J Korean Med Sci.  2014 Aug;29(8):1069-1076. 10.3346/jkms.2014.29.8.1069.

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

• KMID: 2129600
• DOI: http://doi.org/10.3346/jkms.2014.29.8.1069

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.

Keyword

Calcineurin Inhibitor; Kidney Transplantation; Renal Function; Renal Impairment; Sirolimus

MeSH Terms

Adult
Calcineurin Inhibitors/*administration & dosage
Drug Synergism
Female
Graft Rejection/*etiology/*prevention & control
Graft Survival/drug effects
Humans
Immunosuppressive Agents
Kidney Transplantation/adverse effects/*methods
Male
Renal Insufficiency/diagnosis/*therapy
Republic of Korea
Severity of Illness Index
Sirolimus/*administration & dosage
Transplantation Tolerance/drug effects
Treatment Outcome
Calcineurin Inhibitors
Immunosuppressive Agents
Sirolimus

Figure

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  Fig. 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.

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  Fig. 2 Study population. Forty-six patients were screened, and 45 preconversion biopsies were performed. After the 52-week study period, 37 post-conversion biopsies were completed.

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  Fig. 3 Creatinine clearance before and after SRL conversion according to the CNI exposure period. *P value compared to preconversion creatinine clearance.

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  Fig. 4 Serum lipid profile after sirolimus conversion.

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  Fig. 5 Calcineurin inhibitor (CNI) toxicity in the biopsy. (A) Change of modified "ah" score. (B) Proportion of modified "ah" score according to exposure duration to CNI; preconversion versus postconversion 1 yr.

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