Antonio Franco

Immunological Aspects of a Case of Posttransplant Lymphoproliferative Disorder

We describe a female renal transplant recipient with cytomegalovirus and Epstein-Barr virus (EBV) infections who developed aggressive polymorphous polyclonal B cell proliferation. She received two courses of OKT3. We found a majority of transformed B cells bearing EBV membrane receptor CR2 and EBV nuclear antigen. Posttransplant lymphoproliferative disorders may be associated with a significant immunological activation, detected in this case by the sudden increase of beta 2-microglobulin and immunoglobulin levels, including immunoglobulin D. These raised levels persisted throughout the short and rapid course of the disease.

Mammalian Target of Rapamycin Inhibitor Monotherapy: Efficacy in Renal Transplantation.

BACKGROUND Calcineurin inhibitors (CNI) have failed to improve long-term outcomes in renal transplantation. Anti-proliferative and anti-angiogenic effects of mammalian target of rapamycin inhibitors (m-TOR) without nephrotoxicity could improve long-term survival in selected transplant recipients. METHODS We examined the evolution of 98 low-immunological risk renal transplant recipients on m-TOR monotherapy: 7 patients had induction without CNI and 91 were switched to m-TOR at 12 (p25-p75: 4-36) months after transplant. RESULTS Median follow-up time was 46 (p25-p75: 28.5-72.0) months. Fifteen recipients dropped out of the study (15.3%): 8 patients (8.2%) had to change their immunosuppressive treatment because of complications and 7 (7.1%) lost their grafts as a result of chronic rejection (4 cases) or death with a functioning graft (3 cases). At the end of follow-up, 83 of 98 (84.6%) recipients remained on monotherapy. The rates of recipient and graft survivals were 100% and 98.8% at 2 years and 96.9% and 93.5% at 4 years; the percentages of patients on monotherapy after 2 and 4 years were 95.2% and 85.2%, respectively. Renal function improved significantly and proteinuria decreased but not significantly. Those patients switched to m-TOR significantly received more erythropoietin, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, and hypotensive agents than before starting m-TOR, whereas there were no significant changes related to the use of statins, body weight, or percentage of diabetic patients. No case of non-compliance was reported. CONCLUSIONS This study supports the safety and efficacy of monotherapy with m-TOR in selected renal transplant recipients.

Apolipoprotein A-Ib as Biomarker of FSGS Recurrence After Kidney Transplantation: Diagnostic Performance in a Prospective Cohort and Assessment of its Prognostic Value

Grupo Español de actualización en Transplante (GREAT). Background Recurrence of idiopathic FSGS is a serious complication after kidney transplantation. Currently, there are no accurate means to diagnose the relapses or to detect the patients at risk. In a previous study we detected Apolipoprotein A-Ib (ApoA-Ib) specifically in urine of kidney transplanted patients that showed recurrence of FSGS. In the present work we aim to confirm the diagnostic performance of ApoA-Ib to detect FSGS recurrence and assess its possible prognostic value. Methods Between January 2013 and December 2015 a urine sample was obtained in three groups of kidney transplant patients treated at the nephrology department of 16 major Spanish hospitals: FSGS patients that relapsed after kidney transplantation (FSGS-R), FSGS patients that did not show recurrence after kidney transplantation (FSGS-NR) and non-FSGS kidney transplanted patients (No-FSGS). ApoA-Ib was determined in the urine of these patients by immunodetection. To assess the ApoA-Ib predictive ability of detecting patients at risk of relapse, 33 patients with idiopatic FSGS were included before transplantation. Thirteen of them were transplanted and followed up to 1 year after transplantation. In these patients ApoA-Ib was periodically determined. Results In the FSGS-R group 14 out of 15 (93.3 %) were positive for apoA-Ib whereas only 2 out of 22 (9.1 %) in the FSGS-NR group and 3 out of 24 (12.5 %) in the No-FSGS group tested positive for ApoA-Ib (P value < 0.001). ApoA-Ib sensitivity and specificity to detect FSGS recurrence were 94.1% and 90.9% to discriminate non-relapsing FSGS patients or 94.1% and 87.5% to discriminate transplanted patients without FSGS as the primary disease. These results were consistent with the obtained in our previous cohort of FSGS patients. The presence of ApoA-Ib in urine was only related to FSGS recurrence and was independent of proteinuria levels or renal function. ApoA-Ib was present in 37.9 % of the FSGS patients before transplantation which is similar to the FSGS recurrence incidence after transplantation (30-50 %). Four of the 13 followed patients showed FSGS recurrence. ApoA-Ib predated FSGS relapse in 4 out of 5 recurrence episodes observed in 4 patients, while in 9 patients who did not relapse ApoA-Ib was negative in 37 out of 38 samples. Conclusions ApoA-Ib has the potential to be a good complementary diagnostic biomarker of FSGS relapses after transplantation, providing a confident exclusion of relapse even in the presence of high proteinuria. It has also a potential to detect patients at risk of relapse, even before transplantation, which should be further evaluated in a larger cohort. The authors thank Oreto Prat, Estefanía Lozano and Anna Caraben for their technical assistance. Grupo Español de Actualización en Trasplante (GREAT, Spanish Group for New Projects in Transplantation): Carme Cantarell (Hospital Vall d’Hebron, Barcelona), Lluis Guirado (Fundació Puigvert, Barcelona), Francisco Gonzalez Roncero (Hospital Virgen del Rocio, Sevilla), Juan C. Ruiz San Millan (Hospital Marqués de Valdecilla, Santander) Carlos Jiménez (Hospital Universitario La Paz, Madrid), Isabel Beneyto (Hospital La Fe, Valencia), Sofia Zárraga (Hospital de Cruces, Barakaldo), Javier Paul (Hospital Miguel Servet, Zaragoza), Vicenç Torregrosa (Hospital Clínic, Barcelona), Ricardo Lauzurica (Hospital Germans Trias i Pujol, Badalona), Angel Alonso (Hospital de A Coruña, A Coruña), Carmen Díaz (Hospital Central de Asturias, Oviedo), Ana Fernández (Hospital Ramón y Cajal, Madrid), Auxiliadora Mazuecos (Hospital Puerta del Mar, Cadiz), Domingo Hernández (Hospital Carlos Haya, Malaga), Alberto Rodriguez (Hospital Reina Sofia, Cordoba), Antonio Osuna (Hospital Virgen de las Nieves, Granada), Antonio Franco (Hospital General, Alicante), Luisa Jimeno (Hospital Virgen de la Arrixaca, Murcia), Marta Crespo (Hospital del Mar, Barcelona).

Hepatitis C Virus Infection in Kidney Transplant Recipients: Final Results from a Spanish Multicenter Study

Grupo Español De Actualizacion En Trasplante. Background HCV is a relevant negative prognosis factor for graft and transplant recipient survival.New direct-acting antivirals(DAA)allow us to solve this problem in an effective way.It is crucial to know their real impact in our daily practice. Methods Observational,retrospective and prospective study.We analyze treatment results with DAA,in kidney transplant(KT)recipients from 15 hospitals,regarding effectiveness,tolerance and impact on immunosuppression and renal function-proteinuria in a short-medium term. Results Until November 2017,226 KT recipients were included (9combined liver- kidney transplants).69.7%male; average age 54.2±9yo;KT length 11.4±10years. More than 50%showed stage 3-4 chronic kidney disease. Immunosuppressive therapies: tacrolimus(70%) or cyclosporine (18%) with MMF(76%). Predominant genotype was 1b(68.1%), 1a(13.8%),3(7.8 %), 4(6%) and 2(4.3%);51% had grade 3-4 of fibrosis, 17% portal hypertension. The main DAA used was sofosbuvir(91%)combined with ledipasvir(55%), simeprevir(14%)or daclatasvir(13%);in 9 cases(7%)the combination of paritaprevir-ritonavir-ombitasvir-dasabuvir(3D)was employed;18% were treated with Ribavirin as coadjuvant. Side effects were limited,23.5 %,and without relevance, except for anemia caused by Ribavirin.2 patients interrupted the treatment, due to neurotoxicity caused by the interaction between 3D and tacrolimus and anemia caused by Ribavirin (both had virological response).All the patients that completed the treatment (213)are alive and show virological response in 98% of cases and with SVR-12.Liver function analysis improved: 74%normal vs 21% before the treatment (p<0.001). Renal function did not change significantly. Tacrolimus level at the end was lower with respect to the beginning (6.6 vs 7.3 ng/ml, p=0.03), in spite of a slight increase in the dose (3.5 vs 2.6 mg/day p=0.01). Conclusions DAA are highly effective in KT patients, with good tolerance,making it possible to solve the problem and having a good chance to improve the prognosis in our patients.The use of DAA in these patients requires special control and coordination with hepatologists, especially when 3D or Ribavirin is used.