Replacement of calcineurin-inhibitors with sirolimus as primary immunosuppression in stable cardiac transplant recipients

Eugenia Raichlin, Zain Khalpey, Walter Kremers, Robert P. Frantz, Richard J. Rodeheffer, Alfredo L. Clavell, Brooks S. Edwards, Sudhir S. Kushwaha

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Abstract

BACKGROUND. Calcineurin-inhibitor (CNI) nephrotoxicity is a major cause of morbidity and mortality after cardiac transplantation. The aim of this study was to assess over 2 years the safety and effect on renal function of withdrawal of CNI immunosuppression and replacement with sirolimus (SRL) in stable cardiac transplant recipients. METHODS. CNI was substituted with SRL in 78 cardiac transplant recipients (SRL group) of whom 58 (group A) had CNI-induced renal impairment (glomerular filtration rate [GFR] <50 mL/min) and 20 (group B) had preserved renal function (GFR >50 mL/min). Fifty-one patients (CNI group) with renal impairment (GFR ≤50 mL/min) maintained on CNI served as controls. Secondary immunosuppressants were unchanged. RESULTS. In the SRL group, GFR increased from 47.0±18.0 to 61.2±22.2 ml/min (P=0.0001) 24 months after SRL initiation. In Group A, GFR increased from 40.5±12.7 to 53.9±19.8 mL/min (P<0.0001). In Group B, GFR increased marginally from 67.2±15.8 to 83.5±27.8 mL/min (P=0.10). In the CNI group, GFR declined from 40.5±14.0 mL/min to 36.4±12.5 mL/min (P=0.23) after 24 months of follow up. There was no significant difference in cardiac rejection or cardiac allograft function. In SRL group, proteinuria increased from 299±622 mg/day to 517±795 mg/day (P=0.0002) 12 months after SRL initiation and then stabilized; it did not differ from CNI group at 24 months (637±806 vs. 514±744 mg/day, P=0.39). Uric acid decreased from 7.6±2.4 to 6.2±1.9 mg/dL (P=0.0007) in the SRL group. CONCLUSIONS. Graduated substitution of CNI with SRL in cardiac transplant recipients is safe and improves renal function, without cardiac compromise.

Original languageEnglish (US)
Pages (from-to)467-474
Number of pages8
JournalTransplantation
Volume84
Issue number4
DOIs
StatePublished - Aug 1 2007

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Sirolimus
Immunosuppression
Glomerular Filtration Rate
Kidney
Calcineurin Inhibitors
Transplant Recipients
Heart Transplantation
Immunosuppressive Agents
Uric Acid
Proteinuria
Allografts
Morbidity
Safety
Mortality

Keywords

  • Calcineurin inhibitor
  • Cardiac transplantation
  • Renal function
  • Sirolimus

ASJC Scopus subject areas

  • Transplantation

Cite this

Raichlin, E., Khalpey, Z., Kremers, W., Frantz, R. P., Rodeheffer, R. J., Clavell, A. L., ... Kushwaha, S. S. (2007). Replacement of calcineurin-inhibitors with sirolimus as primary immunosuppression in stable cardiac transplant recipients. Transplantation, 84(4), 467-474. https://doi.org/10.1097/01.tp.0000276959.56959.69

Replacement of calcineurin-inhibitors with sirolimus as primary immunosuppression in stable cardiac transplant recipients. / Raichlin, Eugenia; Khalpey, Zain; Kremers, Walter; Frantz, Robert P.; Rodeheffer, Richard J.; Clavell, Alfredo L.; Edwards, Brooks S.; Kushwaha, Sudhir S.

In: Transplantation, Vol. 84, No. 4, 01.08.2007, p. 467-474.

Research output: Contribution to journalArticle

Raichlin, E, Khalpey, Z, Kremers, W, Frantz, RP, Rodeheffer, RJ, Clavell, AL, Edwards, BS & Kushwaha, SS 2007, 'Replacement of calcineurin-inhibitors with sirolimus as primary immunosuppression in stable cardiac transplant recipients', Transplantation, vol. 84, no. 4, pp. 467-474. https://doi.org/10.1097/01.tp.0000276959.56959.69
Raichlin, Eugenia ; Khalpey, Zain ; Kremers, Walter ; Frantz, Robert P. ; Rodeheffer, Richard J. ; Clavell, Alfredo L. ; Edwards, Brooks S. ; Kushwaha, Sudhir S. / Replacement of calcineurin-inhibitors with sirolimus as primary immunosuppression in stable cardiac transplant recipients. In: Transplantation. 2007 ; Vol. 84, No. 4. pp. 467-474.
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abstract = "BACKGROUND. Calcineurin-inhibitor (CNI) nephrotoxicity is a major cause of morbidity and mortality after cardiac transplantation. The aim of this study was to assess over 2 years the safety and effect on renal function of withdrawal of CNI immunosuppression and replacement with sirolimus (SRL) in stable cardiac transplant recipients. METHODS. CNI was substituted with SRL in 78 cardiac transplant recipients (SRL group) of whom 58 (group A) had CNI-induced renal impairment (glomerular filtration rate [GFR] <50 mL/min) and 20 (group B) had preserved renal function (GFR >50 mL/min). Fifty-one patients (CNI group) with renal impairment (GFR ≤50 mL/min) maintained on CNI served as controls. Secondary immunosuppressants were unchanged. RESULTS. In the SRL group, GFR increased from 47.0±18.0 to 61.2±22.2 ml/min (P=0.0001) 24 months after SRL initiation. In Group A, GFR increased from 40.5±12.7 to 53.9±19.8 mL/min (P<0.0001). In Group B, GFR increased marginally from 67.2±15.8 to 83.5±27.8 mL/min (P=0.10). In the CNI group, GFR declined from 40.5±14.0 mL/min to 36.4±12.5 mL/min (P=0.23) after 24 months of follow up. There was no significant difference in cardiac rejection or cardiac allograft function. In SRL group, proteinuria increased from 299±622 mg/day to 517±795 mg/day (P=0.0002) 12 months after SRL initiation and then stabilized; it did not differ from CNI group at 24 months (637±806 vs. 514±744 mg/day, P=0.39). Uric acid decreased from 7.6±2.4 to 6.2±1.9 mg/dL (P=0.0007) in the SRL group. CONCLUSIONS. Graduated substitution of CNI with SRL in cardiac transplant recipients is safe and improves renal function, without cardiac compromise.",
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AU - Raichlin, Eugenia

AU - Khalpey, Zain

AU - Kremers, Walter

AU - Frantz, Robert P.

AU - Rodeheffer, Richard J.

AU - Clavell, Alfredo L.

AU - Edwards, Brooks S.

AU - Kushwaha, Sudhir S.

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N2 - BACKGROUND. Calcineurin-inhibitor (CNI) nephrotoxicity is a major cause of morbidity and mortality after cardiac transplantation. The aim of this study was to assess over 2 years the safety and effect on renal function of withdrawal of CNI immunosuppression and replacement with sirolimus (SRL) in stable cardiac transplant recipients. METHODS. CNI was substituted with SRL in 78 cardiac transplant recipients (SRL group) of whom 58 (group A) had CNI-induced renal impairment (glomerular filtration rate [GFR] <50 mL/min) and 20 (group B) had preserved renal function (GFR >50 mL/min). Fifty-one patients (CNI group) with renal impairment (GFR ≤50 mL/min) maintained on CNI served as controls. Secondary immunosuppressants were unchanged. RESULTS. In the SRL group, GFR increased from 47.0±18.0 to 61.2±22.2 ml/min (P=0.0001) 24 months after SRL initiation. In Group A, GFR increased from 40.5±12.7 to 53.9±19.8 mL/min (P<0.0001). In Group B, GFR increased marginally from 67.2±15.8 to 83.5±27.8 mL/min (P=0.10). In the CNI group, GFR declined from 40.5±14.0 mL/min to 36.4±12.5 mL/min (P=0.23) after 24 months of follow up. There was no significant difference in cardiac rejection or cardiac allograft function. In SRL group, proteinuria increased from 299±622 mg/day to 517±795 mg/day (P=0.0002) 12 months after SRL initiation and then stabilized; it did not differ from CNI group at 24 months (637±806 vs. 514±744 mg/day, P=0.39). Uric acid decreased from 7.6±2.4 to 6.2±1.9 mg/dL (P=0.0007) in the SRL group. CONCLUSIONS. Graduated substitution of CNI with SRL in cardiac transplant recipients is safe and improves renal function, without cardiac compromise.

AB - BACKGROUND. Calcineurin-inhibitor (CNI) nephrotoxicity is a major cause of morbidity and mortality after cardiac transplantation. The aim of this study was to assess over 2 years the safety and effect on renal function of withdrawal of CNI immunosuppression and replacement with sirolimus (SRL) in stable cardiac transplant recipients. METHODS. CNI was substituted with SRL in 78 cardiac transplant recipients (SRL group) of whom 58 (group A) had CNI-induced renal impairment (glomerular filtration rate [GFR] <50 mL/min) and 20 (group B) had preserved renal function (GFR >50 mL/min). Fifty-one patients (CNI group) with renal impairment (GFR ≤50 mL/min) maintained on CNI served as controls. Secondary immunosuppressants were unchanged. RESULTS. In the SRL group, GFR increased from 47.0±18.0 to 61.2±22.2 ml/min (P=0.0001) 24 months after SRL initiation. In Group A, GFR increased from 40.5±12.7 to 53.9±19.8 mL/min (P<0.0001). In Group B, GFR increased marginally from 67.2±15.8 to 83.5±27.8 mL/min (P=0.10). In the CNI group, GFR declined from 40.5±14.0 mL/min to 36.4±12.5 mL/min (P=0.23) after 24 months of follow up. There was no significant difference in cardiac rejection or cardiac allograft function. In SRL group, proteinuria increased from 299±622 mg/day to 517±795 mg/day (P=0.0002) 12 months after SRL initiation and then stabilized; it did not differ from CNI group at 24 months (637±806 vs. 514±744 mg/day, P=0.39). Uric acid decreased from 7.6±2.4 to 6.2±1.9 mg/dL (P=0.0007) in the SRL group. CONCLUSIONS. Graduated substitution of CNI with SRL in cardiac transplant recipients is safe and improves renal function, without cardiac compromise.

KW - Calcineurin inhibitor

KW - Cardiac transplantation

KW - Renal function

KW - Sirolimus

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