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BACKGROUND: The purpose of this study was to investigate the effect of BK polyomavirus (BKPyV infection of glomerular parietal epithelial cells (GPECs) on graft outcome in kidney transplant recipients with BKPyV-associated nephropathy (BKPyVAN). METHODS: A total of 152 kidney transplant recipients with BKPyVAN were divided into 31 with (GPEC-positive group) and 121 without (GPEC-negative group) BKPyV-infected GPECs. Clinicopathological characteristics and allograft survival were compared between the groups. RESULTS: The GPEC-positive group had more patients with advanced-stage BKPyVAN than the GPEC-negative group (P < .001). At the last follow-up, the GPEC-positive group had a significantly higher serum creatinine level than the GPEC-negative group. The graft loss rate in the GPEC-positive group was higher than that in the GPEC-negative group (32.3% vs 12.4%; P = .008). Kaplan-Meier analysis showed that the graft survival rate in the GPEC-positive group was lower than that in the GPEC-negative group (log-rank test, P = .004). Multivariate Cox regression analysis demonstrated that BKPyV infection of GPECs was an independent risk factor for graft survival (hazard ratio, 3.54; 95% confidence interval, 1.43-8.76; P = .006). CONCLUSIONS: GPEC infection in patients with BKPyVAN indicates more-severe pathological damage and a rapid decline in renal function. BKPyV infection of GPECs is an independent risk factor for allograft loss.
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Vírus BK , Rejeição de Enxerto , Glomérulos Renais , Transplante de Rim/efeitos adversos , Infecções por Polyomavirus , Infecções Tumorais por Vírus , Adulto , Feminino , Rejeição de Enxerto/patologia , Rejeição de Enxerto/virologia , Humanos , Rim/patologia , Rim/virologia , Nefropatias/patologia , Nefropatias/virologia , Glomérulos Renais/citologia , Glomérulos Renais/patologia , Glomérulos Renais/virologia , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
AIMS: Various mycophenolate mofetil (MMF) population pharmacokinetic (popPK) models have been developed to describe its PK characteristics and facilitate its optimal dosing in adult kidney transplant recipients co-administered with tacrolimus. However, the external predictive performance has been unclear. Thus, this study aimed to comprehensively evaluate the external predictability of published MMF popPK models in such populations and investigate the potential influencing factors. METHODS: The external predictability of qualified popPK models was evaluated using an independent dataset. The evaluation included prediction- and simulation-based diagnostics, and Bayesian forecasting. In addition, factors influencing model predictability, especially the impact of structural models, were investigated. RESULTS: Fifty full PK profiles from 45 patients were included in the evaluation dataset and 11 published popPK models were identified and evaluated. In prediction-based diagnostics, the prediction error within ±30% was less than 50% in most published models. The prediction- and variability-corrected visual predictive check and posterior predictive check showed large discrepancies between the observations and simulations in most models. Moreover, the normalized prediction distribution errors of all models did not follow a normal distribution. Bayesian forecasting demonstrated an improvement in the model predictability. Furthermore, the predictive performance of two-compartment (2CMT) models incorporating the enterohepatic circulation (EHC) process was not superior to that of conventional 2CMT models. CONCLUSIONS: The published models showed large variability and unsatisfactory predictive performance, which indicated that therapeutic drug monitoring was necessary for MMF clinical application. Further studies incorporating potential covariates need to be conducted to investigate the key factors influencing model predictability of MMF.
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Rejeição de Enxerto/prevenção & controle , Imunossupressores/farmacocinética , Transplante de Rim/efeitos adversos , Modelos Biológicos , Ácido Micofenólico/farmacocinética , Tacrolimo/farmacocinética , Adulto , Idoso , Área Sob a Curva , Conjuntos de Dados como Assunto , Relação Dose-Resposta a Droga , Interações Medicamentosas , Monitoramento de Medicamentos/métodos , Quimioterapia Combinada , Feminino , Rejeição de Enxerto/imunologia , Humanos , Imunossupressores/administração & dosagem , Masculino , Pessoa de Meia-Idade , Ácido Micofenólico/administração & dosagem , Tacrolimo/administração & dosagem , Adulto JovemRESUMO
Early graft loss and poor graft function limit the use of kidneys from infant donors. Six en bloc kidney transplantations were performed from infant donors younger than 10 months into pediatric recipients between November 2012 and September 2015 at our center. We retrospectively analyzed recipient and donor demographics, surgery procedures, complications, graft function and size, and patient and graft survival with a follow-up of 6-39 months (median 15.5 months). Donor age ranged from 1 to 10 months with weight ranging from 3.5 to 10 kg. Recipient age ranged from 10 to 16 years with weight ranging from 30 to 39 kg. One kidney was removed due to arterial thrombosis during surgery, while the other kidney of this en bloc graft remained viable. Urine leak followed by bilateral ureteral obstruction occurred in one recipient. All of the recipients showed immediate graft function. The size of the en bloc kidney increased from 4.2±0.6 cm to 7.6±0.6 cm 6 months after surgery. Patient and graft survival were both 100% at the last follow-up. Our results show that en bloc kidney transplantation from infant donors younger than 10 months into pediatric recipients is effective under the condition of experienced surgical techniques and perioperative management.
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Transplante de Rim/métodos , Insuficiência Renal/cirurgia , Doadores de Tecidos , Adolescente , Artérias/fisiopatologia , Peso Corporal , Criança , Feminino , Taxa de Filtração Glomerular , Sobrevivência de Enxerto , Humanos , Imunossupressores/uso terapêutico , Lactente , Recém-Nascido , Masculino , Estudos Retrospectivos , Trombose/etiologia , Resultado do Tratamento , Obstrução Ureteral/etiologiaRESUMO
OBJECTIVE: To evaluate the outcomes of liver transplant recipients who received liver allografts from hepatitis B surface antigen (HBsAg)-positive donors. METHODS: The medical records of 23 male patients (median age, 42.5 years; range: 29-61) who received HBsAg-(+) liver allografts in our organ transplant center were retrospectively analyzed. All patients had confirmed diagnosis of end-stage liver disease (ESLD) secondary to hepatitis B virus (HBV) infection, including 13 HBsAg(+)/HBeAg(-)/HBcAb(+) cases and 10 HBsAg(+)/HBeAb(+)/HBcAb(+) cases. After transplantation, all patients were administered oral entecavir and intravenous anti-hepatitis B immunoglobulin (HBIG) (2000 IU/d during the first week), along with a steroid-free immune suppression regimen. HBV-related antigen and antibody and HBV DNA were detected on post-transplantation days 1, 7, 14, 21, and 30. The liver allografts were monitored by ultrasound imaging. After discharge, monthly follow-up recorded liver function, renal function, acute rejection, infections, vascular complications, biliary complications, HBV recurrence, cancer recurrence, and patient survival. RESULTS: Two of the recipients died from severe perioperative pneumonia. The remaining 21 recipients were followed-up for 10 to 38 months, and all 21 patients remained HBsAg(+). One recipient developed biliary ischemia and required a second liver transplantation at five months after the primary transplantation. Three recipients (all primary) died from tumor recurrence at 9, 14, and 18 months post-transplantation, respectively. All other recipients survived and had acceptably low HBV DNA copy levels. Color Doppler imaging showed good graft function and normal texture. The patient and graft survival rates were 78.3% (18/23) and 73.9% (17/23), respectively. The recurrence rate of HBV infection was 100% (23/23). In surviving patients, no liver function abnormality, graft loss, or death was found to be related to the recurrence of HBV infection. CONCLUSION: Liver transplantation using HBsAg(+) liver grafts was safe for patients with ESLD secondary to HBV infection.
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Doença Hepática Terminal/cirurgia , Antígenos de Superfície da Hepatite B/imunologia , Transplante de Fígado/imunologia , Transplante de Fígado/métodos , Adulto , Doença Hepática Terminal/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Doadores de TecidosRESUMO
BACKGROUND: BK polyomavirus (BKPyV)-associated nephropathy (BKPyVAN) is an important cause of dysfunction and failure of renal transplants. This study aimed to assess the diagnostic performance of morning urine specific gravity (MUSG) in diagnosing BKPyVAN in kidney transplant recipients. METHODS: A total of 87 patients, including 27 with BKPyVAN, 22 with isolated BKPyV viruria, 18 with T cell-mediated rejection (TCMR), and 20 with stable graft function, were enrolled in the First Affiliated Hospital of Sun Yat-Sen University from March 2015 to February 2017. MUSG at biopsy and during a follow-up period of 24 months after biopsy was collected and analyzed. Receiver operating characteristic (ROC) curve analysis was used to determine the ability of MUSG to discriminate BKPyVAN. RESULTS: At biopsy, the MUSG of BKPyVAN group (1.008â±â0.003) was significantly lower than that of isolated BK viruria group (1.013â±â0.004, Pâ<â0.001), TCMR group (1.011â±â0.003, Pâ=â0.027), and control group (1.014â±â0.006, Pâ<â0.001). There was no significant difference in MUSG among the isolated BK viruria group, TCMR group, and control group (Pâ=â0.253). In BKPyVAN group, the timing and trend of MUSG elevate were consistent with the timing and trend of the decline of viral load in urine and plasma, reaching a statistical difference at 3 months after treatment (1.012â±â0.003, Pâ<â0.001) compared with values at diagnosis. ROC analysis indicated that the optimal cut-off value of MUSG for diagnosis of BKPyVAN was 1.009, with an area under the ROC curve (AUC) of 0.803 (95% confidence interval [CI]: 0.721-0.937). For differentiating BKPyVAN and TCMR, the optimal MUSG cut-off value was 1.010, with an AUC of 0.811 (95% CI: 0.687-0.934). CONCLUSION: Combined detection of MUSG and BKPyV viruria is valuable for predicting BKPyVAN and distinguishing BKPyVAN from TCMR in renal transplant recipients.
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Vírus BK/patogenicidade , Transplante de Rim/efeitos adversos , Infecções por Polyomavirus/urina , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Gravidade Específica , TransplantadosRESUMO
BACKGROUND: The positive predictive value (PPV) of urinary decoy cells for diagnosing BK polyomavirus associated-nephropathy (BKPyVAN) is low. This study was designed to increase the PPV of urinary decoy cells for diagnosing BKPyVAN in kidney transplant recipients. METHODS: A total of 105 urine sediment samples from 105 patients with positive BK viruria and decoy cells were evaluated by automatic double-immunostaining with anti-HGD (a renal tubular marker) antibody + anti-SV40-T antibody or anti-S100P (an urothelial marker) antibody + anti-SV40-T antibody. RESULTS: Of the 105 patients, 76 (72.4%) had both HGD(+)/SV40-T(+) cells and S100P(+)/SV40-T(+) cells (group A), 24 (22.9%) had only S100P(+)/SV40-T(+) cells (group B), and 5 (4.6%) had only S100P(-)/HGD(-)/SV40-T(+) cells (group C). Seventy patients in group A (92.1%), 3 patients in group B (12.5%), and no patients in group C were diagnosed with BKPyVAN. The area under the ROC curve of predicting BKPyVAN by decoy cells was 0.531 (0.431-0.630), with an optimal cut-off value of 29 (per 10 high power field), a sensitivity of 45.8% (95% CI: 34.0-58.0%), and a specificity of 68.8% (95% CI: 50.0-83.9%). Besides, the area under the ROC curve of predicting BKPyVAN by plasma BKPyV load was 0.735 (95% CI: 0.632-0.822), with an optimal cut-off value of 1,000 copies/mL, a sensitivity of 61.1% (95% CI: 48.9-72.4%) and a specificity of 84.2% (95% CI: 60.4-96.6%). In contrast, the PPV, negative predictive value, sensitivity, and specificity of HGD(+)/SV40-T(+) cells for diagnosing BKPyVAN were 92.1% [95% confidence interval (CI): 83.0-96.7%], 89.7% (95% CI: 71.5-97.3%), 95.9% (95% CI: 87.7-98.9%), and 81.3% (95% CI: 63.0-92.1%) respectively. CONCLUSIONS: Double-immunostaining with anti-HGD or anti-S100P and anti-SV40-T antibodies helps to identify the origin of decoy cells and diagnose BKPyVAN.
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Background: The extent and depth of BK polyomavirus (BKPyV) infection in renal allograft correlate with prognosis. This study was designed to evaluate the value of urinary sediment double-immunostaining for predicting BKPyV infection in proximal tubular epithelium. Materials and methods: A total of 76 urine sediment cell blocks, as well as the corresponding transplanted kidney tissues with BK polyomavirus associated-nephropathy (BKPyVAN), were evaluated by automatic double-immunostaining with anti-58-kDa Golgi protein (58K, a proximal renal tubular marker) + anti-SV40-T and anti-homogentisate 1, 2-dioxygenase (HGD, a renal tubular marker) + anti-SV40-T. Results: Immunohistochemical staining demonstrated that 58K was expressed in proximal tubular epithelium but not in distal tubular epithelium or transitional epithelium. Of the 76 patients, 28 (36.8%) had urinary 58K(+)/SV40-T(+) cells and HGD(+)/SV40-T(+) cells, 41 (53.9%) had only HGD(+)/SV40-T(+) cells, one (1.3%) had only 58K(+)/SV40-T(+) cells, and six (7.9%) had only 58K(-)/HGD(-)/SV40-T(+) cells. The presence of urinary 58K(+)/SV40-T(+) cells was correlated with BKPyV infection in proximal tubular epithelium (P < 0.001, r = 0.806). The mean extent of SV40-T staining was significantly more extensive in patients with urinary 58K(+)/SV40-T(+) cells than those without urinary 58K(+)/SV40-T(+) cells (21.4 vs. 12.0%, P < 0.001). The positive predictive value, negative predictive value, sensitivity, and specificity of urinary 58K(+)/SV40-T(+) cells for predicting BKPyV infection in proximal tubular epithelium were 89.7% (95% CI: 71.5-97.3%), 91.5% (95% CI: 78.7-97.2%), 86.7% (95% CI: 68.4-95.6%), and 93.5% (95% CI: 81.1-98.3%), respectively. Conclusion: Urinary sediment double-immunostaining with anti-58K and anti-SV40-T is valuable for predicting the extent and depth of BKPyV infection in renal allograft.
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Aloenxertos/imunologia , Vírus BK/fisiologia , Rejeição de Enxerto/imunologia , Transplante de Rim , Túbulos Renais Proximais/patologia , Infecções por Polyomavirus/imunologia , Urotélio/patologia , Adulto , Aloenxertos/virologia , Estudos Transversais , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Transplantados , Urina/citologiaRESUMO
Background: Studies have shown that plasma donor-derived cell-free DNA (dd-cfDNA) can predict renal allograft antibody-mediated rejection. This study was performed to evaluate the value of urine dd-cfDNA concentration and dd-cfDNA fraction (%) for discriminating BK polyomavirus-associated nephropathy (BKPyVAN) in kidney transplant recipients with urinary BK polyomavirus (BKPyV) infection. Methods: In this retrospective single-center observational study, we enrolled kidney transplant recipients who were diagnosed with urine BKPyV infection between August 2018 and May 2019 at the First Affiliated Hospital of Sun Yat-sen University. Urine dd-cfDNA was measured by using a novel target region capture sequencing methodology. The pathological diagnosis of BKPyVAN was confirmed by anti-SV40-T immunohistochemical staining and classified using the American Society for Transplantation schema. Receiver operating characteristic curve analysis was used to investigate the relations of urine dd-cfDNA and dd-cfDNA% to intrarenal allograft BKPyV infection states. Results: In total, 93 patients were enrolled, including 40 cases of proven BKPyVAN, seven cases of probable BKPyVAN, 23 cases of possible BKPyVAN, and 23 cases of resolving BKPyVAN. Urine dd-cfDNA level in proven BKPyVAN (22.09 ± 21.27 ng/ml) was comparable to that in probable BKPyVAN (15.64 ± 6.73 ng/ml, P = 0.434) but was significantly higher than that in possible BKPyVAN (5.60 ± 3.53 ng/ml) and resolving BKPyVAN (5.30 ± 3.34 ng/ml) (both Ps < 0.05). Urine dd-cfDNA% of proven BKPyVAN (0.71 ± 0.21) was lower than that of probable BKPyVAN (0.91 ± 0.04, P < 0.001), but was significantly higher than that of possible BKPyVAN (0.56 ± 0.30) and resolving BKPyVAN (0.46 ± 0.28) (both Ps < 0.05). For distinguishing biopsy-proven BKPyVAN from biopsy-excluded BKPyVAN, the discrimination capacity of urine dd-cfDNA (AUC: 0.842, 95% CI: 0.735, 0.918) was superior to that of plasma BKPyV DNA load (AUC: 0.660, 95% CI: 0.537, 0.769) with 0.181 (95% CI: 0.043, 0.319) difference between areas under ROC curves (P = 0.010). Conclusion: The elevated urine dd-cfDNA level may help discriminate BKPyVAN in kidney transplant recipients with BKPyV viruria.
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Vírus BK/genética , Ácidos Nucleicos Livres/urina , DNA Viral/urina , Nefropatias/diagnóstico , Transplante de Rim/efeitos adversos , Infecções por Polyomavirus/diagnóstico , Infecções Tumorais por Vírus/diagnóstico , Infecções Urinárias/diagnóstico , Adulto , Diagnóstico Diferencial , Feminino , Humanos , Nefropatias/urina , Nefropatias/virologia , Masculino , Pessoa de Meia-Idade , Infecções por Polyomavirus/urina , Infecções por Polyomavirus/virologia , Valor Preditivo dos Testes , Estudos Retrospectivos , Resultado do Tratamento , Infecções Tumorais por Vírus/urina , Infecções Tumorais por Vírus/virologia , Urinálise , Infecções Urinárias/urina , Infecções Urinárias/virologia , Carga ViralRESUMO
BACKGROUND: This study aimed to investigate the pathological characteristics of BK polyomavirus (BKPyV)-associated nephropathy (BKPyVAN) with glomerular involvement in kidney transplant recipients. METHODS: Forty-four patients with glomerular BKPyV infection were retrospectively included for analysis. Immunohistochemical (IHC) staining was performed on paraffin sections using monoclonal mouse anti-SV40 large T antigen antibody. RESULTS: In BKPyV-infected glomeruli, the glomerular parietal epithelial cells (GPECs) were swollen, hyperchromatic, and enlarged, with an increased nuclear to cytoplasm (N/C) ratio and smudgy basophilic intra-nuclear viral inclusions. IHC staining revealed the distribution of BKPyV involvement in GPECs, podocytes, and shedding cells within Bowman's space. Notably, BKPyV affected GPEC proliferation and caused crescent formation (7 biopsies, 15.9%). Three biopsies exhibited fibrous crescents and the absence of viral inclusions. The other 4 biopsies exhibited cellular and fibro-cellular crescents, with viral cytopathic changes and positive IHC staining in the proliferative GPECs. Electron microscopy showed viral particles in both GPECs and podocytes. BKPyV-infected GPECs were degenerative, with mitochondrial swelling, endoplasmic reticulum expansion, and multi-layered membranous structure formation. Twelve (27.3%) patients received repeat biopsies within 1.6 to 39.5 months (median: 13.5 months), but none revealed persistent glomerular BKPyV infection. CONCLUSIONS: Distinct glomerular changes in BKPyVAN biopsies should raise the possibility of glomerular involvement.
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BACKGROUND: BK virus-associated nephropathy (BKVN) is an important cause of chronic allograft dysfunction. The objective of our study was to evaluate the prognosis of BKVN. METHODS: We retrospectively reviewed the data of 133 renal transplant recipients with BKVN treated at the First Affiliated Hospital of Sun Yat-Sen University between July 2007 and July 2017. BK viral loads, graft function, and pathologic indexes were compared between initial diagnosis and last follow-up. RESULTS: After a mean follow-up period of 14.4 (range, 0.3-109.6) months after diagnosis of BKVN, BK viruria, and BK viremia become negative in 19.5% and 90.2% of patients, respectively. The mean estimated glomerular filtration rate (eGFR) at last follow-up was lower than at diagnosis of BKVN (18.3â±â9.2 vs. 32.8â±â20.6âmL·min·1.73âm, tâ=â7.426, Pâ<â0.001). Eight (6.0%) patients developed acute rejection after reducing immunosuppression. At last follow-up, the eGFR was significantly lower in patients with subsequent rejection than those without (21.6â±â9.8 vs. 33.5â±â20.9âmL·min·1.73âm, tâ=â3.034, Pâ=â0.011). In 65 repeat biopsies, SV40-T antigen staining remained positive in 40 patients and became negative in the other 20 patients. The eGFR (42.6â±â14.3 vs. 26.5â±â12.3âmL·min·1.73âm), urine viral loads (median, 1.3â×â10vs. 1.4â×â10âcopies/mL), and plasma viral load (median, 0 vs. 0âcopies/mL) were all significantly lower in patients with negative SV40-T antigen staining than those with persistent BK involvement (all, Pâ<â0.05). Five (3.8%) recipients lost their graft at diagnosis of BKVN, and 13 (9.8%) lost their graft during the follow-up period. The 1-, 3-, and 5-year graft survival rates after diagnosis of BKVN were 99.2%, 90.7%, and 85.7%, respectively. Higher pathologic stage correlated with lower allograft survival rate (χâ=â6.341, Pâ=â0.042). CONCLUSION: Secondary rejection and persistent histologic infection in BKVN lead to poor prognosis.
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Vírus BK , Sobrevivência de Enxerto , Nefropatias/complicações , Transplante de Rim/efeitos adversos , Infecções por Polyomavirus/complicações , Adolescente , Adulto , Idoso , Criança , Feminino , Taxa de Filtração Glomerular , Rejeição de Enxerto , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Carga Viral , Viremia/complicações , Adulto JovemRESUMO
Background: There is no effective therapy for BK virus (BKV) nephropathy (BKVN). Cyclosporine A (CsA) has a lower immunosuppressive effect than tacrolimus. In vitro studies have shown that CsA inhibits BKV replication. The present study aimed to evaluate the effectiveness of switching from tacrolimus to low-dose CsA in renal transplant recipients with BKVN. Methods: Twenty-four patients diagnosed with BKVN between January 2015 and December 2016 were included. Tacrolimus was switched to low-dose CsA, and patients were followed for 24 months. Primary end points were BKV clearance in blood and graft. Secondary end points were urine specific gravity, serum creatinine, and graft loss. Results: The viremia in all patients cleared at a mean of 2.7 ± 2.0 months after switching to CsA. Urine specific gravity at 3 months after switching to CsA increased significantly compared with that at diagnosis (P=0.002). The timing and trend of urine specific gravity increase was consistent with the timing and trend of blood and urine viral load decrease. Repeated biopsies at a median of 11.2 months (range: 9.1-12.5 months) after switching to CsA showed that 8 patients (42.1%) were negative for BKV, and 11 patients (58.9%) had a decrease in BKV load (P<0.001). There was no statistical difference in the serum creatinine level between the time of diagnosis and 24 months of CsA therapy (P=0.963). The graft survival rate was 100%. Only two patients (8.3%) suffered from acute rejection. Conclusion: Switching from tacrolimus to low-dose CsA may be an effective therapy for BKVN.
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Ciclosporina/uso terapêutico , Imunossupressores/uso terapêutico , Nefropatias/complicações , Nefropatias/terapia , Infecções por Polyomavirus/complicações , Tacrolimo/uso terapêutico , Adulto , Vírus BK/isolamento & purificação , Ciclosporina/administração & dosagem , Feminino , Humanos , Imunossupressores/administração & dosagem , Nefropatias/virologia , Transplante de Rim , Masculino , Pessoa de Meia-Idade , Infecções por Polyomavirus/terapia , Infecções por Polyomavirus/virologia , Tacrolimo/administração & dosagemRESUMO
BACKGROUND: Accumulating studies on computational fluid dynamics (CFD) support the involvement of hemodynamic factors in artery stenosis. Based on a patient-specific CFD model, the present study aimed to investigate the hemodynamic characteristics of transplant renal artery stenosis (TRAS) and its alteration after stent treatment. METHODS: Computed tomography angiography (CTA) data of kidney transplant recipients in a single transplant center from April 2013 to November 2014 were reviewed. The three-dimensional geometry of transplant renal artery (TRA) was reconstructed from the qualified CTA images and categorized into three groups: the normal, stenotic, and stented groups. Hemodynamic parameters including pressure distribution, velocity, wall shear stress (WSS), and mass flow rate (MFR) were extracted. The data of hemodynamic parameters were expressed as median (interquartile range), and Mann-Whitney U-test was used for analysis. RESULTS: Totally, 6 normal, 12 stenotic, and 6 stented TRAs were included in the analysis. TRAS presented nonuniform pressure distribution, adverse pressure gradient across stenosis throat, flow vortex, and a separation zone at downstream stenosis. Stenotic arteries had higher maximal velocity and maximal WSS (2.94 [2.14, 3.30] vs. 1.06 [0.89, 1.15] m/s, 256.5 [149.8, 349.4] vs. 41.7 [37.8, 45.3] Pa at end diastole, P= 0.001; 3.25 [2.67, 3.56] vs. 1.65 [1.18, 1.72] m/s, 281.3 [184.3, 364.7] vs. 65.8 [61.2, 71.9] Pa at peak systole, P= 0.001) and lower minimal WSS and MFRs (0.07 [0.03, 0.13] vs. 0.52 [0.45, 0.67] Pa, 1.5 [1.0, 3.0] vs. 11.0 [8.0, 11.3] g/s at end diastole, P= 0.001; 0.08 [0.03, 0.19] vs. 0.70 [0.60, 0.81] Pa, 2.0 [1.3, 3.3] vs. 16.5 [13.0, 20.3] g/s at peak systole, P= 0.001) as compared to normal arteries. Stent implantation ameliorated all the alterations of the above hemodynamic factors except low WSS. CONCLUSIONS: Hemodynamic factors were significantly changed in severe TRAS. Stent implantation can restore or ameliorate deleterious change of hemodynamic factors except low WSS at stent regions.
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Simulação por Computador , Transplante de Rim/efeitos adversos , Obstrução da Artéria Renal/cirurgia , Adolescente , Adulto , Velocidade do Fluxo Sanguíneo/fisiologia , Prótese Vascular , Feminino , Hemodinâmica , Humanos , Hidrodinâmica , Masculino , Pessoa de Meia-Idade , Modelos Teóricos , Obstrução da Artéria Renal/fisiopatologia , Estresse Mecânico , Adulto JovemRESUMO
BACKGROUND: Polyomavirus associated nephropathy (PVAN) is a significant cause of early allograft loss and the course is difficult to predict. The aim of this study is to identify factors influencing outcome for PVAN. METHODS: Between 2006 and 2014, we diagnosed PVAN in 48 (7.8%) of 615 patients monitored for BK virus every 1-4 weeks after modification of maintenance immunosuppression. Logistic or Cox regression analysis were performed to determine which risk factors independently affected clinical outcome and graft loss respectively. RESULTS: After 32.1±26.4 months follow-up, the frequencies of any graft functional decline at 1 year post-diagnosis, graft loss and any graft functional decline at the last available follow-up were 27.1% (13/48), 25.0% (12/48), and 33.3% (16/48), respectively. The 1, 3, 5 year graft survival rates were 100%, 80.5% and 69.1%, respectively. The mean level of serum creatinine at 1 year post-diagnosis and long-term graft survival rates were the worst in class C (p<0.05). Thirty-eight of 46 (82.6%) BKV DNAuria patients reduced viral load by 90% with a median time of 2.75 months (range, 0.25-34.0 months) and showed better graft survival rates than the 8 patients (17.4%) without viral load reduction (p<0.001). Multivariate logistic regression analysis showed that extensive interstitial inflammation (OR 20.2, p = 0.042) and delayed fall in urinary viral load (>2.75 months for >90% decrease) in urine (OR 16.7, p = 0.055) correlated with worse creatinine at 1 year post-diagnosis. Multivariate Cox regression analysis showed that extensive interstitial inflammation (HR 46988, p = 0.032) at diagnosis, and high PVAN stage (HR 162.2, p = 0.021) were associated with worse long-term graft survival rates. CONCLUSIONS: The extent of interstitial inflammation influences short and long-term graft outcomes in patients with PVAN. The degree of PVAN, rate of reduction in viral load, and viral clearance also can be used as prognostic markers in PVAN.