Malignancies after renal transplantation: experience of a Mexican referral center.

OBJECTIVE: To report the incidence of cancer after renal transplantation at a referral center in a developing country. MATERIALS AND METHODS: Consecutive patients receiving renal transplantations during a 48-year period at Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran were analyzed. The standardized incidence ratio (SIR) was calculated based on data from GLOBOCAN 2012. RESULTS: From 1257 patients, 98 (8%) developed 143 malignancies. The SIR of all the cohort was 4.1 (95% CI 3.2-5.1). The relative risks of male and female transplant recipients were 4.6 and 3.5 times greater than the risk of cancer of the general population, respectively. The most common malignancy was non-melanoma skin cancer (52%). The malignancy that associated with the greater relative risk was Kaposi sarcoma (SIR: 200), followed by lymphomas (SIR: 30). A multivariate analysis comparing patients with cancer and controls confirmed that receiving a three-drug regimen as final treatment, prolonged immunosuppression, and patients undergoing a second renal transplantation were factors associated with increased cancer development. CONCLUSION: To date, there is paucity of data from developing countries. We reported the results from a National Health Institute in Mexico including a large cohort with a long follow-up, demonstrating differences within frequencies and risks compared to other regions of the world.

Ex vivo expansion of regulatory T cells from long-term Belatacept-treated kidney transplant patients restores their phenotype and suppressive function but not their FOXP3 TSDR demethylation status.

We recently reported that Tregs from long-term Belatacept-treated kidney transplant patients displayed an altered phenotype and impaired suppressive function compared to Tregs from healthy controls. However, it remains unknown whether ex vivo expansion of Tregs from patients who underwent long-term immunosuppression may be feasible to be used in their treatment. In this work, Tregs from Belatacept-treated patients were polyclonally expanded in vitro in the presence of rapamycin and IL-2. After four weeks of expansion, Tregs from patients expressed high levels of FOXP3, CD25, CTLA-4, Helios and CCR7, and showed strong suppressive activity, even in the presence of pro-inflammatory cytokines. However, FOXP3 TSDR demethylation remained lower in expanded Tregs from Belatacept-treated patients compared to healthy control Tregs. These data suggest that ex vivo expansion of Tregs from patients undergoing long-term immunosuppression may require the use of epigenetic modifying agents to stabilize FOXP3 expression to be considered as treatment in kidney transplant patients.

Functional Outcomes 18 Months After Total and Midarm Transplantation: A Case Report.

BACKGROUND: The function reported after arm transplantation is deemed beneficial relative to the marked disability that upper arm amputation causes. OBJECTIVE: We report a 51-year-old man with a Disabilities of the Arm, Shoulder and Hand (DASH) score of 75.83 who underwent bilateral arm transplantation in October 2015. PROCEDURE: The right arm was transplanted at the glenohumeral joint level, including transplantation of the humeral head, joint capsule, and rotator cuff ligaments and tendons. Additionally, neurorrhaphies were performed at the origin of the terminal branches of the brachial plexus, including the axillary and musculocutaneous nerves. Therefore, this was considered a total arm transplantation. The left arm was transplanted at the transhumeral level, with complete transplantation of the biceps and triceps brachii, and terminolateral neurorrhaphy of the donor musculocutaneous nerve to the receptor radial nerve. A maintenance triple immunosuppression scheme was administered, with tacrolimus levels kept at 10 ng/mL. RESULTS: At 18 months post-transplantation, the intrinsic musculature in the left hand showed electrical registry, DASH score was 67.5, Carroll test score was 28 in both extremities, Hand Transplant Score System was 67.5 in the right extremity and 77.5 in the left extremity, and Short Form-36 score was 96.1. The patient was healthy, with restored body integrity. He could lift medium-sized weightless objects, eat and go to the bathroom by himself, drink liquids with bimanual grasp, swim, dress almost independently, and drive. CONCLUSION: The functional evolution of the patient was similar to previously reported transplanted arms, even though the right arm transplant involved the glenohumeral joint and axillary and musculocutaneous nerve repair.

Hand-assisted laparoscopic versus open donor nephrectomy: a retrospective comparison of perioperative and functional results in a tertiary care center in Mexico.

BACKGROUND: Laparoscopic nephrectomy for living donors is the current procedure of choice. Hand-assisted laparoscopic donor nephrectomy (HALDN) is the variation of this technique currently used in our institution. Though the advantages and disadvantages have been described for this procedure, the graft function compared with open surgery has been shown to be equal. We compared the outcomes of patients undergoing the former standard open donor nephrectomy (ODN) versus the current HALDN technique. METHODS: In this retrospective, comparative, and analytic study we reviewed our institutional database of renal transplantation procedures from January 2005 to April 2011 for perioperative variables and 1-year follow-up data. Donor renal function was evaluated with serum creatinine concentrations and estimated glomerular filtration rates with the Chronic Kidney Disease-Epidemiology formula. Complications were reported with the Clavien-Dindo classification. RESULTS: The 190 consecutive donors included 99 ODN and 91 HALDN, who did not show baseline differences. ODN had a shorter mean operative time (217 ± 57.5 vs 270 ± 60.1 minutes) and shorter warm ischemia time (2.12 ± 1.4 vs 4.62 ± 2.7 minutes). HALDN had less operative blood loss (274.4 ± 198.1 vs 202.99 ± 157.1 mL) and shorter in-hospital stay (5.58 ± 2.2 vs 4.23 ± 1.8 days). There were no significant differences in 30-day surgical complications or transfusion requirements. No graft loss was reported. No difference in renal function was observed between the groups at days 1-2 or months 1, 6, or 12 after nephrectomy. CONCLUSIONS: Laparoscopic surgery has replaced conventional open surgery for living renal donors. HALDN is a safe and successful procedure compared with ODN. It is now the procedure of choice in our institution.

Role of major histocompatibility complex and ethnicity in acute renal graft rejection.

BACKGROUND: The major histocompatibility complex (MHC) plays a main role in antigen presentation. Class I, II, and III genes form defined "blocks" of conserved DNA sequences (conserved extended haplotypes) that are useful to follow the ancestry of a population. Each variant encodes a specific peptide that determines a particular individual's immune response. In addition, differential expression of HLA antigens in certain physiological and pathological conditions may participate in the pathogenesis of allograft rejection versus tolerance. OBJECTIVES: The aim of this study was to determine whether the specific HLA ancestry was associated with acute renal graft rejection among the Mexican mestizo population. MATERIALS AND METHODS: We studied 544 Mexican mestizo renal donors and their respective recipients for their serologically determined HLA and based on antigens haplotype assignments. The acute rejection group was compared with the nonrejection group among donors and recipients, correspondingly. RESULTS: Frequent Mexican alleles were observed in this study. Moreover, HLA-B*61/-DR*04, HLA-A*35/-DR*06 (Amerindian ancestry), HLA-A*68/-DR*01, HLA-A*28/-B*65/-DR*01 (African ancestry), and HLA-A*33/-B*65 (Caucasian ancestry) in donors were associated with acute renal graft rejection episodes. CONCLUSION: Knowing the ancestry of a donor's HLA molecules may help to individualize immunosuppressive therapy for posttransplant surveillance, because they may be more membrane-exposed in parenchymal cells, making them more susceptible of being recognized by the recipient's immune system.