RENAL FUNCTION OF AN EVEROLIMUS BASED THERAPY AFTER CALCINEURIN INHIBITOR WITHDRAWAL IN MAINTENANCE RENAL TRANSPLANT RECIPIENTS ONE YEAR AFTER CONVERSION

CLINICAL IMMUNOSUPPRESSION - KIDNEY EARLY

T. Rath¹, K. Budde², C. Sommerer³, W. Arns⁴, S. Kramer⁵, E. Vogel⁵, F. Pietruck⁶, P. Reinke⁷, H. Haller^8
1Abteilung Für Nephrologie Und Transplantationsmedizin, Westpfalz Klinikum, Kaiserslautern/GERMANY, ², University Hospital Charité, Berlin/GERMANY, ³, Nierenzentrum, Heidelberg/GERMANY, ⁴, Transplantationszentrum, Koeln-Merheim/GERMANY, ⁵, Novartis Pharma, Nuremberg/GERMANY, ⁶Abteilung Nieren-undhochdruckkranke, Universitätsklinikum Essen, Essen/GERMANY, ⁷Department Of Nephrology And Intensive Care Ccv, Charité-Universitätsmedizin Berlin, Berlin/GERMANY, ⁸, Department of Nephrology, Hannover/GERMANY

Body:
Objective: Assessment of renal function, safety and efficacy of an Everolimus regimen after Calcineurin-Inhibitor (CNI) withdrawal in maintenance kidney allograft recipients. Methods: In an open-label, randomized, controlled, multi-center study 93 renal maintenance patients with a stable renal function defined as serum creatinine < 2.5 mg/dl and on a stable immunosuppressive therapy consisting of CNI, enteric-coated mycophenolate sodium (EC-MPS) with or without corticosteroids were randomized to either continue CNI treatment (trough level (C0): Tacrolimus 5-10ng/ml, Cyclosporine: 80-150ng/ml) and EC-MPS (n=47) or b) convert to an Everolimus (C0: 6-10ng/ml) and EC-MPS (n=46) regimen. Results: 93 pts were randomized to either everolimus/EC-MPS or CNI/EC-MPS with a mean time since the most recent transplantation of 6.4 years. At Month 12 after randomization adjusted mean calculated GFR (Nankivell, primary endpoint) was higher by 3.6 mL/min/1.73m2 for the everolimus compared to the CNI group (62.9 ± 3.69 vs 59.3 ± 3.69 mL/min/1.73m2; ANCOVA adjusted means, p=n.s.). One death occurred in both groups and no graft loss or BPAR was observed in either group. The number and proportion of patients discontinued study regimen due to adverse events were 15/46 (32.6%) in the Everolimus/EC-MPS and 5/47 (10.6%) in CsA/EC-MPS group. Important safety parameters related to study medication are listed in the table:

	CNI/EC-MPS N=47	Everolimus/EC-MPS N=46
Hyperlipiaemia [% of pts]	0	6.5
Total Cholesterol [mmol/L]	5.21	6.1
LDL [mmol/L]	3.10	3.68
HDL [mmol/L]	1.27	1.46
Triglycerides [mmol/L]	2.58	2.49
Anaemia [% of pts]	0	6.5
Leucopenia [% of pts]	2.1	10.9
Thrombocytopenia [% of pts]	0	4.3
Mouth ulceration [% of pts]	0	26.1
Diarrhoea [% of pts]	4.3	6.5
Any infection [% of pts]	53.2	63.0
Serious infection [% of pts]	10.6	17.4

Conclusions: The late conversion to an Everolimus/EC-MPS treatment in maintenance renal transplant patients with a stable renal function after CNI withdrawal leads to a better renal function. Overall late conversion was safe although more side effects were reported but for a complete risk/benefit assessment a long term follow-up is needed which will be attempted.

Disclosure: All authors have declared no conflicts of interest.