Long-Term Results of TPMT Activity Monitoring in Azathioprine-Treated Renal Allograft Recipients

Abstract. Thiopurine methyltransferase (TPMT) is implicated in the metabolism of azathioprine. The consequences of differential TPMT activity induction by azathioprine on the long-term results after renal transplantation were investigated. The erythrocyte TPMT activity in 82 patients on days 0, 7, and 30 was prospectively evaluated. Because various patterns of TPMT activity variation were noted, the population was subsequently divided between inductors (n = 47) and noninductors (n = 35). Data regarding patient and graft survival and acute rejection episodes were collected. Renal allograft assessment was performed at 3 mo and 2 yr to evaluate the renal function and the histologic lesions on routine biopsies. Data regarding azathioprine-related toxicity also were collected. In a subgroup of patients (n = 19), azathioprine blood levels were determined at day 7 and day 30. The graft survival censoring death was statistically improved in TPMT inductor patients when compared with non-TPMT inductors (P < 0.05). Among TPMT inductors, an acute rejection episode was observed in 34% of the patients versus 69% among non-TPMT inductors (P = 0.002). At 3 mo, serum creatinine was significantly lower among TPMT inductors when compared with non-TPMT inductors (123.1 ± 7.6 and 161.4 ± 13.9 μmol/L, respectively; P = 0.01). On routine allograft biopsies at 2 yr (n = 61), grade 2 or 3 chronic lesions were present in 19% versus 25%, respectively (P = NS). At days 7 and 30, the azathioprine blood levels were higher among patients who experienced acute rejection (P < 0.02). TPMT activity induction was observed in 57% of renal transplant recipients who received azathioprine. This induction was associated with better graft outcome. The appropriate conversion from azathioprine, which is a pro-drug, into 6-mercaptopurine could explain both better graft outcome and TPMT induction. Assessing the ability of azathioprine metabolism at an individualized level before transplantation may allow a more accurate choice among the different immunosuppressive treatments.

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THE IMPACT OF AN ACUTE REJECTION EPISODE ON LONG-TERM RENAL ALLOGRAFT SURVIVAL (t1/2)1,2

Transplantation Journal ◽

10.1097/00007890-199403270-00015 ◽

1994 ◽

Vol 57 (6) ◽

pp. 857-859 ◽

Cited By ~ 335

Author(s):

ARTHUE J. MATAS ◽

KRISTEN J. GILLINGHAM ◽

WILLIAM D. PAYNE ◽

JOHN S. NAJARIAN

Keyword(s):

Acute Rejection ◽

Renal Allograft ◽

Rejection Episode ◽

Acute Rejection Episode ◽

Allograft Survival ◽

The Impact

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POSTTRANSPLANT NEOPTERIN EXCRETION IN RENAL ALLOGRAFT RECIPIENTS—A RELIABLE DIAGNOSTIC AID FOR ACUTE REJECTION AND A PREDICTIVE MARKER OF LONG-TERM GRAFT SURVIVAL

Transplantation Journal ◽

10.1097/00007890-199107000-00012 ◽

1991 ◽

Vol 52 (1) ◽

pp. 58-63 ◽

Cited By ~ 64

Author(s):

GILBERT REIBNEGGER ◽

CLAUDIA AICHBERGER ◽

DIETMAR FUCHS ◽

ARNO HAUSEN ◽

MARTIN SPIELBERGER ◽

...

Keyword(s):

Acute Rejection ◽

Graft Survival ◽

Renal Allograft ◽

Predictive Marker ◽

Diagnostic Aid

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Dual Transplant of Marginal Kidneys

Swiss Surgery ◽

10.1024/1023-9332.9.5.213 ◽

2003 ◽

Vol 9 (5) ◽

pp. 213-215

Author(s):

Matter ◽

Venetz ◽

Aubert ◽

Gachet ◽

Burnier ◽

...

Keyword(s):

Case Report ◽

Acute Rejection ◽

Glomerular Filtration ◽

Graft Survival ◽

Long Term Results ◽

Recent Analysis ◽

Donor Kidney ◽

Transplant Outcomes

Introduction: Double transplantation is one possible answer to the shortage of donor organs. While each donor kidney would be unsuitable when considered as a single allograft, use of both kidneys should provide sufficient nephron mass for effective glomerular filtration. Case report: This is the first Swiss report of a dual adult transplant of marginal kidneys in a 46-year-old man, who was transplanted for the fourth time. Follow-up at 6 months is excellent without acute rejection. Conclusion: Recent analysis of dual marginal versus single ideal transplant outcomes, found a comparable 1-yr graft survival in both of the procedures. Long term results are still lacking and guidelines to decide between single, double or no transplantation are emerging.

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The PlA2 Polymorphism of the Platelet Glycoprotein IIIA Gene as a Risk Factor for Acute Renal Allograft Rejection

Journal of the American Society of Nephrology ◽

10.1681/asn.v10122599 ◽

1999 ◽

Vol 10 (12) ◽

pp. 2599-2605 ◽

Cited By ~ 2

Author(s):

EDUARDO SALIDO ◽

BASILIO MARTÍN ◽

YSAMAR BARRIOS ◽

JOSÉ D. LINARES ◽

DOMINGO HERNÁNDEZ ◽

...

Keyword(s):

Risk Factor ◽

Platelet Aggregation ◽

Acute Rejection ◽

Confidence Interval ◽

Serum Creatinine ◽

Graft Survival ◽

Renal Allograft ◽

Acute Rejection Episode ◽

Hla Dr ◽

Glycoprotein Iiia

Abstract. Glycoprotein IIIa/IIb is a membrane receptor for fibrinogen and von Willebrand factor that plays an important role in platelet aggregation. The β integrin chain of this receptor, GPIIIa, is polymorphic, and the allele known as PlA2 has been associated with coronary thrombosis. The GPIIIa genotype of a cohort of 119 consecutive renal allograft recipients (46.3 ± 13 yr; 85 M/34 F; 24.4% diabetic patients) was determined by PCR-restriction fragment length polymorphism, and those patients were followed for at least 12 mo. From 119 patients with at least 1 yr of follow-up, those who suffered an acute rejection (n = 52) showed a lower proportion of HLA-DR β1 identity with the donor (7.7% versus 23.9%; P = 0.03), a higher proportion of cytomegalovirus-positive (CMV+) donors/CMV- recipients (21% versus 7.5%; P = 0.05), and the PlA2 allele was more frequent (48.1% versus 26.9%; P = 0.02) compared with patients free of acute rejection (n = 67). No other variable was associated with acute rejection in the univariate analysis. The impact of the three above-mentioned significant variables on acute rejection was analyzed by stepwise logistic regression. The presence of the PlA2 allele yielded an odds ratio of 2.75 (95% confidence interval, 1.01 to 7.93) and an HLA-DR β1 identity of 0.2 (95% confidence interval, 0.06 to 0.99) for suffering an acute rejection episode. In addition, the serum creatinine at discharge was higher in PlA2-positive versus PlA2-negative patients (2.2 ± 1.6 versus 1.5 ± 0.6 mg/dl, respectively; P = 0.01), and the prevalence of proteinuria > 1.5 g/d 1 yr after transplantation was significantly higher among patients showing the PlA2 allele (16% versus 3%; P = 0.02). Finally, in the entire cohort of patients, the 2-yr graft survival was significantly lower in PlA2-positive (n = 43) compared with PlA2-negative (n = 76) patients (85.7% versus 97.2%; P = 0.015). No differences were found in patient survival (95.2% versus 98.7%, respectively). Proportional hazards regression analysis (Cox regression model) confirmed that serum creatinine level at discharge is the best predictor of allograft survival, followed by CMV status, delayed graft function, and the glycoprotein IIIa/IIb genotype. The PlA2 polymorphism is an independent risk factor for acute renal graft rejection, affecting short-term graft survival. Future studies aimed at preventing the hemostatic imbalance favoring platelet aggregation associated with this polymorphism may be important in preventing acute rejection and its impact on chronic rejection.

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Long-Term Results of Kidney Transplantation in the Elderly: Comparison between Different Donor Settings

Journal of Clinical Medicine ◽

10.3390/jcm10225308 ◽

2021 ◽

Vol 10 (22) ◽

pp. 5308

Author(s):

Renana Yemini ◽

Ruth Rahamimov ◽

Ronen Ghinea ◽

Eytan Mor

Keyword(s):

Graft Survival ◽

Cox Regression ◽

Survival Rates ◽

The Elderly ◽

Long Term Results ◽

Live Donor ◽

Allocation Policy ◽

Cox Regression Analysis ◽

Factors Associated

With scarce organ supply, a selection of suitable elderly candidates for transplant is needed, as well as auditing the long-term outcomes after transplant. We conducted an observational cohort study among our patient cohort >60 years old with a long follow up. (1). Patients and Methods: We used our database to study the results after transplant for 593 patients >60 years old who underwent a transplant between 2000–2017. The outcome was compared between live donor (LD; n = 257) recipients, an old-to-old (OTO, n = 215) group using an extended criteria donor (ECD) kidney, and a young-to-old (YTO, n = 123) group using a standard-criteria donor. The Kaplan−Meir method was used to calculate the patient and graft survival and Cox regression analysis in order to find risk factors associated with death. (2). Results: The 5- and 10-year patient survival was significantly better in the LD group (92.7% and 66.9%) compared with the OTO group (73.3% and 42.8%) and YTO group (70.9% and 40.6%) (p < 0.0001). The 5- and 10-year graft survival rates were 90.3% and 68.5% (LD), 61.7% and 30.9% (OTO), and 64.1% and 39.9%, respectively (YTO group; p < 0.0001 between the LD and the two DD groups). There was no difference in outcome between patients in their 60’s and their 70’s. Factors associated with mortality included: age (HR-1.060), DM (HR-1.773), IHD (HR-1.510), and LD/DD (HR-2.865). (3). Conclusions: Our 17-years of experience seems to justify the rational of an old-to-old allocation policy in the elderly population. Live-donor transplant should be encouraged whenever possible. Each individual decision of elderly candidates for transplant should be based on the patient’s comorbidity and predicted life expectancy.

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MO921PROGNOSTIC OUTCOMES OF TRANSPLANTED KIDNEY USING SOLUBLE CD30 AND Β2- MICROGLOBULIN

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfab112.003 ◽

2021 ◽

Vol 36 (Supplement_1) ◽

Author(s):

Ahmed Abo omar ◽

Gamal Saadi

Keyword(s):

Acute Rejection ◽

Graft Survival ◽

Patient Group ◽

The Other ◽

Kidney Graft ◽

Post Transplantation ◽

Β2 Microglobulin ◽

Transplanted Kidney ◽

Successful Transplantation

Abstract Background and Aims Transplantation is the first successful modality of renal replacement therapy (RRT) for irreversible chronic kidney disease (CKD; stage 5). Identifying additional factors associated with poor long-term prognosis after transplantation may provide clues regarding the pathophysiological mechanisms involved in allograft failure and identify high-risk patients who may benefit from additional monitoring or interventions. Successful kidney transplantation results in a substantial decrease in β2M levels, but a delayed decrease or increasing levels after transplantation may serve as a marker of acute rejection or inflammation. Several reports show that elevated sCD30 levels, pre and post transplantation are associated with a poor prognosis for long term kidney graft survival. These studies found higher CD30 levels in allograft recipients and a good predictor of impending acute rejection. The aim of the work is to study the prognostic outcomes of transplanted kidney using CD30 and β2-Microglobulin Method prospective study was conducted in nephrology unit –internal medicine department at Tanta and Kasr El Ainy university ,over 1 year.20 patients subjected to primary Tx.participated in this study.Cd30 and β2M.at day -1,2weeks and 3 months,with clinical follow up after 1 year to detect graft survival Results At day -1,level of cd30 was higher in rejection group than the other patient group.2 weeks post transplantation ,level of cd30 was higher in rejection group than the other patient group and at 3 monthes post transplantation level of cd30 was higher in rejection group than the other patient group,and these differences are statistically highly significant.(p values :0.003 ,0.005 and 0.002 respectively) Successful transplantation leads to significant decrease in serum cd30 at 2 weeks post tx.(P1 <0.005) and at 3 monthes post tx. (P1<0.001) although in rejection group, significant decrease in cd30 was at 2 weeks post tx.only(P1<0.005) and at 3 monthes serum cd30 began to rise again with( P1 0.157). At day -1,level of β2microglobulin was higher in rejection group than the other patient groupwith statistically significant difference (p. 0.01).2 weeks post transplantation ,level of β2microglobulin was higher in rejection group than the other patient groupbut statistically not significant(p. 0.18 ) and at 3 monthes post transplantation level of β2microglobulin was higher in rejection group than the other patient group but statistically non significant(p. 0.18 ). Successful transplantation leads to significant decrease in serum β2microglobulin at 2 weeks post tx.(P1 <0.002) and at 3 monthes post tx. (P1<0.001) although in rejection group ,significant decrease in β2microglobulin was at 3 monthes post tx.only(P1<0.005) and at 2 weeks no significant decrease(p1 0.15) Conclusion pre transplantation high Cd30 and β2M is associated with poor outcome.failure of decrease of cd30 and β2M post Tx. also associated with poor outcome or infection. Successful transplantation leads to significant decrease in serum cd30 and β2M. which can be used as predictors of graft survival with better sensitivity and specificity than serum creatinin.

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