RESUMEN

BACKGROUND: To explore the correlation between single nucleotide polymorphisms (SNPs) of CYP3A4 rs2740574 and CYP3A5 rs776746 and post-transplant diabetes mellitus (PTDM) in Chinese renal allograft recipients treated with tacrolimus. METHODS: A total of 244 patients treated with tacrolimus were included in this study, wherein DNA sequencing was detected through fluorescence in situ hybridization, and SNP genotyping was performed. RESULTS: Among the 244 patients, 44 (18%) developed PTDM. The PTDM group exhibited higher preoperative body mass index and fasting plasma glucose levels, with higher creatinine values one year after surgery. The CYP3A4 rs2740574 genotype was found to be unique in its homozygous AA form. For CYP3A5 rs776746, the genotypes were distributed as follows: 28 (11.5%) cases with AA, 101 (41.4%) cases with AG, and 115 (47.1%) cases with GG, respectively (P = .042). The AA genotype showed a statistically significant difference from both AG and GG genotypes. Furthermore, the A allele of CYP3A5 rs776746 was found to be associated with an increased risk for PTDM development. CONCLUSIONS: The occurrence of tacrolimus-related PTDM is associated with body mass index, fasting plasma glucose levels, and CYP3A5 genotype before renal transplantation. Post-transplant diabetes mellitus is correlated with unfavorable long-term renal graft function, whereas the expression of the CYP3A5 rs776746 gene is linked to an elevated risk of PTDM.

Asunto(s)

Citocromo P-450 CYP3A , Diabetes Mellitus , Trasplante de Riñón , Tacrolimus , Humanos , Glucemia , Citocromo P-450 CYP3A/genética , Diabetes Mellitus/etiología , Diabetes Mellitus/genética , Genotipo , Inmunosupresores/efectos adversos , Hibridación Fluorescente in Situ , Trasplante de Riñón/efectos adversos , Polimorfismo de Nucleótido Simple , Tacrolimus/efectos adversos

RESUMEN

ABSTRACT: Endometrial injury is associated with poorer pregnancy outcomes. The purpose of this study was to evaluate the diagnostic efficacy of contrast-enhanced ultrasonography (CEUS) in the detection of endometrial injury. This study included women who underwent CEUS of the uterus at the author's hospital between April 2020 and January 2021. The diagnostic performances of the CEUS-derived parameters in the detection of severe endometrial injury were evaluated by receiver operating characteristic curve analyses. The study included 67 participants (healthy control, n = 14; mild endometrial injury, n = 24; severe endometrial injury, n = 29). Enhancement intensity (EI) and area under the time-intensity curve (AUC TIC ) were significantly lower in the severe endometrial injury patients than healthy and mild endometrial injury subjects for both endometrial and subendometrial regions ( P < 0.05). Correlations analysis showed that EI and AUC TIC were positively correlated with endometrial thickness ( r = 0.460, P = 0.01, and r = 0.555, P < 0.01, respectively) and subendometrial thickness ( r = 0.501, P < 0.01, and r = 0.438, P = 0.01, respectively). The area under the receiver operating characteristic curve, sensitivity, and specificity were 0.720 ( P = 0.002), 79.31%, and 66.67% for endometrial EI; 0.818 ( P < 0.001), 75.86%, and 79.17% for subendometrial EI; 0.917 ( P < 0.001), 72.41%, and 95.83% for endometrial AUC TIC ; and 0.810 ( P < 0.001), 89.66%, and 70.83% for subendometrial AUC TIC , respectively. Contrast-enhanced ultrasonography may have clinical utility in the prediction of endometrial injury in women of childbearing age.

Asunto(s)

Endometrio , Resultado del Embarazo , Embarazo , Humanos , Femenino , Ultrasonografía , Endometrio/diagnóstico por imagen , Medios de Contraste

RESUMEN

BACKGROUND: Pneumocystis jirovecii pneumonia (PJP) is an opportunistic infection among solid organ transplantation. The occurrence of PJP is dangerous and fatal if there is no early identification and sufficient treatment. OBJECTIVE: The aim of this study was to evaluate the risk factors and provide appropriate strategies of prophylaxis and treatment for PJP after kidney transplantation in our centre. PATIENTS/METHODS: From January 2009 to December 2018, a total of 167 kidney transplantation recipients with pneumonia were enrolled, including 47 PJP patients as PJP group and 120 non-PJP patients as control group. The clinical characteristics of the two groups were analysed retrospectively. RESULTS: Multivariate analysis showed that high total dosage of ATG [OR, 2.03; 95% CI, 1.12-3.68] and cytomegalovirus (CMV) infection were independent risk factors for PJP. Trimethoprim-sulfamethoxazole (TMP-SMX) (1.44 g q6h)-based treatment was used for 2 weeks, and its dosage and course were adjusted according to the therapeutic effect and side effects. Forty-five cases were recovered after 3 months of follow-up, and two patients died of respiratory failure. TMP-SMX (0.48 g/day) prophylaxis was used for 3-6 months and prolonged to 7-8 months after treatment for acute rejection, which reduced the incidence of PJP compared with those without prophylaxis. CONCLUSION: Our study suggests that the high total dosage of ATG and CMV infection indicate the increased risk of PJP. The strategies of prophylaxis and treatment for PJP after kidney transplantation in our centre were effective.

Asunto(s)

Trasplante de Riñón/efectos adversos , Neumonía por Pneumocystis , Adulto , Profilaxis Antibiótica , Suero Antilinfocítico/efectos adversos , Infecciones por Citomegalovirus/complicaciones , Femenino , Humanos , Terapia de Inmunosupresión , Incidencia , Masculino , Persona de Mediana Edad , Infecciones Oportunistas , Neumonía por Pneumocystis/tratamiento farmacológico , Neumonía por Pneumocystis/epidemiología , Neumonía por Pneumocystis/etiología , Neumonía por Pneumocystis/patología , Estudios Retrospectivos , Factores de Riesgo , Receptores de Trasplantes , Resultado del Tratamiento , Combinación Trimetoprim y Sulfametoxazol/uso terapéutico

RESUMEN

BACKGROUND: Although the use of expanded-criteria donors (ECDs) alleviates the problem of organ shortage, it significantly increases the incidence of delayed graft function (DGF). DGF is a common complication after kidney transplantation; however, the effect of DGF on graft loss is uncertain based on the published literature. Hence, the aim of this study was to determine the relationship between DGF and allograft survival. METHODS: We conducted a retrospective, multicenter, observation cohort study. A total of 284 deceased donors and 541 recipients between February 2012 and March 2017 were included. We used logistic regression analysis to verify the association between clinical parameters and DGF, and Cox proportional hazards models were applied to quantify the hazard ratios of DGF for kidney graft loss. RESULTS: Among the 284 deceased donors, 65 (22.8%) donors were ECD. Of the 541 recipients, 107 (19.8%) recipients developed DGF, and this rate was higher with ECD kidneys than with standard-criteria donor (SCD) kidneys (29.2% vs. 17.1%; P = 0.003). The 5-year graft survival rate was not significantly different between SCD kidney recipients with and without DGF (95.8% vs. 95.4%; P = 0.580). However, there was a significant difference between ECD kidney recipients with and without DGF (71.4% vs. 97.6%; P = 0.001), and the adjusted hazard ratio (HR) for graft loss for recipients with DGF was 1.885 (95% confidence interval [CI] = 1.305-7.630; P = 0.024). Results showed that induction therapy with anti-thymocyte globulin was protective against DGF (odds ratio = 0.359; 95% CI = 0.197-0.652; P = 0.001) with all donor kidneys and a protective factor for graft survival (HR = 0.308; 95% CI = 0.130-0.728; P = 0.007) with ECD kidneys. CONCLUSION: DGF is an independent risk factor for graft survival in recipients with ECD kidneys, but not SCD kidneys.

Asunto(s)

Trasplante de Riñón/métodos , Adulto , Estudios de Cohortes , Femenino , Supervivencia de Injerto/fisiología , Humanos , Masculino , Persona de Mediana Edad , Estudios Multicéntricos como Asunto , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Donantes de Tejidos

RESUMEN

To test the reliability of CEUS on the diagnosis of acute (AR) or chronic rejection (CR) after renal transplantation, patients who received renal transplantation in our center from January 2011 and December 2015 were retrospectively included in the current study. All the included patients underwent contrast-enhanced ultrasonography tests. Two regions of interests were chosen to carry out time-intensity curves (TICs). The main indexes include time indexes, intensity indexes, and difference indexes. Separation of TIC1 and TIC2 was evaluated by the authors. Results revealed that time to peak 1 (TTP-1), TTP-2, absolute time to peak 1 (ATTP-1), and ATTP-2 in the CR group were significantly later than those in the graft function stable group. Peak intensity 2 is smaller in the AR group than that in the GFS group, velocity of intensity ascending 2 is slower in the CR group than that in the GFS group, terminal intensity 1 (TI-1) and TI-2 are lower in the CR group than those in the GFS group, and Vd-1 is faster in the CR group than that in the GFS group (P < 0.05). Those results indicated that contrast-enhanced ultrasonography test can satisfactorily reflect the microcirculation of transplanted kidney and can be used to assist in the early diagnosis of graft rejection.

Asunto(s)

Rechazo de Injerto/diagnóstico por imagen , Trasplante de Riñón , Ultrasonografía/métodos , Adulto , Medios de Contraste , Femenino , Humanos , Riñón/irrigación sanguínea , Riñón/diagnóstico por imagen , Masculino , Microcirculación , Persona de Mediana Edad , Fosfolípidos , Reproducibilidad de los Resultados , Estudios Retrospectivos , Hexafluoruro de Azufre

RESUMEN

BACKGROUND: Primary hyperoxaluria (PH) is a rare inborn disorder of the metabolism of glyoxylate, which causes the hallmark production oxalate and forms insoluble calcium oxalate crystals that accumulate in the kidney and other organs. Since the manifestation of PH varies from recurrent nephrolithiasis, nephrocalcinosis, and end-stage renal disease with age at onset of symptoms ranging from infancy to the sixth decade, the disease remains undiagnosed until after kidney transplantation in some cases. CASE PRESENTATION: Herein, we report 3 cases of PH diagnosed after kidney transplantation failure, providing the comprehensive clinical course, the ultrasonic image of renal graft and pathologic image of the biopsy, highlighting the relevance of biopsy findings and the results of molecular genetic testing. We also focus on the treatment and the unfavorable outcome of the patients. Meanwhile, we review the literature and show the additional 10 reported cases of PH diagnosed after kidney transplantation. Additionally, we discuss the progressive molecular understanding of the mechanisms involved in PH and molecular therapy. CONCLUSIONS: Overall, the necessity of preoperative screening of PH in all patients even with a minor history of nephrolithiasis and the importance of proper treatment are the lessons we learn from the 3 cases, which prompt us to avoid tragedies.

Asunto(s)

Hiperoxaluria Primaria/diagnóstico por imagen , Hiperoxaluria Primaria/etiología , Trasplante de Riñón/efectos adversos , Complicaciones Posoperatorias/diagnóstico por imagen , Complicaciones Posoperatorias/etiología , Insuficiencia del Tratamiento , Adulto , Humanos , Trasplante de Riñón/tendencias , Masculino

RESUMEN

BACKGROUND: Post-transplantation diabetes mellitus (PTDM) remains a major clinical challenge following renal transplant. Identification of pretransplant modifiable risk factors may allow timely interventions to prevent PTDM. This study aims to determine whether pretransplant metabolic syndrome and its components are able to predict PTDM in Chinese patients receiving their first renal transplant. PATIENTS AND METHODS: We conducted a single-center retrospective study of 633 non-diabetic patients receiving a first kidney transplant. PTDM was diagnosed between 1 month and 1 year post-transplant. Multivariable logistic regression and Cox proportional hazards model were applied to detect potential pretransplant risk factors for PTDM. RESULTS: One year post-transplant, 26.2% of recipients had developed PTDM. PTDM patients had significantly higher fasting plasma glucose (FPG) (P=0.026) and body mass index (BMI) (P=0.006) than non-PRDM patients, and lower levels of high-density lipoprotein cholesterol (P=0.015). The presence of metabolic syndrome was an independent risk factor for PTDM, as assessed by multivariable logistic regression analysis (OR 1.28, 95% CI 1.04-1.51, P=0.038) and Cox proportional hazards model (OR 2.75, 95% CI 1.45-6.05, P=0.021). Moreover, both FPG >5.6 mmol/L and BMI >28 kg/m2 (obesity) were able to predict PTDM. CONCLUSION: Our results suggest that the presence of metabolic syndrome and its components, impaired fasting glycemia and obesity, are independent risk factors for PTDM in Chinese non-diabetic patients receiving a first renal transplant. Interventions aimed at improving pretransplant metabolic syndrome may reduce the incidence of PTDM.

RESUMEN

BACKGROUND: Organ donation after brain death (DBD) is the standard strategy for organ transplantation; however, the concept of brain death is not universally accepted due to cultural beliefs and barriers amongst billions of people worldwide. Hence, a novel donation pattern has been established in China which outlines the concept of donation after brain death followed by circulatory death (DBCD). Differently from any current donation classification, this new concept is formulated based on combination of recognizing brain death and circulatory death. Should approval be gained for this definition and approach, DBCD will pave a novel donation option for billions of people who cannot accept DBD due to their cultural beliefs. METHODS: A multi-center, cohort study was conducted from February 2012 to December 2015. 523 kidney transplant recipients from four kidney transplant institutions were enrolled into the study, of which, 383 received kidneys from DBCD, and 140 from DBD. Graft and recipient survivals following transplantation were retrospectively analyzed. Postoperative complications including delayed graft function,, and acute rejection, were also analyzed for both groups. RESULTS: DBCD could achieve comparable graft and recipient survivals in comparison with DBD (Log-rank P = 0.32 and 0.86,respectively). One-year graft and recipient survivals were equal between DBCD and DBD groups (97.4% versus 97.9%, P = 0.10;98.4% versus 98.6%, P = 1.0, respectively). Furthermore, DBCD did not increase incidences of postoperative complications compared with DBD, including delayed graft function (19.3% versus 22.1%, P = 0.46) and acute rejection (9.1% versus 8.6%, P = 1.0). Additionally, antithymocyte globulin as induction therapy and shorter warm ischemia time decreased incidence of delayed graft function in DBCD group (16.8% on antithymocyte globulin versus 27.2% on basiliximab, P = 0.03; 16.7% on ≤18 min versus 26.7% on > 18 min group, P = 0.03). CONCLUSIONS: Kidney donation through DBCD achieves equally successful outcomes as DBD, and could provide a feasible path to graft availability for billions of people who face barriers to organ donation from DBD.

Asunto(s)

Aloinjertos/fisiología , Muerte Encefálica/diagnóstico , Trasplante de Riñón/métodos , Choque/diagnóstico , Obtención de Tejidos y Órganos/métodos , Adulto , Muerte Encefálica/patología , Estudios de Cohortes , Femenino , Supervivencia de Injerto/fisiología , Humanos , Trasplante de Riñón/normas , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Choque/patología , Obtención de Tejidos y Órganos/normas , Resultado del Tratamiento , Adulto Joven

RESUMEN

BACKGROUND/AIMS: Delayed graft function (DGF) is a common complication following kidney transplantation adversely affecting graft outcomes. Donation after brain death followed by circulatory death (DBCD), a novel donation pattern, is expected to correlate with high incidence of DGF. However, little information is available about factors associated with DGF in DBCD. METHODS: A total of 383 kidney transplants from DBCD donation in three institutions were enrolled. Associations of DGF with the clinical characteristics of recipients and donors were quantified. RESULTS: In this retrospective multi-center study, the incidence of DGF was 19.3%. Lower incidence of DGF was found in recipients for whom antithymocyte globulin was used for induction (p < 0.05), which was an independent protective factor against DGF (odds ratio [OR] = 0.48; 95% CI 0.27-0.86). Two novel explicative variables were recognized as independent risk factors, including use of vasoactive drugs (OR = 3.15; 95% CI 1.39-7.14) and cardiopulmonary resuscitation (OR = 2.51; 95% CI 1.05-6.00), which contributed significantly to increased risk of DGF (p < 0.05). Prolonged warm ischemia time (> 18 min; OR = 2.42; 95% CI 1.36-4.32), was also predictive of DGF in DBCD. A prediction model was developed and achieved an area under the curve of 0.89 in predicting DGF when combined with reported parameters. CONCLUSION: The novel factors, confirmed for the first time in our study, will help to improve risk prediction of DGF and to determine optimal interventions to prevent DGF in clinical practice.

Asunto(s)

Funcionamiento Retardado del Injerto/diagnóstico , Trasplante de Riñón/métodos , Donantes de Tejidos , Adulto , Área Bajo la Curva , Muerte Encefálica , Estudios de Cohortes , Funcionamiento Retardado del Injerto/etiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Choque/mortalidad

RESUMEN

Talaromyces marneffei is an emerging opportunistic infection among immunocompromised patients. We observe the first native case of disseminated T. marneffei involving the kidney in a renal transplant recipient in mainland China. We describe the comprehensive clinical course, and ultrasound imaging of renal transplant biopsy, pathologic images, and electron microscopy observation of the biopsy specimen, highlighting the relevance of biopsy findings and the blood culture. We also focus on the treatment and good outcome of the patient. Then we review the literature and show the additional 10 reported cases of T. marneffei in renal transplant recipients. In addition, we discuss the new methods of rapid diagnosis of T. marneffei. In brief, timely diagnosis and proper treatment of T. marneffei infection is important in renal transplant recipients.

Asunto(s)

Antifúngicos/uso terapéutico , Trasplante de Riñón/efectos adversos , Micosis/tratamiento farmacológico , Infecciones Oportunistas/tratamiento farmacológico , Penicillium/aislamiento & purificación , Talaromyces/aislamiento & purificación , Aloinjertos , China , Ciclosporina/uso terapéutico , Humanos , Huésped Inmunocomprometido , Riñón/microbiología , Riñón/patología , Masculino , Persona de Mediana Edad , Micosis/diagnóstico por imagen , Micosis/microbiología , Micosis/patología , Infecciones Oportunistas/diagnóstico por imagen , Infecciones Oportunistas/microbiología , Infecciones Oportunistas/patología , Receptores de Trasplantes , Resultado del Tratamiento

RESUMEN

Myeloid-derived suppressor cells (MDSCs) are recently identified immune suppressive cells in multiple chronic inflammations. Here, we investigated MDSCs in patients with end-stage renal disease (ESRD) and their clinical significance in these patients and healthy individuals (49 each). Polymorphonuclear and mononuclear MDSCs were investigated by flow cytometry. Patients with ESRD before hemodialysis presented a significantly higher level of polymorphonuclear MDSCs. Depletion of polymorphonuclear-MDSCs resolved T cell IFN-γ responses. By co-culture, T cell proliferation and the production of IFN-γ were abrogated by the addition of polymorphonuclear MDSCs in a dose-dependent manner. Both of these effects were reversed by a reactive oxygen species inhibitor. The levels of reactive oxygen species were higher in polymorphonuclear MDSCs derived from patients with ESRD than from normal individuals. The mRNA level of NOX2, the key protein complex responsible for reactive oxygen species production, was higher in ESRD-related polymorphonuclear MDSCs. The phospho-STAT3 level, a key activator of MDSCs, was higher in ESRD-related polymorphonuclear MDSCs. Finally, the polymorphonuclear MDSC level before and after hemodialysis was positively related to infectious diseases. Patients with ESRD were dichotomized into 2 groups by the amount of polymorphonuclear MDSCs. Patients with high levels of polymorphonuclear MDSCs presented with a higher incidence of infectious events. Thus, polymorphonuclear MDSCs were elevated in ESRD patients with strong immune-suppressive capability through a phospho-STAT3/reactive oxygen species pathway. Hence, polymorphonuclear MDSCs might increase the risk of infectious complications.

Asunto(s)

Tolerancia Inmunológica/inmunología , Infecciones/inmunología , Fallo Renal Crónico/inmunología , Células Supresoras de Origen Mieloide/inmunología , Linfocitos T/inmunología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Proliferación Celular , Técnicas de Cocultivo , Femenino , Citometría de Flujo , Estudios de Seguimiento , Humanos , Incidencia , Infecciones/epidemiología , Interferón gamma/inmunología , Fallo Renal Crónico/complicaciones , Fallo Renal Crónico/terapia , Masculino , Glicoproteínas de Membrana/metabolismo , Persona de Mediana Edad , Células Supresoras de Origen Mieloide/metabolismo , NADPH Oxidasa 2 , NADPH Oxidasas/metabolismo , Estudios Prospectivos , ARN Mensajero/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Diálisis Renal , Factor de Transcripción STAT3/metabolismo , Linfocitos T/fisiología , Adulto Joven