THERAPEUTIC STRATEGIES FOR KIDNEY TRANSPLANTATION

L.S. Re, J. Petroni, M.C. Rial, O.E. Guardia, T. Galdo, J. Goldberg, D. Casadei
Renal Transplantation, Instituto de Nefrología, Buenos Aires/ARGENTINA

Body: Introduction. CNI-associated nephrotoxicity and subclinical humoral rejection are important causes of long term allograft deterioration. Our center started to use a CNI-free immunosuppressive protocol in January 2001 based on Thymoglobulin induction followed by Sirolimus, MMF and steroids, reporting excellent results in terms of graft and patient survival and renal function after 5 years of follow-up. Objective:
To evaluate the impact of post.transplant aloimmune response in a cohort of long term (>3 years) transplanted patients treated with a CNI-free protocol Patients and methods
421 patients were treated with this immunosuppressive combination from 01/12/01 to 02/15/10. 256 (61%) are on follow-up. We randomly selected a sample of 40 patients with at least 3 years of post-transplant evolution for determination of Class I and Class II HLA antibodies by Luminex assay and for protocol biopsies with determination of C4d deposition and assessment of the severity of the chronic lesions. We used the chronic Banff’ 97 classification (cg, ct, ci, cv) and we compared each individual score between T0 and protocol biopsies. Results: HLA antibodies: 11/40 (27.5%) were positive for HLA antibodies as determined by Luminex assay ( low HLA class I = 3 low HLA class II= 2, moderate HLA class II: 2; both Ab in different concentrations = 4)). No difference was observed between Ac + or – patients in terms of creatinine clearance ( Ab - 54.44 ± 19.26 ml/min, vs Ab + 51.16 ± 21.18 ml/min p=0.45) and proteinuria ( Ab- 0.31± 0,92 mg/dl vs Ab + 0,17 ±0,27 mg/dl p= 0,65). Biopsies: The protocol biopsies were performed 1703 ± 670 post transplant.T0 biopsies: normal= 11; CAN I= 26; CAN II= 3 . Protocol biopsies: normal= 4; CAN I= 30; CAN II = 6. The comparison between both different biopsies showed CAN progression in 13 cases (32.5%) and no progression in 27 cases ( 62.5%). Histological progression was more frequent in HLA Ab + patients (5/11 vs 5/29, p= 0.07). C4d deposition: 4 patients (10%). 2 peritubular, no antibodies were detected in these patients; 2 periglomerular, both patients had HLA Class II Ab (1 low, 1 moderate) and the biopsy showed transplant glomerulopathy.
Discussion: The incidence of post-transplant HLA Ab positivity was similar to that observed in other series with different IS protocols. HLA Ab positivity was not associated with differences in creatinine clearance or proteinuria, maybe due to the small sample size, but it was associated with histological deterioration.The global low histological progression of the chronic lessions (cg, ct, ci, cv) confirm the low nephrotoxicity of this immunosuppressive combination. A longer follow-up and the determination of HLA specificities are mandatory. Conclusion: The utilization of a CNI-free immunosuppressive protocol is associated with: excellent results in terms of graft function and patient survival ; incidence of post transplant antibodies detection similar to that observed with other IS combinations; low progression rate of histological lesions in the long term and better evolution in those patients Ab - by Luminex assay. The results of HLA specificities will be presented at the Congress.

Disclosure: All authors have declared no conflicts of interest.