout Korea. The data collected were compared with previously published data on 14 American children with DDD. Korean children had lower 24-hr urine protein excretion and higher serum albumin levels than American children. The light microscopic findings revealed that a higher percentage of Korean children had membranoproliferative glomerulonephritis patterns (Korean, 77.8%; American, 28.6%, P = 0.036), whereas a higher percentage of American children had crescents (Korean, 0%; American, 78.6%, P < 0.001). The findings from the electron microscopy revealed that Korean children were more likely to have segmental electron dense deposits in the lamina densa of the glomerular basement membrane (Korean, 100%; American, 28.6%, P = 0.002); mesangial deposit was more frequent in American children (Korean, 66.7%; American, 100%, P = 0.047). The histological findings revealed that Korean children with DDD were more likely to show membranoproliferative glomerulonephritis patterns than American children. The degree of proteinuria and hypoalbuminemia was milder in Korean children than American children.
Assuntos
Glomerulonefrite Membranoproliferativa/patologia , Adolescente , Povo Asiático , Criança , Pré-Escolar , Creatinina/sangue , Edema/etiologia , Feminino , Hematúria/etiologia , Humanos , Lactente , Recém-Nascido , Masculino , Microscopia Eletrônica , Proteinúria/etiologia , República da Coreia , Albumina Sérica/análise , Estados UnidosRESUMO
Tubulointerstitial fibrosis is characterized by accumulation of the extracellular matrix in the interstitium. Lysyl oxidase-like 2 (LOXL2), a member of the lysyl oxidase family, is known for promoting cancer metastasis, invasion and stromal fibrosis in various organs. Our previous study demonstrated expression of LOXL2 in kidney podocytes and tubular epithelial cells, and the association between elevated LOXL2 and tubulointerstitial fibrosis. The present study evaluated the effect of LOXL2 inhibition using an inhibitory monoclonal antibody (AB0023) on tubulointerstitial fibrosis in a folic acid-induced tubulointerstitial fibrosis mouse model. The association of LOXL2 with epithelial-mesenchymal transformation-related molecules was also evaluated in vitro using HK-2 cells. The present data demonstrated that AB0023 prevented the progression of tubulointerstitial fibrosis significantly, as determined by trichrome and picro-sirius red staining, as well as the total collagen assay. The mean expression of phosphorylated Smad2 and Smad4 was lower in the AB0023-treated group although it was not statistically significant. Following transforming growth factor-ß (TGF-ß) challenge, LOXL2-deficient HK-2 cells exhibited significantly lower expression of the mesenchymal markers vimentin and fibronectin than control HK-2 cells. In conclusion, LOXL2 inhibition ameliorates renal fibrosis through the TGF-ß/Smad signalling pathway.
RESUMO
The optic atrophy 3 (OPA3) gene, which has no known homolog or biological function, is mutated in patients with hereditary optic neuropathies. Here, we identified OPA3 as an integral protein of the mitochondrial outer membrane (MOM), with a C-terminus exposed to the cytosol and an N-terminal mitochondrial targeting domain. By quantitative analysis, we demonstrated that overexpression of OPA3 significantly induced mitochondrial fragmentation, whereas OPA3 knockdown resulted in highly elongated mitochondria. Cells with mitochondria fragmented by OPA3 did not undergo spontaneous apoptotic cell death, but were significantly sensitized to staurosporine- and TRAIL-induced apoptosis. In contrast, overexpression of a familial OPA3 mutant (G93S) induced mitochondrial fragmentation and spontaneous apoptosis, suggesting that OPA3 mutations may cause optic atrophy via a gain-of-function mechanism. Together, these results indicate that OPA3, as an integral MOM protein, has a crucial role in mitochondrial fission, and provides a direct link between mitochondrial morphology and optic atrophy.
Assuntos
Mitocôndrias/genética , Doenças do Nervo Óptico/genética , Proteínas/metabolismo , Apoptose/efeitos dos fármacos , Sequência de Bases , Morte Celular/efeitos dos fármacos , Primers do DNA , Dinaminas , Endopeptidase K/metabolismo , GTP Fosfo-Hidrolases/genética , Humanos , Proteínas de Membrana/genética , Proteínas Associadas aos Microtúbulos/genética , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Proteínas de Transporte da Membrana Mitocondrial/genética , Proteínas de Transporte da Membrana Mitocondrial/metabolismo , Proteínas Mitocondriais/genética , Mutação , Doenças do Nervo Óptico/patologia , Proteínas/genética , RNA/genética , RNA Interferente Pequeno/genética , Estaurosporina/farmacologiaRESUMO
BACKGROUND: Some studies reported the correlations between renal parenchymal stiffness measured by transient elastography or acoustic radiation force impulse (ARFI) and the extent of interstitial fibrosis. This study was prospectively designed to evaluate the correlation between clinical, histological findings and the kidney shear wave velocity (SWV, m/s) assessed by ARFI elastography to identify factors affecting the kidney SWV in normal patients. METHODS: Seventy-three adult living kidney transplantation donors were enrolled in our center between September 2010 and January 2013. Before transplantation, all donors were evaluated by ARFI elastography to identify the range of SWV in kidneys. Time-zero biopsies were performed on all graft kidneys before implantation. RESULTS: Mean age of donors was 42.0â±â11.3âyears. The mean SWV and depth were 2.21â±â0.58âm/s and 5.37â±â1.06âcm. All histological findings showed mild degree of the Banff score, only grade I. In univariate analyses, the SWV was not associated with all histological parameters. Age (râ=â-0.274, Pâ=â.019) diastolic blood pressure (DBP, râ=â-0.255, Pâ=â.030) and depth for SWV measurement (râ=â-0.345, Pâ=â.003) were significantly correlated with the SWV. In multivariate linear regression analysis, age, gender, body mass index (BMI), and depth for SWV measurement were significantly correlated with the SWV (Pâ=â.003, .005, .002, and .004, respectively). CONCLUSIONS: We demonstrated that all histological findings are not correlated with the SWV of donor kidney. Otherwise, factors influencing the kidney SWV assessed by ARFI elastography are age, gender, BMI, and depth for the SWV measurement in donors for kidney transplantation.