Clinical trial: switch to combined mycophenolate mofetil and minimal dose calcineurin inhibitor in stable liver transplant patients – assessment of renal and allograft function, cardiovascular risk factors and immune monitoring

Abstract

SUMMARY BackgroundCalcineurin inhibitor (CNI)-related nephrotoxicity significantly contributes to chronic renal failure after liver transplantation.

Long-Term Renal Function in Liver Transplant Recipients After Conversion From Calcineurin Inhibitors to mTOR Inhibitors

“…Renal recovery after conversion was independent of the time period between LT and conversion, indicating that renal recovery can occur after CNI elimination despite existing CNIrelated parenchymal renal damage [17,18]. A multivariate adjusted model found that the only factors having a noticeable negative influence on renal function (e.g., lower eGFR) were increased age and female sex, consistent with studies showing that female sex and increased age were associated with increased renal vulnerability to noxious agents and to drug toxicity [19][20][21].…”

Hot-topic debate on kidney function: Renal-sparing approaches are beneficial

“…On average, the increase in the GFR after switching was approximately 10 mL/minute/1.73 m 2 . 21,22 However, it must be noted that 1 year after the CNI reduction, the average GFR remained less than 60 mL/minute.…”

“…Several controlled studies have shown that a 50% or greater reduction in the CNI dose along with the introduction of MMF (1-3 g/day) results in significant improvements in renal function at 1 year or more [21][22][23] (Table 2). In these studies, improvements were observed in 50% to 70% of the patients who were switched to a combination of MMF and reduced CNI serum concentrations.…”

“…Controlled (29) GFR (1 year) 45 mL/minute 0.04 MMF (2-3 g/day) plus 50% reduction in the CNI dose (27) 52 mL/minute Cicinnati et al 22 (2007) Standard-dose CNIs (25) GFR (1 year) 39 mL/minute 0.01 MMF plus reduced-dose CNIs (50) 47 mL/minute Biselli et al 24 (2009) Standard-dose CNIs (30) GFR (2 years) 46 mL/minute 0.01 MMF plus reduced-dose CNIs (30) 57 mL/minute *The number of patients is shown in parentheses.…”

Interleukin-2 receptor downstream events in regulatory T cells: Implications for the choice of immunosuppressive drug therapy

“…47 In human renal allograft recipients, the use of MMF and calcineurin inhibitor sparing was associated with increased Treg frequencies. 48 Corticosteroids. Dexamethasone (DEX) induces cell death in T cells and could have unfavorable effects on Treg.…”