Nota Técnica N. 2/2022 - SES/GERTRAN/CCM - 19813 - ações relacionadas ao transplante renal em Goiás / Technical Note N. 2/2022 - SES/GERTRAN/CCM-19813 - actions related to kidney transplantation in Goiás

A Portaria MS n.º 78, de 9 de março de 1.999, credenciou a Central Estadual de Transplantes de Goiás - CET/GO e desde então, os transplantes no Estado tem desenvolvido de forma íntegra e abrangente, inclusive no que tange outras instituições, as quais possam participar de forma direta ou indiretamente das ações relacionadas aos transplantes, no Estado. Diante disso, a presente Nota Técnica n.º 2/2022 visa orientar, organizar e publicizar o fluxo das ações relacionadas aos transplantes de rins em Goiás, de modo a atender as legislações vigentes, bem como a necessidade social e médica, em consonância com os princípios do SUS, que são norteadores desse processo

Ordinance MS n.º 78, of March 9, 1999, accredited the Goiás State Transplant Center - CET/GO and since then, transplants in the State have developed in an integral and comprehensive way, including with regard to other institutions, which can participate directly or indirectly in actions related to transplants in the State. Therefore, this Technical Note No. 2/2022 - aims to guide, organize and publicize the flow of actions related to kidney transplants in Goiás, in order to comply with current legislation, as well as the social need and medical, in line with the principles of the SUS, which guide this process

The applications of DNA methylation as a biomarker in kidney transplantation: a systematic review.

BACKGROUND: Although kidney transplantation improves patient survival and quality of life, long-term results are hampered by both immune- and non-immune-mediated complications. Current biomarkers of post-transplant complications, such as allograft rejection, chronic renal allograft dysfunction, and cutaneous squamous cell carcinoma, have a suboptimal predictive value. DNA methylation is an epigenetic modification that directly affects gene expression and plays an important role in processes such as ischemia/reperfusion injury, fibrosis, and alloreactive immune response. Novel techniques can quickly assess the DNA methylation status of multiple loci in different cell types, allowing a deep and interesting study of cells' activity and function. Therefore, DNA methylation has the potential to become an important biomarker for prediction and monitoring in kidney transplantation. PURPOSE OF THE STUDY: The aim of this study was to evaluate the role of DNA methylation as a potential biomarker of graft survival and complications development in kidney transplantation. MATERIAL AND METHODS: A systematic review of several databases has been conducted. The Newcastle-Ottawa scale and the Jadad scale have been used to assess the risk of bias for observational and randomized studies, respectively. RESULTS: Twenty articles reporting on DNA methylation as a biomarker for kidney transplantation were included, all using DNA methylation for prediction and monitoring. DNA methylation pattern alterations in cells isolated from different tissues, such as kidney biopsies, urine, and blood, have been associated with ischemia-reperfusion injury and chronic renal allograft dysfunction. These alterations occurred in different and specific loci. DNA methylation status has also proved to be important for immune response modulation, having a crucial role in regulatory T cell definition and activity. Research also focused on a better understanding of the role of this epigenetic modification assessment for regulatory T cells isolation and expansion for future tolerance induction-oriented therapies. CONCLUSIONS: Studies included in this review are heterogeneous in study design, biological samples, and outcome. More coordinated investigations are needed to affirm DNA methylation as a clinically relevant biomarker important for prevention, monitoring, and intervention.

Long-standing donor diabetes and pathologic findings are associated with shorter allograft survival in recipients of kidney transplants from diabetic donors.

Approximately 6% of deceased kidney donors (DKDs) are diabetic; their kidneys may be associated with worse allograft survival, but published studies suggest that recipient diabetes status has a greater impact on mortality and survival. Since biopsy findings are the most common reason for organ discard, we sought to understand histologic and clinical factors that influence graft survival in patients who receive a kidney from a diabetic DKD. We retrospectively reviewed our institutional experience from 2005 to 2019, and re-evaluated pre-implantation and earliest post-transplant biopsies. Histologic findings were compared against a control cohort of non-diabetic DKD. Of 829 adult DKD transplants, 37 (4.5%) came from diabetic donors. There was no significant difference in diabetic vs. non-diabetic DKD graft survival for all-comers; however, when stratified by duration of donor diabetes, donor diabetes ≥6 years was associated with graft failure. In 25 patients with post-transplant biopsies available, diabetic DKD allografts had significantly greater non-glomerular chronic injury than non-diabetic DKD allografts. Moderate arteriolar hyalinosis (in 24%), moderate tubular atrophy and interstitial fibrosis (IFTA, in 36%), and diabetic glomerulopathy (in 24%) on early post-transplant biopsy were associated with allograft failure. Pre-implantation frozen section discrepancies were more common in long-standing donor diabetes, and arteriolar hyalinosis and IFTA scores on frozen accurately prognosticated graft loss. There was no morphologic improvement in lesions of diabetic nephropathy on short-term follow-up. In conclusion, donor diabetes ≥6 years, and histologic findings on frozen section and early post-transplant biopsy are associated with diabetic DKD allograft loss.

Avoiding delays in time to renal transplantation: Pretransplant thyroid malignancy does not affect patient or graft survival after renal transplantation.

BACKGROUND: Pretransplant malignancy is associated with decreased patient and graft survival. Current US guidelines recommend a 2- to 5-year, tumor-free waiting period before transplantation. No large studies have examined the specific, modern day risk of pretransplant thyroid malignancy on patient and graft survival after renal transplant. METHODS: The United Network for Organ Sharing database was queried for all adult isolated renal transplant recipients between 2003 and 2019. Patient characteristics, rates of post-transplant malignancy, and survival were compared between patients with pretransplant thyroid malignancy and without pretransplant thyroid malignancy. RESULTS: Eighty-six patients had pretransplant thyroid malignancy diagnosed after listing and before renal transplantation. Both overall and graft survival were similar between cohorts (P > .05). There was no significant association between pretransplant thyroid malignancy and patient (hazard ratio: 0.66; P = .31) or graft (hazard ratio:0.32; P = .11) survival on multivariate analysis. Waitlist duration for pretransplant thyroid malignancy patients was significantly increased (1,444 vs 438 days; P < .01), which translated to increased dialysis duration (2,234 vs 1,201 days, P < .01). Pretransplant thyroid malignancy patients did not experience increased post-transplant malignancy (P = .21). CONCLUSION: Given no association with decreased patient or allograft survival, our findings suggest that pretransplant thyroid malignancy patients are unnecessarily subjected to increased wait-list duration before transplant. We recommend an individualized approach for pretransplant thyroid malignancy patients diagnosed before or after listing.

Tratado de regulação para avaliação especializada em transplante, via SUS, em Goiás / Regulatory treaty for specialized evaluation in transplantation, through SUS, in Goiás

Aborda sobre o atendimento por modalidade de transplantes via SUS, em Goiás. Apresenta as unidades de saúde e profissionais responsáveis. Discorre sobre o fluxo de regulação de transplantes no estado, o fluxo de exames para a inscrição, manutenção e acompanhamento do potencial receptor, os direito dos usuários dos serviços de transplantes e o tratamento fora do domicílio. Orienta sobre o Fluxo Geral de Regulação para Consulta de Avaliação em Transplantes

It addresses the care by type of transplant via SUS in the state of Goiás. It presents the health units and responsible professionals. It discusses the flow of regulation of transplants in the state, the flow of exams for the registration, maintenance and monitoring of the potential recipient, the rights of users of transplant services and treatment outside the home. Guidance on the General Regulation Flow for Evaluation Consultation in Transplants

Aborda la atención por tipo de trasplante vía SUS en el estado de Goiás. Presenta las unidades de salud y los profesionales responsables. Discute el flujo de regulación de trasplantes en el estado, el flujo de exámenes para el registro, mantenimiento y seguimiento del potencial receptor, los derechos de los usuarios de los servicios de trasplante y el tratamiento fuera del hogar. Guías sobre el Reglamento General de Flujo para la Consulta de Evaluación en Trasplantes

Exploring the Complexity of Death-Censored Kidney Allograft Failure.

BACKGROUND: Few studies have thoroughly investigated the causes of kidney graft loss (GL), despite its importance. METHODS: A novel approach assigns each persistent and relevant decline in renal function over the lifetime of a renal allograft to a standardized category, hypothesizing that singular or multiple events finally lead to GL. An adjudication committee of three physicians retrospectively evaluated indication biopsies, laboratory testing, and medical history of all 303 GLs among all 1642 recipients of transplants between January 1, 1997 and December 31, 2017 at a large university hospital to assign primary and/or secondary causes of GL. RESULTS: In 51.2% of the patients, more than one cause contributed to GL. The most frequent primary or secondary causes leading to graft failure were intercurrent medical events in 36.3% of graft failures followed by T cell-mediated rejection (TCMR) in 34% and antibody-mediated rejection (ABMR) in 30.7%. In 77.9%, a primary cause could be attributed to GL, of which ABMR was most frequent (21.5%). Many causes for GL were identified, and predominant causes for GL varied over time. CONCLUSIONS: GL is often multifactorial and more complex than previously thought.

Self-advocacy is associated with lower likelihood of living donor kidney transplantation.

BACKGROUND: The Living Donor Navigator (LDN) Program pairs kidney transplant candidates (TC) with a friend or family member for advocacy training to help identify donors and achieve living donor kidney transplantation (LDKT). However, some TCs participate alone as self-advocates. METHODS: In this retrospective cohort study of TCs in the LDN program (04/2017-06/2019), we evaluated the likelihood of LDKT using Cox proportional hazards regression and rate of donor screenings using ordered events conditional models by advocate type. RESULTS: Self-advocates (25/127) had lower likelihood of LDKT compared to patients with an advocate (adjusted hazard ratio (aHR): 0.22, 95% confidence interval (CI): 0.03-1.66, p = 0.14). After LDN enrollment, rate of donor screenings increased 2.5-fold for self-advocates (aHR: 2.48, 95%CI: 1.26-4.90, p = 0.009) and 3.4-fold for TCs with an advocate (aHR: 3.39, 95%CI: 2.20-5.24, p < 0.0001). CONCLUSIONS: Advocacy training was beneficial for self-advocates, but having an independent advocate may increase the likelihood of LDKT.

Impact of pre-transplant biopsy on 5-year outcomes of expanded criteria donor kidney transplantation.

AIM: Compared to Standard Criteria Donors (SCD), Expanded Criteria Donor (ECD) kidneys are associated with poorer outcomes, although pre-transplant biopsy may mitigate risks. This study assessed 5-year outcomes of deceased-donor kidney transplant recipients, comparing recipients of ECD allografts evaluated histologically to recipients of SCD and ECD kidneys assessed clinically. METHODS: This is a single-centre retrospective study. From November 2005 to December 2009 (Era 1), donors were assessed clinically for suitability for kidney donation. From December 2009 to October 2017 (Era 2), kidneys from ECDs and diabetics underwent pre-transplant biopsy and were allocated based on Remuzzi score. Outcomes of Era 1 and 2 recipients were compared. RESULTS: ECD kidney transplantation increased from 30.4% to 40.0% from Era 1 to 2. Univariable Cox regression, stratified by transplant era, found that 5-year graft loss was highest with Era 1 ECD (HR 2.5, 95% CI 1.1-5.5, P = .027) while graft loss for Era 2 ECD recipients was similar to SCD recipients. There was no difference in 5-year recipient survival. Amongst Era 1 ECD recipients, 51.2% experienced rejection compared to 30.8-41.5% for other subgroups. Five-year eGFR was higher with Era 2 ECD at 48.4 (33.3-60.7) ml/min/1.73 m2 compared to 42.2 (35.8-57.3) ml/min/1.73 m2 for Era 1 ECD. However, these differences were not statistically significant. CONCLUSION: Introduction of pre-transplant biopsy assessment may be associated with improved outcomes of ECD kidney recipients such that they are now comparable to SCD kidney recipients, with benefits persisting over 5 years.

A case of latent heterozygous Fabry disease in a female living kidney donor candidate.

A 52-year-old woman had been found to have hematuria at her annual checkup 5 years in a row. She hoped to donate her kidney to her husband, so we performed a percutaneous kidney biopsy at our department. It was difficult for us to detect apparent abnormalities under a light microscopic examination, and she was determined to meet the eligibility criteria for living kidney transplantation. However, the sample for electron microscopy was not evaluated before kidney donation. She subsequently underwent living kidney transplantation as a donor. A 1-h biopsy revealed swelling and obvious vacuolation of the glomerular podocytes, which were characteristic of Fabry disease. Her medical history and examinations were reviewed. No findings or episodes were observed. Pre-donation electronmicroscopy revealed numerous zebra bodies in the podocytes. A definite diagnosis of heterozygous Fabry disease was made based on the GLA gene mutation despite the normal range of leukocyte α-Gal A activity. Based on the pathological deposition of GL-3, chaperone therapy was initiated to suppress the progression of organ damage. In this case, we could not confirm a diagnosis of Fabry disease despite performing a renal biopsy prior to kidney donation. Kidney donor candidates may sometimes have factors that cannot be assumed based on medical or family history. Thus, it is important to perform a renal biopsy before kidney donation when necessary, and to always conduct a detailed evaluation including electron microscopy.