Limits...
Sirolimus conversion efficacy for graft function improvement and histopathology in renal recipients with mild to moderate renal insufficiency.

Joo DJ, Yang CW, Jeong HJ, Lim BJ, Huh KH, Chung BH, Choi YJ, Kang SW, Kim YS - J. Korean Med. Sci. (2014)

Bottom Line: The effect of SRL conversion on graft function was evaluated, and protocol biopsies were performed preconversion and 1 yr after conversion.In contrast, protocol biopsies demonstrated no significant improvements in the modified "ah" score or other Banff scores after SRL conversion.Furthermore, the duration of CNI treatment prior to SRL conversion was not associated with histological findings 1 yr after SRL conversion.

View Article: PubMed Central - PubMed

Affiliation: The Research Institute for Transplantation, Severance Hospital, Yonsei University Health System, Seoul, Korea. ; Department of Transplantation Surgery, Severance Hospital, Yonsei University Health System, Seoul, Korea.

ABSTRACT
This study was designed to evaluate whether sirolimus (SRL) conversion effectively improves renal function and histopathology in calcineurin inhibitor (CNI)-treated renal recipients with mild to moderate renal insufficiency. SRL conversion from CNI was performed in patients who underwent kidney transplantation from 6 months to 5 yr prior to screening. Forty-five patients were enrolled. The effect of SRL conversion on graft function was evaluated, and protocol biopsies were performed preconversion and 1 yr after conversion. Overall graft function after SRL conversion gradually improved, and the improvement in renal function was closely associated with the shorter duration of CNI exposure. When we divided the patients by the duration of CNI exposure, the patients with less than 1 yr of CNI exposure demonstrated significant improvement, but patients with a greater than 1 yr CNI exposure did not exhibit significant improvement. In contrast, protocol biopsies demonstrated no significant improvements in the modified "ah" score or other Banff scores after SRL conversion. Furthermore, the duration of CNI treatment prior to SRL conversion was not associated with histological findings 1 yr after SRL conversion. SRL conversion improved graft function in renal recipients with mild to moderate renal insufficiency, but this effect is not accompanied by histological improvement.

Show MeSH

Related in: MedlinePlus

Study design. After screening, calcineurin inhibitors were converted into sirolimus for a 4-week overlapped period (CNI dose was reduced by 25% each week). *Non-MMF and MPA patients received a loading dose of 8 mg/day and a maintenance dose of 4 mg/day. MMF, mycophenolate mofetil; MPA, mycophenolic acid; CNI, calcineurin inhibitor.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4129197&req=5

Figure 1: Study design. After screening, calcineurin inhibitors were converted into sirolimus for a 4-week overlapped period (CNI dose was reduced by 25% each week). *Non-MMF and MPA patients received a loading dose of 8 mg/day and a maintenance dose of 4 mg/day. MMF, mycophenolate mofetil; MPA, mycophenolic acid; CNI, calcineurin inhibitor.

Mentions: The current study was designed for patients who underwent kidney transplantation from 6 months to 5 yr prior to the screening point. CNI was gradually reduced by 25% of the initial dose each week enrollbeginning from the first administration of SRL (Rapamune®, Pfizer, Philadelphia, PA, USA). A loading dose of SRL was administered on the first day of conversion. The loading dose of SRL was determined based on the previous use of mycophenolate mofetil (MMF) or mycophenolic acid (MPA). MMF or MPA patients received a loading dose of 6 mg/day SRL on the first day and a maintenance dose of 2 mg/day SRL, which was adjusted to target trough levels of 7-15 ng/mL. Non-MMF or MPA patients received an SRL loading dose of 8 mg/day on the first day and a maintenance dose of 4 mg/day SRL, which was adjusted to target trough levels of 10-18 ng/mL. Prednisone or an equivalent dose of deflazacort was maintained with the preconversion dosage (5-10 mg/day). Mandatory protocol biopsies were performed during the preconversion period and 1 yr after conversion (Fig. 1).


Sirolimus conversion efficacy for graft function improvement and histopathology in renal recipients with mild to moderate renal insufficiency.

Joo DJ, Yang CW, Jeong HJ, Lim BJ, Huh KH, Chung BH, Choi YJ, Kang SW, Kim YS - J. Korean Med. Sci. (2014)

Study design. After screening, calcineurin inhibitors were converted into sirolimus for a 4-week overlapped period (CNI dose was reduced by 25% each week). *Non-MMF and MPA patients received a loading dose of 8 mg/day and a maintenance dose of 4 mg/day. MMF, mycophenolate mofetil; MPA, mycophenolic acid; CNI, calcineurin inhibitor.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4129197&req=5

Figure 1: Study design. After screening, calcineurin inhibitors were converted into sirolimus for a 4-week overlapped period (CNI dose was reduced by 25% each week). *Non-MMF and MPA patients received a loading dose of 8 mg/day and a maintenance dose of 4 mg/day. MMF, mycophenolate mofetil; MPA, mycophenolic acid; CNI, calcineurin inhibitor.
Mentions: The current study was designed for patients who underwent kidney transplantation from 6 months to 5 yr prior to the screening point. CNI was gradually reduced by 25% of the initial dose each week enrollbeginning from the first administration of SRL (Rapamune®, Pfizer, Philadelphia, PA, USA). A loading dose of SRL was administered on the first day of conversion. The loading dose of SRL was determined based on the previous use of mycophenolate mofetil (MMF) or mycophenolic acid (MPA). MMF or MPA patients received a loading dose of 6 mg/day SRL on the first day and a maintenance dose of 2 mg/day SRL, which was adjusted to target trough levels of 7-15 ng/mL. Non-MMF or MPA patients received an SRL loading dose of 8 mg/day on the first day and a maintenance dose of 4 mg/day SRL, which was adjusted to target trough levels of 10-18 ng/mL. Prednisone or an equivalent dose of deflazacort was maintained with the preconversion dosage (5-10 mg/day). Mandatory protocol biopsies were performed during the preconversion period and 1 yr after conversion (Fig. 1).

Bottom Line: The effect of SRL conversion on graft function was evaluated, and protocol biopsies were performed preconversion and 1 yr after conversion.In contrast, protocol biopsies demonstrated no significant improvements in the modified "ah" score or other Banff scores after SRL conversion.Furthermore, the duration of CNI treatment prior to SRL conversion was not associated with histological findings 1 yr after SRL conversion.

View Article: PubMed Central - PubMed

Affiliation: The Research Institute for Transplantation, Severance Hospital, Yonsei University Health System, Seoul, Korea. ; Department of Transplantation Surgery, Severance Hospital, Yonsei University Health System, Seoul, Korea.

ABSTRACT
This study was designed to evaluate whether sirolimus (SRL) conversion effectively improves renal function and histopathology in calcineurin inhibitor (CNI)-treated renal recipients with mild to moderate renal insufficiency. SRL conversion from CNI was performed in patients who underwent kidney transplantation from 6 months to 5 yr prior to screening. Forty-five patients were enrolled. The effect of SRL conversion on graft function was evaluated, and protocol biopsies were performed preconversion and 1 yr after conversion. Overall graft function after SRL conversion gradually improved, and the improvement in renal function was closely associated with the shorter duration of CNI exposure. When we divided the patients by the duration of CNI exposure, the patients with less than 1 yr of CNI exposure demonstrated significant improvement, but patients with a greater than 1 yr CNI exposure did not exhibit significant improvement. In contrast, protocol biopsies demonstrated no significant improvements in the modified "ah" score or other Banff scores after SRL conversion. Furthermore, the duration of CNI treatment prior to SRL conversion was not associated with histological findings 1 yr after SRL conversion. SRL conversion improved graft function in renal recipients with mild to moderate renal insufficiency, but this effect is not accompanied by histological improvement.

Show MeSH
Related in: MedlinePlus