RESUMEN
Diabetes is associated with numerous comorbidities, one of which is increased vulnerability to infections. This review will focus on how diabetes mellitus (DM) affects the immune system and its various components, leading to the impaired proliferation of immune cells and the induction of senescence. We will explore how the pathology of diabetes-induced immune dysfunction may have similarities to the pathways of "inflammaging", a persistent low-grade inflammation common in the elderly. Inflammaging may increase the likelihood of conditions such as rheumatoid arthritis (RA) and periodontitis at a younger age. Diabetes affects bone marrow composition and cellular senescence, and in combination with advanced age also affects lymphopoiesis by increasing myeloid differentiation and reducing lymphoid differentiation. Consequently, this leads to a reduced immune system response in both the innate and adaptive phases, resulting in higher infection rates, reduced vaccine response, and increased immune cells' senescence in diabetics. We will also explore how some diabetes drugs induce immune senescence despite their benefits on glycemic control.
Asunto(s)
Diabetes Mellitus , Humanos , Diabetes Mellitus/inmunología , Diabetes Mellitus/patología , Animales , Senescencia Celular/inmunología , Inflamación/inmunología , Inflamación/patología , Sistema Inmunológico/inmunologíaRESUMEN
Diabetes mellitus (DM) is a chronic endocrine disorder that affects more than 20 million people in the United States. DM-related complications affect multiple organ systems and are a significant cause of morbidity and mortality among people with DM. Of the numerous acute and chronic complications, atherosclerosis due to diabetic dyslipidemia is a condition that can lead to many life-threatening diseases, such as stroke, coronary artery disease, and myocardial infarction. The nuclear erythroid 2-related factor 2 (Nrf2) signaling pathway is an emerging antioxidative pathway and a promising target for the treatment of DM and its complications. This review aims to explore the Nrf2 pathway's role in combating diabetic dyslipidemia. We will explore risk factors for diabetic dyslipidemia at a cellular level and aim to elucidate how the Nrf2 pathway becomes a potential therapeutic target for DM-related atherosclerosis.
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Aterosclerosis , Dislipidemias , Factor 2 Relacionado con NF-E2 , Transducción de Señal , Humanos , Factor 2 Relacionado con NF-E2/metabolismo , Aterosclerosis/metabolismo , Aterosclerosis/etiología , Dislipidemias/metabolismo , Dislipidemias/complicaciones , Animales , Complicaciones de la Diabetes/metabolismo , Diabetes Mellitus/metabolismoRESUMEN
Diabetes is a chronic disease that induces many comorbidities, including cardiovascular disease, nephropathy, and liver damage. Many mechanisms have been suggested as to how diabetes leads to these comorbidities, of which increased oxidative stress in diabetic patients has been strongly implicated. Limited knowledge of antioxidative antidiabetic drugs and substances that can address diabetic comorbidities through the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway calls for detailed investigation. This review will describe how diabetes increases oxidative stress, the general impact of that oxidative stress, and how oxidative stress primarily contributes to diabetic comorbidities. It will also address how treatments for diabetes, especially focusing on their effects on the Nrf2 antioxidative pathway, have been shown to similarly affect the Nrf2 pathway of the heart, kidney, and liver systems. This review demonstrates that the Nrf2 pathway is a common pathogenic component of diabetes and its associated comorbidities, potentially identifying this pathway as a target to guide future treatments.
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Diabetes Mellitus , Factor 2 Relacionado con NF-E2 , Humanos , Diabetes Mellitus/tratamiento farmacológico , Comorbilidad , Estrés Oxidativo , Hipoglucemiantes , Antioxidantes/uso terapéuticoRESUMEN
Diabetes is a chronic metabolic disorder characterized by inappropriately elevated glucose levels as a result of impaired pancreatic ß cell function and insulin resistance. Extensive studies have been conducted to elucidate the mechanism involved in the development of ß cell failure and death under diabetic conditions such as hyperglycemia, hyperlipidemia, and inflammation. Of the plethora of proposed mechanisms, endoplasmic reticulum (ER) stress, mitochondrial dysfunction, and oxidative stress have been shown to play a central role in promoting ß cell dysfunction. It has become more evident in recent years that these 3 factors are closely interrelated and importantly aggravate each other. Oxidative stress in particular is of great interest to ß cell health and survival as it has been shown that ß cells exhibit lower antioxidative capacity. Therefore, this review will focus on discussing factors that contribute to the development of oxidative stress in pancreatic ß cells and explore the downstream effects of oxidative stress on ß cell function and health. Furthermore, antioxidative capacity of ß cells to counteract these effects will be discussed along with new approaches focused on preserving ß cells under oxidative conditions.
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Diabetes Mellitus/fisiopatología , Células Secretoras de Insulina/fisiología , Estrés Oxidativo , Animales , Diabetes Mellitus/metabolismo , Humanos , Células Secretoras de Insulina/metabolismo , Transducción de SeñalRESUMEN
PURPOSE OF REVIEW: Despite improvement in short-term renal allograft survival in recent years, renal transplant recipients (RTR) have poorer long-term allograft outcomes. Allograft function slowly declines with periods of stable function similar to natural progression of chronic kidney disease in nontransplant population. Nearly all RTR transitions to failing renal allograft (FRG) period and require transition to dialysis. Conservative chronic kidney disease management before transition to end-stage renal disease is an increasingly important topic; however, there is limited data in RTR regarding how to delay dialysis initiation with conservative management. RECENT FINDINGS: Since immunological and nonimmunological factors unique to RTR contribute to decline in allograft function, therapies to slow progression of FRG should take both sets of factors into account. Renal replacement therapy either incremental dialysis or rekidney transplantation should be explored. This required taking benefits and risks of continuing immunosuppressive medications into account when allograft nephrectomy may be necessary. SUMMARY: FRG may benefit from various interventions to slow progression of worsening allograft function. Until there are stronger evidence to guide interventions to preserve renal function, extrapolating evidence from nontransplant patients and clinical judgment are necessary. The goal is to provide individualized care for conservative management of RTR with FRG.
Asunto(s)
Trasplante de Riñón/métodos , Diálisis Renal , Insuficiencia Renal Crónica/terapia , Supervivencia de Injerto , Humanos , Trasplante HomólogoRESUMEN
With multiple virus epicenters, COVID-19 has been declared a pandemic by the World Health Organization. Consequently, many countries have implemented different policies to manage this crisis including curfew and lockdown. However, the efficacy of individual policies remains unclear with respect to COVID-19 case development. We analyzed available data on COVID-19 cases of eight majorly affected countries, including China, Italy, Iran, Germany, France, Spain, South Korea, and Japan. Growth rates and doubling time of cases were calculated for the first 6 weeks after the initial cases were declared for each respective country and put into context with implemented policies. Although the growth rate of total confirmed COVID-19 cases in China has decreased, those for Japan have remained constant. For European countries, the growth rate of COVID-19 cases considerably increased during the second time interval. Interestingly, the rates for Germany, Spain, and France are the highest measured in the second interval and even surpass the numbers in Italy. Although the initial data in Asian countries are encouraging with respect to case development at the initial stage, the opposite is true for European countries. Based on our data, disease management in the 2 weeks following the first reported cases is of utmost importance.
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Betacoronavirus/patogenicidad , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/transmisión , Política de Salud/legislación & jurisprudencia , Pandemias , Neumonía Viral/epidemiología , Neumonía Viral/transmisión , Salud Pública/legislación & jurisprudencia , Asia/epidemiología , COVID-19 , Control de Enfermedades Transmisibles , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/prevención & control , Europa (Continente)/epidemiología , Humanos , Pandemias/prevención & control , Neumonía Viral/diagnóstico , Neumonía Viral/prevención & control , Cuarentena/organización & administración , SARS-CoV-2 , Factores de Tiempo , Organización Mundial de la SaludRESUMEN
Adolescent age may be a high-risk period for kidney allograft failure. However, the knowledge on this topic is limited mostly to the first transplant. Among 20 960 patients aged ≤21 years at the first kidney transplantation from the US Renal Data System, we evaluated the association of age at the first kidney transplant with risk for the first and subsequent graft failures (1st, 2nd, and 3rd) using the conditional risk set model for recurrent time-to-event data. The median age was 15 (interquartile range: 9-18) years, and 18% received transplants twice or more during a median follow-up of 9.7 years. The risk for graft failures was highest in 16 to <18 years old with an adjusted hazard ratio (aHR) of 1.93 (95% CI, 1.73-2.15; reference: <3 years). When separately analyzed, the highest risk was observed in 17, 19, and 21 years old for the first, second, and third transplant, respectively. Those 16 to <18 years were also strongly associated with the highest risk for death after returning to dialysis (aHR, 4.01; 95% CI, 2.82-5.71). Adolescent recipients remain at high risk for allograft failure for a long time, which may result in high mortality risk, even though they surpass this high-risk period soon after the first transplant.
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Fallo Renal Crónico , Trasplante de Riñón , Adolescente , Aloinjertos , Rechazo de Injerto , Supervivencia de Injerto , Humanos , Fallo Renal Crónico/cirugía , Trasplante de Riñón/efectos adversos , Estudios Retrospectivos , Factores de Riesgo , Receptores de Trasplantes , Estados Unidos/epidemiologíaRESUMEN
There is fast-emerging, cumulative clinical data on coronavirus disease 2019 (COVID-19) in kidney transplant recipients. Although respiratory tract symptoms are often the initial presentation among kidney transplant recipients who contract COVID-19, other clinical features which may indicate underlying SARS-CoV-2-related inflammation, such as gastrointestinal symptoms, are not uncommon. Hyponatremia can develop and may reflect underlying inflammation. Interferon-6 is an important pro-inflammatory cytokine involved in the pathogenesis of severe COVID-19 complications and may play a role in the inappropriately higher secretion of antidiuretic hormone leading to hyponatremia. This pathway is the so-called immuno-neuroendocrine interface. Hyponatremia in COVID-19 has been reported in a few case series of non-kidney transplant patients and only one reported kidney transplant recipient. However, the clinical course and prognostic value of hyponatremia in this population are not described in detail. We report a kidney transplant recipient who was infected with COVID-19 and exhibited severe hyponatremia secondary to the syndrome of inappropriate antidiuretic hormone secretion. Hyponatremia is one of the clinical presentations of COVID-19, although less common, and may occur more frequently in kidney transplant recipients. Thus, the possible underlying immuno-neuroendocrine relationship related to the inflammatory process of COVID-19 leading to hyponatremia and its prognostic value are reviewed.
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COVID-19/inmunología , Hiponatremia/inmunología , Inmunosupresores/uso terapéutico , Síndrome de Secreción Inadecuada de ADH/inmunología , Trasplante de Riñón , COVID-19/metabolismo , Femenino , Rechazo de Injerto/prevención & control , Humanos , Hiponatremia/metabolismo , Síndrome de Secreción Inadecuada de ADH/metabolismo , Persona de Mediana Edad , Neuroinmunomodulación/inmunología , Sistemas Neurosecretores/inmunología , SARS-CoV-2RESUMEN
BACKGROUND: Transplant renal artery stenosis (TRAS) may lead to graft dysfunction and failure. Progressive deterioration of renal allograft function may be exacerbated by contrast-induced nephrotoxicity during iodine contrast administration for renovascular imaging of allografts. We present our institutional experience of endovascular management for TRAS using CO2 digital subtraction angiography (CO2-DSA) and balloon angioplasty to manage failing renal transplants. METHODS: Four patients with renal allografts from March 2017-May 2018 were referred for graft dysfunction and pending renal transplant failure. Indications for referral included refractory hypertension, decreasing renal functioning, and elevated renovascular systolic velocities. RESULTS: Median age of the four patients was 41.5 years (22-60 years). There were two male and female patients. Chronic hypertension and type 2 diabetes mellitus were the most common comorbidities. An average total of 75 mL of CO2 was used, supplemented with 17.4 mL of iodinated contrast. All patients had improvements in renal function following intervention with a mean decrease in systolic and diastolic blood pressure of 25.8% and 21.4%, respectively. We also observed a mean decrease of BUN by 13.6% and creatinine by 37.4%. Additionally, eGFR increased by 37.7%. All allografts survived after surgery, and only one patient required repeat angioplasty for recurrence. CONCLUSIONS: CO2-DSA with balloon angioplasty can be successfully utilized to salvage deteriorating kidney allograft function in patients with TRAS.
Asunto(s)
Angiografía de Substracción Digital , Angioplastia de Balón , Dióxido de Carbono/administración & dosificación , Medios de Contraste/administración & dosificación , Trasplante de Riñón/efectos adversos , Obstrucción de la Arteria Renal/diagnóstico por imagen , Obstrucción de la Arteria Renal/terapia , Arteria Renal/diagnóstico por imagen , Adulto , Angiografía de Substracción Digital/efectos adversos , Angioplastia de Balón/efectos adversos , Presión Sanguínea , Dióxido de Carbono/efectos adversos , Medios de Contraste/efectos adversos , Femenino , Tasa de Filtración Glomerular , Supervivencia de Injerto , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Recuperación de la Función , Recurrencia , Arteria Renal/fisiopatología , Obstrucción de la Arteria Renal/etiología , Obstrucción de la Arteria Renal/fisiopatología , Estudios Retrospectivos , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento , Grado de Desobstrucción Vascular , Adulto JovenRESUMEN
Obesity, a metabolic disorder characterized by excessive accumulation of adipose tissue, has globally become an increasingly prevalent disease. Extensive studies have been conducted to elucidate the underlying mechanism of the development of obesity. In particular, the close association of inflammation and oxidative stress with obesity has become increasingly evident. Obesity has been shown to exhibit augmented levels of circulating proinflammatory cytokines, which have been associated with the activation of pathways linked with inflammation-induced insulin resistance, a major pathological component of obesity and several other metabolic disorders. Oxidative stress, in addition to its role in stimulating adipose differentiation, which directly triggers obesity, is considered to feed into this pathway, further aggravating insulin resistance. Nuclear factor E2 related factor 2 (Nrf2) is a basic leucine zipper transcription factor that is activated in response to inflammation and oxidative stress, and responds by increasing antioxidant transcription levels. Therefore, Nrf2 has emerged as a critical new target for combating insulin resistance and subsequently, obesity. However, the effects of Nrf2 on insulin resistance and obesity are controversial. This review focuses on the current state of research on the interplay of inflammation and oxidative stress in obesity, the role of the Nrf2 pathway in obesity and insulin resistance, and the potential use of Nrf2 activators for the treatment of insulin resistance.
Asunto(s)
Tejido Adiposo/metabolismo , Resistencia a la Insulina , Factor 2 Relacionado con NF-E2/metabolismo , Obesidad/metabolismo , Estrés Oxidativo , Transducción de Señal , Tejido Adiposo/patología , Animales , Humanos , Inflamación/metabolismo , Inflamación/patología , Obesidad/patologíaRESUMEN
BACKGROUND: Abnormally high estimated glomerular filtration rates (eGFRs) are associated with endothelial dysfunction and frailty. Previous studies have shown that low eGFR is associated with increased morbidity, but few reports address high eGFR. The purpose of this study is to evaluate the association of high eGFR with surgical outcomes in patients undergoing surgery for gastrointestinal malignancies. METHODS: We identified patients who underwent elective surgery for gastrointestinal malignancies from 2005 to 2015 in the American College of Surgeons National Surgical Quality Improvement Program database. We evaluated associations of eGFR with surgical outcomes by Cox or logistic models with restricted cubic spline functions, adjusting for case mix variables (i.e. age, gender, race and diabetes). RESULTS: The median eGFR is 83 (interquartile range 67-96) mL/min/1.73 m2. Thirty-day mortality was 1.9% (2555/136 896). There is a U-shaped relationship between eGFR and 30-day mortality. The adjusted hazard ratios (95% confidence intervals) for eGFRs of 30, 60, 105 and 120 mL/min/1.73 m2 (versus 90 mL/min/1.73 m2) are 1.73 (1.52-1.97), 1.00 (0.89-1.11), 1.42 (1.31-1.55) and 2.20 (1.79-2.70), respectively. Similar associations are shown for other surgical outcomes, including return to the operating room and postoperative pneumonia. Subgroup analyses show that eGFRs both higher and lower than the respective medians are consistently associated with a higher risk of adverse outcomes across age, gender and race. CONCLUSIONS: High and low eGFRs are associated with more adverse surgical outcomes in patients undergoing surgery for gastrointestinal malignancies. The eGFR associated with the lowest postoperative risk is approximately at the median eGFR of a given population.
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Procedimientos Quirúrgicos del Sistema Digestivo , Neoplasias Gastrointestinales/cirugía , Tasa de Filtración Glomerular/fisiología , Complicaciones Posoperatorias/epidemiología , Anciano , Femenino , Neoplasias Gastrointestinales/fisiopatología , Humanos , Masculino , Morbilidad/tendencias , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/fisiopatología , Factores de Riesgo , Tasa de Supervivencia/tendencias , Estados Unidos/epidemiologíaAsunto(s)
COVID-19/prevención & control , Trasplante de Riñón , Adulto , Anciano de 80 o más Años , COVID-19/epidemiología , COVID-19/mortalidad , Humanos , Fallo Renal Crónico/mortalidad , Fallo Renal Crónico/cirugía , Fallo Renal Crónico/terapia , Fallo Renal Crónico/virología , Persona de Mediana Edad , Pandemias , Factores de Riesgo , SARS-CoV-2 , Factores de TiempoRESUMEN
The limited supply and rising demand for kidney transplantation has led to the use of allografts more susceptible to ischemic reperfusion injury (IRI) and oxidative stress to expand the donor pool. Organ preservation and procurement techniques, such as machine perfusion (MP) and normothermic regional perfusion (NRP), have been developed to preserve allograft function, though their long-term outcomes have been more challenging to investigate. We performed a systematic review and meta-analysis to examine the benefits of MP and NRP compared to traditional preservation techniques. PubMed (MEDLINE), Embase, Cochrane, and Scopus databases were queried, and of 13,794 articles identified, 54 manuscripts were included (n = 41 MP; n = 13 NRP). MP decreased the rates of 12-month graft failure (OR 0.67; 95%CI 0.55, 0.80) and other perioperative outcomes such as delayed graft function (OR 0.65; 95%CI 0.54, 0.79), primary nonfunction (OR 0.63; 95%CI 0.44, 0.90), and hospital length of stay (15.5 days vs. 18.4 days) compared to static cold storage. NRP reduced the rates of acute rejection (OR 0.48; 95%CI 0.35, 0.67) compared to in situ perfusion. Overall, MP and NRP are effective techniques to mitigate IRI and play an important role in safely expanding the donor pool to satisfy the increasing demands of kidney transplantation.
RESUMEN
BACKGROUND: Chronic kidney disease (CKD) impairs intestinal barrier function which by allowing influx of noxious products causes systemic inflammation. We have recently shown that intestinal barrier dysfunction in CKD is due to degradation of epithelial tight junction (TJ) which is, in part, mediated by influx of urea and its conversion to ammonia by microbial urease. We hypothesized that by adsorbing urea and urea-derived ammonia, oral activated charcoal (AST-120) may ameliorate CKD-induced intestinal epithelial barrier disruption and systemic inflammation. METHODS: Rats were randomized to the CKD or control groups. The CKD group was fed a chow containing 0.7% adenine for 2 weeks. They were then randomized to receive a chow with or without AST-120 (4 g/kg/day) for 2 weeks. Rats consuming regular diet served as controls. Animals were then euthanized, colons were removed and processed for Western blot and immunohistology, and plasma was used to measure endotoxin and oxidative and inflammatory markers. RESULTS: Compared with the controls, the untreated CKD rats showed elevated plasma endotoxin, IL-6, TNF-α, MCP-1, CINC-3, L-selectin, ICAM-1, and malondialdehyde, and depletions of colonic epithelial TJ proteins, claudin-1, occludin, and ZO1. Administration of AST-120 resulted in partial restoration of the epithelial TJ proteins and reduction in plasma endotoxin and markers of oxidative stress and inflammation. CONCLUSIONS: CKD animals exhibited depletion of the key protein constituents of the colonic epithelial TJ which was associated with systemic inflammation, oxidative stress and endotoxemia. Administration of AST-120 attenuated uremia-induced disruption of colonic epithelial TJ and the associated endotoxemia, oxidative stress and inflammation.
Asunto(s)
Carbono/farmacología , Fármacos Gastrointestinales/farmacología , Enfermedades Intestinales/etiología , Mucosa Intestinal/efectos de los fármacos , Óxidos/farmacología , Insuficiencia Renal Crónica/complicaciones , Uniones Estrechas/efectos de los fármacos , Administración Oral , Adsorción , Animales , Claudina-1/efectos de los fármacos , Claudina-1/metabolismo , Endotoxemia/complicaciones , Endotoxinas/metabolismo , Inflamación , Mediadores de Inflamación/inmunología , Enfermedades Intestinales/inmunología , Enfermedades Intestinales/metabolismo , Mucosa Intestinal/inmunología , Mucosa Intestinal/metabolismo , Masculino , Ocludina/efectos de los fármacos , Ocludina/metabolismo , Permeabilidad , Ratas , Ratas Sprague-Dawley , Uniones Estrechas/inmunología , Uniones Estrechas/metabolismo , Urea/inmunología , Urea/metabolismo , Proteína de la Zonula Occludens-1/efectos de los fármacos , Proteína de la Zonula Occludens-1/metabolismoRESUMEN
Th2-type inflammation spontaneously shown in Bcl6-knockout (KO) mice is mainly caused by bone marrow (BM)-derived nonlymphoid cells. However, the function of dendritic cells (DCs) in Bcl6-KO mice has not been reported. We show in this article that the numbers of CD4(+) conventional DCs (cDCs) and CD8α(+) cDCs, but not of plasmacytoid DCs, were markedly reduced in the spleen of Bcl6-KO mice. Generation of cDCs from DC progenitors in BM cells was perturbed in the spleen of irradiated wild-type (WT) mice transferred with Bcl6-KO BM cells, indicating an intrinsic effect of Bcl6 in cDC precursors. Although cDC precursors were developed in a Bcl6-KO BM culture with Fms-like tyrosine kinase 3 ligand, the cDC precursors were more apoptotic than WT ones. Also p53, one of the molecular targets of Bcl6, was overexpressed in the precursors. The addition of a p53 inhibitor to Bcl6-KO BM culture protected apoptosis, suggesting that Bcl6 is required by cDC precursors for survival by controlling p53 expression. Furthermore, large numbers of T1/ST2(+) Th2 cells were naturally developed in the spleen of Bcl6-KO mice. Th2 skewing was accelerated in the culture of WT CD4 T cells stimulated with Ags and LPS-activated Bcl6-KO BM-derived DCs, which produced more IL-6 and less IL-12 than did WT DCs; the addition of anti-IL-6 Abs to the culture partially abrogated the Th2 skewing. These results suggest that Bcl6 is required in cDC precursors for survival and in activated DCs for modulating the cytokine profile.
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Antígenos CD4/biosíntesis , Antígenos CD8/biosíntesis , Diferenciación Celular/inmunología , Proteínas de Unión al ADN/fisiología , Células Dendríticas/inmunología , Animales , Células de la Médula Ósea/inmunología , Células de la Médula Ósea/patología , Células de la Médula Ósea/efectos de la radiación , Antígenos CD4/efectos de la radiación , Antígenos CD8/efectos de la radiación , Diferenciación Celular/genética , Diferenciación Celular/efectos de la radiación , Células Cultivadas , Proteínas de Unión al ADN/deficiencia , Proteínas de Unión al ADN/efectos de la radiación , Células Dendríticas/efectos de la radiación , Células Dendríticas/trasplante , Linfopenia/genética , Linfopenia/inmunología , Linfopenia/patología , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Ratones Noqueados , Ratones Transgénicos , Proteínas Proto-Oncogénicas c-bcl-6 , Bazo/inmunología , Bazo/patología , Bazo/efectos de la radiaciónRESUMEN
In the last decade, the number of patients starting dialysis after a failed kidney transplant has increased substantially. These patients appear to be different from their transplant-naïve counterparts, and so may be the timing of dialysis therapy initiation. An increasing number of studies suggest that in transplant-naïve patients, later dialysis initiation is associated with better outcomes. Very few data are available on timing of dialysis reinitiation in failed transplant recipients, and they suggest that an earlier return to dialysis therapy tended to be associated with worse survival, especially among healthier and younger patients and women. Failed transplant patients may also have unique issues such as continuation of immunosuppression versus withdrawal or the need for remnant allograft nephrectomy with regard to dialysis reinitiation. These patients may have a different predialysis preparation work-up, worse blood pressure control, higher or lower serum phosphorus levels, lower serum bicarbonate concentration, and worse anemia management. The choice of dialysis modality may also represent an important question for these patients, even though there appears to be no difference in mortality between patients starting peritoneal versus hemodialysis. Finally, failed transplant patients returning to dialysis appear to have a higher mortality rate compared with transplant-naïve incident dialysis patients, especially in the first several months of dialysis therapy. In this review, we will summarize the available data related to the timing of dialysis initiation and outcomes in failed kidney transplant patients after returning to dialysis.
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Fallo Renal Crónico/terapia , Trasplante de Riñón , Diálisis Renal , Tasa de Filtración Glomerular , Humanos , Terapia de Inmunosupresión , Fallo Renal Crónico/diagnóstico , Fallo Renal Crónico/mortalidad , Nefrectomía , Selección de Paciente , Factores de Riesgo , Factores de Tiempo , Insuficiencia del TratamientoRESUMEN
Importance: There are over 2 million undocumented immigrants (UI) in California, where currently, all individuals regardless of immigration status have access to kidney transplant. There is a medical perception that UI face a higher risk of transplant failure due to language barriers and lack of access to immunosuppressive medication and health care when compared with US residents (UR). Objective: To elucidate the kidney transplant outcomes of UI at an academic medical center in California. Design, Setting, and Participants: A retrospective cohort study was conducted from a single transplant center during an 8-year study period. Patients who received a kidney transplant at the University of California, Irvine, between January 1, 2012, and September 1, 2019, were included in this study. Data were analyzed from October 2020 to August 2021. Exposures: The primary exposure of this study was citizenship status. UI were defined as immigrants residing in the US without permission or legal documentation. Main Outcomes and Measures: The primary end point was all-cause graft loss defined as the return to dialysis, need for a second kidney transplant, or death. The secondary end points of this study were all-cause mortality and rejection. All-cause mortality between the 2 groups was compared using multiple Cox proportional hazard regression analysis. Other transplant outcomes, including all-cause graft loss and acute rejection, were examined by competing risks regressions with mortality and mortality plus graft loss serving as competing risks, respectively. Results: Of all 446 consecutive kidney transplant recipients, the mean (SD) age was 47 (13) years; 261 patients (59%) were male, and 114 (26%) were UI. During a median (IQR) follow-up time of 3.39 (0.04-8.11) years, 6 UI and 48 UR experienced all-cause graft loss. UR had a 192% (hazard ratio, 2.92; 95% CI, 1.21-6.85; P = .01) and 343% (hazard ratio, 4.34; 95% CI, 1.05-18.69; P = .04) significantly increased unadjusted risk for all-cause graft loss and all-cause mortality, respectively. These results became nonsignificant and were mostly attenuated when adjusted for age and ethnicity. Finally, there was no difference in incidence rate of kidney allograft rejection between the 2 groups (UR, 3.5 per 100 person-years vs UI, 2.4 per 100 person-years; rate ratio, 1.45; 95% CI, 0.90-5.05; P = .08). Conclusions and Relevance: This single-center cohort study found that kidney transplant outcomes of UI were not inferior to those of UR. Across the US, however, UI have consistently had unequal access to transplantation. These findings suggest that extending kidney transplants to UI is safe and does not portend worse outcomes. As a result, denying transplant according to immigration status not only results in higher costs but also worse end stage kidney disease outcomes for an already underserved population.
Asunto(s)
Trasplante de Riñón , Inmigrantes Indocumentados , Humanos , Masculino , Persona de Mediana Edad , Femenino , Estudios de Cohortes , Estudios Retrospectivos , California/epidemiologíaRESUMEN
BACKGROUND: With the recent implementation of bundling reimbursement policy, the use of intravenous (IV) iron preparations for the management of anemia in the end-stage renal disease (ESRD) population has dramatically increased. Iron overload increases the risk of infections in individuals with or without kidney disease. IV iron administration in ESRD patients impairs bacteriocidal capacity of polymorphonuclear leukocytes (PMNs) against Escherichia coli. These preparations consist of an elemental iron core and a carbohydrate shell. In addition to the iron core, the carbohydrate shell may affect PMNs. We therefore examined the effect of iron sucrose, a commonly used preparation, on phagocytic capacity of PMNs from a group of normal individuals against Gram-positive (Staphylococcus aureus) and Gram-negative (E. coli) bacteria. METHODS: Iron sucrose was added to heparinized blood samples at pharmacologically-relevant concentrations and incubated for 4 and 24 h at 37°C to simulate in vivo condition. Blood samples mixed with equal volume of saline solution served as controls. To isolate the effects of the carbohydrate shell, blood samples were co-treated with the iron chelator, desferrioxamine. RESULTS: Iron sucrose caused significant PMN apoptosis and dose-dependent suppression of phagocytic function against both Gram-positive and Gram-negative bacteria. These abnormalities were prevented by desferrioxamine which precluded contribution of the carbohydrate shell to the PMN dysfunction. CONCLUSIONS: At pharmacologically-relevant concentrations, iron sucrose promotes apoptosis and inhibits phagocytic activities of PMNs. The deleterious effect of iron sucrose is mediated by its elemental iron core, not its carbohydrate shell, and as such may be shared by other IV iron preparations.
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Anemia/terapia , Apoptosis , Compuestos Férricos/farmacología , Ácido Glucárico/farmacología , Hematínicos/farmacología , Neutrófilos/patología , Adulto , Carbohidratos/química , Escherichia coli/metabolismo , Femenino , Sacarato de Óxido Férrico , Citometría de Flujo/métodos , Humanos , Fallo Renal Crónico/complicaciones , Fallo Renal Crónico/terapia , Masculino , Neutrófilos/citología , Fagocitosis , Staphylococcus aureus/metabolismo , Factores de TiempoRESUMEN
Islet cell transplantation has become a favorable therapeutic approach in the treatment of Type 1 Diabetes due to the lower surgical risks and potential complications compared to conventional pancreas transplantation. Despite significant improvements in islet cell transplantation outcomes, several limitations hamper long-term graft survival due to tremendous damage and loss of islet cells during the islet cell transplantation process. Oxidative stress has been identified as an omnipresent stressor that negatively affects both the viability and function of isolated islets. Furthermore, it has been established that at baseline, pancreatic ß cells exhibit reduced antioxidative capacity, rendering them even more susceptible to oxidative stress during metabolic stress. Thus, identifying antioxidants capable of conferring protection against oxidative stressors present throughout the islet transplantation process is a valuable approach to improving the overall outcomes of islet cell transplantation. In this review we discuss the potential application of antioxidative therapy during each step of islet cell transplantation.
RESUMEN
Chronic kidney disease is generally progressive and currently has no reliable treatment to reverse a decline in kidney function or to slow the progression of the disease. Diabetic nephropathy is one of the leading causes of end-stage kidney failure. Kidney damage in diabetic nephropathy is largely attributed to the increased oxidative stress, affecting its metabolic activity, metabolic pathways, and hemodynamic pathways. In diabetic patients, hyperglycemia causes an increase in the production of reactive oxygen species that further increase oxidative stress. These reactive oxygen species are created through a variety of pathways, providing the opportunity for treatment using anti-oxidative defense mechanisms to prevent vascular injury. This review will give an overview of oxidative stress, along with the current treatments and limitations of diabetic nephropathy. We will also discuss the potential of antioxidative therapies, with an emphasis on the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway.