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

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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Sulphinpyrazone Does Not Influence Rejection Of Renal Transplants

10.1055/s-0038-1652029 ◽

1981 ◽

Author(s):

J H Turney ◽

M Bewick ◽

M J Weston

Keyword(s):

Renal Transplantation ◽

Renal Transplant ◽

Transplant Rejection ◽

Renal Transplant Recipients ◽

Transplant Recipients ◽

Fibrin Deposition ◽

Chi Squared ◽

And Function ◽

To Receive ◽

Renal Transplant Rejection

Platelet-mediated intravascular fibrin deposition may be the distal arm of the transplant rejection process. There have been reports that anti pi ate let drugs may prevent ameliorate, or even reverse renal transplant rejection. 50 consecutive cadaveric renal transplant recipients were randomly allocated to receive sulphinpyrazone 400 mg twice daily or no treatment additional to conventional immunosuppressive therapy. Patients were followed for 6 months, at which time they were assessed for graft survival and function, and for the number of rejection episodes. Rejection was defined as a rise in serum creatinine for which no other explanation was identified. Results were analysed by the Chi-squared test with Yates’ correction. Results at 6 months: There were no differences between the two groups, neither did the function of the surviving grafts differ.We conclude that, in this study, antiplatelet therapy with sulphinpyrazone does not affect the outcome of cadaveric renal transplantation.

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Clinically Significant Drug−Drug Interaction Between Tacrolimus and Phenobarbital

Journal of Pharmacy Practice ◽

10.1177/0897190010377804 ◽

2010 ◽

Vol 23 (6) ◽

pp. 585-589 ◽

Cited By ~ 10

Author(s):

Nida Siddiqi ◽

Kwaku Marfo

Keyword(s):

Drug Interaction ◽

Renal Transplant ◽

Drug Interactions ◽

Transplant Rejection ◽

Renal Transplant Recipients ◽

Transplant Recipients ◽

Patient Identification ◽

Clinically Significant ◽

Trough Levels ◽

Renal Transplant Rejection

Purpose: The case of a 57-year-old male who experienced acute renal transplant rejection due to subtherapeutic tacrolimus levels as a result of drug interaction with phenobarbital. Summary: Drug interactions with tacrolimus due to its metabolism through the CYP 450 3A4 enzymatic pathway have led to several reports of altered tacrolimus levels, which can lead to acute rejection in renal transplant recipients. We describe the case of a 57-year-old male initiated on immunosuppressive therapy with tacrolimus in addition to his anticonvulsant medications. Conclusion: Upon tacrolimus dose increases, discontinuation of carbamazepine, and minimization of phenobarbital dose, effective tacrolimus trough levels were achieved in our patient. Identification and elimination of such drug−drug interactions is necessary to assure adequate immunosuppression in renal transplant recipients.

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

Archives of Medical Science ◽

10.5114/aoms/126343 ◽

2021 ◽

Author(s):

Guadalup García-Pino ◽

Enrique Luna ◽

Sonia Mota-Zamorano ◽

Luz María González ◽

María Ángeles Tormo ◽

...

Keyword(s):

Renal Transplantation ◽

Renal Transplant ◽

Acute Rejection ◽

Clinical Outcomes ◽

Leptin Receptor ◽

Renal Transplant Recipients ◽

Inverse Association ◽

Transplant Recipients ◽

Lepr Gene ◽

Increased Risk

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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Indicators of acute renal-transplant rejection in patients treated with cyclosporine

Clinical Chemistry ◽

10.1093/clinchem/36.5.759 ◽

1990 ◽

Vol 36 (5) ◽

pp. 759-764 ◽

Cited By ~ 14

Author(s):

P W Mueller ◽

V Delaney ◽

M L MacNeil ◽

S P Caudill ◽

K K Steinberg

Keyword(s):

Renal Transplant ◽

Sensitivity And Specificity ◽

Activity Ratio ◽

Transplant Rejection ◽

Plasma Creatinine ◽

Renal Transplant Recipients ◽

Transplant Recipients ◽

Alanine Aminopeptidase ◽

Optimal Values ◽

Renal Transplant Rejection

Abstract We evaluated the ability of three enzymes--N-acetyl-beta-D-glucosaminidase (NAG; EC 3.2.1.30), alanine aminopeptidase (AAP; microsomal aminopeptidase, EC 3.4.11.2), and gamma-glutamyltransferase (GGT; EC 2.3.2.2)--and adenosine deaminase binding protein (ABP) in urine to predict or confirm renal-transplant rejection in patients treated with cyclosporine. We measured the enzymes daily during the early post-transplant hospital stay of 104 renal-transplant recipients (72 men and 32 women). We also measured ABP in 32 of these patients. We analyzed the data by calculating the activity ratio of each day's test value to the previous day's result and optimized the sensitivity (SN) and specificity (SP) to determine the optimal ratio for each test. The results indicate that cyclosporine treatment reduces the optimal sensitivity and specificity of these tests. Three comparable tests (ABP, GGT, and AAP) yield the best optimal values (SN = 0.77, 0.69, 0.77; and SP = 0.71, 0.74, 0.63, respectively), and the NAG test yields the lowest combination of sensitivity and specificity (SN = 0.62, SP = 0.66). All four tests were less sensitive and specific than the plasma creatinine test (optimal day-to-day difference = 5 mg/L). However, the ABP and AAP tests gave indications of rejection at least 24 h before clinical diagnosis for 50% of the patients experiencing rejection, while early plasma creatinine increases of 5 mg/L occurred in only 19% of this group.

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Improved renal allograft survival for pre-emptive paediatric renal transplant recipients in the UK

Archives of Disease in Childhood ◽

10.1136/archdischild-2020-321277 ◽

2021 ◽

pp. archdischild-2020-321277

Author(s):

Matko Marlais ◽

Kate Martin ◽

Stephen D Marks

Keyword(s):

Peritoneal Dialysis ◽

Renal Transplant ◽

Renal Allograft ◽

Cox Regression ◽

Renal Transplant Recipients ◽

Transplant Recipients ◽

Allograft Survival ◽

Significant Difference ◽

Donor Type ◽

The Uk

BackgroundThe aim of this study was to investigate whether being on dialysis at the time of renal transplantation affected renal allograft survival in paediatric renal transplant recipients (pRTRs).MethodsRetrospective study of UK Transplant Registry (National Health Service Blood and Transplant) data on all children (aged <18 years) receiving a kidney-only transplant from 1 January 2000 to 31 December 2015. Kaplan-Meier estimates of patient and renal allograft survival calculated and Cox regression modelling accounting for donor type. The relationship between time on dialysis and renal allograft survival was examined.Results2038 pRTRs were analysed: 607 (30%) were pre-emptively transplanted, 789 (39%) and 642 (32%) on peritoneal dialysis and haemodialysis, respectively, at the time of transplantation. Five-year renal allograft survival was significantly better in the pre-emptively transplanted group (90.6%) compared with those on peritoneal dialysis and haemodialysis (86.4% and 85.7%, respectively; p=0.02). After accounting for donor type, there was a significantly lower hazard of 5-year renal allograft failure in pre-emptively transplanted children (HR 0.742, p=0.05). Time spent on dialysis pre-transplant negatively correlated with renal allograft survival (p=0.002). There was no significant difference in 5-year renal allograft survival between children who were on dialysis for less than 6 months and children transplanted pre-emptively (87.5% vs 90.5%, p=0.25).ConclusionsPre-emptively transplanted children have improved 5-year renal allograft survival, compared with children on dialysis at the time of transplantation. Although increased time spent on dialysis correlated with poorer renal allograft survival, there was no evidence that short periods of dialysis pre-transplant affected renal allograft survival.

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