Long-term immunosuppression with anti-CD25 monoclonal antibodies in heart transplant patients with chronic kidney disease.
BACKGROUND
Chronic kidney disease (CKD), a frequent and serious complication after heart transplantation, is associated with increased mortality. Current strategies include dose reduction or conversion from calcineurin inhibitors (CNIs) to either mycophenolate mofetil and/or rapamycin, with variable results and side-effect profiles.


METHODS
We evaluated the effectiveness of long-term anti-CD25 monoclonal antibody (MAb)-based immunosuppression in 17 adult heart transplant recipients with CKD at 10 +/- 5 years post-transplant. Seven patients had previously been switched to rapamycin but had untreatable side-effects and 10 patients were still on a CNI. The latter were matched with 10 control heart transplant patients whose renal function had remained stable over a similar post-transplant follow-up period, on CNI.


RESULTS
Anti-CD25 MAb were given over 13 +/- 10 months and were well tolerated with CD25 saturation monitoring (target <2% expression). Side-effects secondary to rapamycin resolved in 6 patients. The slope change of the creatinine clearance improved in patients in whom CNIs were discontinued (+0.335 ml/min/month vs -0.124 ml/min/month in controls, p = 0.03). Four patients died. Three died after 2, 6 and 7 months of follow-up, respectively, with the following diagnoses: acute renal failure (the patient refused dialysis); acute rejection (the patient had refused protocol endomyocardial biopsy); and perforated diverticulitis. The fourth patient died of pneumonia, 3 months after conversion from anti-CD25 MAb to rapamycin, because of poor venous access.


CONCLUSIONS
The use of long-term anti-CD25 MAb therapy as a potential replacement for CNI- and rapamycin-based immunosuppression is feasible. It is crucial that rejection surveillance be intensified. A randomized, controlled trial is required to confirm the benefits and safety of this strategy.
Cantarovich
Marcelo
M
Multiorgan Transplant Program, Department of Medicine, McGill University Health Centre, Montréal, Québec, Canada. marcelo.cantarovich@muhc.mcgill.ca
Giannetti
Nadia
N
Routy
Jean-Pierre
JP
Cecere
Renzo
R
Barkun
Jeffrey
J
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D016572:Cyclosporine / Q000627:therapeutic use; D005500:Follow-Up Studies; D016027:Heart Transplantation / Q000009:adverse effects / Q000276:immunology*; D006801:Humans; D007165:Immunosuppression Therapy / Q000379:methods; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology*; D007674:Kidney Diseases / Q000276:immunology*; D007676:Kidney Failure, Chronic / Q000453:epidemiology / Q000276:immunology; D008875:Middle Aged
D000911:Antibodies, Monoclonal; D007166:Immunosuppressive Agents; D053645:Interleukin-2 Receptor alpha Subunit; D016572:Cyclosporine