Sirolimus Attenuates the Rate of Progression of Early Chronic Allograft Nephropathy

Sumethkul, V.; Changsirikulchai, Siribha; Lothuvachai, Thitima; Chalermsanyakorn, Panas

doi:10.1016/j.transproceed.2006.10.097

Cited by 7 publications

(6 citation statements)

References 7 publications

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“…It has been shown that there is an association between successful conversion and time lag between conversion and transplantation; shorter durations have more favorable outcomes (35,37,44,45). In accordance with this hypothesis, in the present study, no increase in serum creatinine and proteinuria were noted in the patients who were converted within the first year of transplantation; however, proteinuria values increased in the patients who received SRL conversion after the first year.…”

Section: Discussionsupporting

confidence: 88%

Conversion to Sirolimus in Renal Transplant Recipients: A Single‐Center Experience

et al. 2010

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Maintenance immunosuppression with calcineurin inhibitors (CNI) following renal transplantation is associated with nephrotoxicity and accelerated graft loss. Sirolimus (SRL) is a nonnephrotoxic immunosuppressive agent. We retrospectively analyzed our experience with kidney transplant recipients who were converted from CNI to SRL. A total of 58 renal transplant recipients were converted from CNI to SRL. SRL was started at a dose of 0.075 mg/kg and, at the same time, CNI dose was reduced by 50% daily for 3 days. SRL trough levels were targeted between 8 and 12 ng/mL. When target trough levels were achieved, CNI was withdrawn. The main indications for switching were posttransplant malignancies (n = 32) and chronic allograft nephropathy (CAN) (n = 10). The mean time from transplantation to conversion was 84 +/- 71 months. Mean serum creatinine level was 1.63 +/- 0.52 mg/dL before conversion. Serum creatinine levels at the 1, 3, 6 months, and 1, 2, 3 years after conversion were 1.64 +/- 0.58 mg/dL (P = 0.67), 1.52 +/- 0.53 mg/dL (P = 0.414), 1.62 +/- 0.62 mg/dL (P = 0.734), and 1.48 +/- 0.58 mg/dL (P = 0.065), 1.58 +/- 0.53 mg/dL (P = 0.854), 1.88 +/- 0.77 mg/dL (P = 0.083), respectively. Daily proteinuria levels increased from 0.04 +/- 0.11 g/day at baseline to 0.55 +/- 1.33 g/day (P = 0.037) after conversion, in the responders group. In the nonresponders group, baseline proteinuria was 0.13 +/- 0.25 g/day, and increased to 1.44 +/- 2.44 g/day after conversion (P = 0.008). SRL was discontinued in 16 patients (31%) because of the occurrence of severe side effects. The proportion of patients remaining on SRL therapy over time was 43.1% at 1 year, 15.5% at 2 years after conversion, and 10.3% at 3 years after conversion. SRL conversion may be very useful in patients suffering from neoplasia; however, frequent side effects related with this intervention should be considered, and routine conversion from CNI to SRL to reduce nephrotoxicity should be discouraged.

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Section: Discussionsupporting

confidence: 88%

Conversion to Sirolimus in Renal Transplant Recipients: A Single‐Center Experience

et al. 2010

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“…Treatment with sirolimus, from the same class of immunosuppressants, has also been associated with inhibition of graft-specific histologic changes, with evidence suggesting a benefit in prevention (12)(13)(14) and treatment (15) of chronic allograft nephropathy, inhibition of bronchiolitis obliterans in the lung transplant patients (16), and suppression of hepatic fibrosis in a rat model (17).…”

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confidence: 99%

Incidence of Delayed Graft Function and Wound Healing Complications After Deceased-Donor Kidney Transplantation Is not Affected by De Novo Everolimus

Albano¹,

Berthoux²,

Moal³

et al. 2009

Transplantation

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“…The sample size was estimated by the Power Analysis and Sample Size for Windows software (PASS 2000, NCSS, Kaysville, UT, USA). On the basis of a previous pilot study, 15 the rates of renal function decline are 0.18 and 0.04 mL/min/month before and after conversion to an mTOR inhibitor, respectively, with standard deviation of renal function decline of 0.2 mL/min/month. A sample size of 33 would achieve 80% power to detect an improvement of 0.14 mL/min/month after everolimus therapy at a significance level (alpha) of 0.05 using a two-sided paired Student’s t -test.…”

Section: Methodsmentioning

confidence: 96%

Functional and histological improvement after everolimus rescue of chronic allograft dysfunction in renal transplant recipients

Chow

Szeto

Lai

et al. 2015

TCRM

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BackgroundWe tested the strategy of mTOR inhibitors with calcineurin inhibitor minimization in renal transplant recipients with known chronic allograft dysfunction.MethodsIn this open-label, single-arm study, renal transplant patients were recruited after biopsy-confirmed chronic allograft dysfunction in the absence of acute rejection episode within 2 months, with proteinuria <0.8 g/day, and serum creatinine <220 μmol/L or estimated glomerular filtration rate >40 mL/min/1.73 m2. They were converted to everolimus (aiming for trough everolimus level 3–8 ng/mL) with cyclosporine minimization, to assess the effect on renal function, rate of glomerular filtration rate decline, and longitudinal transplant biopsy at 12 months.ResultsSeventeen Chinese patients (median transplant duration, 4.2 years) were recruited; no patients discontinued study medication. The mean slope of the glomerular filtration rate over time was −4.31±6.65 mL/min/1.73 m2 per year in the year before everolimus, as compared with 1.29±5.84 mL/min/1.73 m2 per year in the 12 months of everolimus therapy, a difference of 5.61 mL/min/1.73 m2 per year (95% confidence interval [CI], 0.40–10.8) favoring everolimus therapy (P=0.036). Serial renal biopsy histology showed significant decrease of tubular atrophy (15.7%±11.3% versus 7.1%±7.3%, P=0.005) and interstitial fibrosis (14.8%±11.5% versus 7.2%±8.2%, P=0.013). Intrarenal expression of TGF-β1 mRNA showed a nonsignificant decrease after everolimus treatment.ConclusionIn renal transplant recipients with biopsy-confirmed chronic allograft dysfunction, we found a significant beneficial effect of everolimus rescue therapy and calcineurin inhibitor minimization strategy on the improvement of glomerular filtration rate decline rate. In secondary analysis, everolimus was shown to slow down the disease progression by reducing the tubular atrophy and interstitial fibrosis scoring.

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Sirolimus Attenuates the Rate of Progression of Early Chronic Allograft Nephropathy

Cited by 7 publications

References 7 publications

Conversion to Sirolimus in Renal Transplant Recipients: A Single‐Center Experience

Conversion to Sirolimus in Renal Transplant Recipients: A Single‐Center Experience

Incidence of Delayed Graft Function and Wound Healing Complications After Deceased-Donor Kidney Transplantation Is not Affected by De Novo Everolimus

Functional and histological improvement after everolimus rescue of chronic allograft dysfunction in renal transplant recipients

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