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1.
bioRxiv ; 2024 Jun 03.
Artículo en Inglés | MEDLINE | ID: mdl-38895424

RESUMEN

In the animal kingdom, evolutionarily conserved mechanisms known as cell competition eliminate unfit cells during development. Interestingly, cell competition also leads to apoptosis of donor cells upon direct contact with host cells from a different species during interspecies chimera formation. The mechanisms underlying how host animal cells recognize and transmit cell death signals to adjacent xenogeneic human cells remain incompletely understood. In this study, we developed an interspecies cell contact reporter system to dissect the mechanisms underlying competitive interactions between mouse and human pluripotent stem cells (PSCs). Through single-cell RNA-seq analyses, we discovered that Ephrin A ligands in mouse cells play a crucial role in signaling cell death to adjacent human cells that express EPHA receptors during interspecies PSC co-culture. We also demonstrated that blocking the Ephrin A-EPHA receptor interaction pharmacologically, and inhibiting Ephrin forward signaling genetically in the mouse cells, enhances the survival of human PSCs and promotes chimera formation both in vitro and in vivo . Our findings elucidate key mechanisms of interspecies PSC competition during early embryogenesis and open new avenues for generating humanized tissues or organs in animals, potentially revolutionizing regenerative medicine.

2.
Cell Rep ; 43(6): 114340, 2024 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-38865239

RESUMEN

Whole salivary gland generation and transplantation offer potential therapies for salivary gland dysfunction. However, the specific lineage required to engineer complete salivary glands has remained elusive. In this study, we identify the Foxa2 lineage as a critical lineage for salivary gland development through conditional blastocyst complementation (CBC). Foxa2 lineage marking begins at the boundary between the endodermal and ectodermal regions of the oral epithelium before the formation of the primordial salivary gland, thereby labeling the entire gland. Ablation of Fgfr2 within the Foxa2 lineage in mice leads to salivary gland agenesis. We reversed this phenotype by injecting donor pluripotent stem cells into the mouse blastocysts, resulting in mice that survived to adulthood with salivary glands of normal size, comparable to those of their littermate controls. These findings demonstrate that CBC-based salivary gland regeneration serves as a foundational experimental approach for future advanced cell-based therapies.


Asunto(s)
Blastocisto , Factor Nuclear 3-beta del Hepatocito , Células Madre Pluripotentes , Glándulas Salivales , Animales , Glándulas Salivales/citología , Glándulas Salivales/metabolismo , Blastocisto/metabolismo , Blastocisto/citología , Ratones , Células Madre Pluripotentes/metabolismo , Células Madre Pluripotentes/citología , Factor Nuclear 3-beta del Hepatocito/metabolismo , Factor Nuclear 3-beta del Hepatocito/genética , Linaje de la Célula , Receptor Tipo 2 de Factor de Crecimiento de Fibroblastos/metabolismo , Receptor Tipo 2 de Factor de Crecimiento de Fibroblastos/genética
3.
bioRxiv ; 2023 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-38014349

RESUMEN

Various patients suffer from dry mouth due to salivary gland dysfunction. Whole salivary gland generation and transplantation is a potential therapy to resolve this issue. However, the lineage permissible to design the entire salivary gland generation has been enigmatic. Here, we discovered Foxa2 as a lineage critical for generating a salivary gland via conditional blastocyst complementation (CBC). Foxa2 linage, but not Shh nor Pitx2, initiated to label between the boundary region of the endodermal and the ectodermal oral mucosa before primordial salivary gland formation, resulting in marking the entire salivary gland. The salivary gland was agenesis by depleting Fgfr2 under the Foxa2 lineage in the mice. We rescued this phenotype by injecting donor pluripotent stem cells into the mouse blastocysts. Those mice survived until adulthood with normal salivary glands compatible in size compared with littermate controls. These results indicated that CBC-based salivary gland generation is promising for next-generation cell-based therapy.

4.
Elife ; 122023 10 20.
Artículo en Inglés | MEDLINE | ID: mdl-37861292

RESUMEN

Millions suffer from incurable lung diseases, and the donor lung shortage hampers organ transplants. Generating the whole organ in conjunction with the thymus is a significant milestone for organ transplantation because the thymus is the central organ to educate immune cells. Using lineage-tracing mice and human pluripotent stem cell (PSC)-derived lung-directed differentiation, we revealed that gastrulating Foxa2 lineage contributed to both lung mesenchyme and epithelium formation. Interestingly, Foxa2 lineage-derived cells in the lung mesenchyme progressively increased and occupied more than half of the mesenchyme niche, including endothelial cells, during lung development. Foxa2 promoter-driven, conditional Fgfr2 gene depletion caused the lung and thymus agenesis phenotype in mice. Wild-type donor mouse PSCs injected into their blastocysts rescued this phenotype by complementing the Fgfr2-defective niche in the lung epithelium and mesenchyme and thymic epithelium. Donor cell is shown to replace the entire lung epithelial and robust mesenchymal niche during lung development, efficiently complementing the nearly entire lung niche. Importantly, those mice survived until adulthood with normal lung function. These results suggest that our Foxa2 lineage-based model is unique for the progressive mobilization of donor cells into both epithelial and mesenchymal lung niches and thymus generation, which can provide critical insights into studying lung transplantation post-transplantation shortly.


Asunto(s)
Células Endoteliales , Células Madre Pluripotentes , Ratones , Humanos , Animales , Adulto , Células Madre Pluripotentes/metabolismo , Diferenciación Celular , Pulmón , Blastocisto/metabolismo , Factor Nuclear 3-beta del Hepatocito/genética , Factor Nuclear 3-beta del Hepatocito/metabolismo
5.
Front Cell Dev Biol ; 11: 1070560, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36743411

RESUMEN

Millions of people suffer from end-stage refractory diseases. The ideal treatment option for terminally ill patients is organ transplantation. However, donor organs are in absolute shortage, and sadly, most patients die while waiting for a donor organ. To date, no technology has achieved long-term sustainable patient-derived organ generation. In this regard, emerging technologies of chimeric human organ production via blastocyst complementation (BC) holds great promise. To take human organ generation via BC and transplantation to the next step, we reviewed current emerging organ generation technologies and the associated efficiency of chimera formation in human cells from the standpoint of developmental biology.

6.
Kidney Int Rep ; 8(1): 151-163, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36644361

RESUMEN

Introduction: Proliferative glomerulonephritis with monoclonal IgG deposits (PGNMID) occasionally presents refractory nephrotic syndrome resulting in poor renal prognosis, but its etiology is not fully elucidated. Given that glomerular endothelial cell (GEC) stress or damage may lead to podocytopathy and subsequent proteinuria, as in thrombotic microangiopathy (TMA), diabetic kidney disease, and focal segmental glomerulosclerosis, we investigated the evidence of glomerular endothelial injury by evaluating the expression of plasmalemmal vesicle-associated protein-1 (PV-1), a component of caveolae in the cases of PGNMID. Methods: We measured the immunofluorescent PV-1 intensities of 23 PGNMID cases and compared with those of primary membranoproliferative glomerulonephritis (MPGN) (n = 5) and IgA nephropathy (IgAN) (n = 54) cases. PV-1 localization was evaluated with Caveolin-1, and CD31 staining, and the ultrastructural analysis was performed using a low-vacuum scanning electron microscope (LVSEM). To check the association of podocyte injury, we also conducted 8-oxoguanine and Wilms tumor 1 (WT1) double stain. We then evaluated PV-1 expression in other glomerulitis and glomerulopathy such as lupus nephritis and minimal change disease. Results: The intensity of glomerular PV-1 expression in PGNMID is significantly higher than that in the other glomerular diseases, although the intensity is not associated with clinical outcomes such as urinary protein levels or renal prognosis. Immunostaining and LVSEM analysis revealed that glomerular PV-1 expression is localized in GECs in PGNMID. 8-oxoguanine accumulation was detected in WT1-positive podocytes but not in PV-1-expressing GECs, suggesting GEC-derived podocyte injury in PGNMID. Conclusion: PV-1 overexpression reflects glomerular endothelial injury, which could be associated with podocyte oxidative stress in PGNMID cases.

7.
Kidney Int ; 102(6): 1276-1290, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-36049642

RESUMEN

Activated monocytes/macrophages promote glomerular injury, including crescent formation, in anti-glomerular basement membrane (GBM) glomerulonephritis. Disulfiram, an alcohol-aversion drug, inhibits monocyte/macrophage migration by inhibiting FROUNT, a cytosolic protein that enhances chemokine receptor signaling. Our study found that disulfiram at a human equivalent dose successfully blocked albuminuria and crescent formation with podocyte loss, and later stage kidney fibrotic lesions, in a rat model of anti-GBM glomerulonephritis. A disulfiram derivative, DSF-41, with more potent FROUNT inhibition activity, inhibited glomerulonephritis at a lower dose than disulfiram. Disulfiram markedly reduced the number of monocytes or macrophages at the early stage of glomerulonephritis and that of CD3+ and CD8+ lymphocytes at the established stage. Impaired pseudopodia formation was observed in the glomerular monocytes/macrophages of the disulfiram group; consistent with the in vitro observation that disulfiram blocked chemokine-dependent pseudopodia formation and chemotaxis of bone marrow-derived monocytes/macrophages. Furthermore, disulfiram suppressed macrophage activation as revealed by reduced expression of inflammatory cytokines and chemokines (TNF-α, CCL2, and CXCL9) and reduced CD86 and MHC class II expressions in monocytes/macrophages during glomerulonephritis. The dramatic reduction in monocyte/macrophage number might have resulted from disulfiram suppression of both the chemotactic response of monocytes/macrophages and their subsequent activation to produce cytokines and chemokines, which further recruit monocytes. Additionally, FROUNT was expressed in CD68+ monocytes/macrophages infiltrating the crescentic glomeruli in human anti-GBM glomerulonephritis. Thus, disulfiram can be a highly effective and safe drug for the treatment of glomerulonephritis by blocking the chemotactic responses of monocytes/macrophages and their activation status in the glomerulus.


Asunto(s)
Glomerulonefritis Membranoproliferativa , Glomerulonefritis , Ratas , Humanos , Animales , Disulfiram/farmacología , Disulfiram/uso terapéutico , Ratas Endogámicas WKY , Quimiocinas/metabolismo , Glomerulonefritis/tratamiento farmacológico , Glomerulonefritis/patología , Citocinas/metabolismo
8.
Pathol Int ; 71(6): 406-414, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-33783928

RESUMEN

Monoclonal tubular basement membrane immune deposits (TBMID) are associated with progression of interstitial injury in renal allograft. However, the significance of monoclonal and polyclonal TBMID in the native kidney remains unclear. We retrospectively analyzed 1894 native kidney biopsies and 1724 zero-hour biopsies performed between 2008 and 2018 in our institution. The rate of immunoglobulin G (IgG) TBMID was found to be 8.4% among native kidney biopsies and 0.4% among zero-hour biopsies. Polyclonal TBMID is common in IgG4-related tubulointerstitial nephritis (37.5%), diabetic nephropathy (31.3%) and lupus nephritis (25.5%). Monoclonal IgG TBMID was identified in seven cases, including three zero-hour biopsies. The combination of IgG1κ was observed in two cases, IgG1λ in three, and IgG2κ in two. Electron microscopy revealed powdery electron-dense deposits in all cases. Monoclonal gammopathy of undetermined significance was diagnosed in one case. Although one patient with focal segmental glomerulosclerosis developed renal failure, all others exhibited stable renal function. Monoclonal IgG TBMID in the native kidney is not associated with renal prognosis. However, this may be an interesting immunopathological finding that would help clarify the pathogenesis of TBM immune deposits. Further study for both monoclonal and polyclonal TBMID is required in the future.


Asunto(s)
Inmunoglobulina G/metabolismo , Trasplante de Riñón , Riñón , Membrana Basal/patología , Biopsia , Femenino , Humanos , Riñón/patología , Riñón/ultraestructura , Masculino , Estudios Retrospectivos
9.
Nephron ; 144 Suppl 1: 37-42, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33238276

RESUMEN

INTRODUCTION: Extra efferent arterioles, also known as polar vasculosis (PV), are often observed in the glomerular vascular pole and are associated with glomerular hypertrophy, indicating early recurrent diabetic kidney disease (DKD) in renal allografts. However, its significance in patients without diabetes remains uncertain. METHODS: A total of 9,004 renal allograft biopsy specimens obtained between January 2007 and December 2017 at Tokyo Women's Medical University were retrospectively analyzed to examine the clinical and pathological significance of PV in renal allografts. PV was identified in 186 biopsy specimens obtained from 165 patients. The PV group comprised 46 patients; 35 patients without DKD and 11 patients with DKD as the initial cause of ESRD, whose clinical information was available and treated with the calcineurin inhibitor (CNI) tacrolimus. The non-PV group comprising patients with renal allografts matched for age and postoperative day included 93 patients without DKD and 16 patients with DKD as the initial cause of ESRD. RESULTS: In patients with nondiabetic renal allografts, systolic blood pressure was significantly higher in the PV group than in the non-PV group. The trough tacrolimus levels during the overall study period and at 2 weeks, 1 month, and 2 years after transplantation were significantly higher in the PV group compared with the non-PV group. Glomerulomegaly was significantly more common. Moreover, ah and aah scores in Banff score were significantly higher in the PV group than in the non-PV group. In those with diabetic renal allografts, although the clinical parameters and tacrolimus trough levels in all time periods were not significantly different between the PV and non-PV groups, the ah score was significantly higher in the PV group. CONCLUSION: PV was associated with CNI toxicity in nondiabetic but not in diabetic renal allografts. The pathogenesis of PV in renal allografts is considered to be multifactorial.


Asunto(s)
Inhibidores de la Calcineurina/toxicidad , Nefropatías Diabéticas/patología , Glomérulos Renales/irrigación sanguínea , Trasplante de Riñón/efectos adversos , Neovascularización Patológica/inducido químicamente , Adulto , Anciano , Arteriolas/patología , Biopsia , Femenino , Humanos , Glomérulos Renales/patología , Masculino , Persona de Mediana Edad , Neovascularización Patológica/patología , Estudios Retrospectivos , Tacrolimus/sangre , Trasplante Homólogo
10.
Pathol Int ; 69(11): 655-660, 2019 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-31508868

RESUMEN

Here, we report the case of a patient with renal allograft with full-house immunofluorescence staining in the zero-hour biopsy. Full-house immunofluorescence staining is a well-known characteristic of lupus nephritis. Previous studies have reported patients with full-house immunofluorescence staining, but without other symptoms or serological findings; this condition is referred to as full-house nephropathy. We identified only one case out of 2203 zero-hour biopsies over 13 years. Zero-hour biopsy presented no glomerular changes but showed full-house immunofluorescence staining. Electron microscopy revealed a nonorganized electron-dense deposit mainly in the mesangial lesion. Systemic lupus erythematosus (SLE)-associated antibodies were negative, and complement deficiency was not observed in the donor patients. Deposition of immunoglobulin and complement levels markedly decreased within 1-3 years post transplantation. Neither donor nor recipient developed clinical or biological features of SLE; they showed good renal prognosis.


Asunto(s)
Trasplante de Riñón , Riñón/metabolismo , Nefritis Lúpica/diagnóstico , Femenino , Técnica del Anticuerpo Fluorescente , Humanos , Riñón/patología , Nefritis Lúpica/metabolismo , Persona de Mediana Edad
11.
Medicine (Baltimore) ; 98(2): e14014, 2019 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-30633192

RESUMEN

RATIONALE: Adult-onset hepatitis B virus-associated membranoproliferative glomerulonephritis (HBV-MPGN) is generally refractory, and an effective treatment for this condition has not been established. The indications for steroids in HBV-MPGN are an important clinical concern. PATIENT CONCERNS: A 28-year-old woman with a chronic hepatitis B virus infection developed nephrotic syndrome in her second month of pregnancy, with urinary protein levels of 3 to 10 g/d that continued into her postpartum period. She was a carrier of HBV with HBeAg seroconversion. As her renal impairment could have been a result of pregnancy, we observed her for 10 months postpartum without any intervention. However, spontaneous remission after childbirth was not achieved and urine protein levels were sustained at 1 to 3 g/d. About 10 months after delivery, elevated serum liver enzyme levels were observed. DIAGNOSIS: Biopsies showed MPGN, with deposition of hepatitis B antigen in the glomeruli, and chronic B-type hepatitis with a severity grade of A1F0. She was diagnosed with HBV-MPGN. INTERVENTIONS: The patient was started on entecavir 0.5 mg/d in March 2008. Within 1 month, serum HBV DNA became undetectable; within 3 months, her alanine aminotransferase levels normalized. However, urinary protein excretion did not decrease to <2 g/d. On a second renal biopsy, performed 7 months after entecavir treatment, proliferative lesions of the glomeruli were observed; therefore, prednisolone was started at an initial dose of 30 mg/d. OUTCOMES: Her proteinuria improved immediately and prednisolone was tapered over 10 months. A third renal biopsy showed a remarkable resolution of HBV-MPGN, with a significant decrease in mesangial proliferation and immune complex deposition. HBV reactivation was not observed during the prednisolone treatment. LESSONS: Additional prednisolone therapy in combination with antiviral therapy should be considered for refractory HBV-MPGN, with sufficient care taken regarding HBV reactivation.


Asunto(s)
Antivirales/uso terapéutico , Glomerulonefritis Membranoproliferativa/tratamiento farmacológico , Glomerulonefritis Membranoproliferativa/etiología , Guanina/análogos & derivados , Hepatitis B Crónica/complicaciones , Hepatitis B Crónica/tratamiento farmacológico , Adulto , Femenino , Glomerulonefritis Membranoproliferativa/patología , Glomerulonefritis Membranoproliferativa/virología , Guanina/uso terapéutico , Virus de la Hepatitis B , Hepatitis B Crónica/patología , Humanos , Prednisolona/uso terapéutico , Embarazo , Complicaciones Infecciosas del Embarazo
12.
Nephrol Dial Transplant ; 34(4): 711-717, 2019 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-30124906

RESUMEN

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.


Asunto(s)
Anticuerpos Monoclonales/inmunología , Membrana Basal/inmunología , Glomerulonefritis/inmunología , Inmunoglobulina G/inmunología , Trasplante de Riñón/métodos , Nefritis Intersticial/inmunología , Adolescente , Adulto , Anciano , Aloinjertos , Anticuerpos Monoclonales/metabolismo , Membrana Basal/metabolismo , Niño , Femenino , Glomerulonefritis/metabolismo , Glomerulonefritis/patología , Humanos , Inmunoglobulina G/metabolismo , Masculino , Persona de Mediana Edad , Nefritis Intersticial/metabolismo , Nefritis Intersticial/patología , Pronóstico , Estudios Retrospectivos , Adulto Joven
13.
BMC Nephrol ; 19(1): 72, 2018 03 27.
Artículo en Inglés | MEDLINE | ID: mdl-29587650

RESUMEN

BACKGROUND: Vancomycin is the first-line antibiotic for methicillin-resistant Staphylococcus aureus and coagulase-negative strains. The risk of vancomycin-induced acute kidney injury increases with plasma vancomycin levels. Vancomycin-induced acute kidney injury is histologically characterized by acute interstitial nephritis and/or acute tubular necrosis. However, only 12 biopsy-proven cases of vancomycin-induced acute kidney injury have been reported so far, as renal biopsy is rarely performed for such cases. Current recommendations for the prevention or treatment of vancomycin-induced acute kidney injury are drug monitoring of plasma vancomycin levels using trough level and drug withdrawal. Oral prednisone and high-flux haemodialysis have led to the successful recovery of renal function in some biopsy-proven cases. CASE PRESENTATION: We present the case of a 41-year-old man with type 1 diabetes mellitus, who developed vancomycin-induced acute kidney injury during treatment for Fournier gangrene. His serum creatinine level increased to 1020.1 µmol/L from a baseline of 79.6 µmol/L, and his plasma trough level of vancomycin peaked at 80.48 µg/mL. Vancomycin discontinuation and frequent haemodialysis with high-flux membrane were immediately performed following diagnosis. Renal biopsy showed acute tubular necrosis and focal acute interstitial nephritis, mainly in the medullary rays (medullary ray injury). There was no sign of glomerulonephritis, but mild diabetic changes were detected. He was discharged without continuing haemodialysis (serum creatinine level, 145.0 µmol/L) 49 days after initial vancomycin administration. CONCLUSIONS: This case suggests that frequent haemodialysis and renal biopsy could be useful for the treatment and assessment of vancomycin-induced acute kidney injury, particularly in high-risk cases or patients with other renal disorders.


Asunto(s)
Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/diagnóstico por imagen , Antibacterianos/efectos adversos , Vancomicina/efectos adversos , Lesión Renal Aguda/complicaciones , Adulto , Biopsia , Diabetes Mellitus Tipo 1/complicaciones , Diabetes Mellitus Tipo 1/diagnóstico por imagen , Humanos , Masculino , Nefritis Intersticial/complicaciones , Nefritis Intersticial/diagnóstico por imagen
14.
Nephrology (Carlton) ; 21 Suppl 1: 35-40, 2016 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-26970541

RESUMEN

Transplantation-associated thrombotic microangiopathy (TA-TMA) is relatively rare and requires immediate intervention to avoid irreversible organ damage or death; however, consensus regarding the treatment approach is lacking. Atypical haemolytic uraemic syndrome (aHUS) is a rare disease caused by dysregulation of the alternative complement pathway resulting in TMA. aHUS is histologically similar to TA-TMA; approximately 60% of TA-TMA patients have complement dysregulation. Eculizumab, a humanized anti-C5 monoclonal antibody, inhibits terminal membrane-attack complex formation and TMA progression. Eculizumab has been successfully used to treat aHUS post-transplant. We present two cases of kidney TA-TMA due to unknown causes, suspected antibody-mediated rejection, or calcineurin inhibitor (CNI)-related toxicity that developed on day 1 or 2 post-kidney transplantation. Low platelet count and haemoglobin level with red cell fragments were detected. Despite steroid pulse, plasma exchange (PE), and intravenous immunoglobulin therapy, TA-TMA did not improve; therefore, eculizumab was administered despite no genetic testing. Laboratory data, including renal function, improved immediately. TA-TMA treatment primarily involves PE initiation or CNI discontinuation; eculizumab can be used to safely treat TA-TMA and then be ceased in the short term. Therefore, eculizumab administration might be beneficial for kidney TA-TMA as early as the diagnosis of refractory to PE.


Asunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Inactivadores del Complemento/farmacología , Trasplante de Riñón/efectos adversos , Riñón/efectos de los fármacos , Microangiopatías Trombóticas/tratamiento farmacológico , Adulto , Anciano , Aloinjertos , Biopsia , Activación de Complemento/efectos de los fármacos , Femenino , Humanos , Riñón/inmunología , Riñón/patología , Masculino , Inducción de Remisión , Microangiopatías Trombóticas/diagnóstico , Microangiopatías Trombóticas/inmunología , Factores de Tiempo , Resultado del Tratamiento
15.
Nephrology (Carlton) ; 21 Suppl 1: 48-52, 2016 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-26971743

RESUMEN

Immunoglobulin (Ig) A nephropathy (IgAN) is a known autoimmune disease due to abnormal glycosylation of IgA1, and occasionally, IgG co-deposition occurs. The prognosis of IgG co-deposition with IgAN is adverse, as shown in the previous studies. However, in the clinical setting, monoclonality of IgG co-deposition with IgAN has not been observed. We describe a case of proliferative glomerulonephritis with monoclonal IgG deposits (PGNMID) combined with IgAN in a renal allograft. A-21-year-old man developed end-stage renal failure with unknown aetiology and underwent living-donor kidney transplantation from his mother 2 years after being diagnosed. One year after kidney transplantation, proteinuria 2+ and haematuria 2+ were detected; allograft biopsy revealed mesangial IgA and C3 deposits, indicating a diagnosis of IgAN. After tonsillectomy and steroid pulse therapy, proteinuria and haematuria resolved. However, 4 years after transplantation, pedal oedema, proteinuria (6.89 g/day) and allograft dysfunction (serum creatinine (sCr) 203.3 µmol/L) appeared. A second allograft biopsy showed mesangial expansion and focal segmental proliferative endocapillary lesions with IgA1λ and monoclonal IgG1κ depositions. Electron microscopic analysis revealed a massive amount of deposits, located in the mesangial and subendothelial lesions. A diagnosis of PGNMID complicated with IgAN was made, and rituximab and plasmapheresis were added to steroid pulse therapy. With this treatment, proteinuria was alleviated to 0.5 g/day, and the allograft dysfunction recovered to sCr 132.6 µmol/L. This case suggests a necessity for investigation of PGNMID and IgA nephropathy in renal allografts to detect monoclonal Ig deposition disease.


Asunto(s)
Anticuerpos Monoclonales/análisis , Glomerulonefritis por IGA/inmunología , Glomerulonefritis Membranoproliferativa/inmunología , Glomeruloesclerosis Focal y Segmentaria/inmunología , Inmunoglobulina A/análisis , Inmunoglobulina G/análisis , Cadenas kappa de Inmunoglobulina/análisis , Glomérulos Renales/inmunología , Trasplante de Riñón/efectos adversos , Aloinjertos , Biopsia , Complemento C3/análisis , Técnica del Anticuerpo Fluorescente , Glomerulonefritis por IGA/diagnóstico , Glomerulonefritis por IGA/terapia , Glomerulonefritis Membranoproliferativa/diagnóstico , Glomerulonefritis Membranoproliferativa/terapia , Glomeruloesclerosis Focal y Segmentaria/diagnóstico , Glomeruloesclerosis Focal y Segmentaria/terapia , Hematuria/etiología , Humanos , Glomérulos Renales/ultraestructura , Donadores Vivos , Masculino , Microscopía Electrónica , Plasmaféresis , Proteinuria/etiología , Quimioterapia por Pulso , Rituximab/uso terapéutico , Esteroides/administración & dosificación , Factores de Tiempo , Tonsilectomía , Resultado del Tratamiento , Adulto Joven
16.
ASAIO J ; 59(6): 617-21, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-24172267

RESUMEN

Adequate blood flow (Qb) is necessary for effective hemodialysis (HD). Aim of the study was to examine relationship between the actually delivered Qb (dQb) and reported Qb (rQb) with dialysis machine. One hundred HD patients with arteriovenous fistula were enrolled. Delivered Qb was measured at the beginning and end of each HD session. dQb/rQb < 1 indicated a discrepancy between actual dQb and rQb reported using a dialysis machine. In addition, dQb/rQb was examined in HD patients using needles of different gauges during treatment. The average levels of dQb/rQb at start and end of HD session were 1.01 ± 0.04 and 0.98 ± 0.05, respectively. In the 16 gauge and 17 gauge needle groups, the percentage of patients with dQb/rQb < 1 increased in accordance with the increase in rQb or as the HD session progressed. In the 15 gauge needle group, the percentage of patients with dQb/rQb < 1 was <50% at any level of rQb. Selection of needle gauge is important factors for determining actual dQb in HD patients.


Asunto(s)
Circulación Sanguínea , Diálisis Renal , Derivación Arteriovenosa Quirúrgica , Femenino , Humanos , Masculino , Persona de Mediana Edad
17.
Case Rep Nephrol Urol ; 3(2): 128-35, 2013 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-24570682

RESUMEN

Most cases of type III hyperlipoproteinemia are accounted for by apolipoprotein E2 (apoE2) homozygotes, a genetic mutation of apoE (Arg158Cys). Glomerulopathy with homozygous apoE2 is rare and characterized by marked foam cell infiltration in the glomerular capillaries and mesangium. Here, we report 3 cases of apoE2 homozygote glomerulopathy diagnosed by renal biopsy and DNA analysis. All 3 cases were middle-aged or elderly males complicated with diabetes for at least a decade. The kidney biopsies showed massive foam cell infiltration in the glomerular capillaries and expanded mesangium accompanied by histological findings of diabetic glomerulosclerosis. The lipid profiles showed type III hyperlipoproteinemia and phenotypic/genetic analyses revealed homozygosity of apoE2. Two of the cases showed nephrotic proteinuria and progressed to renal failure in 3 and 8 years after the diagnosis of kidney disease.

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