High Expression of FOXP3 mRNA in Blood and Urine as a Predictive Marker in Kidney Transplantation

2018 ◽  
Vol 28 (2) ◽  
pp. 134-141 ◽  
Author(s):  
Mehri Barabadi ◽  
Sanaz Keshavarz Shahbaz ◽  
Farshad Foroughi ◽  
Morteza Hosseinzadeh ◽  
Mohsen Nafar ◽  
...  

Background: Diagnosis of allograft dysfunction by noninvasive biomarker tests is preferable to invasive allograft biopsies and has been extensively considered in recent years. This study aims to evaluate blood and urinary forkhead box P3 (FOXP3) messenger RNA (mRNA) expression in renal transplant recipients in an attempt to determine whether differential diagnosis of graft dysfunction is feasible using mRNA profiles. Methods: We analyzed FOXP3 mRNA expression in paired urinary and peripheral blood mononuclear cell (PBMC) samples. A total of 91 kidney transplant recipients enrolled in this study that were classified into 3 groups: biopsy-proven acute rejection (AR; n = 27), chronic allograft nephropathy (n = 19), and well-functioning graft (n = 45). The FOXP3 mRNA expression was quantified by TaqMan probe real-time polymerase chain reaction. Results: Acute rejection patients had a higher expression level of transcription factor FOXP3 compared to the chronic nephropathy and control groups. Analysis of receiver operating characteristic curves showed that rejection could be diagnosed with 100% sensitivity and 96% specificity in urine, and 92% sensitivity and 86% specificity in PBMC samples using the optimal FOXP3 mRNA cutoff value. We subdivided the AR group into progressive and nonprogressive patients, which showed a significant difference in FOXP3 mRNA expression. This result confirmed the role of FOXP3 as a diagnostic marker in predicting transplantation outcomes. Conclusion: Our results suggested that elevated expression of FOXP3 in blood and urine samples from kidney transplant recipients could be a useful noninvasive biomarker to diagnose graft dysfunction.

2002 ◽  
Vol 87 (02) ◽  
pp. 194-198 ◽  
Author(s):  
Torsten Slowinski ◽  
Ingeborg Hauser ◽  
Birgit Vetter ◽  
Lutz Fritsche ◽  
Daniela Bachert ◽  
...  

SummaryWe analysed whether the factor V Leiden mutation – the most common hereditary predisposing factor for venous thrombosis – is associated with early and long-term graft dysfunction after kidney transplantation in 394 Caucasian kidney transplant recipients. The presence of factor V Leiden mutation was identified by allele specific PCR. The prevalence of the factor V Leiden mutation was compared to 32216 unselected neonates. The prevalence of the factor V Leiden mutation (GA genotype) was similar in 394 kidney transplant recipients and 32216 neonates. The frequency of known factors predicting long-term graft function were similar in patients with the GA genotype and with the normal factor V gene (GG genotype). The GA genotype was associated with the occurrence of no primary graft function (risk: 2.87; 95% confidence interval: 1.01-8.26; p < 0.05), the number of dialysis after transplantation in patients with no primary graft function until graft function (7.5 ± 2.06 dialysis in GA patients; 4.2 ± 0.36 dialyses in GG patients; p < 0.05), and the risk for at least one acute rejection episode (risk: 3.83; 95% confidence interval: 1.38-10.59; p < 0.02). The slope of 1/creatinine per year was significantly lower in patients with the GA genotype (GA patients: – 0.0204 ± 0.008 dl/mg per year; GG patients: 0.0104 ± 0.004 dl/mg per year; p < 0.02). The annual enhancement of the daily protein excretion rate was elevated in patients with the GA genotype (GA patients: 38.5 ± 16.6 mg/24 h per year; GG patients: 4.9 ± 4.4 mg/24 h per year; p < 0.02). Our study showed that the factor V Leiden mutation is associated with the occurrence of delayed graft function, acute rejection episodes and chronic graft dysfunction after kidney transplantation.


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Arvind Krishnakumar ◽  
Selvin Sundar Raj Mani ◽  
Rizwan Alam ◽  
Manish Lalwani ◽  
Athul Thomas ◽  
...  

Abstract Background and Aims The infections in kidney transplant recipients has been well defined. The timeline of infections and type of infection among patients who received anti-rejection therapy for acute rejection when compared to the patients who did not develop an acute rejection. Method Renal transplant recipients with post-transplant median follow up of four years from July 2009-June 2018 were included in a retrospective cohort study at a tertiary care hospital. Demographic characteristics, biopsy proven rejections, infections and graft and patient outcome were collected from transplant records and the hospital clinical workstation. Early and late acute rejections were defined as less than and more than 3 months respectively. The rates of various infections, type and time to develop an infection in the acute rejection group were compared with the patients who did not develop any rejection. Results A total of 794 patients underwent kidney transplant during the study with mean age of 35.5±12 years and 78% being male. Two hundred and eight four patients (35.8 %) had one or more biopsy proven rejections during the median follow up of 48 months (IQR 28,77). 213 patients (75%) developed early acute rejection (less than 3 months) while the remainder developed late acute rejection. The median time to develop the first acute rejection was 12 days (IQR 6,93.3). Majority of the patients (176, 62%) developed biopsy proven acute cellular rejection, 77 patients (27.1%) acute antibody mediated rejection and rest (10.9%) either mixed or borderline rejection who were treated. The proportion of BKV infection and infective diarrhea were more in rejection group when compared to no rejection group which was statistically significant (refer Table 1). At follow up, the patients who developed rejection had more graft loss (p value 0.010) but no increase in mortality. The predictors of infection among the patients who received anti-rejection therapy were identified. The median time to develop any infection in both groups were also compared. The spectrum of infections and outcome following early and late rejections were compared. Subgroup analysis was done to look at the eGFR, proteinuria trend, graft outcomes in patients with no rejection, rejection without any infection at follow up and rejection with any infection at follow up. The effect of type of anti-rejection therapy on spectrum of infections was also studied. Conclusion This is one of the few studies which looked at the effect of anti-rejection therapy in kidney transplant recipients. Anti-rejection treatment received post kidney transplant resulted in increased rates of BKV infection and infective diarrhea. Patients with acute rejection had more graft loss during follow up with no significant effect on mortality.


2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Filipe S. Mira ◽  
Joana Oliveira ◽  
Filipa Sousa ◽  
Dora Antunes ◽  
Ana Carolina Figueiredo ◽  
...  

Abstract Objectives Maternal and fetal complications can occur in pregnant kidney transplant recipients. Since these are high-risk pregnancies, they require a multidisciplinary follow-up to prematurely detect adverse events. Identifying factors that would affect fetal, maternal and graft outcomes is essential to further stratify the risk of pregnant kidney transplant recipients. Methods All pregnancies in kidney transplant recipients followed in a single center for 30 years were included. Data included previous transplant information and blood and urine tests performed before pregnancy. Impact of graft function on fetal, maternal and graft outcomes was evaluated. Results There were 41 pregnancies among 34 patients. Mean gestational age of 35 ± 3 weeks. Caesarean section was performed in 69.4% of patients. Five pregnancies were unsuccessful (12.2%). Four patients suffered an acute graft dysfunction (9.8%) and 12 (29.3%) had a serious maternal hypertensive disorder (preeclampsia, eclampsia or HELLP syndrome). Graft function before pregnancy showed significant correlation with adverse outcomes. Conclusions A proteinuria >669 mg/g, serum creatinine >1.75 mg/dL and glomerular filtration rate <36.2 mL/min/1.73 m2 before pregnancy were correlated to graft dysfunction during pregnancy. Similar values of proteinuria were also associated with a risk of maternal hypertensive disorders and pregnancy failure. Therefore, in patients with proteinuria and graft dysfunction, follow-up should be stricter to quickly detect complications.


2021 ◽  
Vol 16 ◽  
Author(s):  
Lukas J. Lehner ◽  
Klaus Kalb ◽  
Karl Weigand ◽  
Ulrich Pein ◽  
Peter Schenker ◽  
...  

Background/Objective: Tacrolimus HEXAL®/Crilomus® is an approved generic immunosuppressant for the prevention and treatment of rejection following renal transplantation. For safe and socioeconomically efficient conversion from the innovator to generic formulation, high-quality data are necessary, in view of the different and country-specific comorbidities and pharmacokinetics in kidney transplant recipients. Patients and Methods: From 2014 to 2017, we enrolled 32 kidney transplant recipients, receiving newly prescribed Tacrolimus HEXAL®/Crilomus® in 5 German centers. Efficacy and safety data were collected over 6-8 months and retrospectively compared to the period prior to conversion. Results: The mean tacrolimus trough level was 4.91 ng/mL standard deviation (SD) (SD ±1.7) before and 5.06 ng/mL (SD ±1.97) after conversion. Mean tacrolimus trough concentration-dose-ratio (+/- SD) was 187.1 ng/mL/mg/kg/day (SD 99.2) for the reference and 205.1 ng/mL/mg/kg/day (SD 133) for the generic product, resulting in a non-significant difference of 18.0 ng/mL/mg/kg/day (SD 71.8) (p=0.84, Wilcoxon V=180). Overall, dosing had to be changed in 4 (14.8%) patients. Graft function remained stable and no rejections occurred. Conclusion: In conclusion, conversion to the generic tacrolimus formulation can be considered safe and feasible in long-term kidney transplant recipients in Germany. As suggested by guidelines, a vigilant therapeutic drug monitoring is recommended to account for possible tacrolimus concentration variability on the individual patient level.


2016 ◽  
Vol 26 (4) ◽  
pp. 356-364 ◽  
Author(s):  
Bethany Coyne ◽  
Patricia J. Hollen ◽  
Guofen Yan ◽  
Kenneth Brayman

Background: Improvements in transplantation have increased the survival of children after kidney transplantation. These patients have complex needs, and the current medical system is not prepared to effectively transfer the care of these individuals from pediatric to adult health-care systems. Too often, transfer occurs during moments of crisis and is associated with poor outcomes. Objective: The aim of this study was to use a national database, the Scientific Registry of Transplant Recipients, to test the hypothesis that the increased risk of graft loss after transfer of care (from pediatric to adult services) for young adult kidney transplant recipients over a 2- to 3-year posttransfer follow-up period was related to these posttransfer risk factors (medication noncompliance, acute rejection, insurance status). Design: A retrospective, longitudinal, correlational design using secondary data was used to evaluate the transfer of care of 250 kidney transplant recipients (ages 16-25). Results: Seventy-seven (30.8%) individuals lost their graft within 3 years after transfer of care. Medication noncompliance, acute rejection, and serum creatinine >2.0 mg/dL at transfer were significant predictors of graft loss after accounting for multiple other factors. Conclusion: These individuals are at risk for graft loss after transfer of care and may benefit from increased personalized care during this risky period.


2020 ◽  
Author(s):  
AYSE OZBAN ◽  
OMER GULER ◽  
MURAT OZBAN ◽  
BELDA DURSUN ◽  
CAGATAY AYDIN

Abstract BACKGROUNDThe aim of this study was to evaluate the results of the smear tests in renal transplant recipients, determine the prevalence of abnormal outcomes and compare these patients with the general population in our center.METHODSA total of 79 female patients who underwent renal transplantation at Pamukkale University were retrospectively evaluated. All patients were followed up during and after the surgical procedures by a gynecologist and the smear results were recorded periodically.RESULTSThe mean time of Pap smear results after transplantation in kidney transplant recipients was 36.7±4.5 months. There was a significant difference between the two groups in terms of atrophic cervicitis. In transplantation group, 7 patients (8.86%) had LG-SIL, 3 (3.79%) had ASC-US and 1 (1.26%) had HG-SIL. In control group, the numbers are 3 (3.79%), 2 (2.53%) and 0, respectively. The difference between the patient and control groups in terms of LG-SIL results (7 (8.86%) vs 3 (3.79%) was statistically significant (p<0.05).CONCLUSIONSWe predict that kidney transplant recipients are at higher risk for precancerous cervical lesions and cervical cancer development due to immunosuppressive therapy. Smear screening and HPV testing should be repeated periodically to detect or prevent precancerous lesions and cervical cancer.


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