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Posttransplant proteinuria associated with everolimus
E Bertoni1, M Bruschi, G Candiano
1Renal Unit, Careggi University Hospital, Firenze, Italy.
Transplantation Proceedings
|May 23, 2009
Summary
Everolimus (EVL), an anti-mTOR drug, can cause proteinuria in renal transplant patients. Proteomics revealed mixed glomerular and tubular damage, with specific EVL biomarkers identified.
Area of Science:
- Nephrology
- Immunosuppression
- Proteomics
Background:
- Anti-mTOR agents like everolimus (EVL) are used post-renal transplantation.
- Proteinuria is a known complication, but its pathogenesis and composition remain unclear.
Purpose of the Study:
- To analyze urinary protein composition in renal transplant recipients treated with EVL or enteric-coated mycophenolic acid (EC-MPA).
- To identify specific biomarkers associated with EVL-induced proteinuria.
Main Methods:
- Integrated proteomics approach including quantitative assays, 2D electrophoresis, MALDI-TOF, and Western blots.
- Analysis of 48 renal transplant recipients (31 EVL, 17 EC-MPA).
Main Results:
- Higher incidence of proteinuria in EVL group (39%) vs. EC-MPA group (23%).
- Increased low molecular weight proteins (beta2 microglobulin, alpha1 microglobulin) and glomerular damage markers (albumin, Zn-alpha1 glycoprotein).
- Specific EVL biomarkers identified: alpha1-antitrypsin fragments and monoclonal lambda chains.
Conclusions:
- EVL induces proteinuria of mixed glomerular and tubular origin in renal transplant recipients.
- Proteinuria onset correlates with EVL treatment initiation.
- Identified urinary markers may indicate transplant-related or drug-specific renal alterations.
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