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Conversion to sirolimus for chronic renal allograft dysfunction: risk factors for graft loss and severe side effects.

Abramowicz D, Hadaya K, Hazzan M, Broeders N, Hoang AD, Ghisdal L, Noel C, Wissing KM - Nephrol. Dial. Transplant. (2008)

Bottom Line: Death-censored graft survival was 67% at 1 year and 54% at 2 years.SRL was stopped because of severe side effects in 15 patients.Among these, eight patients developed 'de novo' high-grade proteinuria.

View Article: PubMed Central - PubMed

Affiliation: Nephrology Department, Hopital Erasme, Université Libre de Bruxelles, Brussels, Belgium. dabram@ulb.ac.be

ABSTRACT
We retrospectively reviewed our experience with 45 kidney transplant recipients (KTR) that were switched from CNI to SRL, mainly for chronic allograft dysfunction (CAD) (41/45). The mean serum creatinine at switch was 2.5 +/- 0.8 mg/dl. At 1 year, patient survival was 93%. Death-censored graft survival was 67% at 1 year and 54% at 2 years. SRL was stopped because of severe side effects in 15 patients. Among these, eight patients developed 'de novo' high-grade proteinuria. Univariate analysis revealed that (1) a higher SRL level at 1 month was a predictor of SRL withdrawal due to severe side effects (P = 0.006), and (2) predictors of graft failure after SRL conversion were low SRL loading dose (P = 0.03) and a higher creatinine level at conversion (P = 0.003). In conclusion, the therapeutic index of SRL in patients suffering from CAD is narrow, with high exposure triggering serious adverse events that may mandate SRL discontinuation, while too low exposure may expose patients to under-immunosuppression and graft loss.

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Related in: MedlinePlus

Kaplan–Meier estimate of death-censored graft survival (A) and of patients remaining on sirolimus therapy (B) during 2 years after conversion. Survival estimates are shown with 95% confidence bands (dotted lines). The population at risk at different time points during follow-up is indicated on the plot.
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Figure 1: Kaplan–Meier estimate of death-censored graft survival (A) and of patients remaining on sirolimus therapy (B) during 2 years after conversion. Survival estimates are shown with 95% confidence bands (dotted lines). The population at risk at different time points during follow-up is indicated on the plot.

Mentions: Three deaths occurred after SRL switch. One patient died from multiple organ failure on Day 58, one from sudden death on Day 96 and one from cerebral haemorrhage on Day 156. Actuarial patient survival was 93% at 1 year. Twelve patients experienced loss of graft function and resumed chronic haemodialysis at a median of 107 days after SRL conversion (range, 23–523). Death-censored graft survival was 67% at 1 year and 54% at 2 years (Figure 1a). In addition, SRL was discontinued in 15 patients (33.3%) because of the occurrence of severe side effects (some patients developed more than one side effect): resistant anaemia, N = 1; multiple abdominal abscesses following acute pancreatitis, N = 1; hepatitis, N = 1; peritransplant abscess, N = 1; delayed wound healing, N = 1; stroke, N = 1; infra-therapeutic SRL levels leading to AR, N = 1; raised Screat >25%, N = 1; severe acneiform cutaneous lesions, N = 2; severe hyperlipaemia, N = 2; and de novo high-grade proteinuria, N = 8 (17.7%). In summary, SRL was stopped in 30/45 (66.6%) patients after conversion (3 deaths, 12 graft loss and 15 discontinuation for side effects). The actuarial proportion of patients remaining on SRL therapy over time was 33.6% at 1 year and 26.9% at 2 years after conversion (Figure 1b).


Conversion to sirolimus for chronic renal allograft dysfunction: risk factors for graft loss and severe side effects.

Abramowicz D, Hadaya K, Hazzan M, Broeders N, Hoang AD, Ghisdal L, Noel C, Wissing KM - Nephrol. Dial. Transplant. (2008)

Kaplan–Meier estimate of death-censored graft survival (A) and of patients remaining on sirolimus therapy (B) during 2 years after conversion. Survival estimates are shown with 95% confidence bands (dotted lines). The population at risk at different time points during follow-up is indicated on the plot.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2568008&req=5

Figure 1: Kaplan–Meier estimate of death-censored graft survival (A) and of patients remaining on sirolimus therapy (B) during 2 years after conversion. Survival estimates are shown with 95% confidence bands (dotted lines). The population at risk at different time points during follow-up is indicated on the plot.
Mentions: Three deaths occurred after SRL switch. One patient died from multiple organ failure on Day 58, one from sudden death on Day 96 and one from cerebral haemorrhage on Day 156. Actuarial patient survival was 93% at 1 year. Twelve patients experienced loss of graft function and resumed chronic haemodialysis at a median of 107 days after SRL conversion (range, 23–523). Death-censored graft survival was 67% at 1 year and 54% at 2 years (Figure 1a). In addition, SRL was discontinued in 15 patients (33.3%) because of the occurrence of severe side effects (some patients developed more than one side effect): resistant anaemia, N = 1; multiple abdominal abscesses following acute pancreatitis, N = 1; hepatitis, N = 1; peritransplant abscess, N = 1; delayed wound healing, N = 1; stroke, N = 1; infra-therapeutic SRL levels leading to AR, N = 1; raised Screat >25%, N = 1; severe acneiform cutaneous lesions, N = 2; severe hyperlipaemia, N = 2; and de novo high-grade proteinuria, N = 8 (17.7%). In summary, SRL was stopped in 30/45 (66.6%) patients after conversion (3 deaths, 12 graft loss and 15 discontinuation for side effects). The actuarial proportion of patients remaining on SRL therapy over time was 33.6% at 1 year and 26.9% at 2 years after conversion (Figure 1b).

Bottom Line: Death-censored graft survival was 67% at 1 year and 54% at 2 years.SRL was stopped because of severe side effects in 15 patients.Among these, eight patients developed 'de novo' high-grade proteinuria.

View Article: PubMed Central - PubMed

Affiliation: Nephrology Department, Hopital Erasme, Université Libre de Bruxelles, Brussels, Belgium. dabram@ulb.ac.be

ABSTRACT
We retrospectively reviewed our experience with 45 kidney transplant recipients (KTR) that were switched from CNI to SRL, mainly for chronic allograft dysfunction (CAD) (41/45). The mean serum creatinine at switch was 2.5 +/- 0.8 mg/dl. At 1 year, patient survival was 93%. Death-censored graft survival was 67% at 1 year and 54% at 2 years. SRL was stopped because of severe side effects in 15 patients. Among these, eight patients developed 'de novo' high-grade proteinuria. Univariate analysis revealed that (1) a higher SRL level at 1 month was a predictor of SRL withdrawal due to severe side effects (P = 0.006), and (2) predictors of graft failure after SRL conversion were low SRL loading dose (P = 0.03) and a higher creatinine level at conversion (P = 0.003). In conclusion, the therapeutic index of SRL in patients suffering from CAD is narrow, with high exposure triggering serious adverse events that may mandate SRL discontinuation, while too low exposure may expose patients to under-immunosuppression and graft loss.

Show MeSH
Related in: MedlinePlus