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1.
Can J Surg ; 63(5): E483-E488, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33107815

RESUMO

BACKGROUND: Mannitol and furosemide have been used as diuretics intraoperatively to facilitate early renal allograft function and reduce delayed graft function. As the evidence of any efficacy of these agents is limited, we sought to characterize the use of diuretics among transplant surgeons. METHODS: An anonymous online survey was sent to all Canadian transplant programs where kidney transplants are routinely performed. Questions were related to the use and indications for mannitol and furosemide. Responses were collected and analyzed as counts and percentages of respondents. We used χ2 analysis to assess the relationship between demographic factors and survey responses. RESULTS: Thirty-five surgeons completed the survey (response rate 50%). Seventy per cent of respondents reported performing 26 or more transplants per year, 88% had formal transplant fellowship training and 67% indicated that they currently train fellows. Only 24% and 12% reported believing that delayed graft function is reduced by mannitol and furosemide use, respectively. However, 73% routinely gave mannitol to patients and 53% routinely gave furosemide. The most common justification given for mannitol use was to induce diuresis (54%); 37% of respondents reported using mannitol because of training dogma. Likewise, 57% used furosemide for diuresis, with 23% reporting that their use of this agent was based on dogma. No relationship emerged between fellowship training, case volume or training program status and the use of any agent. Interestingly, 71% of respondents indicated that a randomized controlled trial evaluating the utility of intraoperative diuretics is needed and that they were interested in participating in such a trial. CONCLUSION: Use of intraoperative diuretics and the rationale for their use vary among surgeons. A substantial proportion of surgeons use these medications on the basis of dogma alone. A randomized controlled trial is needed to clarify the role of intraoperative diuretics in kidney transplant surgery.


Assuntos
Função Retardada do Enxerto/prevenção & controle , Diuréticos/administração & dosagem , Cuidados Intraoperatórios/métodos , Transplante de Rim/efeitos adversos , Reperfusão/métodos , Aloenxertos/efeitos dos fármacos , Aloenxertos/fisiologia , Canadá , Função Retardada do Enxerto/etiologia , Função Retardada do Enxerto/fisiopatologia , Diurese/efeitos dos fármacos , Diurese/fisiologia , Furosemida/administração & dosagem , Humanos , Cuidados Intraoperatórios/estatística & dados numéricos , Rim/efeitos dos fármacos , Rim/fisiologia , Transplante de Rim/estatística & dados numéricos , Manitol/administração & dosagem , Reperfusão/estatística & dados numéricos , Inquéritos e Questionários/estatística & dados numéricos , Resultado do Tratamento
2.
PLoS One ; 15(9): e0238115, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32915812

RESUMO

This work provides an in-depth computational performance study of the parallel finite-difference time-domain (FDTD) method. The parallelization is done at various levels including: shared- (OpenMP) and distributed- (MPI) memory paradigms and vectorization on three different architectures: Intel's Knights Landing, Skylake and ARM's Cavium ThunderX2. This study contributes to prove, in a systematic manner, the well-established claim within the Computational Electromagnetic community, that the main factor limiting FDTD performance, in realistic problems, is the memory bandwidth. Consequently a memory bandwidth threshold can be assessed depending on the problem size in order to attain optimal performance. Finally, the results of this study have been used to optimize the workload balancing of simulation of a bioelectromagnetic problem consisting in the exposure of a human model to a reverberation chamber-like environment.


Assuntos
Algoritmos , Campos Eletromagnéticos , Osso e Ossos/fisiologia , Dispositivos de Armazenamento em Computador , Sistemas Computacionais , Humanos , Rim/fisiologia , Fígado/fisiologia , Modelos Teóricos , Software
3.
Lancet Diabetes Endocrinol ; 8(11): 880-893, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32971040

RESUMO

BACKGROUND: Patients with type 2 diabetes have a high risk of developing chronic kidney disease. We examined the effects of semaglutide on kidney function and safety in a large, broad type 2 diabetes population. METHODS: We did a post-hoc analysis of 8416 patients with type 2 diabetes enrolled in the SUSTAIN 1-5 and SUSTAIN 7 randomised controlled trials, and the SUSTAIN 6 cardiovascular outcomes trial, to examine the effects of once-weekly subcutaneous semaglutide 0·5 mg and 1·0 mg versus comparators (active treatments or placebo) on estimated glomerular filtration rate (eGFR), urinary albumin-to-creatinine ratio (UACR), and kidney adverse events. Data from SUSTAIN 1-5 and SUSTAIN 7 were pooled. eGFR and UACR were also analysed by kidney function and albuminuria status. FINDINGS: In SUSTAIN 1-5 and SUSTAIN 7, eGFR decreased from baseline to week 12 with all active treatments; estimated treatment differences (ETDs) versus placebo were -2·15 (95% CI -3·47 to -0·83) mL/min per 1·73 m2 with semaglutide 0·5 mg and -3·00 (-4·31 to -1·68) mL/min per 1·73 m2 with semaglutide 1·0 mg; after week 12, eGFR plateaued. In SUSTAIN 1-5 and SUSTAIN 7, from baseline to end of treatment the decline in eGFR was greater with semaglutide than with placebo (ETD -1·58 [95% CI -2·92 to -0·25] mL/min per 1·73 m2 with semaglutide 0·5 mg and -2·02 [-3·35 to -0·68] mL/min per 1·73 m2 with semaglutide 1·0 mg). In SUSTAIN 6, the decline in eGFR was greater with semaglutide than with placebo from baseline to week 16 (ETD -1·29 [95% CI -2·07 to -0·51] mL/min per 1·73 m2 with semaglutide 0·5 mg and -1·56 [-2·33 to -0·78] mL/min per 1·73 m2 with semaglutide 1·0 mg), but not from week 16 to week 104 (1·29 [0·30 to 2·28] mL/min per 1·73 m2 with semaglutide 0·5 mg and 2·44 [1·45 to 3·44] mL/min per 1·73 m2 with semaglutide 1·0 mg). Overall (ie, from baseline to week 104), the eGFR decline in SUSTAIN 6 was similar between semaglutide and placebo (ETD 0·07 [95% CI -0·92 to 1·07] mL/min per 1·73 m2 with semaglutide 0·5 mg and 0·97 [-0·03 to 1·97] mL/min per 1·73 m2 with semaglutide 1·0 mg). In SUSTAIN 1-5, UACR ratios at end of treatment to baseline were 0·917 with semaglutide 0·5 mg, 0·836 with semaglutide 1·0 mg, and 1·239 with placebo; at end of treatment, greater reductions in UACR were observed with semaglutide versus placebo (estimated treatment ratios 0·74 [95% CI 0·64 to 0·85] for semaglutide 0·5 mg and 0·68 [0·59 to 0·78] for semaglutide 1·0 mg). In SUSTAIN 6, UACR ratios at end of treatment (week 104) to baseline were 0·973 with semaglutide 0·5 mg, 0·858 with semaglutide 1·0 mg, and 1·302 with placebo; at week 104, greater reductions in UACR were observed with semaglutide versus placebo (estimated treatment ratios 0·75 [95% CI 0·66 to 0·85] for semaglutide 0·5 mg and 0·66 [0·58 to 0·75] for semaglutide 1·0 mg). In SUSTAIN 1-7, eGFR initially declined in patients with normal kidney function (and in those with mild kidney impairment with semaglutide 1·0 mg in SUSTAIN 6), but overall (ie, by week 30 for SUSTAIN 1-5 and SUSTAIN 7, and week 104 for SUSTAIN 6), eGFR did not differ between semaglutide and placebo. In SUSTAIN 1-6, UACR decreased in patients with pre-existing microalbuminuria or macroalbuminuria at baseline; it did not change or increased in those with normoalbuminuria at baseline. Kidney adverse events were balanced between treatment groups. INTERPRETATION: Across the SUSTAIN 1-7 trials, semaglutide was associated with initial reductions in eGFR that plateaued, and marked reductions in UACR. This post-hoc analysis suggests no increase in the risk of kidney adverse events with semaglutide versus the active comparators used across SUSTAIN 1-7. FUNDING: Novo Nordisk.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Taxa de Filtração Glomerular/efeitos dos fármacos , Peptídeos Semelhantes ao Glucagon/administração & dosagem , Rim/efeitos dos fármacos , Adulto , Idoso , Diabetes Mellitus Tipo 2/urina , Esquema de Medicação , Feminino , Taxa de Filtração Glomerular/fisiologia , Peptídeos Semelhantes ao Glucagon/efeitos adversos , Humanos , Injeções Subcutâneas , Rim/fisiologia , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
4.
Nat Cell Biol ; 22(9): 1091-1102, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32868900

RESUMO

Organs and cells must adapt to shear stress induced by biological fluids, but how fluid flow contributes to the execution of specific cell programs is poorly understood. Here we show that shear stress favours mitochondrial biogenesis and metabolic reprogramming to ensure energy production and cellular adaptation in kidney epithelial cells. Shear stress stimulates lipophagy, contributing to the production of fatty acids that provide mitochondrial substrates to generate ATP through ß-oxidation. This flow-induced process is dependent on the primary cilia located on the apical side of epithelial cells. The interplay between fluid flow and lipid metabolism was confirmed in vivo using a unilateral ureteral obstruction mouse model. Finally, primary cilium-dependent lipophagy and mitochondrial biogenesis are required to support energy-consuming cellular processes such as glucose reabsorption, gluconeogenesis and cytoskeletal remodelling. Our findings demonstrate how primary cilia and autophagy are involved in the translation of mechanical forces into metabolic adaptation.


Assuntos
Autofagia/fisiologia , Cílios/metabolismo , Cílios/fisiologia , Células Epiteliais/metabolismo , Células Epiteliais/fisiologia , Rim/metabolismo , Rim/fisiologia , Trifosfato de Adenosina/metabolismo , Animais , Linhagem Celular , Gluconeogênese/fisiologia , Glucose/metabolismo , Metabolismo dos Lipídeos/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Mitocôndrias/metabolismo , Estresse Mecânico
7.
Adv Exp Med Biol ; 1265: 71-95, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32761571

RESUMO

The kidneys are developed from the intermediate mesoderm of the embryo. They are important for osmoregulation, regulation of acid-base balance, reabsorption of nutrients, and excretion of metabolites. In fish, the kidneys also serve as a hematopoietic, lymphoid and endocrine organ for the generation of red blood cells, the development of lymphocytes, and the production of hormones (e.g., glucocorticoids, catecholamines, and thyroid hormones). In humans and all animals, kidneys play a vital role in the metabolism and reabsorption of amino acids (AAs) and glucose. Specifically, this organ contributes to glucose synthesis from AAs, lactate and pyruvate via the gluconeogenesis pathway; regulates acid-base balance via inter-organ metabolism of glutamine; and synthesizes arginine, tyrosine, and glycine, respectively, from citrulline, phenylalanine, and 4-hydroxyproline. In mammals and birds, kidneys participate in creatine synthesis. Renal dysfunction adversely alters the concentrations of AAs in blood, while promoting muscle protein breakdown, inflammation, mitochondrial abnormalities, defects in the immune response, and cardiovascular diseases. Moderation of dietary AA intake has a protective and therapeutic effect on chronic kidney disease. Understanding the functions and metabolism of AAs in kidneys is essential for maintaining whole-body homeostasis, improving health and well-being, and preventing or treating renal metabolic diseases in humans and farm animals (including swine, poultry, ruminants, fish and shrimp).


Assuntos
Aminoácidos/metabolismo , Rim/metabolismo , Rim/fisiologia , Animais , Gluconeogênese , Glucose/biossíntese , Humanos
8.
Environ Health ; 19(1): 80, 2020 07 08.
Artigo em Inglês | MEDLINE | ID: mdl-32641055

RESUMO

BACKGROUND: Epidemiological associations between maternal concentrations of perfluoroalkyl substances (PFAS) and birth weight are inconsistent. There is concern that studies based on samples collected in late pregnancy may be confounded by kidney function but studies of the relation between pregnancy-induced changes in PFAS and kidney function are lacking. Our aims were to investigate changes in serum concentrations of perfluorononanoic acid (PFNA), perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS) and perfluorohexane sulfonate (PFHxS) from early to late pregnancy and to explore relations to changes in glomerular filtration rate (GFR) and glomerular pore size. METHODS: We conducted the study in a cohort of 73 pregnancies of normal-weight Swedish women without gestational diabetes and preeclampsia, enrolled 2009-2014. Blood was collected in median weeks 11 and 36, respectively, and analysed PFAS using liquid chromatography-tandem-mass-spectrometry. We estimated GFR based on creatinine and cystatin C and used the ratio eGFRcystatin C/eGFRcreatinine to indicate glomerular pore size. We used Wilcoxon signed-rank test to compare early and late measures and partial Spearman rank correlations to explore relations between changes in PFAS and kidney function. RESULTS: Median concentrations of PFNA, PFOA and PFOS decreased by 15-21% but changes were uncorrelated to changes in kidney function (partial R = - 0.06-0.11). The observed increase in median PFHxS concentration of 69% was likely an artefact of systematic measurement error caused by coeluting endogenous inferences. CONCLUSIONS: Serum concentrations of PFNA, PFOA and PFOS decrease during pregnancy but the magnitudes of change are unrelated to parallel changes in eGFR and glomerular pore size, suggesting that changes in these indicators of kidney function are not important confounders in studies of PFAS and birth weight in pregnancies without gestational diabetes and preeclampsia.


Assuntos
Poluentes Ambientais/sangue , Fluorcarbonetos/sangue , Taxa de Filtração Glomerular , Rim/fisiologia , Adulto , Feminino , Humanos , Testes de Função Renal , Gravidez , Suécia , Fatores de Tempo , Adulto Jovem
9.
PLoS One ; 15(7): e0235680, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32702005

RESUMO

AIMS: The European Senior Program (ESP) aims to avoid waiting list competition between younger and elderly patients applying for renal transplantation. By listing patients ≥65 years on a separate waiting list and locally allocating of grafts ≥65 years exclusively to this cohort, waiting and cold ischemia times are predicted to be shortened, potentially resulting in improved kidney transplantation outcomes. This study compared a historic cohort of renal transplant recipients being simultaneously listed on the general and the ESP waiting lists with a collective exclusively listed on the ESP list in terms of surrogates of the transplantation outcome. METHODS: Total 151 eligible patients ≥ 65 years from Münster transplant Center, Germany, between 1999 and 2014 were included. Graft function, graft and patient survival were compared using surrogate markers of short- and long-term graft function. Patients were grouped according to their time of transplantation. RESULTS: Recipients and donors in the newESP (nESP) cohort were significantly older (69.6 ± 3.5 years vs 67.1 ± 2 years, p<0.05; 72.0 ± 5.0 years vs 70.3 ± 5.0 years, p = 0.039), had significantly shorter dialysis vintage (19.6 ± 21.7 months vs 60.2 ± 28.1 months, p<0.001) and suffered from significantly more comorbidities (2.2 ± 0.9 vs 1.8 ± 0.8, p = 0.009) than the historic cohort (HC). Five-year death-censored graft survival was better than in the HC, but 5-year graft and patient survival were better in the ESP cohort. After 2005, cold ischemia time between groups was comparable. nESP grafts showed more primary function and significantly better long-term graft function 18 months after transplantation and onwards. CONCLUSION: nESP recipients received significantly older grafts, but experienced significantly shorter time on dialysis. Cold ischemia times were comparable, but graft function in the nESP cohort was significantly better in the long term.


Assuntos
Rejeição de Enxerto/patologia , Sobrevivência de Enxerto , Transplante de Rim , Idoso , Idoso de 80 Anos ou mais , Isquemia Fria/métodos , Comorbidade , Creatinina/sangue , Taxa de Filtração Glomerular , Rejeição de Enxerto/mortalidade , Humanos , Estimativa de Kaplan-Meier , Rim/fisiologia , Masculino , Modelos de Riscos Proporcionais , Diálise Renal , Estudos Retrospectivos , Doadores de Tecidos , Transplante Homólogo
10.
Medicine (Baltimore) ; 99(27): e20749, 2020 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-32629651

RESUMO

Dimethylformamide (DMF) is widely used as a solvent in the production of synthetic leather. Previous studies have focused on workers exposed to DMF in leather factories; however, little attention has been paid to the general population. This study was conducted to examine the effects of DMF exposure on elderly residents living near synthetic leather factories. A total of 962 subjects over 60 years of age in proximity to these factories (monitoring points) were enrolled as the exposure group, and 1924 permanent residents living distant from the factories were enrolled as the control group. The exposure group was divided into 3 groups according to their distance from the monitoring points. Physical examination, routine blood tests, and liver and renal function data were collected, and the DMF concentration in the air was analyzed by gas chromatography-mass spectroscopy. The prevalence of abnormal heart rhythm, electrocardiogram and B-mode ultrasound results in the exposure group was significantly greater than in the control group. Aspartate transaminase (AST), alanine transaminase (ALT), and blood urea nitrogen (BUN) levels in the exposure group also were higher than those in the control group (P < .01). There was an effect of distance from leather factories on liver and kidney dysfunction in the 3 exposure groups. Compared with the exposure group at >3 km distance from the source, the prevalence of increased AST, ALT, and BUN in the exposure group at <1 km was significantly greater (P < .001). It was concluded that DMF exposure was related to an increased risk of a cardiac injury and liver and kidney dysfunction.


Assuntos
Dimetilformamida/efeitos adversos , Exposição Ambiental/efeitos adversos , Rim/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Alanina Transaminase/sangue , Aspartato Aminotransferases/sangue , Nitrogênio da Ureia Sanguínea , Estudos de Casos e Controles , Estudos Transversais , Feminino , Humanos , Rim/fisiologia , Fígado/fisiologia , Masculino , Pessoa de Meia-Idade , Curtume
11.
Am J Physiol Gastrointest Liver Physiol ; 319(2): G133-G141, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-32538141

RESUMO

Xenometabolites from microbial and plant sources are thought to confer beneficial as well as deleterious effects on host physiology. Studies determining absorption and tissue uptake of xenometabolites are limited. We utilized a conscious catheterized pig model to evaluate interorgan flux of annotated known and suspected xenometabolites, derivatives, and bile acids. Female pigs (n = 12, 2-3 mo old, 25.6 ± 2.2 kg) had surgically implanted catheters across portal-drained viscera (PDV), splanchnic compartment (SPL), liver, kidney, and hindquarter muscle. Overnight-fasted arterial and venous plasma was collected simultaneously in a conscious state and stored at -80°C. Thawed samples were analyzed by liquid chromatography-mass spectrometry. Plasma flow was determined with para-aminohippuric acid dilution technology and used to calculate net organ balance for each metabolite. Significant organ uptake or release was determined if net balance differed from zero. A total of 48 metabolites were identified in plasma, and 31 of these had at least one tissue with a significant net release or uptake. All bile acids, indole-3-acetic acid, indole-3-arylic acid, and hydrocinnamic acid were released from the intestine and taken up by the liver. Indole-3-carboxaldehyde, p-cresol glucuronide, 4-hydroxyphenyllactic acid, dodecanendioic acid, and phenylacetylglycine were also released from the intestines. Liver or kidney uptake was noted for indole-3-acetylglycine, p-cresol glucuronide, atrolactic acid, and dodecanedioic acid. Indole-3-carboxaldehyde, atrolactic acid, and dodecanedioic acids showed net release from skeletal muscle. The results confirm gastrointestinal origins for several known xenometabolites in an in vivo overnight-fasted conscious pig model, whereas nongut net release of other putative xenometabolites suggests a more complex metabolism.NEW & NOTEWORTHY Xenometabolites from microbe origins influence host health and disease, but absorption and tissue uptake of these metabolites remain speculative. Results herein are the first to demonstrate in vivo organ uptake and release of these metabolites. We used a conscious catheterized pig model to confirm gastrointestinal origins for several xenometabolites (e.g., indolic compounds, 4-hydroxyphenyllactic acid, dodecanendioic acid, and phenylacetylgycine). Liver and kidney were major sites for xenometabolite uptake, likely highlighting liver conjugation metabolism and renal excretion.


Assuntos
Intestinos/fisiologia , Rim/fisiologia , Fígado/metabolismo , Músculo Esquelético/fisiologia , Ácido p-Aminoipúrico/farmacocinética , Animais , Transporte Biológico , Feminino , Fenóis/sangue , Fenóis/metabolismo , Sistema Porta , Suínos , Ácido p-Aminoipúrico/sangue
12.
Clin Nephrol ; 94(2): 86-96, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32589133

RESUMO

Serum creatinine (SCr) levels depend on muscle mass and are therefore elevated in people with high muscle mass, potentially leading to underestimation of kidney function in this population. Although recent therapeutic guidelines have shown measurement of serum cystatin C (ScysC) to be useful, this method has not been validated in people with high muscle mass. We conducted this study to investigate methods for more accurately estimating kidney function in people with high muscle mass. Linear regression analysis was used to assess the correlation of endogenous creatinine clearance (24-hour CLcr) and 24-hour CLcr × 0.715 (i.e., modified glomerular filtration rate (GFR)); with estimated kidney function from SCr and ScysC in 15 healthy young adult men with high muscle mass. A significant but weak positive correlation was observed between 24-hour CLcr and estimated CLcr by the Cockcroft and Gault formula (CG CLcr; R2 = 0.371, p = 0.016). The estimated GFR calculated from ScysC (eGFRcys) was significantly higher than CLcr × 0.715, but the two were not correlated (R2 = 0.125, p = 0.197). However, when CG CLcr and eGFRcr were adjusted by muscle mass parameters, the correlation between measured and estimated values improved. Further improvement was seen when participants with a fat mass greater than 25% were excluded (R2 = 0.623, p = 0.004; R2 = 0.510, p = 0.014; n = 11 for both). The results of our study suggest that currently used formulas for estimating kidney function, including eGFRcys, may not be appropriate for people with high muscle mass, but use of muscle mass parameters may improve predictivity.
.


Assuntos
Rim/fisiologia , Músculo Esquelético/fisiologia , Adulto , Creatinina/sangue , Taxa de Filtração Glomerular/fisiologia , Humanos , Modelos Lineares , Masculino , Adulto Jovem
13.
PLoS One ; 15(6): e0232177, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32525880

RESUMO

To overcome organ shortage, expanded criteria donors, including elderly deceased donors (DDs), should be considered. We analyzed outcomes of kidney transplantation (KT) from elderly DDs in a nationwide study. In total, data of 1049 KTs from DDs using the database of Korean Organ Transplantation Registry (KOTRY) were retrospectively analyzed based on the age of DDs: age ≥60 years vs. <60 years. Clinical information, graft status, and adverse events were reviewed in DDs and recipients. The mean age of the 1006 DDs was 51.04±10.54 years, and 21.5% of donors were aged ≥60 years. Elderly DDs had a significantly higher prevalence of diabetes and hypertension and higher Kidney Donor Risk Index (KDRI) and Kidney Donor Profile Index (KDPI). The mean age of the recipients was 47.45±14.87 years. Patients who received KT from elderly DDs were significantly older (53.12±15.14 vs. 45.88±14.41, P<0.001) and had a higher rate of diabetes (41.9 vs. 24.4%, P<0.001). Graft outcomes were not significantly different. Renal function was similar between the groups at the time of discharge and at 6 months, 1 year, and 2 years after KT. The rate of delayed graft function (DGF) was not significantly different. Risk factors of DGF were significantly different in DDs aged ≥60 years and <60 years. In the multivariable model, male sex (odds ratio: 3.99, 95% confidence interval: 1.42-11.22; P = 0.009) and KDRI (12.17, 2.23-66.34; P = 0.004) were significant risk factors for DGF in DDs aged ≥60 years. In DDs aged <60 years, thymoglobulin induction (2.62, 1.53-4.48; P<0.001) and continuous renal replacement therapy (3.47, 1.52-7.96; P = 0.003) were significant factors. Our data indicated that graft outcomes, including renal function and DGF, were similar for elderly DDs and DDs aged <60 years. Elderly DDs might be considered tolerable donors for KT, with active preoperative surveillance.


Assuntos
Transplante de Rim , Doadores de Tecidos , Adulto , Fatores Etários , Idoso , Soro Antilinfocitário/metabolismo , Bases de Dados Factuais , Função Retardada do Enxerto/patologia , Humanos , Rim/fisiologia , Pessoa de Meia-Idade , Razão de Chances , Sistema de Registros , República da Coreia , Estudos Retrospectivos , Fatores de Risco , Doadores de Tecidos/estatística & dados numéricos , Resultado do Tratamento
14.
J Sports Med Phys Fitness ; 60(7): 1034-1039, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32597619

RESUMO

BACKGROUND: Creatine represents a natural supplement and ergogenic aid for sport performance, but there are several concerns regarding its safety for health. The present double-blind placebo-controlled study evaluated the effect of creatine monohydrate supplementation on a panel of blood and urine health indicators in resistance training practitioners. METHODS: Eighteen males performing resistance training three times per week were supplemented with 0.3 g/kg per day creatine monohydrate for 7 days and compared with matched controls supplemented with dextrosol. Blood and urine samples were collected pre- and 30 days post-supplementation to evaluate 41 biochemical parameters and renal function. RESULTS: Creatine monohydrate supplementation did not cause adverse events and, as expected, promoted an increase of the performance and body weight. No modification of red blood cells parameters, white blood cells profile, blood lipid profile, metabolic and urine markers, hepatic and renal function were observed in the supplemented group. CONCLUSIONS: Despite the expected weight increase, the creatine monohydrate supplementation is safe for health and no detrimental effects on different organs and physiological systems were observed in our cohort of volunteers.


Assuntos
Desempenho Atlético/fisiologia , Creatina/administração & dosagem , Creatina/efeitos adversos , Suplementos Nutricionais , Substâncias para Melhoria do Desempenho/administração & dosagem , Substâncias para Melhoria do Desempenho/efeitos adversos , Treinamento de Resistência , Adulto , Biomarcadores/sangue , Biomarcadores/urina , Método Duplo-Cego , Testes Hematológicos , Humanos , Rim/fisiologia , Contagem de Leucócitos , Lipídeos/sangue , Fígado/fisiologia , Masculino , Músculo Esquelético/metabolismo , Ganho de Peso , Adulto Jovem
15.
PLoS One ; 15(6): e0234080, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32479525

RESUMO

In the present study we have characterized the biophysical properties of wild-type (WT) α1ß2 and α3ß2 GABAA receptors and probed the molecular basis for the observed differences. The activation and desensitization behavior and the residual currents of the receptors expressed in HEK293 cells were determined in whole-cell patch clamp recordings. Kinetic parameters of α1ß2 and α3ß2 activation differed significantly, with α1ß2 and α3ß2 exhibiting rise times (10-90%) of 24 ± 2 ms and 51 ± 7 ms, respectively. In contrast, the two receptors exhibited largely comparable desensitization behavior with decay currents that could be fitted to exponential functions with two or three components. Most notably, the two receptor compositions displayed different degrees of desentization, with the residual currents of α1ß2 and α3ß2 constituting 34 ± 2% and 21 ± 2% of the peak current, respectively. The respective contributions of the extracellular domains and the transmembrane/intracellular domains of the α-subunit to these physiological profiles were next assessed in recordings from cells expressing αß2 receptors comprising chimeric α-subunits. The rise times displayed by α1ECD/α3TMDß2 and α3ECD/α1TMDß2 receptors were intermediate to those of WT α1ß2 and WT α3ß2, and the distribution of the different components of the current decays exhibited by the two chimeric receptors followed the same pattern as the two WT receptors. The residual current exhibited by α1ECD/α3TMDß2 (23 ± 3%) was similar to that of α3ß2 but significantly different from that of α1ß2, whereas the residual current displayed by α3ECD/α1TMDß2 (27 ± 2%) was intermediate to and did not differ significantly from either of the WT receptors. This points to molecular differences in the transmembrane/intracellular domains of the α-subunit as the main determinants of the observed differences in receptor physiology between α1ß2 and α3ß2 receptors.


Assuntos
Receptores de GABA-A/metabolismo , Potenciais de Ação/efeitos dos fármacos , Células HEK293 , Humanos , Rim/fisiologia , Cinética , Técnicas de Patch-Clamp , Domínios Proteicos , Subunidades Proteicas/genética , Subunidades Proteicas/metabolismo , Receptores de GABA-A/genética , Ácido gama-Aminobutírico/farmacologia
16.
PLoS One ; 15(6): e0234910, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32559200

RESUMO

Aging in mammals is the gradual decline of an organism's physical, mental, and physiological capacity. Aging leads to increased risk for disease and eventually to death. Here, we show that Brd2 haploinsufficiency (Brd2+/-) extends lifespan and increases healthspan in C57B6/J mice. In Brd2+/- mice, longevity is increased by 23% (p<0.0001), and, relative to wildtype animals (Brd2+/+), cancer incidence is reduced by 43% (p<0.001). In addition, relative to age-matched wildtype mice, Brd2 heterozygotes show healthier aging including: improved grooming, extended period of fertility, and lack of age-related decline in kidney function and morphology. Our data support a role for haploinsufficiency of Brd2 in promoting healthy aging. We hypothesize that Brd2 affects aging by protecting against the accumulation of molecular and cellular damage. Given the recent advances in the development of BET inhibitors, our research provides impetus to test drugs that target BRD2 as a way to understand and treat/prevent age-related diseases.


Assuntos
Longevidade/genética , Fatores de Transcrição/genética , Animais , Feminino , Fertilidade , Asseio Animal , Haploinsuficiência , Rim/crescimento & desenvolvimento , Rim/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL
17.
Eur J Epidemiol ; 35(7): 699-707, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32440788

RESUMO

BACKGROUND: Live donor nephrectomy is a safe procedure. However, long-term donor prognosis is debated, necessitating high-quality studies. METHODS: A follow-up study of 761 living kidney donors was conducted, who visited the outpatient clinic and were propensity score matched and compared to 1522 non-donors from population-based cohort studies. Primary outcome was kidney function. Secondary outcomes were BMI (kg/m2), incidences of hypertension, diabetes, cardiovascular events, cardiovascular and overall mortality, and quality of life. RESULTS: Median follow-up after donation was 8.0 years. Donors had an increase in serum creatinine of 26 µmol/l (95% CI 24-28), a decrease in eGFR of 27 ml/min/1.73 m2 (95% CI - 29 to - 26), and an eGFR decline of 32% (95% CI 30-33) as compared to non-donors. There was no difference in outcomes between the groups for ESRD, microalbuminuria, BMI, incidence of diabetes or cardiovascular events, and mortality. A lower risk of new-onset hypertension (OR 0.45, 95% CI 0.33-0.62) was found among donors. The EQ-5D health-related scores were higher among donors, whereas the SF-12 physical and mental component scores were lower. CONCLUSION: Loss of kidney mass after live donation does not translate into negative long-term outcomes in terms of morbidity and mortality compared to non-donors. TRIAL REGISTRATION: Dutch Trial Register NTR3795.


Assuntos
Transplante de Rim/efeitos adversos , Rim/fisiologia , Doadores Vivos/psicologia , Nefrectomia/efeitos adversos , Qualidade de Vida/psicologia , Estudos de Casos e Controles , Creatinina/sangue , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/etiologia , Feminino , Taxa de Filtração Glomerular , Humanos , Hipertensão/epidemiologia , Hipertensão/etiologia , Incidência , Testes de Função Renal , Doadores Vivos/estatística & dados numéricos , Masculino , Nefrectomia/psicologia , Vigilância da População , Complicações Pós-Operatórias/epidemiologia , Pontuação de Propensão , Resultado do Tratamento
18.
Nat Rev Nephrol ; 16(7): 372, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32472033
19.
Am J Physiol Renal Physiol ; 319(1): F1-F7, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32463729

RESUMO

Albuminuria in the pathological range is a significant predictor of preeclampsia. In healthy persons, high normal urinary albumin predicts a later incidence of hypertension and is associated with salt sensitivity of blood pressure. We hypothesized that in pregnancy urinary albumin in the normal range associates with blood pressure through activation of distal Na+ reabsorption and renal salt retention by plasma factors cofiltered with albumin. We analyzed 24-h urine collections and plasma samples from gestational week 29 of 560 pregnant women from the Odense Child Cohort, a Danish population-based cohort. Plasma and urinary aldosterone were measured by ELISA. Plasma and urinary Na+, K+, Cl-, and creatinine were also determined. Predictive values of urinary albumin were assessed by linear mixed, multiple, and Cox regression analyses. Primary outcomes were blood pressure and renal electrolyte handling. Twenty-four-hour urinary albumin excretion at gestational week 29 associated with gestational blood pressure trajectory, with adjusted ß coefficients (95% confidence intervals) for each 10-fold increase in urinary albumin as follows: 5.71 (1.60 to 9.81) mmHg for systolic blood pressure and 4.39 (1.41 to 7.38) mmHg for diastolic blood pressure. Urinary albumin was inversely associated with fractional excretion rates of Na+, K+, and Cl-, with adjusted ß coefficients (95% confidence intervals) for each 10-fold increase in urine albumin as follows: -0.25 (-0.35 to -0.14), -5.06 (-6.81 to -3.30), and -0.28 (-0.41 to -0.15), respectively. In conclusion, at gestational week 29, urinary albumin excretion in the normal range associated with blood pressure and renal electrolyte handling independent of potential confounders.


Assuntos
Albuminúria/fisiopatologia , Pressão Sanguínea/fisiologia , Rim/fisiologia , Adulto , Feminino , Humanos , Gravidez , Valores de Referência , Adulto Jovem
20.
Harefuah ; 159(4): 231-234, 2020 Apr.
Artigo em Hebraico | MEDLINE | ID: covidwho-99331

RESUMO

INTRODUCTION: COVID-19, is a new corona virus of the Beta Coronavirus genus which originated in bats. The virus first emerged in China in December 2019 and has rapidly spread since to other areas worldwide. The World Health Organization (WHO) has therefore recently declared it as the source of a pandemic. The disease caused by the virus manifests in most cases as a lower respiratory tract infection leading to fever, cough and dyspnea, while more severe cases can led to respiratory failure and/or multi organ failure. COVID-19 enters the human cell using the ACE2, an enzyme abundant in renal tubular epithelial cells. Theoretically, this may be significant in several ways: acute kidney injury (AKI) as well as proteinuria and/or microhematuria could be associated with the penetration of COVID-19 into the cells. Moreover, medications based on RAAS inhibition, such and ACE inhibitors and ARBs, upregulate the enzyme ACE2 and could therefore hypothetically explain the high prevalence of hypertension and diabetes reported as previous diagnoses in severe cases. In the setting of chronic kidney disease, the risk of infection with COVID-19 is not clear at this time. However, hemodialysis patients represent a unique group of patients, mostly elderly and immunocompromised, for whom dialysis is a life-saving treatment which cannot be stopped. Hence, the COVID-19 pandemic has presented a complex medical and logistic challenge for the medical staff in hospital and community based dialysis units.


Assuntos
Lesão Renal Aguda/etiologia , Infecções por Coronavirus/complicações , Hipertensão/complicações , Pneumonia Viral/complicações , Lesão Renal Aguda/complicações , Idoso , Betacoronavirus , China , Infecções por Coronavirus/epidemiologia , Humanos , Rim/fisiologia , Pandemias , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/epidemiologia , Populações Vulneráveis
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