Kidney-Derived c-Kit(+) Cells Possess Regenerative Potential

Kidney-derived c-Kit(+) cells exhibit progenitor/stem cell properties in vitro (self-renewal capacity, clonogenicity, and multipotentiality). These cells can regenerate epithelial tubular cells following ischemia-reperfusion injury and accelerate foot processes effacement reversal in a model of acute proteinuria in rats. Several mechanisms are involved in kidney regeneration by kidney-derived c-Kit(+ )cells, including cell engraftment and differentiation into renal-like structures, such as tubules, vessels, and podocytes. Moreover, paracrine mechanisms could also account for kidney regeneration, either by stimulating proliferation of surviving cells or modulating autophagy and podocyte cytoskeleton rearrangement through mTOR-Raptor and -Rictor signaling, which ultimately lead to morphological and functional improvement. To gain insights into the functional properties of c-Kit(+) cells during kidney development, homeostasis, and disease, studies on lineage tracing using transgenic mice will unveil their fate. The results obtained from these studies will set the basis for establishing further investigation on the therapeutic potential of c-Kit(+) cells for treatment of kidney disease in preclinical and clinical studies.Conselho Nacional em Pesquisa e Desenvolvimento (CNPq)Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)European Foundation for the Study of Diabetes (EFSD)Univ Sao Paulo, Renal Div, Lab Cellular Genet & Mol Nephrol, Sao Paulo, SP, BrazilUniv Miami, Leonard M Miller Sch Med, Interdisciplinary Stem Cell Inst, Miami, FL USAUniv Miami, Leonard M Miller Sch Med, Dept Mol & Cellular Pharmacol, Miami, FL USAUniv Miami, Div Cardiol, Leonard M Miller Sch Med, Miami, FL USAHosp Israelita Albert Einstein, Inst Israelita Ensino & Pesquisa Albert Einstein, Albert Einstein Ave,627-701 Bldg A, BR-05652900 Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Div Nephrol, Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Div Nephrol, Sao Paulo, SP, BrazilCNPq: 456959/2013-0FAPESP: 13/19560-6Web of Scienc

Impact of delayed pancreatic graft function in simultaneous pancreas-kidney transplantation

OBJECTIVE: Simultaneous pancreas-kidney transplantation is an effective treatment for patients with type 1 diabetes melli>tus and end-stage chronic kidney disease. Delayed pancreatic graft function is a common and multifactor condition with significant impact in short-term outcome of simultaneous pancreas-kidney transplantations. The aim of this study was to analyze the impact of pancreatic delayed pancreatic graft function on simultaneous pancreas-kidney transplantation. METHODS: Donor and recipient's demographic data, percentage of panel reactivity, acute rejection incidence, and patient and grafts survivals were retrospectively analyzed in 180 SPKT performed between 2002 and 2007. RESULTS: The incidence of pancreatic delayed pancreatic graft function was 11%. Donors older than 45 years had significant risk of pancreatic delayed pancreatic graft function (OR 2.26; p < 0,05). Patients with pancreatic delayed pancreatic graft function had higher rates of acute renal rejection (47 versus 24%; p < 0.05), altered fasting plasma glucose (25 versus 5%; p < 0.05) and mean glycated hemoglobin (5.8 versus 5.4%; p < 0.05), than patients without pancreatic delayed pancreatic graft function at the end of the first year of follow up. There were no significant differences between patients with and without pancreatic delayed pancreatic graft function regarding patient survival (95 versus 88.7%; p = 0.38), pancreatic graft survival (90 versus 85.6%; p = 0.59) and renal graft survival (90 versus 87.2%; p = 0.70), respectively at the sample period of time. CONCLUSION: Pancreatic delayed pancreatic graft function had no significant impact in the short-term outcome of simultaneous pancreas-kidney transplantations. Although delayed pancreatic graft function had no impact on 1-year pancreas graft survival, it contributed to early pancreas graft dysfunction, as assessed by enhanced insulin and oral anti-diabetic drugs requirements.OBJETIVO: O transplante pâncreas-rim é efetivo para pacientes com doença renal crônica terminal e diabetes mellitus insulino-dependente. A função retardada do enxerto pancreático é condição frequente exercendo impacto significativo nos resultados em curto prazo dos transplantes pâncreas-rim. O objetivo foi analisar o impacto da função retardada do enxerto pancreático no transplante pâncreas-rim. MÉTODOS: Análise retrospectiva de 180 receptores de transplante pâncreas-rim, incluindo dados demográficos dos doadores e dos receptores, a reatividade contra painel, a incidência de rejeição aguda e as sobrevidas do paciente e dos enxertos pancreático e renal. RESULTADOS: A incidência de função retardada do enxerto pancreático foi 11%. A idade do receptor superior a 45 anos apresentou associação com o risco de desenvolvimento de função retardada do enxerto pancreático (Razão de chances 2,26; p < 0,05). Os pacientes com função retardada do enxerto pancreático apresentaram maior incidência de rejeição aguda renal (47 versus 24%; p < 0,05), glicemia de jejum alterada (25 versus 5%; p < 0,05) e média de hemoglobina glicada (5,8 versus 5,4%; p < 0,05) ao final do primeiro ano de acompanhamento em relação aos pacientes sem função retardada do enxerto pancreático. Não houve diferenças estatisticamente significativas entre os grupos de pacientes com e sem função retardada do enxerto pancreático quanto à sobrevida do paciente (95 versus 88,7%; p = 0,38), do enxerto pancreático (90 versus 85,6%; p = 0,59) e do enxerto renal (90 versus 87,2%; p = 0,70), respectivamente, nesse mesmo período. CONCLUSÃO: A função retardada do enxerto pancreático não exerceu impacto significativo nos resultados em curto prazo dos transplantes pâncreas-rim desta casuística. Embora a função retardada do enxerto pancreático não tenha influenciado a sobrevida do enxerto pancreático ao final do primeiro ano após o transplante, contribuiu para a disfunção pancreática precoce, indicando maior necessidade de uso de insulina e hipoglicemiantes orais.Universidade Federal de São Paulo (UNIFESP) Departamento de MedicinaUNIFESP Departamento de CirurgiaUNIFESP, Depto. de MedicinaUNIFESP, Depto. de CirurgiaSciEL

The 2021–2022 position of Brazilian Diabetes Society on diabetic kidney disease (DKD) management : an evidence-based guideline to clinical practice. Screening and treatment of hyperglycemia, arterial hypertension, and dyslipidemia in the patient with DKD

Background: Diabetic kidney disease is the leading cause of end-stage renal disease and is associated with increased morbidity and mortality. This review is an authorized literal translation of part of the Brazilian Diabetes Society (SBD) Guidelines 2021–2022. This evidence-based guideline provides guidance on the correct management of Diabetic Kidney Disease (DKD) in clinical practice. Methods: The methodology was published elsewhere in previous SBD guidelines and was approved by the internal institutional Steering Committee for publication. Briefly, the Brazilian Diabetes Society indicated 14 experts to constitute the Central Committee, designed to regulate methodology, review the manuscripts, and make judgments on degrees of recommendations and levels of evidence. SBD Renal Disease Department drafted the manuscript selecting key clinical questions to make a narrative review using MEDLINE via PubMed, with the best evidence available including high-quality clinical trials, metanalysis, and large observational studies related to DKD diagnosis and treatment, by using the MeSH terms [diabetes], [type 2 diabetes], [type 1 diabetes] and [chronic kidney disease]. Results: The extensive review of the literature made by the 14 members of the Central Committee defined 24 recommendations. Three levels of evidence were considered: A. Data from more than 1 randomized clinical trial or 1 metanalysis of randomized clinical trials with low heterogeneity ( I2 < 40%). B. Data from metanalysis, including large observational studies, a single randomized clinical trial, or a pre-specified subgroup analysis. C: Data from small or non-randomized studies, exploratory analyses, or consensus of expert opinion. The degree of recommendation was obtained based on a poll sent to the panelists, using the following criteria: Grade I: when more than 90% of agreement; Grade IIa 75–89% of agreement; IIb 50–74% of agreement, and III, when most of the panelist recommends against a defined treatment. Conclusions: To prevent or at least postpone the advanced stages of DKD with the associated cardiovascular complications, intensive glycemic and blood pressure control are required, as well as the use of renin–angiotensin–aldosterone system blocker agents such as ARB, ACEI, and MRA. Recently, SGLT2 inhibitors and GLP1 receptor agonists have been added to the therapeutic arsenal, with well-proven benefits regarding kidney protection and patients’ survival

Pancreas and islet transplantation in patients with diabetes mellitus

Pancreas and kidney transplants have specific indications, benefits and risks. The procedure has become more common and more often as long-term success has improved and risks have decreased. Compared with a patient being on dialysis, simultaneous pancreas-kidney transplant offers a distinct advantage when it comes to mortality, quality of life and diabetic complications. Since there can be a living-donor kidney transplant,, a possibly similar patient and graft survival by 10 years follow-up, this procedure should be considered. Pancreas after kidney transplants, when successful, can improve microvascular complications compared with kidney transplant alone, but immediate mortality may be higher. Solitary pancreas transplantation can improve the quality of life in selected patients, but it may also increase the immediate risk of mortality due to the complexity of the surgery and the risks of immunosupression. The results of Islet transplantation differ from the higher metabolic performance achieved by whole pancreas allotransplantation and its applicability is limited to selected adult diabetic patients.O transplante simultâneo de pâncreas/rim tem indicações específicas, riscos e benefícios. O procedimento, cada vez mais realizado, traz vantagens se comparado ao paciente em diálise, em relação à qualidade de vida, anos de vida ganhos e evolução das complicações crônicas. Se o paciente tiver a opção de realizar o transplante de rim com doador vivo, que apresenta sobrevida semelhante do enxerto e do paciente aos dez anos, o procedimento deverá ser considerado. O transplante de pâncreas após rim, quando efetivo, pode melhorar a evolução das complicações cardiovasculares, mas em contrapartida provoca maior mortalidade nos primeiros meses após a cirurgia. O transplante isolado de pâncreas também ocasiona a maior mortalidade pós-operatória, resultado da complexidade do procedimento e da imunossupressão. O transplante de ilhotas tem sua indicação para um seleto grupo de diabéticos com instabilidade glicêmica.Universidade Federal de São Paulo (UNIFESP) Departamento de Medicina Departamento de CirurgiaPontifícia Universidade Católica do Rio Grande do Sul Hospital São Lucas Serviço de NefrologiaUniversidade de São Paulo Núcleo de Terapia Celular e MolecularSistema de Saúde Centro de Pesquisa Médica Notre-Dame IntermédicaUSP Faculdade de Medicina Departamento de Clínica MédicaUniversidade Federal do Rio Grande do Sul Departamento de Medicina InternaHospital Israelita Albert Einstein Serviço de Transplante de PâncreasUNIFESP, Depto. de Medicina Depto. de CirurgiaSciEL

Gender Differences in COVID-19 Among Liver Transplant Recipients: Results from a Multicenter Brazilian Cohort

Introduction: Existing literature presents varying perspectives on the impact of COVID-19 on liver transplant recipients.However, no research has specifically investigated the role of gender differences in the manifestation of COVID-19 among liver transplant recipients. This study aims to examine the effects of COVID-19 on liver transplant recipients, with a focus on gender differences in disease presentation and progression. Methods: Conducted as a multicenter historical cohort study, this research collected patient records through an online questionnaire. Assessing COVID-related mortality was the main objective. Additionally, demographic, clinical, and laboratory data pertaining to disease presentation and progression werecollected. Results: The study included a total of 283 patients, of whom 76 were female and 206 were male. The median follow-up period for males was 99 days (IQR 38-283), while for females, it was 126 days (IQR 44-291). A higher prevalence of cardiovascular disease was observed in males (p=0.002). Females frequently experienced a loss of smell (p=0.021), whereas males commonly exhibited fever (p=0.031). Levels of ALT and gamma-glutamyl transferase were significantly elevated in males (p=0.008 and 0.004, respectively). Although there was a trend towards increased mortality in males, it did not reach statistical significance. Conclusion: This study is the first attempt to investigate gender differences in COVID-19 among liver transplant recipients. Our findings highlight the need for a comprehensive and personalised approach to treating this patient population and underscore the importance of further elucidating the disease presentation in these individuals

Family History of Diabetes as a New Determinant of Insulin Sensitivity and Secretion in Patients Who Have Undergone a Simultaneous Pancreas-Kidney Transplant

Objectives: We used homeostasis model assessment to investigate insulin sensitivity and secretion after a simultaneous pancreas-kidney transplant or kidney transplant alone. In that model, fasting plasma glucose and C-peptide levels are used to evaluate insulin sensitivity and beta-cell function.Materials and Methods: Factors (eg, age, sex, race, delayed kidney allograft function) were correlated with homeostasis model assessment of beta-cell function and homeostasis model assessment of insulin sensitivity values after simultaneous pancreas-kidney transplant (n=89) or kidney transplant alone (n=68), and the results were compared with those in healthy subjects (n=49).Results: Homeostasis model assessment of beta-cell function values were similar in patients who underwent kidney transplant alone or a simultaneous pancreas-kidney transplant, and were higher than homeostasis model assessment of beta-cell function values in healthy subjects. The homeostasis model assessment of insulin sensitivity showed intermediate values for patients who underwent a simultaneous pancreas-kidney transplant and correlated with prednisone dosages (in those who underwent kidney transplant alone) and tacrolimus levels (in patients who underwent a simultaneous pancreas-kidney transplant). Homeostasis model assessment of beta-cell function values correlated with prednisone dosages in both groups and with tacrolimus levels in only those who underwent a simultaneous pancreas-kidney transplant. The body mass index of subjects who underwent kidney transplant alone correlated with both homeostasis model assessment of beta-cell function results and homeostasis model assessment of insulin sensitivity results. A family history of diabetes in subjects who underwent a simultaneous pancreas-kidney transplant correlated with homeostasis model assessment of beta-cell function results and homeostasis model assessment of insulin sensitivity results.Conclusions: Immunosuppressive regimen and body mass index were linked with reduced insulin sensitivity after kidney transplant. A family history of diabetes was linked with higher values of insulin secretion and lower insulin sensitivity in patients who underwent a simultaneous pancreas-kidney transplant.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Univ Fed Sao Paulo, Div Nephrol, BR-04023900 Sao Paulo, BrazilUniv Fed Sao Paulo, Div Endocrinol, BR-04023900 Sao Paulo, BrazilUniv Fed Sao Paulo, Dept Surg, BR-04023900 Sao Paulo, BrazilUniv Fed Sao Paulo, Div Nephrol, BR-04023900 Sao Paulo, BrazilUniv Fed Sao Paulo, Div Endocrinol, BR-04023900 Sao Paulo, BrazilUniv Fed Sao Paulo, Dept Surg, BR-04023900 Sao Paulo, BrazilWeb of Scienc