Chronic Kidney Disease Risk Profile in Renal Donors in Aguascalientes, Mexico: A Retrospective Cohort Study.

BACKGROUND: In the last decade, kidney donation has been recognized as a risk factor for end-stage renal disease (ESRD). ESRD risk calculators have been recently perfected in North American populations. In Mexico, the rates of overweight, obesity, and diabetes mellitus (DM) are among the highest worldwide; nevertheless, most kidney transplants are obtained from living donors. This study aims to describe the risk profile for chronic kidney disease (CKD) development in kidney donors in a highly active transplant center in Central Mexico. METHODS: We conducted a retrospective, observational, descriptive cohort study of kidney donors followed at the Hospital Centenario Miguel Hidalgo (CHMH). We used the pretransplant CKD risk calculator at 15 years and over a lifetime (www.transplantmodels.com/esrdrisk). Aside from the calculator of kidney failure risk, we also used the calculator for postdonation CKD risk (www.transplantmodels.com/donesrd/). Factors associated with a glomerular filtration rate (GFR) <60 mL/min were evaluated by univariate and multivariate analysis. RESULTS: The study included 543 donors. The average follow-up period was 1.7 years (±2.7) with a median of 0.7 years (interquartile range, 0.2-2.1). The average predicted risk for ESRD development at 15 years was 0.08% (±0.1); 25.6% had a risk >0.1%, and only 1 patient had a risk >1%. The lifetime ESRD risk was 0.62% (±0.5); 15% had a risk >1%, and the greatest risk was 3.5%. The median of patients at risk of developing postdonation ESRD was 1 in 10,000 donors (0.6-1.5) at 5 years, 5.7 in 10,000 donors (3.5-8.8) at 10 years, 15 in 10,000 donors (9.1-23.2) at 15 years, and 31 in 10,000 donors (18.9-47.7) at 20 years. During the follow-up period, 52 patients developed a GFR of <60 mL/min. Both risk estimation formulas were significantly associated with a GFR of <60 mL/min. Among the individual factors, the GFR (hazard ratio 0.96, 95% confidence interval 0.94-0.97, P < .001) and the urinary albumin to creatinine ratio (hazard ratio 1.009, 95% confidence interval 1.005-1.01, P < .001) remained statistically significant. CONCLUSION: The risk of ESRD in kidney donors in Aguascalientes, Mexico, is similar to that described in the United States. Risk calculators are an indispensable decision-making tool to better understand kidney donors in our milieu.

High prevalence of end-stage renal disease of unknown origin in Aguascalientes Mexico: role of the registry of chronic kidney disease and renal biopsy in its approach and future directions.

BACKGROUND: Chronic kidney disease (CKD) is one of the pathologies with the greatest impact on the public health system. Over the last few decades, the relevance of CKD in Mexico has increased, with associated overwhelming costs for care of renal disease. There are no reliable CKD statistics in Mexico. METHODOLOGY: In June 2018, the government of Aguascalientes called on all Health Institutions to create a state registry of treated end-stage renal disease (ESRD). In the same system, a renal biopsy result registry included all the native kidney biopsies obtained in the state of Aguascalientes since 2012. We herein describe the prevalence, incidence and characteristics of the patients included in the CKD and renal biopsy registry in the state of Aguascalientes. RESULTS: As of April 2020, the state has documented 2827 patients on renal replacement therapy (RRT), 1877 on dialysis and 950 that have been transplanted. The prevalence of patients on dialysis is 1326 per million population (p.m.p.), and if transplanted individuals are included, it is 1997 p.m.p. The incidence of treated ESRD in 2019 was 336 p.m.p. (n = 474) in individuals with an average age of 45.6 years (standard deviation ±18), and in a higher proportion of men (61%). There is a bimodal distribution of the age at which RRT was initiated. The first and the most significant peaks are between the ages of 20 and 40 years and are usually the result of CKD of unknown cause (73%). The second peak is between 50 and 70 years of age, and CKD is usually the result of diabetes mellitus and systemic arterial hypertension (59.6%). Since January 2012, 423 biopsies have been recorded. The patient's ages were between 20 and 30 years (n = 112), and the most frequent diagnosis was focal segmental glomerulosclerosis (FSGS) (54%). CONCLUSIONS: The prevalence of treated ESRD in the state of Aguascalientes is high. The disease mostly afflicts young people between 20 and 40 years of age, and there is a clear male predominance. In this age group, the main clinical diagnosis is CKD of unknown origin, and the most frequent biopsy diagnosis was FSGS.

Changes in the commercial brand of tacrolimus lead to subtherapeutic trough levels and acute rejection in renal transplant recipients.

BACKGROUND: The vigilance of tacrolimus (TAC) trough levels is an essential part of renal transplant follow up. Reduced TAC trough levels and high variability are related to adverse outcomes. The aim of this study was to evaluate the impact of brand changes on tacrolimus (TAC) subtherapeutic (SubT) trough levels, acute rejection (AR), and kidney function. METHODS: This is a prospective, observational cohort study of renal transplant recipients, between January 2016 and October 2018. Tacrolimus trough levels and brand used by the patient were both registered at every consult. Tacrolimus values ≤3.5 ng/mL were considered SubT. RESULTS: 445 patients were included. The median number of TAC brand changes was 2 (IQR, 1-4). Patients were grouped according to the number of brand changes: Group 1 = 0 (n = 107), Group 2 = 1-4 (n = 236), and Group 3 = ≥5 (n = 102). Patients with the greatest number of brand changes had a greater proportion and number of SubT TAC trough levels (Group 1 = 36.4%, average 0.53; Group 2 = 39.8%, average 0.65, Group 3 = 59.8%, average 1.17, P < .001) and AR (Group 1 = 0.9%, Group 2 = 11%, Group 3 = 14.7%, P < .001). On multivariate analysis, SubT levels and the number of brand changes were related to AR. CONCLUSIONS: In Mexico, changes in TAC brand are associated with an elevated frequency of SubT levels. Brand changes and SubT levels are independently associated with acute rejection. The supply policies on TAC brands in Mexico require revision to avoid changing brands as much as possible.

Trasplantes en mmérica latina y el caribe: difusión del documento de aguascalientes / Transplants n laatin america and the caribbean: release of the aguascalientes document / Transpantes na aamérica latina e no caribe: difusão do documento de aguascaiientes

Durante el primer Foro de Bioética de la Sociedad de Trasplantes de Latinoamérica y el Caribe 2010 se redactó el Documento de Aguascalientes que busca salvaguardar la integridad del donante vivo. El artículo tiene por objeto indagar sobre el Documento de Aguascalientes entre los participantes del Congreso de la SLANH 2012. Se aplicó un cuestionario con 21 preguntas sobre temas abordados por el dicho documento. Los resultados muestran que el 36,3% acepta al donante vivo no relacionado; 36,3% considera que hay margen de crecimiento en la tasa de donantes fallecidos; 57,9% garantiza la salud con medicamentos inmunosupresores de calidad; 61,5% no conoce el documento. Se concluye que el Documento de Aguascalientes tiene recomendaciones útiles para vigilar aspectos bioéticos de trasplantes.

The Aguascalientes Document was drafted during the first 2010 Bioethics Forum of the Transplantation Society in Latin America and the Caribbean. The object of the document is to safeguard the integrity of the living donor. This article aims to investigate the Aguascalientes Document among the participants to the 2012 SLANH Congress. A questionnaire was applied, with 21 questions on topics covered by said document. The results show that 36.3% of the respondents accepts the unrelated living donor; 36.3% believes there is a margin of growth in the rate of deceased donors; 57.9% guarantees health with quality immunosuppressive drugs; 61.5% does not know the document. In view of the above, it is concluded that the Aguascalientes Document contains useful recommendations for monitoring the bioethical aspects of transplants.

Durante o primeiro Fórum de Bioética da Sociedade de Transplantes da América Latina e do Caribe 2010, redigiu-se o Documento de Aguascalientes, que pretende assegurar a integridade do doador vivo. O artigo tem por objetivo indagar sobre o Documento de Aguascalientes entre os participantes do Congresso da SLANH 2012. Aplicou-se um questionário com 21 perguntas sobre temas abordados por tal documento. Os resultados mostram que 36,3% aceitam o doador vivo não relacionado; 36,3% consideram que há margem de crescimento na taxa de doadores falecidos; 57,9% garantem a saúde com medicamentos imunossupressores de qualidade; 61,5% não conhecem o documento. Conclui-se que o Documento de Aguascalientes tem recomendações úteis para vigiar aspectos bioéticos de transplantes.

Immunophenotyping of peripheral immunoregulatory as well as Th17A and Th22 cell subpopulations in kidney transplant recipients under belatacept or cyclosporine treatment.

OBJECTIVE: Regulatory Foxp3-expressing T cells (Tregs), IL-10-producing B cells (Bregs), and IDO-expressing dendritic cells (DCregs) downregulate inflammatory processes and induce peripheral tolerance, while Th17A and Th22 cell subpopulations are of proinflammatory nature. The aims of the study were to characterize and to enumerate peripheral Tregs, Bregs, and DCregs and Th17A and Th22 cell subpopulations in kidney transplant recipients (KTRs) under belatacept or cyclosporine treatment. METHODS: Forty-one KRT patients (30 under belatacept treatment and 11 under cyclosporine treatment) and 26 healthy donors (HDs) were included in the study. CD19(+)-expressing peripheral B lymphocytes were purified by positive selection. IL-10-producing B cells, CD4(+)/CD25(high)Foxp3(+), and CD8(+)/CD28(-)Foxp3(+) Tregs, CCR6(+)/CD123(+)/IDO(+) DCs, as well as Th17A and Th22 cell subpopulations were quantitated by flow cytometry. RESULTS: Of the IL-10-producing Bregs, CD19(+)/CD24(high)/CD38(high)/CD5(+), CD19(+)/CD24(high)/CD38(high)/CD10(+), CD19(+)/CD24(high)/CD38(high)/CD20(+), and CD19(+)/CD24(high)/CD38(high)/CD27(-) had significant higher frequency in patients under belatacept treatment when compared with those under cyclosporine. Only CD19(+)/CD24(high)/CD38(high)/CD27(+) and CD19(+)/CD24(high)/CD38(high)/CXCR7(+) cells had significant higher frequency in patients under cycloporine treatment when compared to those under belatacept. The percentages of IDO-expressing pDC, CD4(+)/CD25(high)Foxp3(+), and CD8(+)/CD28(-)Foxp3(+) were significantly higher in the belatacept group when compared the cyclosporine one, while Th17A and Th22 cells had significant higher frequency in the latter group. CONCLUSION: Belatacept seems to maintain and enhance, at least systemically, a tolerant profile to renal allograft in transplant recipients by means of higher circulatory frequencies of regulatory B, T and pDC subpopulations.

La ley de volunaad anticipada del distrito federal en Mexico: trasplantes e ideología / The federa distrrict law on advance directives in Mexico: transplants and ideolggy / A lei davontade antecipada do distrito federal no México: transplante e ideologia

La Ley de voluntad anticipada (LVA) de la Ciudad de México regula la voluntad de cualquier persona para no someterse a tratamientos que prolonguen su vida innecesariamente. La Ley pide, en el artículo 8º, la manifestación respecto de la donación de órganos para trasplante. El objetivo de este trabajo es documentar el conocimiento de la LVA. Para esto se realizó una investigación cualitativa con una entrevista semiestructurada, previamente validada. Como resultadose realizaron 278 entrevistas. El 64% de los encuestados no conocen la LVA. De la población encuestada que sí tiene conocimiento de la LVA (n=100) solamente el 43% saben lo referente a la donación de órganos. Se concluye que es evidente el desconocimiento por falta de difusión de la LVA.

The law on advance directives (LAD) in México City regulates the will or intent of any person not to undergo unnecessarily life-prolonging treatment. Article 8 of the law stipulates the donation of organs for transplant must be manifest. Objective: The aim of this paper is to document knowledge of LAD. Materials and methods: A qualitative study was conducted using a previously validated semi-structured interview. Results: In all, 278 interviews were carried out and 64% of those surveyed were unfamiliar with LAD. Among those who are familiar with LAD (n = 100), only 43% know what it stipulates regarding organ donation. Conclusion: There is an evident lack of knowledge about LAD, because the public has not been duly informed.

A Lei da Vontade Antecipada (LVA) da Cidade do México regula a vontade de qualquer pessoa para não se submeter a tratamentos que prolonguem sua vida desnecessariamente. A Lei pede, no artigo 8°, a manifestação a respeito da doação de órgãos para transplantes. O objetivo deste trabalho é documentar o conhecimento da LVA. Para isso, realizou-se uma pesquisa qualitativa com uma entrevista semiestruturada, previamente validada. Como resultado, realizaram-se 278 entrevistas. 64% dos entrevistados não conhecem a LVA. Da população entrevistada que tem conhecimento da LVA (n = 100) somente 43% sabem sobre a doação de órgãos. Conclui-se que é evidente o desconhecimento por falta de difusão da LVA.

[Renal transplantation program at the Centenario Hospital Miguel Hidalgo in Aguascalientes, Mexico]. / Programa de trasplante renal del centenario Hospital Miguel Hidalgo en Aguascalientes, México.

INTRODUCTION: Miguel Hidalgo Hospital in Aguascalientes is dependent from the Federal Secretary of Health and operates in integrity with State health system in Aguascalientes. It capacity is based on 132 censored beds and 71 no censored beds. Is considered a specialty hospital in the region of Bajío. Renal transplant program activity was initiated in 1990 and gives care for adult and pediatric population. MATERIAL AND METHODS: Retrospective, comparative and longitudinal study to describe and analyze our experience. Data base and clinical charts of renal transplant recipients were reviewed. Age, gender, date of transplant, etiology of renal disease, type of donor, HLA compatibility and PRA, immunosuppressive therapy, acute rejection, serum creatinina, graft loss and mortality were registered. Statistical analysis included 2, unpaired Student T test and Kaplan-Meier survival analysis with Log Rank test. Cox Analysis was also done. RESULTS: 1050 renal transplants were done from November 1990 to June 2011. 50 were excluded because follow-up was not longer than 3 months. 1000 consecutive renal transplant patients from January 1995 to June 2011 were included for analysis. Patients were divided in 2 groups: group A transplanted January 1995 to December 2004; group B transplanted January 2005 to June 2011. Etiology for end stage renal disease is unknown in 61% of cases, 11% developed renal disease to diabetes mellitus. 93% patient survival was observed at median follow-up and 84.9% graft survival at median follow-up (6 years). Biopsy proven acute rejection in group A 19.9 vs. 10% in group B. Two haplotype matching shows 92% graft survival. Diabetic patients exhibit 73% graft survival vs. other as hypertension (87%). PRA >0 and serum creatinine > 2.0 mg/dL increase risk for graft loss according to Cox analysis. CONCLUSION. Results are comparable to international data. Importance of developing regional transplant centers is emphasized.

[Prevalence of posttransplant hypertension in pediatric kidney transplant recipients: effect on long term allograft survival]. / Prevalencia de la hipertensión arterial postrasplante renal en receptores pediátricos: Efecto en la supervivencia del injerto a largo plazo.

BACKGROUND: Arterial hypertension after renal transplantation has been identified as an adverse factor over the long term allograft function, thus identification and treatment of this entity has an impact on graft survival, as in patient survival. Studies about pediatric receptor populations have reported a prevalence of hypertension after renal transplantation ranging from 58 to 90%. In Mexico, the pre-valence of arterial hypertension after renal transplantation has been reported as 71% for an adult population attending a main hospital center in Mexico. No pediatric receptor studies in Mexico have reported the prevalence of hypertension after renal transplantation so far. The purpose of our study was to document the prevalence of arterial hypertension after renal transplantation in pediatric receptors, as well as its impact on allograft survival on a long term basis. MATERIAL AND METHODS: We performed a retrospective analysis among pediatric patients who underwent renal transplantation at our center, Centenario Hospital Miguel Hidalgo, between years 2000 to 2006. RESULTS: A total of 111 pediatric renal transplantation receptors were included, among whom 56 patients were classified as hypertensive (HT) and 54 patients were classified as nomotensive (NT) (one patient had to be excluded due to early allograft dysfunction). The mean age at the time of transplantation for the population under study was 14 +/- 3 years, with a predominance of male gender over females (1.5:1). In 89% of the transplantations, the source of the allograft was a living donor. The prevalence of arterial hypertension after renal transplantation in our population was 50.5%. Among patients in the HT group at least an episode of acute rejection presented in 8.9% (n=5) of the cases, compared to only 3.7% (n=2) of patients in the NT group with an episode of acute rejection. Likewise, the prevalence of chronic allograft nephropathy detected in the HT group was 11% (n=6) vs. 7% (n=4) in the NT group. The mean serum creatinine levels were 1.0 +/- 0.4 mg/dL for the HT group and 0.9 +/- 0.3 mg/dL for the NT group at the first month followup, however mean serum creatinine levels addressed at the last consult were different among groups: 1.7 +/- 1.8 mg/dL for the HT group versus 1.1 +/- 0.5 mg/dL for the NT group. Patient survival was similar for both groups (98%) and the follow-up period was also similar, being 39 +/- 12 months for the HT group and 39 +/- 17 months for the NT group. The multivariate Cox proportional hazard analysis demonstrated that the number of antihypertensive drugs needed to achieve the control of blood pressure, and the presence of chronic allograft nephropathy, were the independent risk factors associated to a graft loss at long term. CONCLUSION: The prevalence of hypertension after renal transplantation in our pediatric population was 50.5%, which is clearly towards the inferior limit of the reported prevalence in other studies (50-90%). The tight control of blood pressure is an intervention that may have a significant impact on graft survival at long term. In our study, the severity of arterial hypertension after renal transplantation represented as the number of antihypertensive drugs needed to achieve control of blood pressure, as well as the presence of chronic allograft nephropathy, were the factors associated to long term graft loss.

Ética y trasplantes de órganos: búsqueda continua de lo que es aceptable / Ethics and organ transplantation: continous search for defining what is acceptable

In the past 50 years, Transplant Medicine has been adopted worldwide as a growing option for treatment of many organic diseases. Ethical Issues in organ replacement therapy have emerged since the begining. Significant advancements in the care of critically ill patients, as well as the increasing need of cadaveric organs for transplantation, definitively influenced a complex discussion about new criteria for definition of death, one of the most complex ethic debates in last century. Criteria for organ assignment are also cause of profound debate, especially when the number of patients waiting for an organ is extremely high compared with organ availability. Living donor represents a very complex figure in modern medicine, security issues as well as the need to offer them absolute respect to their capacity to decide must be considered in every patient. Ethics in transplantation represent a continuous search for defining what is acceptable.

La práctica de la medicina de trasplante ha sido adoptada, como primera opción terapéutica, para un número creciente de enfermedades orgánicas durante los últimos 50 años. Diversos y complejos cuestionamientos éticos han surgido desde los primeros años. El desarrollo paralelo de formas avanzadas de cuidado en el paciente críticamente enfermo y la necesidad de órganos para trasplante, obligaron a una rápida reconsideración acerca de los criterios para definir la muerte, uno de los debates más encarnizados del siglo XX. La selección de receptores para trasplante es también motivo de profunda controversia y discusión, diversos cuestionamientos de orden ético se plantean en relación con la asignación de órganos cadavéricos para trasplante, estos puntos de debate adquieren inusitada importancia en un escenario de enorme demanda de órganos para trasplante. La compleja figura del donador vivo en la práctica de la medicina de trasplante obliga a la precisa definición de los criterios de seguridad y de respeto a la capacidad de decisión respecto a la donación. Ética en trasplante de órganos representa una continua búsqueda por definir lo que es aceptable.

[Ethics in organ transplantation: continous search for defining what is acceptable]. / Etica y trasplantes de organos: búsqueda continua de lo que es aceptable.

In the past 50 years, Transplant Medicine has been adopted worldwide as a growing option for treatment of many organic diseases. Ethical Issues in organ replacement therapy have emerged since the beginning. Significant advancements in the care of critically ill patients, as well as the increasing need of cadaveric organs for transplantation, definitively influenced a complex discussion about new criteria for definition of death, one of the most complex ethic debates in last century. Criteria for organ assignment are also cause of profound debate, especially when the number of patients waiting for an organ is extremely high compared with organ availability. Living donor represents a very complex figure in modern medicine, security issues as well as the need to offer them absolute respect to their capacity to decide must be considered in every patient. Ethics in transplantation represent a continuous search for defining what is acceptable.