M-Tor Inhibitors Monotherapy in Low Immunological Risk Renal Transplant Recipients. A Good Choice?

Abstract

Calcineurin inhibitors (CNI) nephrotoxicity and death with functioning graft jeopardize long term outcome of renal transplant recipients. Therapy with steroids is associated with many deleterious effects. The use of m-TOR inhibitors (m-TOR), with non nephrotoxic and antiangiogenic properties might be suitable without steroids or CNI. Besides that, monotherapy diminishes no compliance in chronic patients. We have studied the evolution of 47 low immunological risk renal transplant recipients with m-TOR monotherapy, aged 45±10 years (18-69), 25 males y 22 females. We performed an immunologic study before and at 3 and 9 months after starting monotherapy by detection of specific antibodies against donor by beads cytometry and determination of lymphocitary activity by production of ATP by TCD 4+ lymphocites activated with PHA mitogen. We consider low risk immunological recipients to be enrol iwhen the patient had an ATP production less than 520 ng/dl and neither any report of acute rejection episode, nor specific antibody against donor. Five of the enrolled patients had received immunosuppression induction without CNI (micophenolate, prednisone, m-TOR and anti CD25) and 42 were converted to m-TOR due to CNI secondary effects or malignancies. Eighteen out 47 patients (38.2%) received prednisone and 29 (61.7%) micophenolate with m-Tor before starting monotherapy. A total of 34 recipients received sirolimus and 13 everolimus. No compliance was evaluated by personal interview and detection of m-Tor levels in serum. The follow- up after starting monotherapy was 69,7. months. IC 95%: 61.3-78.0. At the end of the follow -up 7 out of 47 recipients (11,5%) had to change immunosuppression without losing their grafts, due to heavy proteinuria 2, pulmonary infection 1, acute rejection 1, hepatotoxicity 1, vasculitis 1 and the last patient by temporary inclusion on dialisys after acute pielonephritis. Four out 47 patients (8,5%) lost their grafts due to chronic rejection 3 and death with a functioning graft 1. Acute rejection rate was 2,1%, one episode, solved with steroid pulses and switching m-TOR to FK 506 and micophenolate. No patient developed specific antibody against donor or increased ATP production after starting monotherapy. The graft and recipient survivals were 100% at 1 year, 88,7 and 95,7% at 5 years. The percentajes of patients on monotherapy were 97,9% and 70.,5 %. at 1 and 5 years. At the end of the follow -up 36 out of 47 recipients remained on monotherapy. Their serum creatinine and Glomerular Filtration Rate(MDRD-4) improved significantly, from 2.16 ± 1,05 mg/dl to 1.49 ± 0.56 mg/dl (p=0.001)and from 39,23 ± 25,23 to 52.23 ± 23,20 ml/mn (p=0.001) at the end of th follow-up, respectively. Proteinuria increased but with no statistical significance, from 306.6 ± 400 to 418.1 ± 514.1mg/24h (p=0.17). A total of 33 out of 47 patients (70,2%) received concomitant medication: 24 statins (51%), 8 erythropoietin (17%) y 13 angiotensin converting enzyme (27,6%). No case of no compliance was observed during the follow-up. The present study supports the safety and efficacy of m-TOR monotherapy in selected renal transplant recipients,.