Biomaterial Database

Mycophenolate mofetil versus azathioprine in kidney transplant recipients on steroid-free, low-dose cyclosporine immunosuppression (ATHENA): A pragmatic randomized trial. 2021

Piero Ruggenenti, and Paolo Cravedi, and Eliana Gotti, and Annarita Plati, and Maddalena Marasà, and Silvio Sandrini, and Nicola Bossini, and Franco Citterio, and Enrico Minetti, and Domenico Montanaro, and Ettore Sabadini, and Regina Tardanico, and Davide Martinetti, and Flavio Gaspari, and Alessandro Villa, and Annalisa Perna, and Francesco Peraro, and Giuseppe Remuzzi

Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Bergamo, Italy.

We compared protection of mycophenolate mofetil (MMF) and azathioprine (AZA) against acute cellular rejection (ACR) and chronic allograft nephropathy (CAN) in kidney transplant recipients on steroid-free, low-dose cyclosporine (CsA) microemulsion maintenance immunosuppression. ATHENA, a pragmatic, prospective, multicenter trial conducted by 6 Italian transplant centers, compared the outcomes of 233 consenting recipients of a first deceased donor kidney transplant induced with low-dose thymoglobulin and basiliximab and randomized to MMF (750 mg twice/day, n = 119) or AZA (75 to 125 mg/day, n = 114) added-on maintenance low-dose CsA microemulsion and 1-week steroid. In patients without acute clinical or subclinical rejections, CsA dose was progressively halved. Primary endpoint was biopsy-proven CAN. Analysis was by intention to treat. Participants were included between June 2007 and July 2012 and followed up to August 2016. Between-group donor and recipient characteristics, donor/recipient mismatches, and follow-up CsA blood levels were similar. During a median (interquartile range (IQR)) follow-up of 47.7 (44.2 to 48.9) months, 29 of 87 biopsied patients on MMF (33.3%) versus 31 of 88 on AZA (35.2%) developed CAN (hazard ratio (HR) [95% confidence interval (CI)]: 1.147 (0.691 to 1.904, p = 0.595). Twenty and 21 patients on MMF versus 34 and 14 on AZA had clinical [HR (95% CI): 0.58 (0.34 to 1.02); p = 0.057) or biopsy-proven subclinical [HR (95% CI): 1.49 (0.76 to 2.92); p = 0.249] ACR, respectively. Combined events [HR (95% CI): 0.85 (0.56 to 1.29); p = 0.438], patient and graft survival, delayed graft function (DGF), 3-year glomerular filtration rate (GFR) [53.8 (40.6;65.7) versus 49.8 (36.8;62.5) mL/min/1.73 m2, p = 0.50], and adverse events (AEs) were not significantly different between groups. Chronicity scores other than CAN predict long-term graft outcome. Study limitations include small sample size and unblinded design. In this study, we found that in deceased donor kidney transplant recipients on low-dose CsA and no steroids, MMF had no significant benefits over AZA. This finding suggests that AZA, due to its lower costs, could safely replace MMF in combination with minimized immunosuppression. ClinicalTrials.gov NCT00494741; EUDRACT 2006-005604-14.

UI	MeSH Term	Description	Entries
D007166	Immunosuppressive Agents	Agents that suppress immune function by one of several mechanisms of action. Classical cytotoxic immunosuppressants act by inhibiting DNA synthesis. Others may act through activation of T-CELLS or by inhibiting the activation of HELPER CELLS. While immunosuppression has been brought about in the past primarily to prevent rejection of transplanted organs, new applications involving mediation of the effects of INTERLEUKINS and other CYTOKINES are emerging.	Immunosuppressant,Immunosuppressive Agent,Immunosuppressants,Agent, Immunosuppressive,Agents, Immunosuppressive
D007558	Italy	A country in southern Europe, a peninsula extending into the central Mediterranean Sea, northeast of Tunisia. The capital is Rome.	Sardinia
D008297	Male		Males
D008875	Middle Aged	An adult aged 45 - 64 years.	Middle Age
D009173	Mycophenolic Acid	Compound derived from Penicillium stoloniferum and related species. It blocks de novo biosynthesis of purine nucleotides by inhibition of the enzyme inosine monophosphate dehydrogenase (IMP DEHYDROGENASE). Mycophenolic acid exerts selective effects on the immune system in which it prevents the proliferation of T-CELLS, LYMPHOCYTES, and the formation of antibodies from B-CELLS. It may also inhibit recruitment of LEUKOCYTES to sites of INFLAMMATION.	Cellcept,Mycophenolate Mofetil,Mycophenolate Mofetil Hydrochloride,Mycophenolate Sodium,Mycophenolic Acid Morpholinoethyl Ester,Myfortic,RS 61443,RS-61443,Sodium Mycophenolate,Mofetil Hydrochloride, Mycophenolate,Mofetil, Mycophenolate,Mycophenolate, Sodium,RS61443
D011446	Prospective Studies	Observation of a population for a sufficient number of persons over a sufficient number of years to generate incidence or mortality rates subsequent to the selection of the study group.	Prospective Study,Studies, Prospective,Study, Prospective
D004359	Drug Therapy, Combination	Therapy with two or more separate preparations given for a combined effect.	Combination Chemotherapy,Polychemotherapy,Chemotherapy, Combination,Combination Drug Therapy,Drug Polytherapy,Therapy, Combination Drug,Chemotherapies, Combination,Combination Chemotherapies,Combination Drug Therapies,Drug Polytherapies,Drug Therapies, Combination,Polychemotherapies,Polytherapies, Drug,Polytherapy, Drug,Therapies, Combination Drug
D005260	Female		Females
D006084	Graft Rejection	An immune response with both cellular and humoral components, directed against an allogeneic transplant, whose tissue antigens are not compatible with those of the recipient.	Transplant Rejection,Rejection, Transplant,Transplantation Rejection,Graft Rejections,Rejection, Graft,Rejection, Transplantation,Rejections, Graft,Rejections, Transplant,Rejections, Transplantation,Transplant Rejections,Transplantation Rejections
D006085	Graft Survival	The survival of a graft in a host, the factors responsible for the survival and the changes occurring within the graft during growth in the host.	Graft Survivals,Survival, Graft,Survivals, Graft