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Background: Skin cancer is a primary health concern in renal transplant recipients (RTRs). Existing research mainly stems from North America, Europe, and Australia, with limited data from Latin America., Methods: This 56-year (1967-2023) retrospective cohort study explores skin cancer incidence in Mexican RTRs. Our objective was to assess the long-term incidence of malignant cutaneous neoplasms in Mexican RTRs., Results: Over 56 years, 1642 RTRs (58% male) were studied. Median follow-up was 8.4 years; median age at transplantation was 32.6 years. Skin cancer incidence was 6.6% (95% CI: 5.5-7.9), with an incidence density rate of 6.5 (95% CI: 5.4-7.9) per 1000 person-years and a median latency of 9.8 years. Incidence increased with longer transplantation-related immunosuppression (TRI), with a relative risk for >30 years of TRI of 4.8 (95% CI: 2.6-9.1) for any skin cancer and 7.5 (95% CI: 3.8-14.6) for squamous cell carcinoma (SCC). SCC was the most common malignancy (76.1%), followed by basal cell carcinomas (BCC), with a 3.6:1 ratio. Metastatic SCC occurred in 6.5% of skin cancer patients, with a skin cancer-related mortality rate of 2.7%. Limitations of the study include its single-center and retrospective design and unassessed factors such as human papillomavirus infection and sun exposure., Conclusions: Our study provides unique insights into the epidemiology of skin cancer among Mexican RTRs. It constitutes the largest cohort of skin cancer cases among RTRs in Mexico and, to our knowledge, in Latin America. Despite the lack of recognition of a high skin cancer incidence in non-White RTRs, our 6.6% incidence underscores the need to enhance surveillance programs., (© 2024 the International Society of Dermatology.)

Background: Chronic kidney disease (CKD) is a global health problem. As it progresses to end stages, renal replacement therapy is required but ultimately, the best treatment is transplantation. Decreased renal function has been associated with an inflammatory state associated to primary CKD and in kidney transplant recipients (KTRs)., Objective: To establish how the serum concentrations of some cytokines, such as interleukin (IL)-2, IL-8, IL-22, IL-17α, interferon-gamma, IL-4, and transforming growth factor-β, correlate with various CKD stages., Methods: One hundred and forty-one KTRs between the ages of 18 and 75 years were included in the study. We also included 112 live kidney donors, 37 CKD PG CKD+3 , and 76 GP healthy . Participants were grouped according to their glomerular filtration rate (GFR) and their circulating cytokine levels, previously quantified by ELISA., Results: By linear regression analysis, we established the relation of each cytokine with the GFR. Transforming growth factor-β correlated positively with the GFR in the study population, except in healthy individuals. A negative correlation of IL-8 and IL-17α and GFR was found in all cases., Conclusions: Whether these cytokines (IL-8 and IL-17α) could be used as inflammatory biomarkers indicating CKD progression, regardless of the type of population, remains to be prospectively determined., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

Background and Aims: Oxidative stress (OS) induces the production of fibroblast growth factor 21 (FGF21). Previous data have revealed that FGF21 protects cells from OS injury and death, making it a potential therapeutic option for many diseases with increased OS. However, the association of this growth factor with OS markers in humans with chronic kidney disease (CKD) remains unknown. This study aims to evaluate the association of serum FGF21 with serum total antioxidant capacity (TAC) and oxidized low-density lipoproteins (OxLDL) in subjects in different stages of kidney disease., Methods: This is a cross-sectional study that included 382 subjects with different stages of CKD, irrespective of type 2 diabetes (T2D) diagnosis. Associations of serum FGF21 with OxLDL, TAC, sex, age, body mass index (BMI), fasting plasma glucose, estimated glomerular filtration rate (eGFR), T2D, and smoking, were evaluated through bivariate and partial correlation analyses. Independent associations of these variables with serum FGF21 were evaluated using multiple linear regression analysis., Results: Serum FGF21 was significantly and positively correlated with age ( r  = 0.236), TAC (lnTAC) ( r  = 0.217), and negatively correlated with eGFR ( r  = -0.429) and male sex ( r  = -0.102). After controlling by age, sex, BMI, T2D, smoking, and eGFR; both TAC and OxLDL were positively correlated with FGF21 ( r  = 0.117 and 0.158 respectively, p  < 0.05). Using multiple linear regression analysis, eGFR, male sex, T2D, OxLDL, and TAC were independently associated with serum FGF21 (STDβ = -0.475, 0.162, -0.153, 0.142 and 0.136 respectively; p  < 0.05 for all) adjusted for age, BMI, smoking, and fasting plasma glucose., Conclusion: A positive association between serum FGF21 and OS has been found independently of renal function in humans. Results from the present study provide novel information for deeper understanding of the role of FGF21 in OS in humans with CKD and T2D; mechanistic studies to explain the association of serum FGF21 with oxidative stress in CKD are needed., Competing Interests: Conflict of interest statement: The authors declare that there is no conflict of interest., (© The Author(s), 2021.)

Regulatory T cells play an important role in the control of autoimmune diseases and maintenance of tolerance. In the context of transplantation, regulatory T cells (Tregs) have been proposed as new therapeutic tools that may induce allospecific tolerance toward the graft, avoiding the side effects induced by generalized immunosuppressors. Although most clinical trials are based on the use of thymic Tregs in adoptive therapy, some reports suggest the potential use of in vitro induced Tregs (iTregs), based on their functional stability under inflammatory conditions, indicating an advantage in a setting of allograft rejection. The aim of this work was to generate and expand large numbers of allospecific Tregs that maintain stable suppressive function in the presence of pro-inflammatory cytokines. Dendritic cells were derived from monocytes isolated from healthy donors and were co-cultured with CTV-labeled naïve T cells from unrelated individuals, in the presence of TGF-β1, IL-2, and retinoic acid. After 7 days of co-culture, proliferating CD4 + CD25 ++ CTV - cells (allospecific iTregs) were sorted and polyclonally expanded for 6 weeks in the presence of TGF-β1, IL-2, and rapamycin. After 6 weeks of polyclonal activation, iTregs were expanded 230,000 times, giving rise to 4,600 million allospecific iTregs. Allospecific iTregs were able to specifically suppress the proliferation of autologous CD4 + and CD8 + T cells in response to the allo-MoDCs used for iTreg generation, but not to third-party allo-MoDCs. Importantly, 88.5% of the expanded cells were CD4 + CD25 + FOXP3 + , expressed high levels of CCR4 and CXCR3, and maintained their phenotype and suppressive function in the presence of TNF-α and IL-6. Finally, analysis of the methylation status of the FOXP3 TSDR locus demonstrated a 40% demethylation in the purified allospecific iTreg, prior to the polyclonal expansion. Interestingly, the phenotype and suppressive activity of expanded allospecific iTregs were maintained after 6 weeks of expansion, despite an increase in the methylation status of the FOXP3 TSDR. In conclusion, this is the first report that demonstrates a large-scale generation of allospecific iTregs that preserve a stable phenotype and suppressor function in the presence of pro-inflammatory cytokines and pave the way for adoptive cell therapy with iTregs in transplanted patients., (Copyright © 2020 Alvarez-Salazar, Cortés-Hernández, Arteaga-Cruz, Alberú-Gómez and Soldevila.)

Introduction: Ureteral stricture (US) in the kidney transplant recipient is a rare complication that can lead to morbidity and graft loss. Risk factor recognition is crucial in the prevention and management of this entity. Delayed graft function (DGF), as defined by the need for dialysis in the first week after transplantation, has been proposed as a risk factor in previous studies. Our objective is to determine the impact of DGF in US development in kidney transplant patients., Methods: We designed a matched case-control study. US cases in kidney transplant recipients were identified in the 2008-2017 period. We defined US as the rise in serum creatinine associated with findings suggesting obstruction in ultrasound, scintigraphy, or retrograde pyelogram; any other cause of graft dysfunction was excluded. Controls were defined as kidney transplant recipients from the same population and period without US, matched in a 1:2 fashion by age, sex, and donor type., Results: From 532 kidney transplant patients, 31 cases and 62 controls were included. Cumulative US incidence was 58 per 1000 cases. When calculating for odds ratio (OR), post-operative urinoma (OR 3.2; 95% confidence interval [CI] 2.36-4.37) and ureteral duplication (OR 3.29; 95% CI 2.40-4.51) were associated with an increased risk for US, while DGF was not found to be statistically significant as a risk factor (OR 3.3; 95% CI 0.96-11.52). No statistically significant differences were found between groups in other pre- and post-transplant-related factors CONCLUSIONS:: DGF was not associated with US in our cohort; however, ureteral duplication and postoperative urinoma were associated with an increased risk of graft ureteral stenosis development.

It is often unclear to the clinical investigator whether observational studies should be submitted to a research ethics committee (REC), mostly because, in general, no active or additional interventions are performed. Moreover, obtaining an informed consent under these circumstances may be challenging, either because these are very large epidemiological registries, or the subject may no longer be alive, is too ill to consent, or is impossible to contact after being discharged. Although observational studies do not involve interventions, they entail ethical concerns, including threats such as breaches in confidentiality and autonomy, and respect for basic rights of the research subjects according to the good clinical practices. In this context, in addition to their main function as evaluators from an ethical, methodological, and regulatory point of view, the RECs serve as mediators between the research subjects, looking after their basic rights, and the investigator or institution, safeguarding them from both legal and unethical perils that the investigation could engage, by ensuring that all procedures are performed following the international standards of care for research. The aim of this manuscript is to provide information on each type of study and its risks, along with actions to prevent such risks, and the function of RECs in each type of study., (Copyright: © 2019 Permanyer.)

Vulnerability in research occurs when the participant is incapable of protecting his or her interests and therefore, has an increased probability of being intentionally or unintentionally harmed. This manuscript aims to discuss the conditions that make a group vulnerable and the tools and requirements that can be used to reduce the ethical breaches when including them in research protocols. The vulnerability can be due either to an inability to understand and give informed consent or to unequal power relationships that hinder basic rights. Excluding subjects from research for the only reason of belonging to a vulnerable group is unethical and will bias the results of the investigation. To consider a subject or group as vulnerable depends on the context, and the investigator should evaluate each case individually., (Copyright: © 2019 Permanyer.)

Objectives: Here, we describe the presentation, treatment, and outcomes of acute appendicitis in kidney transplant recipients at a tertiary care hospital in Mexico City., Materials and Methods: We conducted a retrospective case series study at a tertiary care hospital in Mexico City from January 2000 to January 2015., Results: During our study period, 1186 patients received a kidney transplant; among these patients, we identified 10 cases of acute appendicitis (0.008%). Four patients (40%) were diagnosed on day 5 of symptom onset. Nine patients (90%) showed abdominal pain, 2 patients (20%) presented with a typical migratory pattern, and 2 patients (20%) showed symptoms of small bowel intestinal obstruction. Thirty percent of patients (3/10) presented a rule-out Alvarado score (≤ 3 points). A computed tomography scan was performed in all but one patient; among these 9 patients, 1 (11.1%) had a false-negative result. Among all patients with acute appendicitis, 50% (5/10) presented with a periappendiceal abscess and 40% (4/10) showed localized peritonitis. An open and laparoscopic appendectomy was performed in 7 of 10 patients (70%) and 3 of 10 patients (30%), respectively. All patients received ceftriaxone plus metronidazole or ertapenem for 5 to 7 days. There were no reported treatment failures or recurrence of symptoms., Conclusions: The diagnosis of acute appendicitis in kidney transplant recipients requires a high index of suspicion. Kidney transplant recipients with acute appendicitis had good outcomes with a therapeutic approach similar to that used in the general population.

Problem: The effect of donor/recipient age disparity on living-donor renal graft function is controversial. The objective of this study is to find new clinical predictors of renal graft function and evaluate the effect of donor/recipient age disparity in our series., Methods: A retrospective review of our institutional renal transplantation database was performed. We calculated the glomerular filtration rate of our patients with the Chronic Kidney Disease Epidemiology Collaboration formula. Our receptors were categorized using a cut-off of 60 ml/min calculated glomerular filtration rate. An index called "Donor/Recipient Age Index" was created based on the interaction between donor/recipient ages. Univariable and multivariable regression analysis were performed. The Mantel-Cox model was used for statistical analysis., Results: A total of 220 donor/recipient pairs were selected from January 2005 to August 2013. Only 186 pairs completed the one-year follow-up. The mean age of the donors was 35.3 ± 10.4 years and 31.6 ± 11.7 years for the recipients. The Donor/Recipient Age Index significantly predicted a glomerular filtration rate < 60 ml/min at one-year follow-up in univariable (p = 0.02) and multivariable (p = 0.033) regression models., Conclusion: We propose the Donor/Recipient Age Index as a significant predictor of long-term graft function.

Introduction: Donor-to-recipient gender match and mismatch may be a potential prognostic factor for living donor renal graft function., Methods: A retrospective review of donor-to-recipient pairs undergoing living donor kidney transplantation was done. They were classified according to gender match as: male-to-male, female-to-female, male-to-female, and female-to-male. Serum creatinine was recorded during one year for donors and for up to four years for recipients. Renal function was evaluated by estimating the glomerular filtration rate with the Chronic Kidney Disease-Epidemiology Collaboration formula. A comparative statistical analysis was performed., Results: The analysis included 217 donor-to-recipient pairs. No significant differences across the four groups in estimated glomerular filtration rate and serum creatinine at any cut-off time point except at day one serum creatinine were found. Recipients had a significant difference in serum creatinine up to the first year of follow-up, with higher values for male recipients; no significant differences were found during the second through fourth year of follow-up. A significant difference was observed in estimated glomerular filtration rate throughout all follow-ups among the four groups, favoring female recipients of male kidneys., Conclusions: Donor-recipient mismatch may have a deleterious effect over long-term graft function. Female recipients of male kidneys have the best prognosis.

Background: Non-melanoma skin cancer (NMSC) is the most common malignancy in transplant patients. The incidence of basal cell carcinoma (BCC) is 10 times greater than in the general population, while squamous cell carcinoma (SCC) is 100 times greater. The relationship between the BCC and SCC reverses and increases according to the degree of immunosuppression and sun exposure. One way to predict the risk of NMSC should be based on factors such as: total sun burden factor (TSB)., Objective: To determine the influence of various risk factors in the development of NMSC and its relation to the type and duration of immunosuppressive treatment, type of transplant, and TSB., Methods: We worked with a fledgling historical cohort in which patients with kidney or liver transplant were identified and recorded if they developed some form of skin cancer. To study the factors associated with NMSC, we resorted to the strategy of a case-control study. Dermatological examination was performed and a questionnaire of risk factors made in both groups., Results: Of the 140 patients enrolled, 51 were women and 89 men, 120 were renal transplant recipients and 20 liver transplants. Of patients who developed NMSC, 100% were renal transplant recipients. The median age was 48.5 years. Most cancer patients worked outdoors. A total of 78 lesions were found in 40 NMSC patients, 59 (76%) of them were SCC, and 19 (24%) BCC; 45% of all skin cancer patients had more than one injury. The worst affected areas were those photoexposed: 60% head and neck, trunk and upper extremities 18% 50%. In 30% of patients (12/40) 22 new tumors were identified (SCC 18 and BCC 4). No lesions were identified for melanoma. In multivariate logistic regression analysis, statistically significant features were: type-based immunosuppressive regimen of cyclosporine A, azathioprine and prednisone (OR: 59.7; 95% CI: 10.2-348), TSB > 10 (OR: 19; 95% CI: 3-120) and duration of use of immunosuppressive therapy (OR: 1.06; 95% CI: 0.9-1.1). The mean time from transplantation to first dermatological assessment was six years (+5.4). Of the patients, 93% had not regularly used sunscreen before and after transplantation., Conclusions: The dermatological assessment is convenient and easy to perform. Primary prevention, close monitoring, diagnosis, and treatment of skin lesions are essential components of a comprehensive program for the evaluation of transplant recipients, the purpose of which is to reduce the incidence and morbidity associated with cancer.

Introduction: Acute rejection has been identified as the main cause of renal graft dysfunction during the first year after transplantation; it is associated with chronic structural and functional damage, which causes loss of graft and decrease in patient survival., Material and Methods: We performed a retrospective and descriptive research consisting in a review of the final reports of biopsies performed due to renal graft dysfunction during the postransplant period. Patients included were transplanted at the Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán (INCMNSZ) from January 2007 to December 2011., Results: A total number of 223 patients underwent renal transplantation during the period considered for this study purpose, 222 biopsies were performed due to renal graft dysfunction in 118 patients (52.9%). 74.5% of patients developed graft dysfunction in the first year after transplantation. The main histopathological findings reported were immunologic events in both living donor (LDRTR) and deceased donor renal transplant recipients (DDRTR), borderline changes were the most common diagnosis. The median time to detect immune events as cause of dysfunction was shorter for DDRTR and they tend to occur in the first 4 months after transplantation., Conclusion: We observed an incidence of 11.8% for acute rejection in the first year after transplantation for LDRTR and 17.4% for DDRTR. Further studies are needed to determine the causes of immunological events and their implications in the evolution of renal graft and patient's survival.

Background: HLA and MICA antibodies are increasingly associated with poorer graft survival. The aim of this study is to report the frequency of graft loss 2 years after the detection of HLA abs and MICA abs among a group of kidney transplant recipients., Methods: We tested 196 patients with a functioning graft. Sera were screened for HLA and MICA IgG abs by Luminex, using the LABScreen Mixed, and LABScreen PRA. The sera were screened for MICA abs by Luminex., Results: Of 196 kidney transplant recipients (mean age 36.7 years, 42% female), one hundred twenty four (63.3%) were negative to all tested abs, and 72 (36.7%) were positive for: HLA abs alone = 34, MICA abs alone = 29, and HLA+MICA abs = 9. At a median followup of 20.5 (1.2-25.2) months, 8 patients lost their grafts due to biopsy-confirmed chronic allograft injury: 2/124 (1.6%) ab-negative, and 6/72 (8.3%) ab-positive, with a significantly lower survival for the Ab-positive group (p = 0.046, log-rank test)., Conclusions: The presence of circulating abs was associated with an increased risk of graft loss, and the coexistence of HLA and MICA abs increases the risk of graft loss.

Systemic hypertension after kidney transplant (HAPT) has been associated with a reduction in graft survival and increased morbidity and mortality of kidney transplant recipients. With the use of calcinuerin inhibitors, prevalence of HAPT has increased to 60-80%. The purpose of this study was to document the prevalence of HAPT in kidney transplant recipients attending the Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán" associated risk factors and the effect of hypertension in long term graft survival. We retrospectively reviewed the clinical charts of all the patients that underwent kidney transplant from 1984 to 1994. The following risk factors were studied: age, gender, cause of renal failure, presence of hypertension before kidney transplant, histocompatibility, acute rejection episodes, chronic rejection, serum creatinine values and use of cyclosporine. We divided subjects in two groups: normotensive (NT) and hypertensive (HT). HAPT included 3140/90 mmHg blood pressure level observed at least during two consecutive evaluations or the use of antihypertensive medication. We analyzed 215 grafts from 205 patients (10 patients had two kidney transplants); mean age at transplant of 30 +/- 9 years, 131 subjects were female and 84 male. One hundred and eighty eight patients (88%) displayed pretransplant hypertension. The mean follow up was 56+/-32 months. In the postransplant period 152 (71%) were HT and 63 (29%) NT. The HT group had significantly higher blood pressure and serum creatinine values than the NT group (P < 0.001), in spite of an adequate blood pressure control in 65% of the patients from the HT group. The NT group displayed a higher graft survival than the HT group; 60 +/- 30 months vs. 51 +/- 32 months respectively (p<0.01). Multivariate analysis did not show any risk factors independently associated with the development of HAPT. The prevalence of HAPT in our series is similar to the one reported in the literature. During the postransplant period there was a reduction of hypertensive patients (88% pretransplant vs. 71% postransplant). HAPT is a significant risk factor associated with long term survival of the graft.