RESUMO
Transplantation outcomes are affected by the increase in rejection associated with ischemia reperfusion injury (IRI). Fractalkine (FKN), a chemokine for recruitment of CX3CR1+ leukocytes, contributes to the pathogenesis of various inflammatory diseases. Herein, we evaluated the importance of the FKN-CX3CR1 axis during IRI-related rejections using a mouse heterotopic heart transplantation model. FKN expression and graft survival was compared between wild-type C57BL/6 recipients transplanted with BALB/c hearts preserved for 8 (WT-IRI) and 0.5 h (WT-control) at 4°C. Graft survival of WT-IRI was shorter than that of WT-control. FKN was expressed on the vascular endothelium in WT-IRI allografts, but minimally in WT-control. The role of the FKN-CX3CR1 axis in IRI-related rejection was directly investigated using the transplant model with CX3CR1-deficient recipients (CX3CR1 KO-IRI) or treatment with anti-mouse FKN monoclonal antibodies. Graft survival of CX3CR1 KO-IRI was longer than that of WT-IRI; antibody treatment prolonged graft survival. The contribution of CX3CR1+ monocytes to IRI-related rejection was evaluated by adoptive transfer to CX3CR1 KO-IRI. Adoptive transfer of CX3CR1+ monocytes attenuated the effect of prolonged graft survival in CX3CR1 KO-IRI. Overall, the FKN-CX3CR1 axis plays a major role during IRI-related rejection; its blockade has the potential to improve the outcomes of deceased donor transplantation.
Assuntos
Receptor 1 de Quimiocina CX3C , Quimiocina CX3CL1 , Rejeição de Enxerto , Transplante de Coração , Traumatismo por Reperfusão , Transferência Adotiva , Aloenxertos , Animais , Receptor 1 de Quimiocina CX3C/metabolismo , Quimiocina CX3CL1/metabolismo , Sobrevivência de Enxerto , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , MonócitosRESUMO
BACKGROUND: Cholesterol crystal embolization syndrome (CES) occurs when an atherosclerotic plaque causes small-vessel embolization, resulting in multi-organ damage. Although CES is pathologically characterized by an infiltration of eosinophils, the implication of the systemic inflammatory response represented by hypereosinophilia is unclear in clinical practice. Herein we present the case of a patient diagnosed with CES who developed multiple allergic organ injuries, including daptomycin-related dermatitis and later vancomycin-induced acute tubulointerstitial nephritis, which was successfully treated by the withdrawal of each medicine with or without corticosteroid therapy, one by one. CASE PRESENTATION: A 76-year-old Japanese man diagnosed with thoracic aneurysm rupture underwent total arch replacement through the open stent graft technique. Postoperatively, he developed methicillin-resistant Staphylococcus epidermidis bacteremia, which was treated with daptomycin. Subsequently, he presented with palpable purpura on both dorsal feet, erythema around his body, and hypereosinophilia. Daptomycin was replaced with vancomycin due to suspicion of drug-induced erythema. The erythema gradually faded. On nine days after vancomycin therapy, the systemic erythema rapidly reappeared followed by acute renal failure. The renal function decline prompted hemodialysis. A skin biopsy revealed cholesterol embolization, whereas a kidney biopsy revealed acute tubulointerstitial nephritis. After vancomycin discontinuation and initiation of systemic corticosteroid treatment, his kidney function was restored to the baseline level. CONCLUSIONS: The present case highlights cholesterol embolization can cause allergic complications in addition to direct organ damage.
Assuntos
Daptomicina , Embolia de Colesterol , Staphylococcus aureus Resistente à Meticilina , Idoso , Colesterol , Embolia de Colesterol/complicações , Embolia de Colesterol/diagnóstico , Humanos , Imunidade , Masculino , Nefrite Intersticial , Vancomicina/uso terapêuticoRESUMO
BACKGROUND: Several clinical parameters and pathological findings are known to be predictors of the deterioration of diabetic nephropathy (DN). Glomerular basement membrane duplication (GBM-DP) is a pathological feature representing endothelial injury, which is commonly observed in DN. In the present study, we investigated the association between GBM-DP and the renal prognosis in DN. METHODS: The study enrolled 80 patients with renal biopsy-proven DN who were managed at Chiba-East Hospital from 2005 to 2012. We confirmed the pathological findings according to the Renal Pathology Society classifications, and we further evaluated the GBM-DP, which was defined as double contours of the GBM that expanded more than 10% of capillary loops in the most affected nonsclerotic glomerulus. We used Cox regression models to estimate hazard ratios (HRs) for end-stage renal disease (ESRD), with adjustment for age, sex, systolic blood pressure, HbA1c, estimated glomerular filtration rate (eGFR), and urinary protein excretion (UP) at baseline. RESULTS: Of the 80 patients, 56 were male (70.0%) and the mean age was 59.1 years. The median eGFR and UP were 42 ml/min/1.73 m2 (IQR 30, 59) and 3.1 g/gCr (IQR 1.2, 5.2). Twenty-seven patients progressed to ESRD and one patient died during the median observational period of 2.9 years (IQR 1.5, 4.3). The multivariable analyses showed that GBM-DP was significantly associated with ESRD (HR 3.18 [95% confidence interval (CI): 1.02-9.87], p = 0.045). CONCLUSION: We newly identified GBM-DP as a strong prognostic predictor in DN patients. Further study is needed to clarify the pathogenic mechanism of GBM-DP in DN.
Assuntos
Diabetes Mellitus Tipo 2/complicações , Nefropatias Diabéticas/patologia , Nefropatias Diabéticas/fisiopatologia , Membrana Basal Glomerular/patologia , Falência Renal Crônica/etiologia , Falência Renal Crônica/fisiopatologia , Túbulos Renais/patologia , Idoso , Atrofia/patologia , Nefropatias Diabéticas/complicações , Progressão da Doença , Feminino , Fibrose , Taxa de Filtração Glomerular , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Fatores de RiscoRESUMO
The extent of recurrence of original kidney disease after kidney transplantation has been underestimated for several reasons. First, the duration of observation varies among studies. Second, the criteria used to schedule protocol and episode biopsies differ among institutions. And third, diagnostic modalities used for early detection of recurrent original kidney disease also vary. Thus, rates of graft loss attributable to a recurrence of original kidney disease vary among institutions and are often underestimated. However, the recurrence of original disease is often thought to be less important than chronic rejection followed by loss of a functioning allograft. It is important to note that recent data have shown that in patients with certain limited primary kidney diseases (e.g., membranous proliferative glomerulonephritis [MPGN], IgA nephritis [IgAN], focal segmental glomerulonephritis [FSGS], and membranous nephropathy [MN]), the predominant (60%) cause of graft loss is the recurrence of original kidney disease. In addition, the rate of 5-year graft survival in patients with recurrent original kidney disease averages 45%. Thus, research must address the recurrence of original kidney disease. Here we focus on this recurrence and discuss diagnoses, preventive strategies, treatments, and future research directions.
Assuntos
Nefropatias/cirurgia , Transplante de Rim/efeitos adversos , Sobrevivência de Enxerto , Humanos , Nefropatias/diagnóstico , Recidiva , Fatores de Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
AIM: Arteriolar hyalinosis (AH) is a common lesion in allograft biopsies taken following kidney transplantation. Recent studies have shown that severe AH may predict transplant outcomes and provide information about previous exposure to certain drugs, such as calcineurin inhibitors (CNI). However, the incidence of AH as a direct result of diabetic nephropathy (DN) after kidney transplantation has not been fully evaluated. This study aimed to assess the impact of primary DN on the development of AH lesions in patients who underwent kidney transplantation. METHODS: Eighty-three patients who underwent living-donor kidney transplantation between April 2005 and June 2015 were enrolled in this study. A total of 33 patients had DN prior to transplantation. Allograft biopsies were scored according to the Banff classification, and the relationship between the individual histological lesions and clinical baseline data was assessed. RESULTS: At early biopsy (3-12 months), there were no differences in the rates of AH lesions between the DN group and the non-DN group (ah ≥ 1: 37% vs. 41.3%, P = 0.719; aah ≥ 1: 14.8% vs. 6.5%; P = 0.453). However, there were significant differences between the groups in biopsies taken more than 3 years after the transplant (ah ≥ 2: 83.3% vs. 36.8%, P = 0.013; aah ≥ 2: 66.7% vs. 21.1%, P = 0.011). Multivariable analysis showed that both the length of time after transplantation and the presence of DN were independent risk factors for ah ≥ 2 (odds ratio [OR]: 2.55, 95% confidence interval [CI]: 1.47-19.54, P = 0.011) and aah ≥ 2 (OR: 7.55, 95% CI: 1.49-38.33, P = 0.015). CONCLUSION: This is the first report showing that the presence of primary DN disease contributes to the development of severe AH late in the course after kidney allografts.
Assuntos
Arteríolas/química , Nefropatias Diabéticas/epidemiologia , Hialina , Transplante de Rim/efeitos adversos , Rim/irrigação sanguínea , Doenças Vasculares/metabolismo , Adulto , Idoso , Aloenxertos , Arteríolas/patologia , Biópsia , Distribuição de Qui-Quadrado , Nefropatias Diabéticas/patologia , Feminino , Humanos , Incidência , Japão/epidemiologia , Transplante de Rim/métodos , Doadores Vivos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Doenças Vasculares/epidemiologia , Doenças Vasculares/patologiaRESUMO
Herein, we report a case of antibody-mediated rejection (ABMR) due to anti-HLA-DQ antibody after pregnancy and delivery in a female kidney transplant recipient. A 34-year-old female recipient was admitted at 2 years after delivery for an examination of an elevated serum creatinine (S-Cr) level. The patient had received a living kidney transplantation from her mother at 22 years of age, and her kidney graft function was almost stable. The episode biopsy showed peritubular capillaritis and transplant capillaropathy with C4d immunoreactivity in the peritubular capillaries. Additional examination revealed expression of a donor-specific antibody (DSA) against HLA-DQ5, leading to the diagnosis of chronic active ABMR. Intravenous immunoglobulin, plasma exchange, and rituximab were administered, and her S-Cr level was maintained stable. This case demonstrates a possible relationship between pregnancy/delivery and development of ABMR due to a de novo DSA in a female kidney transplant recipient.
Assuntos
Rejeição de Enxerto/imunologia , Antígenos HLA-DQ/imunologia , Isoanticorpos/sangue , Transplante de Rim/efeitos adversos , Rim/imunologia , Parto , Adulto , Biópsia , Complemento C4b/análise , Feminino , Rejeição de Enxerto/diagnóstico , Rejeição de Enxerto/terapia , Sobrevivência de Enxerto/efeitos dos fármacos , Humanos , Imunoglobulinas Intravenosas/administração & dosagem , Imuno-Histoquímica , Imunossupressores/administração & dosagem , Rim/efeitos dos fármacos , Rim/patologia , Doadores Vivos , Fragmentos de Peptídeos/análise , Troca Plasmática , Gravidez , Rituximab/administração & dosagem , Fatores de Tempo , Resultado do TratamentoRESUMO
Plasma cell-rich acute rejection (PCAR) is a rare type of acute rejection in renal transplantation. Despite aggressive immunotherapy, approximately 40-60% of patients develop graft loss within 1 year after an episode of PCAR. However, the reason for this outcome remains obscure. This study retrospectively identified six patients with PCAR diagnosed between 2009 and 2015 at a single university hospital. Clinicopathological data were collected. Five of the six patients were male, and mean age at the onset of PCAR was 49.0 ±14.5 years. None of the patients showed overall poor adherence to medication. Mean time to diagnosis was 302 ±234 days post-transplantation. All patients had preceding or concurrent viral infection. Four patients developed PCAR alone and two patients developed PCAR with antibody-mediated rejection. One of the six patients showed both severe tubulointerstitial and microvascular inflammation (total of Banff tubulitis 't' + interstitial inflammation 'i' + glomerulitis 'g' + peritubular capillaritis 'ptc' scores >10). This patient had progressive worsening of graft function and re-initiated dialysis at 74 months after a PCAR episode. In addition, three of the six patients had long-term recurrence of PCAR. With the recurrence of PCAR, patients with both moderate tubulointerstitial and microvascular inflammation (total of Banff 't' + 'i' + 'g' + 'ptc' scores >6) had progressive worsening of graft function. In summary, the present results suggest that concurrent moderate to severe tubulointerstitial and microvascular inflammation may lead to poor outcomes of graft function after a PCAR episode.
Assuntos
Rejeição de Enxerto/imunologia , Transplante de Rim/efeitos adversos , Rim/imunologia , Plasmócitos/imunologia , Doença Aguda , Adulto , Aloenxertos , Feminino , Rejeição de Enxerto/diagnóstico , Rejeição de Enxerto/terapia , Sobrevivência de Enxerto , Hospitais Universitários , Humanos , Imunossupressores/uso terapêutico , Rim/efeitos dos fármacos , Rim/patologia , Masculino , Pessoa de Meia-Idade , Plasmócitos/efeitos dos fármacos , Plasmócitos/patologia , Troca Plasmática , Recidiva , Estudos Retrospectivos , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Both prevention and treatment of recurrent immunoglobulin A nephropathy (IgAN) in kidney transplant recipients are important since recurrent IgAN seems to affect long-term graft survival. We present here a case of recurrent IgAN that was successfully treated using steroid pulse therapy plus tonsillectomy 10 years after kidney transplantation. CASE PRESENTATION: A 46-year-old male was admitted for an episode biopsy with a serum creatinine level of 1.8 mg/dl and proteinuria (0.7 g/day). Histological features showed recurrent IgAN (only focal segmental mesangial proliferation) and severe arteriolar hyalinosis partly associated with calcineurin inhibitor toxicity, with limited interstitial fibrosis and tubular atrophy (5%) (IF/TA) 8 years after transplantation. Sodium restriction and conversion from cyclosporine to tacrolimus successfully reduced his proteinuria to the level of 0.15 g/day. However, 2 years later, his proteinuria increased again (1.0 g/day) and a second episode biopsy showed global mesangial proliferation with glomerular endocapillary and extracapillary proliferation accompanied by progressive IF/TA (20%). The steroid pulse therapy plus tonsillectomy successfully decreased his proteinuria and he achieved clinical remission 3 years after this treatment. CONCLUSION: This case, presented with a review of relevant literature, demonstrates the difficulty and importance of the treatment of recurrent IgAN and calcineurin inhibitor arteriolopathy, especially in long-term kidney allograft management.
Assuntos
Glomerulonefrite por IGA/tratamento farmacológico , Glomerulonefrite por IGA/cirurgia , Transplante de Rim/tendências , Esteroides/administração & dosagem , Tonsilectomia , Terapia Combinada/métodos , Glomerulonefrite por IGA/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Pulsoterapia , Recidiva , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: IgA vasculitis, a rare condition resulting in end-stage renal disease, is a small-vessel vasculitis that affects the kidney in 49-83 % of adults. The reported recurrence rate of IgA vasculitis in renal transplant recipients is 11.5-60 %, leading to graft loss in 0-50 % of these patients. However, limited data are available on recurrence and graft loss after renal transplantation. METHODS: We evaluated renal transplant recipients seen from 1987 to 2015 at the Jikei University School of Medicine and the Department of Urology, Tokyo Women's Medical University. Using a 1:2 match, 21 patients with IgA vasculitis and 42 controls were selected. The mean post-transplant follow-up was 121 ± 69 months for IgA vasculitis and 147 ± 66 months for the controls. RESULTS: The 15-year patient survival was 100 % in IgA vasculitis and 97.6 % in the controls (p = 0.22). The 5-, 10-, and 15-year graft survival rates were 95.2, 90.5, and 81 % in IgA vasculitis and 100, 90.5, and 88.1 % in the controls, respectively (p = 0.63). The recurrence rate was 28.6 % (6 of 21 cases) and half of them (3 of 6 cases) showed histological activity (ISKDC III). We treated them with methylprednisolone pulse therapy and/or tonsillectomy. None of the recurrence cases lost the allograft. CONCLUSION: The long-term patient and graft survival of IgA vasculitis in renal transplantation were comparable with the previous reports. The recurrence rate was 28.6 %, but none of the recurrent cases showed allograft loss in this study. We speculate that methylprednisolone pulse therapy and/or tonsillectomy prevent the progression of recurrent IgA vasculitis.
Assuntos
Sobrevivência de Enxerto , Imunoglobulina A/imunologia , Falência Renal Crônica/cirurgia , Transplante de Rim/efeitos adversos , Vasculite/imunologia , Adulto , Aloenxertos , Feminino , Humanos , Imunossupressores/administração & dosagem , Estimativa de Kaplan-Meier , Falência Renal Crônica/diagnóstico , Falência Renal Crônica/imunologia , Falência Renal Crônica/mortalidade , Transplante de Rim/mortalidade , Masculino , Metilprednisolona/administração & dosagem , Pulsoterapia , Recidiva , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Tóquio , Tonsilectomia , Resultado do Tratamento , Vasculite/diagnóstico , Vasculite/mortalidadeRESUMO
The low sensitivity of C4d immunoreactivity in peritubular capillaries (PTCs) hinders its use in the diagnosis of chronic active antibody-mediated rejection (CAAMR). C4d-negative CAAMR was defined in the 2013 Banff classification, which included the expression of endothelial-associated transcripts (ENDATs). We previously showed that the ENDAT caveolin-1 (CAV-1) is a distinct feature of CAAMR. In this study, we investigated the prognostic value of CAV-1 immunoreactivity in PTCs in kidney transplant patients. Ninety-eight kidney transplant recipients were included in this study. The prognostic value of CAV-1 immunoreactivity in PTCs was evaluated by double immunostaining for CAV-1 and pathologische Anatomie Leiden endothelium (PAL-E, a PTC marker) in the PTCs of kidney allograft biopsy samples. The patients were divided into two groups: CAV-1/PAL-E<50% and CAV-1/PAL-E≥50%. Kaplan-Meier curves showed that CAV-1/PAL-E≥50% patients had a significantly worse prognosis than that of CAV-1/PAL-E<50% patients (log-rank; P<.001). C4d staining of PTCs was not associated with the development of graft failure (log-rank; P=.345), whereas in a multivariate Cox regression analysis, CAV-1 immunoreactivity in PTCs was independently associated with graft failure (hazard ratio: 11.1; P=.0324). CAV-1 immunoreactivity in PTCs may serve as a prognostic marker for kidney allograft survival.
Assuntos
Capilares/metabolismo , Caveolina 1/metabolismo , Rejeição de Enxerto/diagnóstico , Transplante de Rim , Túbulos Renais/irrigação sanguínea , Adulto , Biomarcadores/metabolismo , Capilares/imunologia , Feminino , Seguimentos , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/metabolismo , Sobrevivência de Enxerto/imunologia , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Túbulos Renais/imunologia , Túbulos Renais/metabolismo , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Estudos RetrospectivosRESUMO
A 56-year-old man who had undergone cadaveric kidney transplantation 21 months earlier was admitted to our hospital for a protocol biopsy; he had a serum creatinine level of 1.2 mg/dL and no proteinuria. Histological features showed two distinct entities: (i) inflammatory cell infiltration, in the glomerular and peritubular capillaries and (ii) focal, aggressive tubulointerstitial inflammatory cell infiltration, predominantly plasma cells, with mild tubulitis (Banff 13 classification: i2, t1, g2, ptc2, v0, ci1, ct1, cg0, cv0). Immunohistological studies showed mildly positive C4d immunoreactivity in the peritubular capillaries. The patient had donor specific antibody to human-leucocyte-antigen-DR53. We diagnosed him with subclinical antibody-mediated rejection accompanied by plasma cell-rich acute rejection. Both antibody-mediated rejection due to anti- human-leucocyte-antigen -DR53 antibodies and plasma cell-rich acute rejection are known to be refractory and have a poor prognosis. Thus, we started plasma exchange with intravenous immunoglobulin and rituximab for the former and 3 days of consecutive steroid pulse therapy for the latter. Three months after treatment, a follow-up allograft biopsy showed excellent responses to treatment for both histological features. This case report considers the importance of an early diagnosis and appropriate intervention for subclinical antibody-mediated rejection due to donor specific antibody to human-leucocyte-antigen-DR53 and plasma cell-rich acute rejection.
Assuntos
Rejeição de Enxerto/imunologia , Antígenos HLA-DR/imunologia , Cadeias HLA-DRB4/imunologia , Isoanticorpos/imunologia , Transplante de Rim/efeitos adversos , Rim/imunologia , Plasmócitos/imunologia , Doença Aguda , Biópsia , Rejeição de Enxerto/sangue , Rejeição de Enxerto/patologia , Rejeição de Enxerto/terapia , Sobrevivência de Enxerto , Histocompatibilidade , Humanos , Imunoglobulinas Intravenosas/administração & dosagem , Imunossupressores/administração & dosagem , Isoanticorpos/sangue , Rim/efeitos dos fármacos , Rim/patologia , Masculino , Pessoa de Meia-Idade , Plasmócitos/efeitos dos fármacos , Plasmócitos/patologia , Troca Plasmática , Pulsoterapia , Rituximab/administração & dosagem , Esteroides/administração & dosagem , Fatores de Tempo , Resultado do TratamentoRESUMO
We report a rare case of nephrocalcinosis caused by hereditary renal hypouricaemia 3 months after kidney transplantation. A 41-year-old man who underwent living-related kidney transplantation from his father was admitted to our hospital for a protocol biopsy; he had a serum creatinine (S-Cr) of 1.37 mg/dL and no proteinuria. Histologically, there was no evidence of rejection or calcineurin inhibitor toxicity, although scattered nephrocalcinosis was observed in the distal tubules. Perioperatively, the patient had a serum uric acid (S-UA) of 1.9 mg/dL with a fractional excretion of uric acid (FEUA) of 29% (normal, <10%) and UA clearance of 26.8 mL/min (normal, 7.3-14.7 mL/min) 3 days after kidney transplantation. The donor also had a relatively low S-UA of 2.4 mg/dL and high FEUA of 10.3%. Subsequent DNA direct sequencing followed by restriction fragment length polymorphism revealed that both the recipient's and donor's urate transporter 1 (URAT1) gene had a heterozygous nonsense mutation in exon 5 (C889T). Further, the immunoreactivity of antibodies for the C terminus of URAT1 revealed a partial deletion. De Galantha and von Kossa staining revealed that the nephrocalcinosis was due to urate crystals and calcium stones. Therefore, we diagnosed hereditary renal hypouricaemia. We directed the patient to avoid hard exercise, drink plenty of water, and alkalize the urine. The 1-year follow-up allograft biopsy showed no evidence of nephrocalcinosis in the distal tubules. This is the first report of nephrocalcinosis in the distal tubules as a diagnostic clue to hereditary renal hypouricaemia. We also review the related literature.
Assuntos
Transplante de Rim/efeitos adversos , Túbulos Renais Distais/patologia , Nefrocalcinose/etiologia , Erros Inatos do Transporte Tubular Renal/complicações , Cálculos Urinários/complicações , Adulto , Aloenxertos , Biópsia , Códon sem Sentido , Éxons , Pai , Predisposição Genética para Doença , Hereditariedade , Heterozigoto , Humanos , Doadores Vivos , Masculino , Nefrocalcinose/diagnóstico , Nefrocalcinose/terapia , Transportadores de Ânions Orgânicos/genética , Proteínas de Transporte de Cátions Orgânicos/genética , Fenótipo , Erros Inatos do Transporte Tubular Renal/diagnóstico , Erros Inatos do Transporte Tubular Renal/genética , Erros Inatos do Transporte Tubular Renal/terapia , Fatores de Tempo , Resultado do Tratamento , Cálculos Urinários/diagnóstico , Cálculos Urinários/genética , Cálculos Urinários/terapiaRESUMO
We report a case of recurrent Henoch-Schönlein purpura nephritis (HSPN) treated successfully with a tonsillectomy and steroid pulse therapy in a kidney transplant patient. A 29-year-old woman was admitted to our hospital for an episode biopsy; she had a serum creatinine (S-Cr) of 1.0 mg/dL and 1.34 g/day proteinuria 26 months after kidney transplantation. Histological examination revealed increased amounts of mesangial matrix and mesangial hypercellularity with IgA deposition. Of note, one glomerulus showed focal endocapillary proliferation and tuft necrosis. We diagnosed active recurrent HSPN. Considering both the histological findings and refractory clinical course of the native kidney, she was treated for 3 consecutive days with steroid pulse therapy and a tonsillectomy. The patient's proteinuria decreased gradually to less than 150 mg/day 6 months later. A second biopsy 6 years after kidney transplantation showed an excellent response to treatment and revealed a marked reduction in both the mesangial matrix and mesangial hypercellularity, with trace IgA deposition. We conclude that a tonsillectomy and steroid pulse therapy appeared to be useful in this patient with active recurrent HSPN. This paper is the first to report a tonsillectomy and steroid pulse therapy as a therapeutic option for active recurrent HSPN. Further studies are needed to elucidate the efficacy and mechanisms of tonsillectomy with recurrent HSPN in kidney transplant patients.
Assuntos
Vasculite por IgA/terapia , Transplante de Rim/efeitos adversos , Rim/efeitos dos fármacos , Esteroides/administração & dosagem , Tonsilectomia , Adulto , Aloenxertos , Biópsia , Terapia Combinada , Feminino , Humanos , Vasculite por IgA/diagnóstico , Vasculite por IgA/imunologia , Imuno-Histoquímica , Rim/imunologia , Rim/patologia , Proteinúria/etiologia , Pulsoterapia , Recidiva , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Both immunological and non-immunological etiologies affect graft function after kidney transplantation, including acute rejection, calcineurin inhibitor toxicity, and a recurrence of glomerulonephritis. Glomerular enlargement or glomerular sclerosis due to glomerular hyperfiltration related to increased renal blood flow is another cause. Although the glomerular volume in baseline biopsies predicts late allograft function, the relationship between allograft function and the annual changes in glomerular volume after kidney transplantation are unclear. AIM: We investigated changes in glomerular volume after kidney transplantation and their clinicopathological relationship. METHODS: We enrolled 23 patients with stable kidney function without an episode of rejection or any complication resulting in a functional decrease in the graft. We measured glomerular volume (GV) using the Weibel-Gomez method and glomerular density (GD) using 0,1 h biopsy samples as baseline controls and 1 yr biopsy samples and investigated the association between the changes in them and clinical parameters, including graft function, proteinuria, and renal hemodynamic markers, including effective renal plasma flow (ERPF) and filtration fraction (FF). The ERPF was calculated from a 99mTc-mercaptoacetyltriglycine (MAG3) renogram. RESULTS: The GV and ERPF increased significantly 1 yr after kidney transplantation. In contrast, proteinuria decreased significantly and Δproteinuria (1 yr - 1 month after transplantation) was correlated with ΔGV (P < 0.05, rs = -0.467). CONCLUSION: Glomerular enlargement 1 yr after transplantation may be related to improved proteinuria. It is possible that glomerular enlargement serves as a renal adaptation after kidney transplantation.
Assuntos
Glomérulos Renais/patologia , Glomérulos Renais/transplante , Transplante de Rim , Adaptação Fisiológica , Adulto , Idoso , Aloenxertos , Biópsia , Feminino , Hemodinâmica , Humanos , Glomérulos Renais/irrigação sanguínea , Glomérulos Renais/fisiopatologia , Transplante de Rim/efeitos adversos , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão , Valor Preditivo dos Testes , Proteinúria/etiologia , Compostos Radiofarmacêuticos , Fluxo Plasmático Renal Efetivo , Tecnécio Tc 99m Mertiatida , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Previous studies have shown that a donor/recipient body weight mismatch affects long-term graft survival and graft function after kidney transplantation. However, the mechanisms are not fully understood. AIM: To address the mechanisms, we compared the pathological and physiological features between patients with a donor/recipient body weight mismatch and those without a mismatch 1 yr after kidney transplantation. Furthermore, we investigated the correlation with the donor/recipient body weight ratio. METHODS: We examined allograft biopsy specimens from 10 recipients with stable kidney function, with body weight mismatch (donor/recipient body weight ratio [D/R BWR] < 0.9), and compared them with samples from 13 patients without mismatch. We measured glomerular volume (GV) using the Weibel-Gomez method and glomerular density (GD) defined by nonsclerotic glomerular number/renal cortical area as pathological findings. The physiological parameters included estimated glomerular filtration rate and proteinuria (mg/day). These data were evaluated to identify a correlation with D/R BWR. RESULTS: The pathological features showed that GV and GD were identical in the two groups. However, when glomerular enlargement was defined by ΔGV (GV at the 1-yr biopsy minus GV at baseline biopsy), ΔGV was higher in mismatch cases compared with that in cases without a mismatch (10.6 ± 4.6 vs. 5.5 ± 7.1 × 10(5) µm(3) ; P = 0.049). Furthermore, D/R BWR was significantly correlated with ΔGV (P = 0.03, r = -0.436). eGFR values were physiologically identical between the two groups, but the mismatch cases had significantly higher proteinuria levels than that of the cases without a mismatch at 1 yr after kidney transplantation. CONCLUSION: A donor/recipient body weight mismatch could affect glomerular enlargement and increased proteinuria 1 yr after kidney transplantation. How these two features affect long-term graft survival and function must be addressed in the future.
Assuntos
Peso Corporal , Seleção do Doador , Glomérulos Renais/patologia , Glomérulos Renais/transplante , Transplante de Rim , Doadores de Tecidos , Aloenxertos , Biópsia , Feminino , Taxa de Filtração Glomerular , Sobrevivência de Enxerto , Humanos , Glomérulos Renais/fisiopatologia , Transplante de Rim/efeitos adversos , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão , Valor Preditivo dos Testes , Proteinúria/etiologia , Fatores de Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
We report a case of probable C4d-negative accelerated acute antibody-mediated rejection due to non-HLA antibodies. A 44 year-old male was admitted to our hospital for a kidney transplant. The donor, his wife, was an ABO minor mismatch (blood type O to A) and had Gitelman syndrome. Graft function was delayed; his serum creatinine level was 10.1 mg/dL at 3 days after transplantation. Open biopsy was performed immediately; no venous thrombosis was observed during surgery. Histology revealed moderate peritubular capillaritis and mild glomerulitis without C4d immunoreactivity. Flow cytometric crossmatching was positive, but no panel-reactive antibodies against HLA or donor-specific antibodies (DSAbs) to major histocompatibility complex class I-related chain A (MICA) were detected. Taken together, we diagnosed him with probable C4d-negative accelerated antibody-mediated rejection due to non-HLA, non-MICA antibodies, the patient was treated with steroid pulse therapy (methylprednisolone 500 mg/day for 3 days), plasma exchange, intravenous immunoglobulin (40 g/body), and rituximab (200 mg/body) were performed. Biopsy at 58 days after transplantation, at which time S-Cr levels were 1.56 mg/dL, found no evidence of rejection. This case, presented with a review of relevant literature, demonstrates that probable C4d-negative accelerated acute AMR can result from non-HLA antibodies.
Assuntos
Complemento C4b/análise , Rejeição de Enxerto/imunologia , Imunidade Humoral , Isoanticorpos/sangue , Transplante de Rim/efeitos adversos , Rim/imunologia , Fragmentos de Peptídeos/análise , Sistema ABO de Grupos Sanguíneos/imunologia , Doença Aguda , Adulto , Aloenxertos , Biópsia , Incompatibilidade de Grupos Sanguíneos/imunologia , Quimioterapia Combinada , Rejeição de Enxerto/patologia , Rejeição de Enxerto/terapia , Histocompatibilidade , Humanos , Imunossupressores/administração & dosagem , Rim/patologia , Masculino , Troca Plasmática , Pulsoterapia , Esteroides/administração & dosagem , Fatores de Tempo , Resultado do TratamentoRESUMO
Herein, we report a complicated case of acute T-cell-mediated rejection (ACR) accompanied by C4d-negative acute antibody-mediated rejection (AMR) and cell debris in tubulus. A 32 year-old male was admitted for an episode biopsy with a serum creatinine (S-Cr) level of 1.83 mg/dL and pyuria (20-29 white blood cells per high power field) 49 days following kidney transplantation. Histological features included three distinct entities, mainly, in one of the three specimens: 1) focal aggressive tubulointerstitial inflammatory cell infiltration with moderate tubulitis, 2) inflammatory cell infiltration in peritubular capillaries (including neutrophils) and glomerular capillaries, and 3) cell debris consisting mainly of neutrophils in tubulus. Laboratory examination revealed evidence of non-human leukocyte antigen donor-specific antibodies. However, urinary culture and gram staining were negative. Considering both the histological and laboratory findings, the patient was diagnosed with ACR accompanied by C4d-negative AMR and suspicion of a urinary tract infection (UTI). The patient was treated for three consecutive days with steroid pulse therapy. The patient's S-Cr level decreased to ~1.5 mg/dL following treatment and did not increase thereafter. A second biopsy 133 days following kidney transplantation showed an excellent response to treatment and revealed no evidence of rejection. This case report demonstrates the difficulty in the diagnosis of, and therapy for, the complicated pathological findings of ACR, AMR and suspicion of a UTI.
Assuntos
Complemento C4b/análise , Rejeição de Enxerto/imunologia , Imunidade Celular , Imunidade Humoral , Transplante de Rim/efeitos adversos , Túbulos Renais/imunologia , Fragmentos de Peptídeos/análise , Linfócitos T/imunologia , Infecções Urinárias/imunologia , Doença Aguda , Adulto , Aloenxertos , Biópsia , Rejeição de Enxerto/tratamento farmacológico , Rejeição de Enxerto/patologia , Humanos , Imunidade Celular/efeitos dos fármacos , Imunidade Humoral/efeitos dos fármacos , Imunossupressores/uso terapêutico , Túbulos Renais/efeitos dos fármacos , Túbulos Renais/patologia , Masculino , Valor Preditivo dos Testes , Pulsoterapia , Fatores de Risco , Esteroides/uso terapêutico , Linfócitos T/efeitos dos fármacos , Resultado do TratamentoRESUMO
We report a case of acute vascular rejection occurring during antituberculosis therapy in a patient who had received a kidney transplant. A 29 year-old man was admitted for a protocol biopsy; he had a serum creatinine (S-Cr) level of 1.5 mg/dL 1 year after primary kidney transplantation. Histological examination yielded no evidence of rejection but a routine chest CT scan revealed typical lung tuberculosis and his serum was positive for QFT. We commenced antituberculosis therapy, including rifampicin, on June 29 2012. We paid close attention to the weekly trough tacrolimus (TAC) level but the S-Cr concentration increased to 3.7 mg/dL on October 16 2012, and he was admitted for biopsy. Histological examination revealed, first, a diffuse aggressive infiltration of tubulointerstitial inflammatory cells accompanied by severe tubulitis and mild intimal arteritis and, second, peritubular capillary infiltration by inflammatory cells (including neutrophils). Laboratory data revealed that our patient did not express donor-specific antibody and the peritubular capillaries did not exhibit C4d immunoreactivity. Upon consideration of both histological and laboratory findings, we diagnosed acute vascular rejection of Banff 2007 class ACR IIA. We commenced 3-day sessions of intravenous steroid pulse therapy twice weekly and adjusted the trough TAC level to 5-8 ng/mL by varying the TAC dose. We next performed an allograft biopsy and found no evidence of rejection (the S-Cr level was 2.7 mg/dL on April 1 2013). The present case report demonstrates the difficulties associated with management of TAC-based regimens in kidney transplant patients undergoing antituberculosis therapy. We also review the relevant literature.
Assuntos
Antituberculosos/efeitos adversos , Rejeição de Enxerto/induzido quimicamente , Rejeição de Enxerto/tratamento farmacológico , Transplante de Rim/efeitos adversos , Complicações Pós-Operatórias/tratamento farmacológico , Tuberculose Pulmonar/tratamento farmacológico , Doença Aguda , Adulto , Humanos , Masculino , Complicações Pós-Operatórias/microbiologia , Esteroides/uso terapêuticoRESUMO
BACKGROUND: Prophylaxis of antibody-mediated rejection (AMR) caused by donor-specific antibodies remains challenging. Given the critical roles of complement activity in antibody-mediated graft injury, we developed a lipid nanoparticle (LNP) formulation of small-interfering RNA against complement C5 (C5 siRNA-LNP) and investigated whether C5 siRNA-LNP could downregulate the complement activity and act as an effective treatment for AMR. METHODS: Lewis recipient rats were sensitized by skin grafting from Brown Norway donor rats. Kidney transplantation was performed at 4 wk post-skin grafting.C5 siRNA- or control siRNA-LNP was administered intravenously, and the weekly injections were continued until the study's conclusion. Cyclosporin (CsA) and/or deoxyspergualin (DSG) were used as adjunctive immunosuppressants. Complement activity was evaluated using hemolysis assays. The deposition of C5b9 in the grafts was evaluated using immunohistochemical analysis on day 7 posttransplantation. RESULTS: C5 siRNA-LNP completely suppressed C5 expression and complement activity (hemolytic activity ≤ 20%) 7 d postadministration. C5 siRNA-LNP in combination with CsA and DSG (median survival time: 56.0 d) prolonged graft survival compared with control siRNA-LNP in combination with CsA and DSG (median survival time: 21.0 d; P = 0.0012; log-rank test). Immunohistochemical analysis of the grafts revealed that downregulation of C5 expression was associated with a reduction in C5b9-positive area ( P = 0.0141, Steel-Dwass test). CONCLUSIONS: C5 siRNA-LNP combined with immunosuppressants CsA and DSG downregulated C5 activity and significantly prolonged graft survival compared with control siRNA-LNP with CsA and DSG. Downregulation of C5 expression using C5 siRNA-LNP may be an effective therapeutic approach for AMR.
Assuntos
Complemento C5 , Sobrevivência de Enxerto , Transplante de Rim , RNA Interferente Pequeno , Animais , Ratos , Anticorpos , Rejeição de Enxerto/prevenção & controle , Imunossupressores/farmacologia , Ratos Endogâmicos Lew , RNA Interferente Pequeno/genéticaRESUMO
BACKGROUND: Posttransplant anemia (PTA) is associated with the progression of kidney disease and mortality in kidney transplant recipients. Although the main causes of PTA are recipient factors, donor factors have not been fully investigated. In this study we investigated the association of donor pathological findings with the incidence of PTA in kidney transplant recipients after 3 years of transplantation. METHODS: We conducted a retrospective cohort study at a single university hospital. A total of 50 consecutive adult recipients and donors were enrolled. To assess the structure of interstitial lesions, immunohistochemical staining of interstitial fibrosis and fibroblasts were assessed in 0-h biopsies for quantitative analysis. RESULTS: The incidence of PTA in this cohort was 30%. The mean hemoglobin (Hb) was 11.6 ± 0.8 g/dL in patients with PTA and 14.3 ± 1.5 g/dL in patients without PTA. An inverse association was observed in biopsies between interstitial fibrosis area and interstitial fibroblast area (P < 0.01) and each pathological finding was examined for its association with PTA incidence after multivariate adjustment. For the interstitial fibrosis area, the odds ratio (OR) was 1.94 [95% confidence interval (CI) 1.26-2.99; P < 0.01]. For the interstitial fibroblast area, the OR was 0.01 (95% CI 0.00-0.16; P < 0.01). Receiver operating characteristics curve analysis indicated that the interstitial fibroblast area had high predictive power for the incidence of PTA. CONCLUSIONS: The presence of interstitial fibroblasts in donor kidneys may play an important role in predicting the incidence of PTA.