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1.
Best Pract Res Clin Anaesthesiol ; 35(3): 449-459, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34511232

RESUMO

Coronavirus disease (COVID-19) causes many deleterious effects throughout the body. Prior studies show that the incidence of acute kidney injury in COVID-19 patients could be as high as 25%. There are also autopsy reports showing evidence of viral tropism to the renal system. In this regard, COVID-19 can damage the kidneys and increase a patient's risk of requiring dialysis. Available evidence suggests that renal involvement in COVID-19 infection is not uncommon, and there has been an increased incidence of chronic kidney disease related to the pandemic. In this literature analysis, we address COVID-19 and its effects on the renal system, including the pathophysiologic mechanisms. We also address current studies on the causes of injury to the renal system, the cause of kidney failure, its effect on mortality, the impact on dialysis patients, and the impact on renal transplant patients. COVID-19 disease may have unique features in individuals on chronic dialysis and kidney transplant recipients, requiring increased vigilance in limiting viral transmission in perioperative, in-patient, and dialysis center settings.


Assuntos
COVID-19/fisiopatologia , Nefropatias/fisiopatologia , Rim/fisiopatologia , COVID-19/epidemiologia , COVID-19/terapia , Humanos , Rim/virologia , Nefropatias/epidemiologia , Nefropatias/terapia , Nefropatias/virologia , Diálise Renal/métodos , Diálise Renal/tendências , Resultado do Tratamento
2.
Anticancer Res ; 41(9): 4443-4446, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34475067

RESUMO

BACKGROUND: Androgen deprivation therapy (ADT) is one of the most effective treatments for advanced prostate cancer (PCa). However, it has been reported that the use of ADT is significantly associated with an increased risk of acute kidney injury (AKI) among patients with newly diagnosed non-metastatic PCa. We investigated changes in renal function that occurred in Japanese patients with PCa after ADT was discontinued. PATIENTS AND METHODS: Among 121 patients who underwent prostate biopsies, were pathologically diagnosed with PCa, and received ADT for ≥6 months at our Institution between 2009 and 2014, 60 patients who underwent radiotherapy for stage B or C PCa were eligible for inclusion in this retrospective study. Renal function was assessed using the estimated glomerular filtration rate (eGFR) before treatment and at 1, 3, 6, 9, and 12 months after the initiation of ADT and the rate of change in the eGFR (ΔeGFR) during ADT and after the discontinuation of ADT was investigated. We divided patients into two groups: Group 1 received ADT for 6 months, and group 2 received ADT for 12 months. Age; ΔeGFR; prostate-specific antigen, testosterone and hemoglobin levels; clinical stage; Gleason score; comorbidities; body mass index; heart rate; and the cardiothoracic ratio were analyzed. RESULTS: A total of 60 patients (group 1: n=23, group 2: n=37) were analyzed. The Gleason score of group 2 was higher than that of group 1 (p=0.0011). Regarding clinical stage, group 1 had more patients with stage B disease, and group 2 had more with stage C (p<0.0001). The eGFR decreased with the duration of ADT treatment. At 12 months, renal function had started to recover in group 1, while it had continued to decrease in group 2. CONCLUSION: Discontinuation of ADT tended to result in improvements in renal function. Furthermore, this study indicated that renal dysfunction caused by 6 months of ADT is transient. Normalization of the serum testosterone level seen after the discontinuation of ADT may be associated with improvements in renal function. Thus, intermittent ADT may be a useful treatment for PCa, as it would help to preserve renal function.


Assuntos
Antagonistas de Androgênios/efeitos adversos , Taxa de Filtração Glomerular/efeitos dos fármacos , Rim/fisiopatologia , Neoplasias da Próstata/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Antagonistas de Androgênios/uso terapêutico , Humanos , Japão , Rim/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/sangue , Neoplasias da Próstata/patologia , Estudos Retrospectivos , Testosterona/sangue , Fatores de Tempo , Suspensão de Tratamento
3.
BMC Nephrol ; 22(1): 297, 2021 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-34465289

RESUMO

BACKGROUND: Kidney disease and renal failure are associated with hospital deaths in patients with COVID - 19. We aimed to test if contrast enhancement affects short-term renal function in hospitalized COVID - 19 patients. METHODS: Plasma creatinine (P-creatinine) was measured on the day of computed tomography (CT) and 24 h, 48 h, and 4-10 days after CT. Contrast-enhanced (n = 142) and unenhanced (n = 24) groups were subdivided, based on estimated glomerular filtration rates (eGFR), > 60 and ≤ 60 ml/min/1.73 m2. Contrast-induced acute renal failure (CI-AKI) was defined as ≥27 µmol/L increase or a > 50% rise in P-creatinine from CT or initiation of renal replacement therapy during follow-up. Patients with renal replacement therapy were studied separately. We evaluated factors associated with a > 50% rise in P-creatinine at 48 h and at 4-10 days after contrast-enhanced CT. RESULTS: Median P-creatinine at 24-48 h and days 4-10 post-CT in patients with eGFR> 60 and eGFR≥30-60 in contrast-enhanced and unenhanced groups did not differ from basal values. CI-AKI was observed at 48 h and at 4-10 days post contrast administration in 24 and 36% (n = 5/14) of patients with eGFR≥30-60. Corresponding figures in the eGFR> 60 contrast-enhanced CT group were 5 and 5% respectively, (p < 0.037 and p < 0.001, Pearson χ2 test). In the former group, four of the five patients died within 30 days. Odds ratio analysis showed that an eGFR≥30-60 and 30-day mortality were associated with CK-AKI both at 48 h and 4-10 days after contrast-enhanced CT. CONCLUSION: Patients with COVID - 19 and eGFR≥30-60 had a high frequency of CK-AKI at 48 h and at 4-10 days after contrast administration, which was associated with increased 30-day mortality. For patients with eGFR≥30-60, we recommend strict indications are practiced for contrast-enhanced CT. Contrast-enhanced CT had a modest effect in patients with eGFR> 60.


Assuntos
Injúria Renal Aguda/induzido quimicamente , COVID-19/complicações , Meios de Contraste/efeitos adversos , Creatinina/sangue , Iodo/efeitos adversos , Rim/efeitos dos fármacos , Injúria Renal Aguda/sangue , Injúria Renal Aguda/mortalidade , Injúria Renal Aguda/terapia , Idoso , COVID-19/sangue , COVID-19/mortalidade , COVID-19/fisiopatologia , Feminino , Taxa de Filtração Glomerular , Humanos , Rim/diagnóstico por imagem , Rim/fisiopatologia , Masculino , Pessoa de Meia-Idade , Razão de Chances , Análise de Regressão , Terapia de Substituição Renal , Estudos Retrospectivos , Fatores de Tempo , Tomografia Computadorizada por Raios X
4.
FASEB J ; 35(9): e21823, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34396581

RESUMO

Exercise training exerts protective effects against diabetic nephropathy. This study aimed to investigate whether exercise training could attenuate diabetic renal injury via regulating endogenous hydrogen sulfide (H2 S) production. First, C57BL/6 mice were allocated into the control, diabetes, exercise, and diabetes + exercise groups. Diabetes was induced by intraperitoneal injection of streptozotocin (STZ). Treadmill exercise continued for four weeks. Second, mice was allocated into the control, diabetes, H2 S and diabetes + H2 S groups. H2 S donor sodium hydrosulfide (NaHS) was intraperitoneally injected once daily for four weeks. STZ-induced diabetic mice exhibited glomerular hypertrophy, tissue fibrosis and increased urine albumin levels, urine protein- and albumin-to-creatinine ratios, which were relieved by exercise training. Diabetic renal injury was associated with apoptotic cell death, as evidenced by the enhanced caspase-3 activity, the increased TdT-mediated dUTP nick-end labeling -positive cells and the reduced expression of anti-apoptotic proteins, all of which were attenuated by exercise training. Exercise training enhanced renal sirtuin 1 (SIRT1) expression in diabetic mice, accompanied by an inhibition of the p53-#ediated pro-apoptotic pathway. Furthermore, exercise training restored the STZ-mediated downregulation of cystathionine-ß-synthase (CBS) and cystathionine-γ-lyase (CSE) and the reduced renal H2 S production. NaHS treatment restored SIRT1 expression, inhibited the p53-mediated pro-apoptotic pathway and attenuated diabetes-associated apoptosis and renal injury. In high glucose-treated MPC5 podocytes, NaHS treatment inhibited the p53-mediated pro-apoptotic pathway and podocyte apoptosis in a SIRT1-dependent manner. Collectively, exercise training upregulated CBS/CSE expression and enhanced the endogenous H2 S production in renal tissues, thereby contributing to the modulation of the SIRT1/p53 apoptosis pathway and improvement of diabetic nephropathy.


Assuntos
Nefropatias Diabéticas/metabolismo , Sulfeto de Hidrogênio/metabolismo , Condicionamento Físico Animal/fisiologia , Sirtuína 1/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Animais , Apoptose/fisiologia , Caspase 3/metabolismo , Linhagem Celular , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/fisiopatologia , Nefropatias Diabéticas/fisiopatologia , Rim/metabolismo , Rim/fisiopatologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Podócitos/metabolismo , Transdução de Sinais/fisiologia
5.
Medicine (Baltimore) ; 100(30): e26431, 2021 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-34397684

RESUMO

BACKGROUND: Sodium glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide 1 receptor agonists (GLP-1 RAs) have been demonstrated to be able to improve the cardiovascular and renal prognosis in patients with type 2 diabetes (T2D). However, the relative efficacy of various SGLT2 inhibitors and GLP-1 RAs on cardiorenal outcomes is unestablished. METHODS: We searched PubMed and Embase for relevant cardiovascular or renal outcome trials (CVOTs). Endpoints of interest were major adverse cardiovascular events (MACE), stroke, myocardial infarction (MI), cardiovascular death (CVD), all-cause death (ACD), kidney function progression (KFP), and hospitalization for heart failure (HHF). Bayesian network meta-analysis was conducted to produce pooled hazard ratio (HR) and 95% confidence interval (CI). We calculated the probability values of surface under the cumulative ranking curve to rank active and placebo interventions. RESULTS: Fourteen COVTs were included in analysis. Sotagliflozin (HR 0.76, 95% CI 0.61-0.94), subcutaneous semaglutide, and albiglutide lowered MACE versus lixisenatide among others. Sotagliflozin (HR 0.59, 95% CI 0.40-0.89), canagliflozin, and empagliflozin lowered HHF versus subcutaneous semaglutide among others. Dapagliflozin and empagliflozin lowered KFP versus exenatide among others. Empagliflozin and oral semaglutide lowered CVD versus dapagliflozin among others. Sotagliflozin (HR 0.65, 95% CI 0.47-0.91) and albiglutide lowered MI versus ertugliflozin among others. Sotagliflozin (HR 0.56, 95% CI 0.37-0.85) and subcutaneous semaglutide lowered stroke versus empagliflozin among others. Oral semaglutide and empagliflozin lowered ACD versus subcutaneous semaglutide among others. The maximum surface under the cumulative ranking curve values followed sotagliflozin, subcutaneous semaglutide, and albiglutide in lowering MACE; sotagliflozin, canagliflozin, and empagliflozin in lowering HHF; dapagliflozin and empagliflozin in lowering KFP; empagliflozin and oral semaglutide in lowering CVD; sotagliflozin and albiglutide in lowering MI; sotagliflozin and subcutaneous semaglutide in lowering stroke; and oral semaglutide and empagliflozin in lowering ACD. CONCLUSIONS: This updated network meta-analysis reproduced the findings in the first network meta-analysis, and moreover revealed that sotagliflozin was one of the most effective drugs as for lowering MI, stroke, MACE, and HHF, whereas ertugliflozin was not. These findings will provide the according evidence regarding the usage of specific SGLT2 inhibitors and GLP-1 RAs in T2D patients for prevention of specific cardiorenal endpoints.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Receptor do Peptídeo Semelhante ao Glucagon 1/antagonistas & inibidores , Coração/efeitos dos fármacos , Rim/efeitos dos fármacos , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Diabetes Mellitus Tipo 2/fisiopatologia , Receptor do Peptídeo Semelhante ao Glucagon 1/uso terapêutico , Coração/fisiopatologia , Humanos , Rim/fisiopatologia , Metanálise em Rede , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Resultado do Tratamento
6.
Nutrients ; 13(8)2021 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-34444907

RESUMO

Background-Some data suggest favorable effects of a high potassium intake on kidney function. The present population-based study investigated cross-sectional and longitudinal relations of urinary potassium with kidney function. Methods-Study cohort included 2027 Gubbio Study examinees (56.9% women) with age ≥ 18 years at exam-1 and with complete data on selected variables at exam-1 (1983-1985), exam-2 (1989-1992), and exam-3 (2001-2007). Urinary potassium as urinary potassium/creatinine ratio was measured in daytime spot samples at exam-1 and in overnight timed collections at exam-2. Estimated glomerular filtration rate (eGFR) was measured at all exams. Covariates in analyses included demographics, anthropometry, blood pressure, drug treatments, diabetes, smoking, alcohol intake, and urinary markers of dietary sodium and protein. Results-In multivariable regression, urinary potassium/creatinine ratio cross-sectionally related to eGFR neither at exam-1 (standardized coefficient and 95%CI = 0.020 and -0.059/0.019) nor at exam-2 (0.024 and -0.013/0.056). Exam-1 urinary potassium/creatinine ratio related to eGFR change from exam-1 to exam-2 (0.051 and 0.018/0.084). Exam-2 urinary potassium/creatinine ratio related to eGFR change from exam-2 to exam-3 (0.048 and 0.005/0.091). Mean of urinary potassium/creatinine ratio at exam-1 and exam-2 related to eGFR change from exam-1 to exam-3 (0.056 and 0.027/0.087) and to incidence of eGFR < 60 mL/min per 1.73 m2 from exam-1 to exam-3 (odds ratio and 95%CI = 0.78 and 0.61/0.98). Conclusion-In the population, urinary potassium did not relate cross-sectionally to eGFR but related to eGFR decline over time. Data support the existence of favorable effects of potassium intake on ageing-associated decline in kidney function.


Assuntos
Envelhecimento/urina , Saúde da População/estatística & dados numéricos , Potássio/urina , Adolescente , Adulto , Idoso , Creatinina/urina , Estudos Transversais , Feminino , Taxa de Filtração Glomerular , Humanos , Rim/fisiopatologia , Testes de Função Renal , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Análise de Regressão , Adulto Jovem
7.
Theranostics ; 11(16): 7984-7994, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34335975

RESUMO

Rationale: Acute myocardial infarction (MI) triggers a systemic inflammatory response including crosstalk along the heart-kidney axis. We employed radionuclide-based inflammation-targeted whole-body molecular imaging to identify potential cardio-renal crosstalk after MI in a translational setup. Methods: Serial whole-body positron emission tomography (PET) with the specific CXCR4 ligand 68Ga-Pentixafor was performed after MI in mice. Tracer retention in kidneys and heart was compared to hematopoietic organs to evaluate systemic inflammation, validated by ex vivo analysis and correlated with progressive contractile dysfunction. Additionally, 96 patients underwent 68Ga-Pentixafor PET within the first week after MI, for systems-based image analysis and to determine prognostic value for adverse renal outcome. Results: In mice, transient myocardial CXCR4 upregulation occurred early after MI. Cardiac and renal PET signal directly correlated over the time course (r = 0.62, p < 0.0001), suggesting an inflammatory link between organs. Ex-vivo autoradiography (r = 0.9, p < 0.01) and CD68 immunostaining indicated signal localization to inflammatory cell content. Renal signal at 7d was inversely proportional to left ventricular ejection fraction at 6 weeks after MI (r = -0.79, p < 0.01). In patients, renal CXCR4 signal also correlated with signal from infarct (r = 0.25, p < 0.05) and remote myocardium (r = 0.39, p < 0.0001). Glomerular filtration rate (GFR) was available in 48/96 (50%) during follow-up. Worsening of renal function (GFR loss >5 mL/min/1.73m2), occurred a mean 80.5 days after MI in 16/48 (33.3%). Kaplan-Meier analysis revealed adverse renal outcome for patients with elevated remote myocardial CXCR4 signal (p < 0.05). Multivariate Cox analysis confirmed an independent predictive value (relative to baseline GFR, LVEF, infarct size; HR, 5.27). Conclusion: Systems-based CXCR4-targeted molecular imaging identifies inflammatory crosstalk along the cardio-renal axis early after MI.


Assuntos
Coração/fisiopatologia , Rim/fisiopatologia , Infarto do Miocárdio/fisiopatologia , Animais , Complexos de Coordenação/farmacologia , Humanos , Inflamação/metabolismo , Inflamação/fisiopatologia , Masculino , Camundongos , Imagem Molecular/métodos , Infarto do Miocárdio/metabolismo , Miocárdio/metabolismo , Peptídeos Cíclicos/farmacologia , Tomografia por Emissão de Pósitrons/métodos , Receptores CXCR4/metabolismo , Volume Sistólico , Função Ventricular Esquerda , Remodelação Ventricular/fisiologia , Imagem Corporal Total/métodos
8.
Nutrients ; 13(7)2021 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-34371925

RESUMO

Renal dysfunction and sarcopenia are important prognostic factors in patients with chronic liver disease (CLD). Muscle atrophy can cause the overestimation of renal function based on serum creatinine. However, the frequency of overestimated renal function in Japanese patients with CLD and its relationship with sarcopenia are unclear. In present study, we evaluated the frequency of overestimated renal function, defined as a >20% higher eGFR using creatinine than using cystatin C, in 307 patients with CLD as well as its relationship with indicators of sarcopenia. In total, 24.8% of patients had overestimated renal function. In a multivariate regression analysis, liver cirrhosis (p = 0.004) and psoas muscle mass index (p = 0.049) were significantly associated with overestimated renal function. Loss of skeletal muscle mass was significantly more frequent in both male and female patients with overestimated renal function than without. In males, the loss of muscle strength and rate of sarcopenia, defined as loss of muscle mass and strength, were significantly higher in patients with than without overestimated renal function. The high frequency of overestimated renal function in Japanese patients suggests that indicators of renal function should be carefully considered; furthermore, monitoring and interventions for both renal function and sarcopenia are needed in patients with CLD.


Assuntos
Composição Corporal , Taxa de Filtração Glomerular , Nefropatias/fisiopatologia , Rim/fisiopatologia , Hepatopatias/fisiopatologia , Músculos Psoas/fisiopatologia , Sarcopenia/fisiopatologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Doença Crônica , Creatinina/sangue , Cistatina C/sangue , Feminino , Humanos , Japão/epidemiologia , Nefropatias/diagnóstico , Nefropatias/epidemiologia , Hepatopatias/diagnóstico , Hepatopatias/epidemiologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Músculos Psoas/diagnóstico por imagem , Reprodutibilidade dos Testes , Estudos Retrospectivos , Sarcopenia/diagnóstico por imagem , Sarcopenia/epidemiologia , Tomografia Computadorizada por Raios X , Adulto Jovem
9.
Br J Anaesth ; 127(3): 415-423, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34246461

RESUMO

BACKGROUND: Remimazolam is a new benzodiazepine for procedural sedation and general anaesthesia. The aim of this study was to characterise its pharmacokinetic properties and safety in renally and hepatically impaired subjects. METHODS: Two separate trials were conducted in patients with hepatic (n=11) or renal impairment (n=11) compared with matched healthy subjects (n=9 and n=12, respectively). The hepatic impairment trial was an open-label adaptive 'Reduced Design' trial, using a single bolus of remimazolam 0.1 mg kg-1 i.v., whereas the renal impairment trial was an open-label trial of a single bolus dose of remimazolam 1.5 mg i.v. Remimazolam plasma concentrations over time were analysed by population pharmacokinetic modelling. RESULTS: Remimazolam pharmacokinetic properties were adequately described by a three-compartment, recirculatory model. Exposure in subjects with severe hepatic impairment was 38.1% higher (i.e. clearance was 38.1% lower) compared with healthy volunteers. This increase caused a slightly delayed recovery (8.0 min for healthy, 12.1 min for moderate, and 16.7 min for severe hepatic impairment). With renal impairment, plasma clearance was comparable with that measured in healthy subjects. Simulations of Cmax after a bolus dose of 10 mg showed no relevant impact of hepatic or renal impairment. The overall incidence of adverse events was low, and all adverse events were mild. CONCLUSIONS: As Cmax after a remimazolam bolus i.v. was not affected by hepatic or renal impairment, no dose adjustments are required. No unexpected adverse events related to remimazolam were seen in subjects with renal or hepatic impairment. CLINICAL TRIAL REGISTRATION: Hepatic impairment trial: ClinicalTrials.gov, NCT01790607 (https://clinicaltrials.gov/ct2/show/NCT01790607). Renal impairment trial: EudraCT Number: 2014-004575-23.


Assuntos
Benzodiazepinas/farmacocinética , Taxa de Filtração Glomerular , Hipnóticos e Sedativos/farmacocinética , Nefropatias/fisiopatologia , Rim/fisiopatologia , Hepatopatias/fisiopatologia , Fígado/fisiopatologia , Adulto , Benzodiazepinas/administração & dosagem , Benzodiazepinas/efeitos adversos , Benzodiazepinas/sangue , Simulação por Computador , Monitoramento de Medicamentos , Feminino , Humanos , Hungria , Hipnóticos e Sedativos/administração & dosagem , Hipnóticos e Sedativos/efeitos adversos , Hipnóticos e Sedativos/sangue , Injeções Intravenosas , Nefropatias/diagnóstico , Hepatopatias/diagnóstico , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Medição de Risco , Fatores de Risco , Índice de Gravidade de Doença , Estados Unidos
10.
Am J Kidney Dis ; 78(3): 442-458, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34275659

RESUMO

Medications are an important part of the management of patients with kidney disease. When used appropriately, pharmacotherapy can slow disease progression and reduce morbidity and mortality. Unfortunately, reduced kidney function can significantly alter the pharmacokinetics and pharmacodynamics of many medications, putting patients at risk for drug toxicity if modifications to therapy are not appropriately managed. Adding complexity to the appropriateness of medication and dosage selection is the difficulty in estimating kidney function and the discordance between the Cockcroft-Gault-derived dosing cut points in most medication package inserts and the estimations of glomerular filtration rate by newer and generally more accurate guideline-recommended equations. This installment of the AJKD Core Curriculum in Nephrology provides recent updates and practical considerations for designing optimal medication regimens. Given the prevalence of abnormal kidney function and its importance in medication selection and dose adjustment, additional focus and specific recommendations are provided for anticoagulant, anti-infective, analgesic, antidiabetic, and antihypertensive agents.


Assuntos
Currículo , Taxa de Filtração Glomerular/fisiologia , Nefropatias/tratamento farmacológico , Rim/fisiopatologia , Nefrologistas/normas , Humanos , Nefropatias/fisiopatologia
11.
Diabetes ; 70(8): 1603-1616, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34285119

RESUMO

Prospective studies in informative populations are crucial to increasing our knowledge of disease. In this perspective, we describe a half century of studies in an American Indian population that transformed our understanding of kidney disease in type 2 diabetes, now recognized as the leading cause of kidney failure worldwide. Serial examinations conducted for many years that included the collection of data and samples across multiple domains captured an unprecedented volume of clinical, physiologic, morphometric, genomic, and transcriptomic data. This work permitted us to extensively characterize the course and determinants of diabetic kidney disease, its pathophysiologic underpinnings, and important secular trends of urgent concern to populations worldwide, including the emergence of youth-onset type 2 diabetes and its effect on development of diabetic kidney disease in midlife. By combining these data using the tools of integrative biology, we are developing new mechanistic insights into the development and progression of diabetic kidney disease in type 2 diabetes. These insights have already contributed to the identification and successful therapeutic targeting of a novel pathway in DKD. We anticipate that this work will continue to expand our understanding of this complex disease and influence its management in the coming years.


Assuntos
Nativos Estadunidenses , Nefropatias Diabéticas/etnologia , Rim/fisiopatologia , Nefropatias Diabéticas/fisiopatologia , Humanos
12.
Diabetes ; 70(8): 1754-1766, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34285121

RESUMO

Half of the mortality in diabetes is seen in individuals <50 years of age and commonly predicted by the early onset of diabetic kidney disease (DKD). In type 1 diabetes, increased urinary albumin-to-creatinine ratio (uACR) during adolescence defines this risk, but the pathological factors responsible remain unknown. We postulated that early in diabetes, glucose variations contribute to kidney injury molecule-1 (KIM-1) release from circulating T cells, elevating uACR and DKD risk. DKD risk was assigned in youth with type 1 diabetes (n = 100; 20.0 ± 2.8 years; males/females, 54:46; HbA1c 66.1 [12.3] mmol/mol; diabetes duration 10.7 ± 5.2 years; and BMI 24.5 [5.3] kg/m2) and 10-year historical uACR, HbA1c, and random blood glucose concentrations collected retrospectively. Glucose fluctuations in the absence of diabetes were also compared with streptozotocin diabetes in apolipoprotein E -/- mice. Kidney biopsies were used to examine infiltration of KIM-1-expressing T cells in DKD and compared with other chronic kidney disease. Individuals at high risk for DKD had persistent elevations in uACR defined by area under the curve (AUC; uACRAUC0-10yrs, 29.7 ± 8.8 vs. 4.5 ± 0.5; P < 0.01 vs. low risk) and early kidney dysfunction, including ∼8.3 mL/min/1.73 m2 higher estimated glomerular filtration rates (modified Schwartz equation; Padj < 0.031 vs. low risk) and plasma KIM-1 concentrations (∼15% higher vs. low risk; P < 0.034). High-risk individuals had greater glycemic variability and increased peripheral blood T-cell KIM-1 expression, particularly on CD8+ T cells. These findings were confirmed in a murine model of glycemic variability both in the presence and absence of diabetes. KIM-1+ T cells were also infiltrating kidney biopsies from individuals with DKD. Healthy primary human proximal tubule epithelial cells exposed to plasma from high-risk youth with diabetes showed elevated collagen IV and sodium-glucose cotransporter 2 expression, alleviated with KIM-1 blockade. Taken together, these studies suggest that glycemic variations confer risk for DKD in diabetes via increased CD8+ T-cell production of KIM-1.


Assuntos
Glicemia/metabolismo , Diabetes Mellitus Tipo 1/sangue , Nefropatias Diabéticas/sangue , Receptor Celular 1 do Vírus da Hepatite A/sangue , Rim/patologia , Adolescente , Adulto , Diabetes Mellitus Tipo 1/patologia , Diabetes Mellitus Tipo 1/fisiopatologia , Nefropatias Diabéticas/patologia , Nefropatias Diabéticas/fisiopatologia , Feminino , Taxa de Filtração Glomerular/fisiologia , Humanos , Rim/fisiopatologia , Testes de Função Renal , Masculino , Estudos Retrospectivos , Adulto Jovem
13.
Biomolecules ; 11(6)2021 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-34207942

RESUMO

Blood pressure (BP) follows a circadian rhythm, it increases on waking in the morning and decreases during sleeping at night. Disruption of the circadian BP rhythm has been reported to be associated with worsened cardiovascular and renal outcomes, however the underlying molecular mechanisms are still not clear. In this review, we briefly summarized the current understanding of the circadian BP regulation and provided therapeutic overview of the relationship between circadian BP rhythm and cardiovascular and renal health and disease.


Assuntos
Pressão Sanguínea/fisiologia , Doenças Cardiovasculares/fisiopatologia , Ritmo Circadiano/fisiologia , Nefropatias/fisiopatologia , Doenças Cardiovasculares/metabolismo , Sistema Cardiovascular/fisiopatologia , China , Humanos , Hipertensão/fisiopatologia , Rim/fisiopatologia , Nefropatias/metabolismo
14.
Vasc Health Risk Manag ; 17: 389-394, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34262283

RESUMO

Background: The World Health Organization (WHO) proposed the integrated care for older people (ICOPE) screening tool to identify functional impairment. We explore the association of geriatric functional impairment and hypertension, diabetes, dyslipidemia in the community-dwelling elderly. Methods: We enrolled individuals aged at least 65 with hypertension, diabetes, or dyslipidemia; or those aged at least 75 from May to July 2019. We applied ICOPE tools to evaluate six function assessments: cognitive decline, limited mobility, malnutrition, visual impairment, hearing loss, and depressive symptoms. Factors were analyzed using stepwise multivariable linear regression for ICOPE scores and logistic regression for geriatric functional impairment. All analyses were adjusted for age and glomerular filtration rate. Results: We enrolled 457 participants including 303 (66.3%) participants with hypertension, 296 (64.8%) diabetes, and 221 (48.4%) dyslipidemia. Seventy-eight (17.1%) participants have at least one geriatric functional impairment, including 41 (25.9%) participants aged ≥ 75 and 37 (12.4%) aged 65-74. The ICOPE score (0.4 ± 0.6) of participants aged at least 75 was higher than that (0.1 ± 0.4) of the participants aged 65-74 (p < 0.001). Dyslipidemia (p = 0.002) was positively associated with ICOPE score. Dyslipidemia (odds ratio: 2.15, 95% confidence interval: 1.27-3.70, p = 0.005), not hypertension (p = 0.3) and diabetes (p = 0.9), was associated with geriatric functional impairment. Visual impairment was the most common function impairment. Female was linked to limited mobility, renal function was associated with mobility (p < 0.001) and nutrition (p = 0.02). Conclusion: Dyslipidemia but not hypertension, diabetes is linked to geriatric functional impairment in community-dwelling elderly. Lower renal function is associated with decreased mobility and nutrition. More studies are needed to determine if treatment of dyslipidemia reduces geriatric functional impairment.


Assuntos
Dislipidemias/diagnóstico , Idoso Fragilizado , Fragilidade/diagnóstico , Avaliação Geriátrica , Vida Independente , Afeto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Cognição , Estudos Transversais , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/fisiopatologia , Diabetes Mellitus/psicologia , Dislipidemias/fisiopatologia , Dislipidemias/psicologia , Dislipidemias/terapia , Feminino , Fragilidade/fisiopatologia , Fragilidade/psicologia , Fragilidade/terapia , Estado Funcional , Taxa de Filtração Glomerular , Audição , Humanos , Hipertensão/diagnóstico , Hipertensão/fisiopatologia , Hipertensão/psicologia , Rim/fisiopatologia , Masculino , Saúde Mental , Limitação da Mobilidade , Estado Nutricional , Valor Preditivo dos Testes , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores Sexuais , Visão Ocular
15.
BMC Infect Dis ; 21(1): 663, 2021 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-34238232

RESUMO

BACKGROUND: Coronavirus disease 2019 (COVID-19) is associated with a high mortality rate, especially in patients with severe illness. We conducted a systematic review and meta-analysis to assess the potential predictors of mortality in patients with COVID-19. METHODS: PubMed, EMBASE, the Cochrane Library, and three electronic Chinese databases were searched from December 1, 2019 to April 29, 2020. Eligible studies reporting potential predictors of mortality in patients with COVID-19 were identified. Unadjusted prognostic effect estimates were pooled using the random-effects model if data from at least two studies were available. Adjusted prognostic effect estimates were presented by qualitative analysis. RESULTS: Thirty-six observational studies were identified, of which 27 were included in the meta-analysis. A total of 106 potential risk factors were tested, and the following important predictors were associated with mortality: advanced age, male sex, current smoking status, preexisting comorbidities (especially chronic kidney, respiratory, and cardio-cerebrovascular diseases), symptoms of dyspnea, complications during hospitalization, corticosteroid therapy and a severe condition. Additionally, a series of abnormal laboratory biomarkers of hematologic parameters, hepatorenal function, inflammation, coagulation, and cardiovascular injury were also associated with fatal outcome. CONCLUSION: We identified predictors of mortality in patients with COVID-19. These findings could help healthcare providers take appropriate measures and improve clinical outcomes in such patients.


Assuntos
COVID-19/diagnóstico , COVID-19/mortalidade , Corticosteroides/administração & dosagem , Distribuição por Idade , Doenças Cardiovasculares/epidemiologia , Comorbidade , Bases de Dados Factuais , Dispneia/epidemiologia , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Inflamação/epidemiologia , Rim/fisiopatologia , Fígado/fisiopatologia , Masculino , Estudos Observacionais como Assunto , Prognóstico , Fatores de Risco , Distribuição por Sexo , Fumantes/estatística & dados numéricos
16.
Biomed Pharmacother ; 138: 111465, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34311522

RESUMO

Acidic mammalian chitinase (CHIA) belongs to the 18-glycosidase family and is expressed in epithelial cells and certain immune cells (such as neutrophils and macrophages) in various organs. Under physiological conditions, as a hydrolase, CHIA can degrade chitin-containing pathogens, participate in Type 2 helper T (Th2)-mediated inflammation, and enhance innate and adaptive immunity to pathogen invasion. Under pathological conditions, such as rhinitis, ocular conjunctivitis, asthma, chronic atrophic gastritis, type 2 diabetes, and pulmonary interstitial fibrosis, CHIA expression is significantly changed. In addition, studies have shown that CHIA has an anti-apoptotic effect, promotes epithelial cell proliferation and maintains organ integrity, and these effects are not related to chitinase degradation. CHIA can also be used as a biomolecular marker in diseases such as chronic atrophic gastritis, dry eye, and acute kidney damage caused by sepsis. Analysis of the authoritative TCGA database shows that CHIA expression in gastric adenocarcinoma, liver cancer, renal clear cell carcinoma and other tumors is significantly downregulated compared with that in normal tissues, but the specific mechanism is unclear. This review is based on all surveys conducted to date and summarizes the expression patterns and functional diversity of CHIA in various organs. Understanding the physiological and pathophysiological relevance of CHIA in multiple organs opens new possibilities for disease treatment.


Assuntos
Encéfalo/enzimologia , Quitinases/metabolismo , Sistema Digestório/enzimologia , Olho/enzimologia , Rim/enzimologia , Sistema Respiratório/enzimologia , Animais , Encéfalo/fisiopatologia , Diabetes Mellitus Tipo 2/enzimologia , Diabetes Mellitus Tipo 2/fisiopatologia , Sistema Digestório/fisiopatologia , Olho/fisiopatologia , Humanos , Rim/fisiopatologia , Sistema Respiratório/fisiopatologia , Transdução de Sinais
17.
Biomed Pharmacother ; 138: 111509, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34311524

RESUMO

The effect of hyper-mineral waters on human health has long been debated. This pilot study evaluated the influence of San Martino® water (Sardinia, Italy), on clinical and biological parameters, following the treatment of 10 hospitalized patients. Crenotherapy consisted of 1-2 L of the water daily for 10 days. A complete blood count, serum electrolytes, liver and kidney function tests, fasting lipid profile and plasma glucose, and abdominal ultrasound imaging were assessed before and at the end of treatment. In addition, body weight, dyspeptic symptoms, bowel movements, diuresis, uricuria and blood pressure were evaluated daily. According to its physico-chemical properties, the water is hyper-mineral (TDS 2808 mg/L) with a high content of bicarbonate and iron. At the end of the study, diuresis increased by 60% (850 vs 1295 ml/24 h, P = 0.009) and uricuria by 41% (362 vs 490 mg/24 h, P = 0.022) respectively, whereas plasma uric acid level decreased by 7% (4.7 vs 4.3 mg/dL, P = 0.043). Compared to the basal values, serum gamma-glutamyl transferase, alkaline phosphatase and total bilirubin levels, showed a reduction of 65% (31 vs 18 U/L, P = 0.022), 15% (96 vs 90 U/L, P = 0.041), and 11% (0.53 vs 0.45 g/dL, P = 0.041), respectively. Bowel movements improved in 62.5% of patients with constipation, and 80% of dyspeptic patients experienced symptoms relief. Compliance to the treatment reached 100%. Mild differences were observed in body weight and blood pressure, although not in ultrasound imaging during crenotherapy. These findings suggest that the San Martino® hyper-mineral water may have some benefits to human health. Additional studies with a larger-sized cohort and for a longer period are needed to confirm these preliminary results.


Assuntos
Balneologia , Defecação , Diurese , Intestinos/fisiopatologia , Rim/fisiopatologia , Águas Minerais/uso terapêutico , Fosfatase Alcalina/sangue , Bilirrubina/sangue , Biomarcadores/sangue , Biomarcadores/urina , Feminino , Humanos , Pacientes Internados , Itália , Masculino , Projetos Piloto , Recuperação de Função Fisiológica , Fatores de Tempo , Resultado do Tratamento , Ácido Úrico/sangue , Ácido Úrico/urina , gama-Glutamiltransferase/sangue
18.
Ecotoxicol Environ Saf ; 221: 112442, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34166936

RESUMO

Arsenic (As) and antimony (Sb) are commonly accumulated environmental pollutants that often coexist in nature and cause serious widespread biological toxicity. To investigate the nephrotoxicity induced by As and Sb in detail, we explored the mechanism by which As and Sb cotreatment induced autophagy and pyroptosis in vivo and in vitro. In this study, mice were treated with 4 mg/kg arsenic trioxide (ATO) or/and 15 mg/kg antimony trichloride (SbCl3) by intragastric intubation for 60 days. TCMK-1 cells were treated with ATO (12.5 µM), SbCl3 (25 µM) or a combination of As and Sb for 24 h. The results of the in vivo experiment demonstrated that As or/and Sb exposure could induce histopathological changes in the kidneys, and increase the levels of biochemical indicators of nephrotoxicity. In addition, As and Sb can co-induce oxidative stress, which further activate autophagy and pyroptosis. In an in vitro experiment, As and/or Sb coexposure increased ROS generation and decreased MMP. Moreover, the results of related molecular experiments further confirmed that As and Sb coactivated autophagy and pyroptosis. In conclusion, our results indicated that As and Sb co-exposure could cause autophagy and pyroptosis via the ROS pathway, and these two metals might have a synergistic effect on nephrotoxicity.


Assuntos
Antimônio/toxicidade , Trióxido de Arsênio/toxicidade , Cloretos/toxicidade , Rim/efeitos dos fármacos , Piroptose/efeitos dos fármacos , Animais , Autofagia/efeitos dos fármacos , Linhagem Celular , Poluentes Ambientais/toxicidade , Rim/fisiopatologia , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo
19.
Nutrients ; 13(5)2021 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-34067952

RESUMO

The goal of this retrospective study was to document any alterations in plasma amino acids (AAs) in subjects with cardiorenal syndrome type 2 (CRS 2). We analyzed data from sixteen patients with CRS 2 and eight healthy subjects (control group, C), whose plasma arterial (A) and venous (V) AA concentrations had been measured. Compared to C, the group of CRS 2 patients showed significant reductions by more than 90% in A (p < 0.01) and V (p < 0.01) individual AAs, whereas negative A-V differences that indicated a net muscle AA release (muscle hypercatabolism) were found in 59% of CRS 2 patients (p < 0.03). No significant differences in plasma A and V AA concentrations nor in A-V differences were found between patients with mild kidney damage (N = 5; estimated glomerular filtration rate, eGFR ≥ 60 mL/min/1.73 m2) and patients with moderate-severe kidney damage (N = 11; eGFR < 60 mL/min/1.73 m2). Several plasma arterial AAs correlated with hemodynamic variables, but not with GFR. The study showed that patients with CRS 2 had very low concentrations of circulating AAs, independent of the degree of GFR damage.


Assuntos
Aminoácidos/metabolismo , Síndrome Cardiorrenal/metabolismo , Aminoácidos/sangue , Síndrome Cardiorrenal/sangue , Síndrome Cardiorrenal/fisiopatologia , Síndrome Cardiorrenal/terapia , Estudos de Casos e Controles , Feminino , Taxa de Filtração Glomerular , Coração/fisiopatologia , Hemodinâmica , Humanos , Rim/fisiopatologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
20.
Int J Mol Sci ; 22(11)2021 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-34072329

RESUMO

At the onset of diabetes, the kidney grows large and the glomerular filtration rate becomes abnormally high. These structural and hemodynamics changes affect kidney function and may contribute to the development of chronic kidney disease. The goal of this study is to analyze how kidney function is altered in patients with diabetes and the renal effects of an anti-hyperglyceamic therapy that inhibits the sodium-glucose cotransporter 2 (SGLT2) in the proximal convoluted tubules. To accomplish that goal, we have developed a computational model of kidney function in a patient with diabetes and conducted simulations to study the effects of diabetes and SGLT2 inhibition on solute and water transport along the nephrons. Simulation results indicate that diabetes-induced hyperfiltration and tubular hypertrophy enhances Na+ transport, especially along the proximal tubules and thick ascending limbs. These simulations suggest that SGLT2 inhibition may attenuate glomerular hyperfiltration by limiting Na+-glucose transport, raising luminal [Cl-] at the macula densa, restoring the tubuloglomerular feedback signal, thereby reducing single-nephron glomerular filtration rate.


Assuntos
Diabetes Mellitus/metabolismo , Suscetibilidade a Doenças , Rim/metabolismo , Rim/fisiopatologia , Modelos Biológicos , Animais , Transporte Biológico/efeitos dos fármacos , Biomarcadores , Diabetes Mellitus/etiologia , Nefropatias Diabéticas/etiologia , Nefropatias Diabéticas/metabolismo , Nefropatias Diabéticas/patologia , Humanos , Rim/efeitos dos fármacos , Testes de Função Renal , Glomérulos Renais/efeitos dos fármacos , Glomérulos Renais/metabolismo , Túbulos Renais/efeitos dos fármacos , Túbulos Renais/metabolismo , Transportador 2 de Glucose-Sódio/metabolismo , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia
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