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

Abstract Background In renal transplant recipients (RTRs), cardiovascular mortality is the most common cause of long-term renal graft loss. Oxidative stress (OS) has been associated with cardiovascular disease and is known to be enhanced in RTRs. We aimed to prospectively investigate whether the concentration of the OS biomarker malondialdehyde (MDA) is associated with long-term risk of cardiovascular mortality in a large cohort of RTRs. Methods The plasma MDA concentration was measured using the thiobarbituric acid reaction assay in 604 extensively phenotyped RTRs with a functioning allograft for ≥1 year. The association between MDA and cardiovascular mortality was assessed using Cox proportional hazard regression analyses in the overall cohort and within subgroups according to significant effect modifiers. Results Median circulating MDA concentration at baseline was 5.38 [interquartile range (IQR) 4.31–6.45] μmol/L. During a follow-up period of 6.4 (IQR 5.6–6.8) years, 110 (18%) RTRs died, with 40% of deaths due to cardiovascular causes. MDA concentration was significantly associated with the risk for cardiovascular mortality {hazard ratio [HR] 1.31 [95% confidence interval (CI) 1.03–1.67] per 1-SD increment}, independent of adjustment for potential confounders, including renal function, immunosuppressive therapy, smoking status and blood pressure. The association between MDA concentration and the risk for cardiovascular mortality was stronger in RTRs with relatively lower plasma ascorbic acid concentrations [≤42.5 µmol/L; HR 1.79 (95% CI 1.30–2.48) per 1-SD increment] or relatively lower estimated glomerular filtration rates [≤45 mL/min/1.73 m2; HR 2.09 (95% CI 1.45–3.00) per 1-SD increment]. Conclusions Circulating MDA concentration is independently associated with long-term risk for cardiovascular mortality, particularly in RTRs with relatively lower ascorbic acid concentrations or renal function. Further studies are warranted to elucidate whether OS-targeted interventions could decrease cardiovascular mortality in RTRs.

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LONG-TERM IMPROVEMENT IN RENAL FUNCTION AFTER CYCLOSPORINE REDUCTION IN RENAL TRANSPLANT RECIPIENTS WITH HISTOLOGICALLY PROVEN CHRONIC CYCLOSPORINE NEPHROPATHY

Transplantation Journal ◽

10.1097/00007890-199803150-00010 ◽

1998 ◽

Vol 65 (5) ◽

pp. 661-667 ◽

Cited By ~ 70

Author(s):

Georges Mourad ◽

Carlos Vela ◽

Jean Ribstein ◽

Albert Mimran

Keyword(s):

Renal Function ◽

Renal Transplant ◽

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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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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