Conversion from a calcineurin inhibitor-based immunosuppressive regimen to everolimus in renal transplant recipients: effect on renal function and proteinuria.
New immunosuppressive agents are being actively researched to avoid complications of chronic allograft nephropathy (CAN), calcineurin inhibitor (CNI) nephrotoxicity, and posttransplantation cancer. The family of mTOR inhibitors offers a unique immunosuppressive opportunity to avoid CNI toxicity and reduce the incidence of malignancy. Nevertheless, increasing data have demonstrated that sirolimus (SRL), the first mTOR introduced in the treatment of solid organ transplant recipients, induces proteinuria, an adverse event that could produce deterioration of long-term renal function. In this short-term study of patients followed for 1 to 16 months, we examined changes in renal function and proteinuria among renal transplant recipients converted from a CNI-based regimen to an everolimus (EVL)-based one, a recently introduced mTOR inhibitor. Our data showed that renal function can be optimized after conversion to EVL by up to 42% in recipients showing CAN grade 1 or 2, or CNI nephrotoxicity. Importantly, patients who improved their creatinine clearance did not show increased proteinuria measured in a voided specimen as the ratio of urinary protein and creatinine concentration (P/C). These results, if confirmed with long-term follow-up and a larger number of patients, would allow us to consider EVL as a promising agent for maintenance immunosuppressive regimens in kidney transplantation.
Morales
J
J
Unidad de Trasplante, Clinica Las Condes, Santiago, Chile. jmorales@clinicalascondes.cl
Fierro
A
A
Benavente
D
D
Zehnder
C
C
Ferrario
M
M
Contreras
L
L
Herzog
C
C
Buckel
E
E
D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D000961:Antilymphocyte Serum; D001379:Azathioprine / Q000627:therapeutic use; D000077552:Basiliximab; D065095:Calcineurin Inhibitors; D016572:Cyclosporine / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D000068338:Everolimus; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D016030:Kidney Transplantation / Q000276:immunology / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000031:analogs & derivatives / Q000627:therapeutic use; D011507:Proteinuria / Q000517:prevention & control*; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use; D020123:Sirolimus / Q000009:adverse effects* / Q000031:analogs & derivatives* / Q000627:therapeutic use
D000911:Antibodies, Monoclonal; D000961:Antilymphocyte Serum; D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D011993:Recombinant Fusion Proteins; D016572:Cyclosporine; D000077552:Basiliximab; D000068338:Everolimus; C512542:thymoglobulin; D009173:Mycophenolic Acid; D001379:Azathioprine; D020123:Sirolimus