Conversion from calcineurin inhibitors to sirolimus maintenance therapy in renal allograft recipients

24-month efficacy and safety results from the CONVERT trial

Francesco P. Schena, Michael D. Pascoe, Josefina Alberu, Maria Del Carmen Rial, Rainer Oberbauer, Daniel Brennan, Josep M. Campistol, Lorraine C Racusen, Martin S. Polinsky, Robert Goldberg-Alberts, Huihua Li, Joseph Scarola, John F. Neylan

Research output: Contribution to journalArticle

Abstract

BACKGROUND.: The efficacy and safety of converting maintenance renal transplant recipients from calcineurin inhibitors (CNIs) to sirolimus (SRL) was evaluated. METHODS.: Eight hundred thirty renal allograft recipients, 6 to 120 months posttransplant and receiving cyclosporine or tacrolimus, were randomly assigned to continue CNI (n=275) or convert from CNI to SRL (n=555). Primary endpoints were calculated Nankivell glomerular filtration rate (GFR; stratified at baseline: 20-40 vs. >40 mL/min) and the cumulative rates of biopsy-confirmed acute rejection (BCAR), graft loss, or death at 12 months. Enrollment in the 20 to 40 mL/min stratum was halted prematurely because of a higher incidence of safety endpoints in the SRL conversion arm. RESULTS.: Intent-to-treat analyses at 12 and 24 months showed no significant treatment difference in GFR in the baseline GFR more than 40 mL/min stratum. On-therapy analysis of this cohort showed significantly higher GFR at 12 and 24 months after SRL conversion. Rates of BCAR, graft survival, and patient survival were similar between groups. Median urinary protein-to-creatinine ratios (UPr/Cr) were similar at baseline but increased significantly after SRL conversion. Malignancy rates were significantly lower at 12 and 24 months after SRL conversion. Post hoc analyses identified a subgroup with baseline GFR more than 40 mL/min and UPr/Cr less than or equal to 0.11, whose risk-benefit profile was more favorable after conversion than that for the overall SRL conversion cohort. CONCLUSIONS.: At 2 years, SRL conversion among patients with baseline GFR more than 40 mL/min was associated with excellent patient and graft survival, no difference in BCAR, increased urinary protein excretion, and a lower incidence of malignancy compared with CNI continuation. Superior renal function was observed among patients who remained on SRL through 12 to 24 months, particularly in the subgroup of patients with baseline GFR more than 40 mL/min and UPr/Cr less than or equal to 0.11.

Original languageEnglish (US)
Pages (from-to)233-242
Number of pages10
JournalTransplantation
Volume87
Issue number2
DOIs
StatePublished - Jan 27 2009

Fingerprint

Sirolimus
Allografts
Kidney
Safety
Creatinine
Therapeutics
Graft Survival
Biopsy
Proteins
Calcineurin Inhibitors
Incidence
Graft Rejection
Tacrolimus
Glomerular Filtration Rate
Cyclosporine
Neoplasms
Arm
Cohort Studies
Maintenance
Survival

Keywords

  • Calcineurin inhibitor
  • Immunosuppression
  • Kidney transplantation
  • Sirolimus

ASJC Scopus subject areas

  • Transplantation

Cite this

Conversion from calcineurin inhibitors to sirolimus maintenance therapy in renal allograft recipients : 24-month efficacy and safety results from the CONVERT trial. / Schena, Francesco P.; Pascoe, Michael D.; Alberu, Josefina; Del Carmen Rial, Maria; Oberbauer, Rainer; Brennan, Daniel; Campistol, Josep M.; Racusen, Lorraine C; Polinsky, Martin S.; Goldberg-Alberts, Robert; Li, Huihua; Scarola, Joseph; Neylan, John F.

In: Transplantation, Vol. 87, No. 2, 27.01.2009, p. 233-242.

Research output: Contribution to journalArticle

Schena, FP, Pascoe, MD, Alberu, J, Del Carmen Rial, M, Oberbauer, R, Brennan, D, Campistol, JM, Racusen, LC, Polinsky, MS, Goldberg-Alberts, R, Li, H, Scarola, J & Neylan, JF 2009, 'Conversion from calcineurin inhibitors to sirolimus maintenance therapy in renal allograft recipients: 24-month efficacy and safety results from the CONVERT trial', Transplantation, vol. 87, no. 2, pp. 233-242. https://doi.org/10.1097/TP.0b013e3181927a41
Schena, Francesco P. ; Pascoe, Michael D. ; Alberu, Josefina ; Del Carmen Rial, Maria ; Oberbauer, Rainer ; Brennan, Daniel ; Campistol, Josep M. ; Racusen, Lorraine C ; Polinsky, Martin S. ; Goldberg-Alberts, Robert ; Li, Huihua ; Scarola, Joseph ; Neylan, John F. / Conversion from calcineurin inhibitors to sirolimus maintenance therapy in renal allograft recipients : 24-month efficacy and safety results from the CONVERT trial. In: Transplantation. 2009 ; Vol. 87, No. 2. pp. 233-242.
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abstract = "BACKGROUND.: The efficacy and safety of converting maintenance renal transplant recipients from calcineurin inhibitors (CNIs) to sirolimus (SRL) was evaluated. METHODS.: Eight hundred thirty renal allograft recipients, 6 to 120 months posttransplant and receiving cyclosporine or tacrolimus, were randomly assigned to continue CNI (n=275) or convert from CNI to SRL (n=555). Primary endpoints were calculated Nankivell glomerular filtration rate (GFR; stratified at baseline: 20-40 vs. >40 mL/min) and the cumulative rates of biopsy-confirmed acute rejection (BCAR), graft loss, or death at 12 months. Enrollment in the 20 to 40 mL/min stratum was halted prematurely because of a higher incidence of safety endpoints in the SRL conversion arm. RESULTS.: Intent-to-treat analyses at 12 and 24 months showed no significant treatment difference in GFR in the baseline GFR more than 40 mL/min stratum. On-therapy analysis of this cohort showed significantly higher GFR at 12 and 24 months after SRL conversion. Rates of BCAR, graft survival, and patient survival were similar between groups. Median urinary protein-to-creatinine ratios (UPr/Cr) were similar at baseline but increased significantly after SRL conversion. Malignancy rates were significantly lower at 12 and 24 months after SRL conversion. Post hoc analyses identified a subgroup with baseline GFR more than 40 mL/min and UPr/Cr less than or equal to 0.11, whose risk-benefit profile was more favorable after conversion than that for the overall SRL conversion cohort. CONCLUSIONS.: At 2 years, SRL conversion among patients with baseline GFR more than 40 mL/min was associated with excellent patient and graft survival, no difference in BCAR, increased urinary protein excretion, and a lower incidence of malignancy compared with CNI continuation. Superior renal function was observed among patients who remained on SRL through 12 to 24 months, particularly in the subgroup of patients with baseline GFR more than 40 mL/min and UPr/Cr less than or equal to 0.11.",
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T2 - 24-month efficacy and safety results from the CONVERT trial

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AU - Pascoe, Michael D.

AU - Alberu, Josefina

AU - Del Carmen Rial, Maria

AU - Oberbauer, Rainer

AU - Brennan, Daniel

AU - Campistol, Josep M.

AU - Racusen, Lorraine C

AU - Polinsky, Martin S.

AU - Goldberg-Alberts, Robert

AU - Li, Huihua

AU - Scarola, Joseph

AU - Neylan, John F.

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N2 - BACKGROUND.: The efficacy and safety of converting maintenance renal transplant recipients from calcineurin inhibitors (CNIs) to sirolimus (SRL) was evaluated. METHODS.: Eight hundred thirty renal allograft recipients, 6 to 120 months posttransplant and receiving cyclosporine or tacrolimus, were randomly assigned to continue CNI (n=275) or convert from CNI to SRL (n=555). Primary endpoints were calculated Nankivell glomerular filtration rate (GFR; stratified at baseline: 20-40 vs. >40 mL/min) and the cumulative rates of biopsy-confirmed acute rejection (BCAR), graft loss, or death at 12 months. Enrollment in the 20 to 40 mL/min stratum was halted prematurely because of a higher incidence of safety endpoints in the SRL conversion arm. RESULTS.: Intent-to-treat analyses at 12 and 24 months showed no significant treatment difference in GFR in the baseline GFR more than 40 mL/min stratum. On-therapy analysis of this cohort showed significantly higher GFR at 12 and 24 months after SRL conversion. Rates of BCAR, graft survival, and patient survival were similar between groups. Median urinary protein-to-creatinine ratios (UPr/Cr) were similar at baseline but increased significantly after SRL conversion. Malignancy rates were significantly lower at 12 and 24 months after SRL conversion. Post hoc analyses identified a subgroup with baseline GFR more than 40 mL/min and UPr/Cr less than or equal to 0.11, whose risk-benefit profile was more favorable after conversion than that for the overall SRL conversion cohort. CONCLUSIONS.: At 2 years, SRL conversion among patients with baseline GFR more than 40 mL/min was associated with excellent patient and graft survival, no difference in BCAR, increased urinary protein excretion, and a lower incidence of malignancy compared with CNI continuation. Superior renal function was observed among patients who remained on SRL through 12 to 24 months, particularly in the subgroup of patients with baseline GFR more than 40 mL/min and UPr/Cr less than or equal to 0.11.

AB - BACKGROUND.: The efficacy and safety of converting maintenance renal transplant recipients from calcineurin inhibitors (CNIs) to sirolimus (SRL) was evaluated. METHODS.: Eight hundred thirty renal allograft recipients, 6 to 120 months posttransplant and receiving cyclosporine or tacrolimus, were randomly assigned to continue CNI (n=275) or convert from CNI to SRL (n=555). Primary endpoints were calculated Nankivell glomerular filtration rate (GFR; stratified at baseline: 20-40 vs. >40 mL/min) and the cumulative rates of biopsy-confirmed acute rejection (BCAR), graft loss, or death at 12 months. Enrollment in the 20 to 40 mL/min stratum was halted prematurely because of a higher incidence of safety endpoints in the SRL conversion arm. RESULTS.: Intent-to-treat analyses at 12 and 24 months showed no significant treatment difference in GFR in the baseline GFR more than 40 mL/min stratum. On-therapy analysis of this cohort showed significantly higher GFR at 12 and 24 months after SRL conversion. Rates of BCAR, graft survival, and patient survival were similar between groups. Median urinary protein-to-creatinine ratios (UPr/Cr) were similar at baseline but increased significantly after SRL conversion. Malignancy rates were significantly lower at 12 and 24 months after SRL conversion. Post hoc analyses identified a subgroup with baseline GFR more than 40 mL/min and UPr/Cr less than or equal to 0.11, whose risk-benefit profile was more favorable after conversion than that for the overall SRL conversion cohort. CONCLUSIONS.: At 2 years, SRL conversion among patients with baseline GFR more than 40 mL/min was associated with excellent patient and graft survival, no difference in BCAR, increased urinary protein excretion, and a lower incidence of malignancy compared with CNI continuation. Superior renal function was observed among patients who remained on SRL through 12 to 24 months, particularly in the subgroup of patients with baseline GFR more than 40 mL/min and UPr/Cr less than or equal to 0.11.

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