EFFECT OF LEPTIN CONCENTRATIONS AND LEPTIN RECEPTOR GENE POLYMORPHISMS ON THE OUTCOME OF RENAL TRANSPLANTATION

IntroductionLeptin is a pro-inflammatory adipocytokine implicated in cardiovascular disease, insulin resistance, obesity and chronic kidney disease.Material and methodsIn a cohort of 236 renal transplant recipients, we aimed to determine whether circulating leptin concentrations and/or three polymorphisms in the leptin receptor (LEPR) gene, namely rs1137100, rs1137101 and rs1805094, were related to clinical outcomes in renal transplantation. Plasma leptin concentrations were measured by ELISA. Genetic variants were determined by conventional real-time PCR assays and statistical associations with clinical outcomes were obtained by logistic regression modelling.ResultsPatients with elevated leptin levels were at higher risk of acute rejection [OR=1.03 (1.01–1.05), p=0.03] and displayed worse renal clearance (p=0.001) than patients with lower levels. Leptin levels were not significantly affected by any of the three LEPR SNPs. The rs1137101 G variant showed an inverse association with the risk of delayed graft function (DGF) [OR=0.42 (0.22-0.81), p=0.009], whilst the homozygous rs1805094 CC genotype was associated with increased risk of acute rejection [OR=11.38 (2.15-60.16), p=0.004]. A statistically significant association was also observed between the rs1137100 GG genotype and better renal function [mean difference vs. AA/AG =20.20 (4.91-35.49) ml/min, p=0.010].ConclusionsOur results show that both leptin plasma concentrations and polymorphisms in the LEPR gene may affect clinical outcomes in renal transplant recipients, suggesting that the determination of these parameters could be useful in predicting post-transplant adverse events.

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INCREASED RISK OF GRAFT LOSS IN MYCOPHENOLATE MOFETIL (MMF) AND TACROLIMUS (TACRO)-TREATED RENAL TRANSPLANT RECIPIENTS (RTRʼS) WITH ACUTE REJECTION

ASAIO Journal ◽

10.1097/00002480-200103000-00162 ◽

2001 ◽

Vol 47 (2) ◽

pp. 141

Author(s):

Mariana Markell ◽

Moro Salifu ◽

Dhiren Haria ◽

Harrison King ◽

Dale Distant ◽

...

Keyword(s):

Mycophenolate Mofetil ◽

Renal Transplant ◽

Acute Rejection ◽

Graft Loss ◽

Renal Transplant Recipients ◽

Transplant Recipients ◽

Increased Risk

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Comparison of the Emit Immunoassay with HPLC for Therapeutic Drug Monitoring of Mycophenolic Acid in Pediatric Renal-Transplant Recipients on Mycophenolate Mofetil Therapy

Clinical Chemistry ◽

10.1093/clinchem/48.3.517 ◽

2002 ◽

Vol 48 (3) ◽

pp. 517-525 ◽

Cited By ~ 90

Author(s):

Lutz T Weber ◽

Maria Shipkova ◽

Victor W Armstrong ◽

Natalie Wagner ◽

Ekkehard Schütz ◽

...

Keyword(s):

Mycophenolate Mofetil ◽

Renal Transplant ◽

Acute Rejection ◽

Mycophenolic Acid ◽

Therapeutic Drug ◽

Renal Transplant Recipients ◽

Transplant Recipients ◽

Increased Risk ◽

Pediatric Renal Transplant ◽

Pediatric Renal Transplant Recipients

Abstract Background: HPLC is currently the preferred method for accurate measurement of mycophenolic acid (MPA). This study was designed to validate the Emit compared with HPLC in relation to clinical outcome measurements. Methods: Pediatric renal-transplant recipients (n = 50) on an immunosuppressive triple regimen consisting of cyclosporin A, prednisone, and mycophenolate mofetil (600 mg/m2 twice per day) were investigated in an open-label prospective study. Pharmacokinetic profiles over 12 h were obtained at 1 week, 3 weeks, 3 months, and 6 months posttransplant. Plasma MPA was measured by both reversed-phase HPLC and the Emit immunoassay. Results: There was an association between the risk of acute rejection episodes and low area under the curve values from t0 to t12h (AUC0–12) for MPA (MPA-AUC0–12) or predose concentrations of MPA derived from both HPLC and Emit measurements. According to ROC analysis, an AUC value of 33.8 mg · h/L for MPA from t0 to t12h (MPA-AUC0–12) determined by HPLC had a diagnostic sensitivity of 80% and a diagnostic specificity of 57%. The corresponding value of the Emit was 36.1 mg · h/L. For the predose concentration (MPA-c12), a concentration of 1.2 mg/L determined by HPLC and 1.4 mg/L determined by Emit gave a sensitivity of 80% and a specificity of 60%, respectively. There was no association of any pharmacokinetic variables derived from total MPA measurements with an increased risk of side effects related to mycophenolate mofetil. Conclusions: The Emit assay appears to have a comparable diagnostic efficacy to HPLC for assessing the risk of acute rejection in pediatric renal-transplant recipients. However, because of the cross-reactivity of the antibody used in the Emit assay with the active MPA acyl glucuronide metabolite, the decision thresholds for the Emit were higher than those calculated from HPLC measurements.

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Lymphocyte depletion and risk of acute rejection in renal transplant recipients at increased risk for delayed graft function

American Journal of Transplantation ◽

10.1111/ajt.15102 ◽

2018 ◽

Vol 19 (3) ◽

pp. 781-789 ◽

Cited By ~ 7

Author(s):

Kadiyala V. Ravindra ◽

Scott Sanoff ◽

Deepak Vikraman ◽

Ahmad Zaaroura ◽

Aditya Nanavati ◽

...

Keyword(s):

Renal Transplant ◽

Acute Rejection ◽

Graft Function ◽

Delayed Graft Function ◽

Renal Transplant Recipients ◽

Transplant Recipients ◽

Lymphocyte Depletion ◽

Increased Risk

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Comparison of clinical outcomes in hepatitis B virus positive and negative renal transplant recipients

International Surgery ◽

10.9738/intsurg-d-15-00144.1 ◽

2016 ◽

Author(s):

Vural Taner Yilmaz ◽

Ramazan Cetinkaya ◽

Halide Akbas ◽

Sebahat Ozdem ◽

Burak Veli Ulger ◽

...

Keyword(s):

Renal Transplant ◽

Acute Rejection ◽

Acute Hepatitis ◽

Clinical Outcomes ◽

Patient Survival ◽

Survival Rates ◽

Renal Transplant Recipients ◽

Transplant Recipients ◽

Group 2 ◽

Rejection Rates

Abstract Aim: Our aim was to compare the short and long term clinical outcomes of HbsAg(+) renal transplant recipients with HbsAg(-) recipients. Patients and Methods: Two hundered and four patients who underwent renal transplantation in our center between 2001 and 2014 were included in the study. The patients were divided into two groups. Group 1: HbsAg(-) group (n=136) and Group 2: HbsAg(+) group (n=68). There was no significant difference between the groups in terms of lymphocyte cross matches, numbers of mismatches, immunosuppressive treatment protocols and induction treatments. In HbsAg(+) group, 51 patients were HBV DNA(+), 64 patients were HbeAg(-) and 4 patients were HbeAg(+). Fifty-seven (83.8%) patients were treated with Lamivudine, 4 (5.9%) patients with Entecavir and 7 (10.3%) patients with Tenofovir for Hepatitis B infection. Graft and patient survival rates, graft functions, acute hepatitis rates, acute rejection rates and other clinical outcomes of the groups were compared. Results: Demographic data and immuologic risk profiles of the groups were similar. Acute rejection rates, graft survival rates and patient survival rates were similar. Acute hepatitis rates, glomerular filtration rates on the last controls and delayed graft function rates were higher in Group 2, while chronic allograft disfunction and new onset diabetes mellitus after transplantation (NODAT) rates were similar between the groups. Conclusion: Our study revealed that, graft and patient survival and acute rejection rates were similar between HbsAg(+) and HbsAg(-) recipients, while acute hepatitis rate was higher in HbsAg(+) recipients.

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Torquetenovirus Serum Load and Long-Term Outcomes in Renal Transplant Recipients

Journal of Clinical Medicine ◽

10.3390/jcm9020440 ◽

2020 ◽

Vol 9 (2) ◽

pp. 440 ◽

Cited By ~ 1

Author(s):

Edmund J. Gore ◽

António W. Gomes-Neto ◽

Lei Wang ◽

Stephan J. L. Bakker ◽

Hubert G. M. Niesters ◽

...

Keyword(s):

Renal Transplantation ◽

Renal Transplant ◽

Renal Transplant Recipients ◽

Transplant Recipients ◽

Long Term Outcomes ◽

Post Transplantation ◽

Increased Risk ◽

All Cause Mortality ◽

One Year

Following transplantation, patients must take immunosuppressive medication for life. Torquetenovirus (TTV) is thought to be marker for immunosuppression, and TTV–DNA levels after organ transplantation have been investigated, showing high TTV levels, associated with increased risk of infections, and low TTV levels associated with increased risk of rejection. However, this has been investigated in studies with relatively short follow-up periods. We hypothesized that TTV levels can be used to assess long term outcomes after renal transplantation. Serum samples of 666 renal transplant recipients were tested for TTV DNA. Samples were taken at least one year after renal transplantation, when TTV levels are thought to be relatively stable. Patient data was reviewed for graft failure, all-cause mortality and death due to infectious causes. Our data indicates that high TTV levels, sampled more than one year post-transplantation, are associated with all-cause mortality with a hazard ratio (HR) of 1.12 (95% CI, 1.02–1.23) per log10 increase in TTV viral load, (p = 0.02). Additionally, high TTV levels were also associated with death due to infectious causes (HR 1.20 (95% CI 1.01–1.43), p = 0.04). TTV levels decrease in the years following renal transplantation, but remain elevated longer than previously thought. This study shows that TTV level may aid in predicting long-term outcomes, all-cause mortality and death due to an infectious cause in renal transplant patients sampled over one year post-transplantation.

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Chemokine Receptor Polymorphism and Risk of Acute Rejection in Human Renal Transplantation

Journal of the American Society of Nephrology ◽

10.1681/asn.v133754 ◽

2002 ◽

Vol 13 (3) ◽

pp. 754-758 ◽

Cited By ~ 2

Author(s):

Reza Abdi ◽

Tran Thi Bich Huong ◽

Alfredo Sahagun-Ruiz ◽

Philip M. Murphy ◽

Barry M. Brenner ◽

...

Keyword(s):

Renal Transplantation ◽

Renal Transplant ◽

Acute Rejection ◽

Chemokine Receptor ◽

Chemokine Receptors ◽

Renal Allograft ◽

Transplant Rejection ◽

Renal Transplant Recipients ◽

Transplant Recipients ◽

Renal Transplant Rejection

ABSTRACT. Chemokines regulate the trafficking of leukocytes in immunity and inflammation and have been implicated in mouse models in acute cardiac and renal allograft rejection; however, their significance to human transplantation is not yet defined. The association of human chemokine receptor genetic variants, CCR5-Δ32, CCR5-59029-A/G, CCR2-V64I, CX3CR1-V249I, and CX3CR1-T280M, with outcome in 163 renal transplant recipients was examined here. Significant reductions were found in risk of acute renal transplant rejection in recipients who possessed the CCR2-64I allele (odds ratio [OR], 0.30; 95% confidence interval [CI], 0.12 to 0.78; P = 0.014) or who were homozygous for the 59029-A allele (OR, 0.37; 95% CI, 0.16 to 0.85; P = 0.016). There were no significant differences in the incidence of rejection among patients stratified as with or without CCR5-Δ32 or by the CX3CR1-V249I or CX3CR1-T280M genotypes. Adjustment for known risk factors for transplant rejection confirmed the univariate findings for possession of the CCR2-64I allele (OR, 0.20; P = 0.032) and homozygosity for the 59029-A allele (OR, 0.26; P = 0.027). It was concluded that the risk of acute rejection in renal transplantation is associated with genetic variation in the chemokine receptors CCR2 and CCR5.

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Impact of hyperuricemia on long-term clinical outcomes of renal transplant recipients: a systematic review and meta-analysis

Journal of Pharmacy & Pharmaceutical Sciences ◽

10.18433/jpps31620 ◽

2021 ◽

Vol 24 ◽

pp. 292-307

Author(s):

Hui Yang ◽

Qing Chen ◽

Aiwen Huang ◽

Xiaojia Yu ◽

Gang Chen ◽

...

Keyword(s):

Uric Acid ◽

Renal Transplant ◽

Clinical Outcomes ◽

Cardiovascular Event ◽

Graft Loss ◽

Renal Transplant Recipients ◽

Transplant Recipients ◽

Increased Risk ◽

Significant Difference

Purpose: To evaluate the effect of hyperuricemia on clinical outcomes of renal transplant recipients (RTRs). Methods: A literature search of PubMed, Cochrane, Embase was conducted up to March 20, 2020. The primary outcome was the estimated glomerular filtration rate (eGFR). The second outcomes were the risk of graft loss, death, cardiovascular event and the level of triglyceride. The following search terms were utilized: ((Hyperuricemic group) OR (Hyperuricaemia) OR (Hyperuric) OR (Urea acid) OR (Uric acid) OR (Acid urate) OR (Urate) OR (Gout)) and ((Transplantation) OR (Transplantations) OR (Transplant) OR (Transplants) OR (Graft)). Results: 28 studies with 18224 patients were eligible for inclusion. There was no significant difference in eGFR (<12 months, p=0.07), the risk of graft loss (<60 months, p=0.07) and death (<60months, p=0.19) between the hyperuricemic and normouricemic group in the early post-transplantation period. But increased uric acid levels contributed to the long-term decline of eGFR, the risk of graft loss and death increased after transplantation. Hyperuricemia increased the risk of cardiovascular event with no significant difference in the level of triglyceride between the two groups. Conclusions: Increased uric acid levels contributed to the long-term decline of eGFR, increased risk of graft loss and death after transplantation. Although there was no significant effect on triglyceride, hyperuricemia increased the risk of cardiovascular event.

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