Renal function three years after early conversion from a calcineurin inhibitor to everolimus: results from a randomized trial in kidney transplantation

Lars Mjörnstedt; Søren Schwartz Sørensen; Bengt von Zur Mühlen; Bente Jespersen; Jesper M Hansen; Claus Bistrup; Helene Andersson; Bengt Gustafsson; Dag Solbu; Hallvard Holdaas

doi:10.1111/tri.12437

Renal function three years after early conversion from a calcineurin inhibitor to everolimus: results from a randomized trial in kidney transplantation

Lars Mjörnstedt, Søren Schwartz Sørensen, Bengt von Zur Mühlen, Bente Jespersen, Jesper M Hansen, Claus Bistrup, Helene Andersson, Bengt Gustafsson, Dag Solbu, Hallvard Holdaas

Department of Clinical Medicine

27 Citations (Scopus)

Abstract

Summary In a 36-month, open-label, multicenter trial, 202 kidney transplant recipients were randomized at week 7 post-transplant to convert to everolimus or remain on cyclosporine: 182 were analyzed to month 36 (92 everolimus, 90 controls). Mean (SD) change in measured GFR (mGFR) from randomization to month 36 was 1.3 (14.0) ml/min with everolimus versus -1.7 (15.4) ml/min in controls (P = 0.210). In patients who remained on treatment, mean mGFR improved from randomization to month 36 by 7.9 (11.5) ml/min with everolimus (n = 37) but decreased by 1.4 (14.7) ml/min in controls (n = 62) (P = 0.001). During months 12-36, death-censored graft survival was 100%, patient survival was 98.9% and 96.7% in the everolimus and control groups, respectively, and 13.0% and 11.1% of everolimus and control patients, respectively, experienced mild biopsy-proven acute rejection (BPAR). Protocol biopsies in a limited number of on-treatment patients showed similar interstitial fibrosis progression. Donor-specific antibodies were present at month 36 in 6.3% (2/32) and 18.0% (9/50) of on-treatment everolimus and control patients with available data (P = 0.281). During months 12-36, adverse events were comparable, but discontinuation was more frequent with everolimus (33.7% vs. 10.0%). Conversion from cyclosporine to everolimus at 7 weeks post-transplant was associated with a significant benefit in renal function at 3 years when everolimus was continued.

Original language	English
Journal	Transplant International
Volume	28
Issue number	1
Pages (from-to)	42-51
Number of pages	10
ISSN	0934-0874
DOIs	https://doi.org/10.1111/tri.12437
Publication status	Published - 1 Jan 2015

Keywords

Adult
Aged
Biopsy
Calcineurin Inhibitors
Cyclosporine
Everolimus
Female
Fibrosis
Glomerular Filtration Rate
Graft Rejection
Graft Survival
Humans
Immunosuppression
Immunosuppressive Agents
Kidney
Kidney Transplantation
Male
Middle Aged
Renal Insufficiency
Sirolimus
Treatment Outcome

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Mjörnstedt, L., Schwartz Sørensen, S., von Zur Mühlen, B., Jespersen, B., Hansen, J. M., Bistrup, C., Andersson, H., Gustafsson, B., Solbu, D., & Holdaas, H. (2015). Renal function three years after early conversion from a calcineurin inhibitor to everolimus: results from a randomized trial in kidney transplantation. Transplant International, 28(1), 42-51. https://doi.org/10.1111/tri.12437

Renal function three years after early conversion from a calcineurin inhibitor to everolimus : results from a randomized trial in kidney transplantation. / Mjörnstedt, Lars; Schwartz Sørensen, Søren; von Zur Mühlen, Bengt et al.

In: Transplant International, Vol. 28, No. 1, 01.01.2015, p. 42-51.

Research output: Contribution to journal › Journal article › Research › peer-review

Mjörnstedt, L, Schwartz Sørensen, S, von Zur Mühlen, B, Jespersen, B, Hansen, JM, Bistrup, C, Andersson, H, Gustafsson, B, Solbu, D & Holdaas, H 2015, 'Renal function three years after early conversion from a calcineurin inhibitor to everolimus: results from a randomized trial in kidney transplantation', Transplant International, vol. 28, no. 1, pp. 42-51. https://doi.org/10.1111/tri.12437

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abstract = "Summary In a 36-month, open-label, multicenter trial, 202 kidney transplant recipients were randomized at week 7 post-transplant to convert to everolimus or remain on cyclosporine: 182 were analyzed to month 36 (92 everolimus, 90 controls). Mean (SD) change in measured GFR (mGFR) from randomization to month 36 was 1.3 (14.0) ml/min with everolimus versus -1.7 (15.4) ml/min in controls (P = 0.210). In patients who remained on treatment, mean mGFR improved from randomization to month 36 by 7.9 (11.5) ml/min with everolimus (n = 37) but decreased by 1.4 (14.7) ml/min in controls (n = 62) (P = 0.001). During months 12-36, death-censored graft survival was 100%, patient survival was 98.9% and 96.7% in the everolimus and control groups, respectively, and 13.0% and 11.1% of everolimus and control patients, respectively, experienced mild biopsy-proven acute rejection (BPAR). Protocol biopsies in a limited number of on-treatment patients showed similar interstitial fibrosis progression. Donor-specific antibodies were present at month 36 in 6.3% (2/32) and 18.0% (9/50) of on-treatment everolimus and control patients with available data (P = 0.281). During months 12-36, adverse events were comparable, but discontinuation was more frequent with everolimus (33.7% vs. 10.0%). Conversion from cyclosporine to everolimus at 7 weeks post-transplant was associated with a significant benefit in renal function at 3 years when everolimus was continued.",

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AU - Mjörnstedt, Lars

AU - Schwartz Sørensen, Søren

AU - von Zur Mühlen, Bengt

AU - Jespersen, Bente

AU - Hansen, Jesper M

AU - Bistrup, Claus

AU - Andersson, Helene

AU - Gustafsson, Bengt

AU - Solbu, Dag

AU - Holdaas, Hallvard

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N2 - Summary In a 36-month, open-label, multicenter trial, 202 kidney transplant recipients were randomized at week 7 post-transplant to convert to everolimus or remain on cyclosporine: 182 were analyzed to month 36 (92 everolimus, 90 controls). Mean (SD) change in measured GFR (mGFR) from randomization to month 36 was 1.3 (14.0) ml/min with everolimus versus -1.7 (15.4) ml/min in controls (P = 0.210). In patients who remained on treatment, mean mGFR improved from randomization to month 36 by 7.9 (11.5) ml/min with everolimus (n = 37) but decreased by 1.4 (14.7) ml/min in controls (n = 62) (P = 0.001). During months 12-36, death-censored graft survival was 100%, patient survival was 98.9% and 96.7% in the everolimus and control groups, respectively, and 13.0% and 11.1% of everolimus and control patients, respectively, experienced mild biopsy-proven acute rejection (BPAR). Protocol biopsies in a limited number of on-treatment patients showed similar interstitial fibrosis progression. Donor-specific antibodies were present at month 36 in 6.3% (2/32) and 18.0% (9/50) of on-treatment everolimus and control patients with available data (P = 0.281). During months 12-36, adverse events were comparable, but discontinuation was more frequent with everolimus (33.7% vs. 10.0%). Conversion from cyclosporine to everolimus at 7 weeks post-transplant was associated with a significant benefit in renal function at 3 years when everolimus was continued.

AB - Summary In a 36-month, open-label, multicenter trial, 202 kidney transplant recipients were randomized at week 7 post-transplant to convert to everolimus or remain on cyclosporine: 182 were analyzed to month 36 (92 everolimus, 90 controls). Mean (SD) change in measured GFR (mGFR) from randomization to month 36 was 1.3 (14.0) ml/min with everolimus versus -1.7 (15.4) ml/min in controls (P = 0.210). In patients who remained on treatment, mean mGFR improved from randomization to month 36 by 7.9 (11.5) ml/min with everolimus (n = 37) but decreased by 1.4 (14.7) ml/min in controls (n = 62) (P = 0.001). During months 12-36, death-censored graft survival was 100%, patient survival was 98.9% and 96.7% in the everolimus and control groups, respectively, and 13.0% and 11.1% of everolimus and control patients, respectively, experienced mild biopsy-proven acute rejection (BPAR). Protocol biopsies in a limited number of on-treatment patients showed similar interstitial fibrosis progression. Donor-specific antibodies were present at month 36 in 6.3% (2/32) and 18.0% (9/50) of on-treatment everolimus and control patients with available data (P = 0.281). During months 12-36, adverse events were comparable, but discontinuation was more frequent with everolimus (33.7% vs. 10.0%). Conversion from cyclosporine to everolimus at 7 weeks post-transplant was associated with a significant benefit in renal function at 3 years when everolimus was continued.

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KW - Aged

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KW - Cyclosporine

KW - Everolimus

KW - Female

KW - Fibrosis

KW - Glomerular Filtration Rate

KW - Graft Rejection

KW - Graft Survival

KW - Humans

KW - Immunosuppression

KW - Immunosuppressive Agents

KW - Kidney

KW - Kidney Transplantation

KW - Male

KW - Middle Aged

KW - Renal Insufficiency

KW - Sirolimus

KW - Treatment Outcome

U2 - 10.1111/tri.12437

DO - 10.1111/tri.12437

M3 - Journal article

C2 - 25176389

SN - 0934-0874

VL - 28

SP - 42

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JO - Transplant International

JF - Transplant International

IS - 1

ER -

Renal function three years after early conversion from a calcineurin inhibitor to everolimus: results from a randomized trial in kidney transplantation

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Keywords

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