Conversion from Cyclosporine to Sirolimus in Stable Renal Transplant Recipients

Sennesael, Jacques; Bosmans, Johan; Bogers, Johannes; Verbeelen, Dierik; Verpooten, Gert A.

doi:10.1097/01.tp.0000184623.35773.6a

Cited by 55 publications

(38 citation statements)

References 61 publications

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“…Oleandrin and oleandrogenin inhibit export of fibroblast growth factor-2 possibly by interacting with membrane Na + /K + -ATPase pump [6]. Oleandrin was found to activate NF-κB in different cell types and induce apoptosis by caspase-dependent PARP cleavage and DNA fragmentation [7,8].…”

Section: Introductionmentioning

confidence: 99%

RETRACTED ARTICLE: Cardiac glycoside induces cell death via FasL by activating calcineurin and NF-AT, but apoptosis initially proceeds through activation of caspases

et al. 2007

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Decrease in caspase activity is a common phenomenon in drug resistance. For effective therapeutic intervention, detection of such agents, which affects other pathway independent of caspases to promote cell death, might be important. Oleandrin, a polyphenolic glycoside induced cell death through activation of caspases in a variety of human tumour cells. In this report we provide evidence that besides caspases activation, oleandrin interacts with plasma membrane, changes fluidity of the membrane, disrupts Na + /K + -ATPase pump, enhances intracellular free Ca 2+ and thereby activates calcineurin. Calcineurin, in turns, activates nuclear transcription factor NF-AT and its dependent genes such as FasL, which induces cell death as a late response of oleandrin. Cell death at early stages is mediated by caspases where inhibitors partially protected oleandrin-mediated cell death in vectortransfected cells, but almost completely in Bcl-xL-overexpressed cells. Overall, our data suggest that oleandrin might be important therapeutic molecule in case of tumors where cell death pathway occurs due to deregulation of caspase-mediated pathway

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Section: Introductionmentioning

confidence: 99%

RETRACTED ARTICLE: Cardiac glycoside induces cell death via FasL by activating calcineurin and NF-AT, but apoptosis initially proceeds through activation of caspases

et al. 2007

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“…Dotted lines correspond to the time after sirolimus withdrawal, and time of conversion to tacrolimus is indicated by an arrow. times of nephrotic range, after conversion from CNI to sirolimus (1)(2)(3)(4)(5)(6)11,12). The main interest of this study is the first demonstration that renal transplant recipients who are treated by sirolimus de novo may develop FSGS lesions, distinct from collapsing glomerulopathy, suggesting a direct involvement of sirolimus itself.…”

Section: Discussionmentioning

confidence: 86%

“…First, we previously observed a dramatic increase in urinary protein excretion and the existence of nephrotic-range proteinuria after the conversion from CNI to sirolimus in individual patients who had no significant proteinuria before (5). Conversion in stable renal transplant recipients (without evidence for renal lesions) is associated with the development of proteinuria in 30% of the patients (6).…”

Section: Sirolimus-induced Proteinuria and Glomerular Lesionsmentioning

confidence: 99%

High Sirolimus Levels May Induce Focal Segmental Glomerulosclerosis De Novo

Letavernier¹,

Bruneval²,

Mandet³

et al. 2007

Clinical Journal of the American Society of Nephrology

181

112

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Sirolimus has been associated with high-range proteinuria when used in replacement of calcineurin inhibitors in renal transplant recipients with chronic allograft nephropathy (CAN). Primary FSGS was demonstrated previously in some such patients, but the coexistence of CAN lesions made the interpretation uneasy. However, nephrotic syndrome and FSGS were observed recently in three patients who received sirolimus de novo, without medical history of primary FSGS or CAN. Markers of podocyte differentiation were studied in kidney biopsies of the three patients who received sirolimus de novo and of five patients who switched to sirolimus. All patients developed FSGS lesions of classic type (not otherwise specified), but only switched patients exhibited advanced sclerotic lesions. Immunohistochemistry showed that some podocytes in FSGS lesions had absent or diminished expression of the podocyte-specific epitopes synaptopodin and p57, reflecting dedifferentiation, and had acquired expression of cytokeratin and PAX2, reflecting a immature fetal phenotype. Such a pattern of epitope expression provides evidence for podocyte dysregulation. Moreover, a decrease in vascular endothelial growth factor expression was observed in some glomeruli. In conclusion, sirolimus induces FSGS that is responsible for proteinuria in some transplant patients.

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“…This association is of interest but need to be confirmed in a larger cohort of patients. Ten patients in this study received sirolimus, a drug that has been associated with proteinuria (10,11). This number of patients is too small to reach firm conclusions but in evaluating post-transplant proteinuria, the possible contribution of sirolimus should be considered.…”

Section: Discussionmentioning

confidence: 99%

Interpreting Post-Transplant Proteinuria in Patients with Proteinuria Pre-Transplant

Myślak

Amer

Morales

et al. 2006

American Journal of Transplantation

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Increasing numbers of patients receive kidney transplants before initiation of dialysis or shortly thereafter. Some of these patients have significant proteinuria pre-transplant making the interpretation of post-transplant proteinuria problematic. In this study, we evaluated post-transplant proteinuria in 115 patients who had urine protein measured within 3 months of transplant and assessed the association of proteinuria with allograft pathology. Proteinuria declined rapidly from 3650 ± 3702 mg/day pretransplant to 550 + 918 at 3 weeks (p < 0.0001) and continued to decline until 1 year post-transplant (472 ± 1116, p < 0.0001 vs. 3 weeks). Proteinuria greater than 3000 mg/day was present in 48 patients (42%) pre-transplant, in 1 patient (1%) at 3 weeks and in 4 patients (4%) at 1 year. Surveillance graft biopsies were done at 1 year in 93% of patients. Proteinuria ≥1500 mg/day and/or an absolute increase in proteinuria >500 mg/day after 3 weeks post-transplant was associated with allograft glomerular pathology. In conclusion, pre-transplant proteinuria, even when high grade, declines rapidly after transplantation. Failure to decline or persistence of proteinuria greater than 1500 mg/day is indicative of allograft pathology.

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Conversion from Cyclosporine to Sirolimus in Stable Renal Transplant Recipients

Abstract: Conversion of stable renal transplant recipients from a CsA-MMF-ST to a SRL-MMF-ST regimen is safe and results in improved renal function but is associated with the development of proteinuria in 30% of the patients requiring renin-angiotensin blockade.

Cited by 55 publications

References 61 publications

RETRACTED ARTICLE: Cardiac glycoside induces cell death via FasL by activating calcineurin and NF-AT, but apoptosis initially proceeds through activation of caspases

RETRACTED ARTICLE: Cardiac glycoside induces cell death via FasL by activating calcineurin and NF-AT, but apoptosis initially proceeds through activation of caspases

High Sirolimus Levels May Induce Focal Segmental Glomerulosclerosis De Novo

Interpreting Post-Transplant Proteinuria in Patients with Proteinuria Pre-Transplant

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