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

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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Initial mycophenolate dose in tacrolimus treated renal transplant recipients, a cohort study comparing leukopaenia, rejection and long-term graft function

Scientific Reports ◽

10.1038/s41598-020-76379-6 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Vatsa Dave ◽

Kevan R. Polkinghorne ◽

Khai Gene Leong ◽

John Kanellis ◽

William R. Mulley

Keyword(s):

Renal Function ◽

Cohort Study ◽

Renal Transplant ◽

Graft Function ◽

Renal Transplant Recipients ◽

Transplant Recipients ◽

Post Transplantation ◽

Post Transplant ◽

Increased Risk

Abstract The evidence supporting an initial mycophenolate mofetil (MMF) dose of 2 g daily in tacrolimus-treated renal transplant recipients is limited. In a non-contemporaneous single-centre cohort study we compared the incidence of leukopaenia, rejection and graft dysfunction in patients initiated on MMF 1.5 g and 2 g daily. Baseline characteristics and tacrolimus trough levels were similar by MMF group. MMF doses became equivalent between groups by 12-months post-transplant, driven by dose reductions in the 2 g group. Leukopaenia occurred in 42.4% of patients by 12-months post-transplant. MMF 2 g was associated with a 1.80-fold increased risk of leukopaenia compared to 1.5 g. Rejection occurred in 44.8% of patients by 12-months post-transplantation. MMF 2 g was associated with half the risk of rejection relative to MMF 1.5 g. Over the first 7-years post-transplantation there was no difference in renal function between groups. Additionally, the development of leukopaenia or rejection did not result in reduced renal function at 7-years post-transplant. Leukopaenia was not associated with an increased incidence of serious infections or rejection. This study demonstrates the initial MMF dose has implications for the incidence of leukopaenia and rejection. Since neither dose produced superior long-term graft function, clinical equipoise remains regarding the optimal initial mycophenolate dose in tacrolimus-treated renal transplant recipients.

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High-Urgency Renal Transplantation: Indications and Long-Term Outcomes

Journal of Transplantation ◽

10.1155/2013/314239 ◽

2013 ◽

Vol 2013 ◽

pp. 1-6 ◽

Cited By ~ 1

Author(s):

Lampros Kousoulas ◽

Nikos Emmanouilidis ◽

Wilfried Gwinner ◽

Jürgen Klempnauer ◽

Frank Lehner

Keyword(s):

Renal Transplantation ◽

Renal Transplant ◽

Graft Survival ◽

Survival Rates ◽

Renal Transplant Recipients ◽

Transplant Recipients ◽

Long Term Outcomes ◽

High Urgency ◽

Study Population

The concept of high-urgency (HU) renal transplantation was introduced in order to offer to patients, who are not able to undergo long-term dialysis treatment, a suitable renal graft in a short period of time, overcoming by this way the obstacle of the prolonged time spent on the waiting list. The goal of this study was to evaluate the patient and graft survivals after HU renal transplantation and compare them to the long-term outcomes of the non-high-urgency renal transplant recipients. The clinical course of 33 HU renal transplant recipients operated on at our center between 1995 and 2010 was retrospectively analyzed. The major indication for the HU renal transplantation was the imminent lack of access for either hemodialysis or peritoneal dialysis (67%). The patient survival of the study population was 67%, 56%, and 56%, whereas the graft survival was 47%, 35% and 35%, at 5, 10, and 15 years, respectively. In the comparison between our study population and the non-HU renal transplant recipients, our study population presented statistically significant(P<0.05)lower patient survival rates. The HU renal transplant recipients also presented lower graft survival rates, but statistical significance(P<0.05)was reached only in the 5-year graft survival rate.

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No detrimental effect on renal function during long-term use of fluvastatin in renal transplant recipients in the Assessment of Lescol in Renal Transplantation (ALERT) study

Clinical Transplantation ◽

10.1111/j.1399-0012.2006.00555.x ◽

2006 ◽

Vol 20 (6) ◽

pp. 732-739 ◽

Cited By ~ 9

Author(s):

Bengt Fellström ◽

Sadollah Abedini ◽

Hallvard Holdaas ◽

Alan G. Jardine ◽

Beatrix Staffler ◽

...

Keyword(s):

Renal Function ◽

Renal Transplantation ◽

Renal Transplant ◽

Detrimental Effect ◽

Renal Transplant Recipients ◽

Transplant Recipients

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Efficacy and Safety of Sitagliptin for the Treatment of New-Onset Diabetes after Renal Transplantation

International Journal of Endocrinology ◽

10.1155/2014/617638 ◽

2014 ◽

Vol 2014 ◽

pp. 1-9 ◽

Cited By ~ 32

Author(s):

Brian P. Boerner ◽

Clifford D. Miles ◽

Vijay Shivaswamy

Keyword(s):

Renal Transplantation ◽

Renal Transplant ◽

Kidney Transplant ◽

Hemoglobin A1c ◽

Renal Transplant Recipients ◽

Transplant Recipients ◽

Kidney Transplant Recipients ◽

First Line ◽

New Onset

New-onset diabetes after transplantation (NODAT) is a common comorbidity after renal transplantation. Though metformin is the first-line agent for the treatment of type 2 diabetes, in renal transplant recipients, metformin is frequently avoided due to concerns about renal dysfunction and risk for lactic acidosis. Therefore, alternative first-line agents for the treatment of NODAT in renal transplant recipients are needed. Sitagliptin, a dipeptidyl-peptidase-4 (DPP-4) inhibitor, has a low incidence of hypoglycemia, is weight neutral, and, in a small study, did not affect immunosuppressant levels. However, long-term sitagliptin use for the treatment of NODAT in kidney transplant recipients has not been studied. We retrospectively analyzed renal transplant recipients diagnosed with NODAT and treated with sitagliptin to assess safety and efficacy. Twenty-two patients were started on sitagliptin alone. After 12 months of followup, 19/22 patients remained on sitagliptin alone with a significant improvement in hemoglobin A1c. Renal function and immunosuppressant levels remained stable. Analysis of long-term followup (32.5±17.8 months) revealed that 17/22 patients remained on sitagliptin (mean hemoglobin A1c < 7%) with 9/17 patients remaining on sitagliptin alone. Transplant-specific adverse events were rare. Sitagliptin appears safe and efficacious for the treatment of NODAT in kidney transplant recipients.

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Impact of Pharmacogenetic Determinants of Tacrolimus and Mycophenolate on Adverse Events in Renal Transplant Patients

Current Drug Metabolism ◽

10.2174/1389200222666210114123349 ◽

2021 ◽

Vol 22 ◽

Author(s):

Kalluri Thishya ◽

Boddupally Sreenu ◽

Shree Bhushan Raju ◽

Vijay Kutala

Keyword(s):

Renal Transplant ◽

Adverse Events ◽

Metabolic Pathways ◽

Early Stage ◽

Maintenance Phase ◽

Solid Organ ◽

Renal Transplant Recipients ◽

Transplant Recipients ◽

Post Transplantation ◽

Increased Risk

Background: Graft acceptance against immunity is one of themajor challenges in solid organ transplant. Immunosuppressive medications have effectively improved the post-transplantation outcome; however it has its own limitations. Genetic polymorphisms in drug-metabolizing enzymes have been identified as the potential targets in developing a pharmacogenetic strategy, to individualize drug dose and also in preventing the adverse events. Objective: The rationale of the study was to explore polymorphisms in tacrolimus and mycophenolate metabolic pathways that influence the adverse clinical outcomes in renal transplant recipients. Methods: A total of 255 renal transplant recipients were analyzed for the pharmacogenetic determinants of tacrolimus (CYP3A5*3, ABCB1 1236 T>C, ABCB1 2677 G>A/T, ABCB1 3435 T>C) and mycophenolate (UGT1A8*3, UGT1A9, IMPDH I, IMPDH II c.787C>T , ABCC2 -24 C>T and c.3972C>T) using Sanger sequencing. Results: Acute rejection (AR) was observed in 5.88% of the transplant recipients, whereas, acute tubular necrosis (ATNs) was observed in 7.45% of the patients, within early stage of the maintenance phase. Infections, such as urinary tract infection (UTI) and cytomegalovirus (CMV) infection were observed in 11.37% and 12.16% of the patients. The AUC of mycophenolate was significantly higher in patients with increased risk for infections. ABCC2 -24 C>T, c.3972C>T polymorphisms and ABCB1 3435 C-allele, were associated with reduced risk for infections. ABCC2 rs3740066 was associated with 2.06-fold all-cause mortality risk. CYP3A5 AG- and UGT1A9-440 CC-genotypes showed increased risk, and ABCC 3972C>T, CC-genotype showed protection against adverse events. Conclusion: Genetic variants in tacrolimus and mycophenolate metabolic pathways were found to influence the morbidity and mortality in renal transplant recipients.

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