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Conversion to sirolimus-based maintenance immunosuppression using daclizumab bridge therapy in renal transplant recipients.
Clin Transplant. 2004; 18 Suppl 12:61-6.CT

Abstract

INTRODUCTION

Conversion from calcineurin inhibitor (CI)-based maintenance immunosuppression to sirolimus (SRL)-based immunosuppression may be beneficial in selected renal transplant recipients. The purpose of this study was to evaluate the safety and efficacy of a daclizumab (DAC) bridge protocol in patients converted from CI- to SRL-based maintenance immunosuppression.

METHODS

We conducted a retrospective chart review of renal transplant recipients who were converted to SRL at least 2 months post-transplant. The protocol consisted of an abrupt discontinuation of either cyclosporin (CsA) or tacrolimus (TAC), initiation of SRL within 48 h of CI discontinuation, and DAC 2 mg/kg at the time of CI discontinuation and again at 14 d (depending on the SRL serum concentration). The SRL starting dose was based on risk stratification in each patient.

RESULTS

Twenty-one renal transplant patients were converted to SRL (11 from TAC, 10 from CsA) between October 2001 and July 2003. Conversion occurred at a mean of 23 months post-transplant. Indications for SRL conversion included 12 for chronic allograft nephropathy (CAN), four for CI-associated neurotoxicity, two for thrombotic microangiopathy (TMA), two for post-transplant diabetes mellitus (PTDM), and one for polyomavirus interstitial nephritis (PVN). Mean follow-up was 16 months from time of conversion. Therapeutic SRL levels were reached at a mean of 14 d. Total serum cholesterol levels increased from a mean of 205 (+/- 47) to 234 (+/- 55) mg/dL (P = 0.014), and serum triglyceride levels increased from a mean of 186 (+/- 66) to 257 (+/- 88) mg/dL (P = 0.002). In addition, mean haemoglobin level decreased from 12.0 (+/- 2.3) to 10.5 (+/- 2.1) g/dL (P = 0.002); total white blood cell count decreased from 8300 (+/- 4300) to 4700 (+/- 1400)/mm(3) (P < 0.001); and platelet count decreased from 238 000 (+/- 72 800) to 186 000 (+/- 51 900)/mm(3) (P = 0.002) from before to after conversion. Patients experienced the following side-effects while taking SRL: diarrhoea (n = 6), peripheral oedema (n = 5), arthralgias (n = 4), anaemia (n = 4), oral ulcers (n = 1), deep vein thrombosis (n = 1), shortness of breath (n = 1), and mild increase in serum transaminases (n = 1). Two patients (9.5%) discontinued SRL due to side-effects, both secondary to severe arthralgias. There were two serious infections noted after conversion: one Pseudomonas aeruginosa urosepsis, and one PVN (that was ongoing prior to conversion). Patient survival was 100%, and kidney graft survival was 76%. Five patients (24%) lost their allograft after conversion due to progression of CAN (n = 2), persistent TMA in the kidney (n = 1), patient self-discontinuation of sirolimus (n = 1), and preexisting PVN unresponsive to cidofovir therapy (n = 1). Of the five patients who lost their allograft, the mean serum creatinine at the time of conversion was 3.5 (+/-1.1) mg/dL compared with 2.2 (+/- 0.8) mg/dL in patients who did not lose their allograft (P = 0.034). No acute rejection episodes occurred after conversion to sirolimus.

CONCLUSIONS

DAC bridge therapy provides safe and effective immunosuppressive coverage while converting renal transplant recipients from CI- to SRL-based maintenance immunosuppressive therapy. A pharmacoeconomic analysis, however, is necessary to determine the cost-effectiveness of this conversion protocol.

Authors+Show Affiliations

Department of Pharmacy, Wake Forest University Baptist Medical Center and School of Medicine, Winston-Salem, NC, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

15217410

Citation

Sundberg, Aimee K., et al. "Conversion to Sirolimus-based Maintenance Immunosuppression Using Daclizumab Bridge Therapy in Renal Transplant Recipients." Clinical Transplantation, vol. 18 Suppl 12, 2004, pp. 61-6.
Sundberg AK, Rohr MS, Hartmann EL, et al. Conversion to sirolimus-based maintenance immunosuppression using daclizumab bridge therapy in renal transplant recipients. Clin Transplant. 2004;18 Suppl 12:61-6.
Sundberg, A. K., Rohr, M. S., Hartmann, E. L., Adams, P. L., & Stratta, R. J. (2004). Conversion to sirolimus-based maintenance immunosuppression using daclizumab bridge therapy in renal transplant recipients. Clinical Transplantation, 18 Suppl 12, 61-6.
Sundberg AK, et al. Conversion to Sirolimus-based Maintenance Immunosuppression Using Daclizumab Bridge Therapy in Renal Transplant Recipients. Clin Transplant. 2004;18 Suppl 12:61-6. PubMed PMID: 15217410.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Conversion to sirolimus-based maintenance immunosuppression using daclizumab bridge therapy in renal transplant recipients. AU - Sundberg,Aimee K, AU - Rohr,Michael S, AU - Hartmann,Erica L, AU - Adams,Patricia L, AU - Stratta,Robert J, PY - 2004/6/26/pubmed PY - 2004/11/17/medline PY - 2004/6/26/entrez SP - 61 EP - 6 JF - Clinical transplantation JO - Clin Transplant VL - 18 Suppl 12 N2 - INTRODUCTION: Conversion from calcineurin inhibitor (CI)-based maintenance immunosuppression to sirolimus (SRL)-based immunosuppression may be beneficial in selected renal transplant recipients. The purpose of this study was to evaluate the safety and efficacy of a daclizumab (DAC) bridge protocol in patients converted from CI- to SRL-based maintenance immunosuppression. METHODS: We conducted a retrospective chart review of renal transplant recipients who were converted to SRL at least 2 months post-transplant. The protocol consisted of an abrupt discontinuation of either cyclosporin (CsA) or tacrolimus (TAC), initiation of SRL within 48 h of CI discontinuation, and DAC 2 mg/kg at the time of CI discontinuation and again at 14 d (depending on the SRL serum concentration). The SRL starting dose was based on risk stratification in each patient. RESULTS: Twenty-one renal transplant patients were converted to SRL (11 from TAC, 10 from CsA) between October 2001 and July 2003. Conversion occurred at a mean of 23 months post-transplant. Indications for SRL conversion included 12 for chronic allograft nephropathy (CAN), four for CI-associated neurotoxicity, two for thrombotic microangiopathy (TMA), two for post-transplant diabetes mellitus (PTDM), and one for polyomavirus interstitial nephritis (PVN). Mean follow-up was 16 months from time of conversion. Therapeutic SRL levels were reached at a mean of 14 d. Total serum cholesterol levels increased from a mean of 205 (+/- 47) to 234 (+/- 55) mg/dL (P = 0.014), and serum triglyceride levels increased from a mean of 186 (+/- 66) to 257 (+/- 88) mg/dL (P = 0.002). In addition, mean haemoglobin level decreased from 12.0 (+/- 2.3) to 10.5 (+/- 2.1) g/dL (P = 0.002); total white blood cell count decreased from 8300 (+/- 4300) to 4700 (+/- 1400)/mm(3) (P < 0.001); and platelet count decreased from 238 000 (+/- 72 800) to 186 000 (+/- 51 900)/mm(3) (P = 0.002) from before to after conversion. Patients experienced the following side-effects while taking SRL: diarrhoea (n = 6), peripheral oedema (n = 5), arthralgias (n = 4), anaemia (n = 4), oral ulcers (n = 1), deep vein thrombosis (n = 1), shortness of breath (n = 1), and mild increase in serum transaminases (n = 1). Two patients (9.5%) discontinued SRL due to side-effects, both secondary to severe arthralgias. There were two serious infections noted after conversion: one Pseudomonas aeruginosa urosepsis, and one PVN (that was ongoing prior to conversion). Patient survival was 100%, and kidney graft survival was 76%. Five patients (24%) lost their allograft after conversion due to progression of CAN (n = 2), persistent TMA in the kidney (n = 1), patient self-discontinuation of sirolimus (n = 1), and preexisting PVN unresponsive to cidofovir therapy (n = 1). Of the five patients who lost their allograft, the mean serum creatinine at the time of conversion was 3.5 (+/-1.1) mg/dL compared with 2.2 (+/- 0.8) mg/dL in patients who did not lose their allograft (P = 0.034). No acute rejection episodes occurred after conversion to sirolimus. CONCLUSIONS: DAC bridge therapy provides safe and effective immunosuppressive coverage while converting renal transplant recipients from CI- to SRL-based maintenance immunosuppressive therapy. A pharmacoeconomic analysis, however, is necessary to determine the cost-effectiveness of this conversion protocol. SN - 0902-0063 UR - https://www.unboundmedicine.com/medline/citation/15217410/Conversion_to_sirolimus_based_maintenance_immunosuppression_using_daclizumab_bridge_therapy_in_renal_transplant_recipients_ L2 - https://doi.org/10.1111/j.1399-0012.2004.00220.x DB - PRIME DP - Unbound Medicine ER -