Nonnephrotoxic immunosuppression in patients after liver transplantation

Kniepeiss, Daniela; Iberer, F.; Schaffellner, S.; Jakoby, E.; Duller, D.; Tscheliessnigg, Karlheinz

doi:10.1016/j.intimp.2004.09.016

Cited by 13 publications

(10 citation statements)

References 7 publications

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“…Similar results have been reported from retrospective studies 15, 16. Other studies have suggested that using sirolimus to facilitate minimization of tacrolimus, rather than replacement, might also result in improved renal function,17, 18 although experience in renal transplantation suggests that the combination of CNI with sirolimus is not desirable since it might actually enhance nephrotoxicity.…”

Section: Discussionsupporting

confidence: 74%

A randomized controlled trial of late conversion from calcineurin inhibitor (CNI)-based to sirolimus-based immunosuppression in liver transplant recipients with impaired renal function

et al. 2007

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Renal impairment is common in patients after liver transplantation and is attributable in large part to the use of calcineurin inhibitor (CNI)-based immunosuppression. We sought to determine whether conversion to sirolimus-based immunosuppression was associated with improved renal function. In a single-center, randomized, controlled trial, 30 patients at least 6 months post liver transplantation were randomized to remain on CNI-based immunosuppression or to switch to sirolimus-based immunosuppression. The primary outcome measure was change in measured glomerular filtration rate (GFR) between baseline and 12 months. Of 30 patients randomized, 3 were withdrawn at randomization, leaving 14 patients on CNI and 13 on sirolimus. There was a significant improvement in delta GFR following conversion to sirolimus at 3 months (7.7 mL/minute/1.73 m 2 ; 95% confidence interval, 3.5-11.9) and 1 yr (6.1 mL/minute/1.73 m 2 ; 95% confidence interval, 0.9-11.4). The difference in absolute GFR between the 2 study groups was significant at 3 months (P ϭ 0.02), but not at 12 months (P ϭ 0.07). The principal adverse events following conversion were the development of skin rash (9 of 13 patients, 69%) and mouth ulcers (5 of 13 patients, 38%). Two patients developed acute rejection at 2 and 3 months following conversion, 1 in association with low sirolimus levels and 1 having stopped the drug inadvertently. In conclusion, overall, this study suggests that conversion to sirolimus immunosuppression is associated with a modest improvement in renal function. Side effects were common, but tolerable in most patients and controlled with dose reduction.

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Section: Discussionsupporting

confidence: 74%

A randomized controlled trial of late conversion from calcineurin inhibitor (CNI)-based to sirolimus-based immunosuppression in liver transplant recipients with impaired renal function

et al. 2007

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“…Strategies to minimize the adverse renal effects of CNIs in patients include reducing the CNI dose (11)(12)(13)(14) or complete withdrawal of the CNI (14,15), while adding other immunosuppressive agents such as mycophenolate mofetil (MMF) (12)(13)(14)16) or sirolimus (11,15) (17)(18)(19) …”

Section: Introductionmentioning

confidence: 99%

“…Late renal failure is associated with both pre-and postliver transplant factors, including higher concentrations of CNIs both early and late posttransplant (7,8) and can be predicted by creatinine levels in the first posttransplant year (9,10). Strategies to minimize the adverse renal effects of CNIs in patients include reducing the CNI dose (11)(12)(13)(14) or complete withdrawal of the CNI (14,15), while adding other immunosuppressive agents such as mycophenolate mofetil (MMF) (12)(13)(14)16) or sirolimus (11,15). Alternatively, a preemptive strategy may be adopted by attempting to avoid CNI-induced renal impairment.…”

Section: Introductionmentioning

confidence: 99%

Delayed Introduction of Reduced-Dose Tacrolimus, and Renal Function in Liver Transplantation: The ‘ReSpECT’ Study

Neuberger

Mamelok

Neuhaus

et al. 2009

American Journal of Transplantation

253

194

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We report a multicenter, prospective, randomized, open-label trial investigating the effect of lower levels and delayed introduction of tacrolimus on renal function in liver transplant recipients. Adult patients with good renal function undergoing primary liver transplant were randomized to either: group A (standarddose tacrolimus [target trough levels >10 ng/mL] and corticosteroids; n = 183); group B (mycophenolate mofetil [MMF] 2g/day, reduced-dose tacrolimus [target trough levels ≤8 ng/mL], and corticosteroids; n = 170); group C (daclizumab induction, MMF, reduced-dose tacrolimus delayed until the fifth day posttransplant and corticosteroids, n = 172). The primary endpoint was change from baseline in estimated glomerular filtration rate (eGFR) at 52 weeks. The eGFR decreased by 23.61, 21.22 and 13.63 mL/min in groups A, B and C, respectively (A vs C, p = 0.012; A vs B, p = 0.199). Renal dialysis was required less frequently in group C versus group A (4.2% vs. 9.9%; p = 0.037). Biopsy-proven acute rejection rates were 27.6%, 29.2% and 19.0%, respectively. Patient and graft survival was similar. In conclusion, daclizumab induction, MMF, corticosteroids and delayed reduced-dose tacrolimus was associated with less nephrotoxicity than therapy with standard-dose tacrolimus and corticosteroids without compromising efficacy or tolerability.

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“…Randomized, controlled trials comparing SRL with conventional immunosuppressive drugs have not been yet completed in liver transplantation (LT) but several publications have documented the efficacy and safety of SRL in terms of graft and patient survival 1. Conversion from CNI to SRL or addition of SRL to achieve lower CNI target levels improved renal function in pediatric2–4 as well as in adult LT recipients 5–12. CNI‐related neurotoxicity also decreased or resolved after conversion to SRL 7, 13–15.…”

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confidence: 99%

Conversion to sirolimus-based immunosuppression in maintenance liver transplantation patients

et al. 2007

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Sirolimus (SRL) has been proposed to replace calcineurin inhibitors (CNI) in case of CNI-induced toxicity. The aim of this study was to evaluate the efficacy and safety of conversion from CNI to SRL in maintenance liver transplantation (LT) patients. Between 2002 and 2006, conversion was performed in 48 patients (17 female, 31 male; mean age 57 Ϯ 10 yr) after a median delay of 19.4 months (range 0.2-173 months) after LT. Indication for conversion was renal impairment (RI) (78%), CNI neurotoxicity (13%), or post-LT cancer (9%). Median follow-up was 22.6 Ϯ 11 months. Median SRL dosage and trough levels were 2.4 Ϯ 1.3 mg and 8.1 Ϯ 2.7 g/L. Immunosuppression consisted of SRL alone (33%), or SRL ϩ mycophenolate mofetil (MMF) (39%), SRL ϩ prednisone (15%), SRL ϩ CNI (4%), or SRL ϩ MMF ϩ prednisone (8%). Mean glomerular filtration rate (GFR) improved from 33 to 48 mL/minute in patients with severe RI (P ϭ 0.022) and from 56 to 74 mL/minute in patients with moderate RI (P ϭ 0.0001). After conversion, main complications were albuminuria (36%), hyperlipidemia (49%), dermatitis (14%), edema (14%), oral ulcers (12%), joint pain (4%), infection (2%), and pneumonia (2%). Acute rejection (AR) occurred in 17% of the patients. SRL was withdrawn in 17% of the patients. In conclusion, conversion from CNI to SRL is safe and is associated with significant renal function improvement. Liver Transpl 13:658-664, 2007.

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Nonnephrotoxic immunosuppression in patients after liver transplantation

Cited by 13 publications

References 7 publications

A randomized controlled trial of late conversion from calcineurin inhibitor (CNI)-based to sirolimus-based immunosuppression in liver transplant recipients with impaired renal function

A randomized controlled trial of late conversion from calcineurin inhibitor (CNI)-based to sirolimus-based immunosuppression in liver transplant recipients with impaired renal function

Delayed Introduction of Reduced-Dose Tacrolimus, and Renal Function in Liver Transplantation: The ‘ReSpECT’ Study

Conversion to sirolimus-based immunosuppression in maintenance liver transplantation patients

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