RESUMO
OBJECTIVE: To examine changes in glomerular hyperfiltration and other measures of kidney function in youth with type 2 diabetes treated with dulaglutide or placebo. RESEARCH DESIGN AND METHODS: Post hoc analysis was performed on kidney laboratory data from 154 youths (age 10-18 years) with type 2 diabetes enrolled in a completed placebo-controlled glycemic control trial of dulaglutide. RESULTS: Mean estimated glomerular filtration rate (eGFR) decreased from baseline to 26 weeks in participants treated with dulaglutide versus placebo (-5.8 vs. -0.1 mL/min/1.73 m2; P = 0.016). Decreases in eGFR were observed primarily in participants with baseline glomerular hyperfiltration. At 26 weeks, the prevalence of both glomerular hyperfiltration and proteinuria increased with placebo but decreased with dulaglutide (P = 0.014 and 0.004 vs. placebo, respectively). CONCLUSIONS: Dulaglutide was associated with attenuated glomerular hyperfiltration and proteinuria in youth with type 2 diabetes. The impact of these changes on the risk of diabetic kidney disease is unclear.
Assuntos
Albuminúria , Diabetes Mellitus Tipo 2 , Taxa de Filtração Glomerular , Peptídeos Semelhantes ao Glucagon , Fragmentos Fc das Imunoglobulinas , Proteinúria , Proteínas Recombinantes de Fusão , Humanos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/fisiopatologia , Diabetes Mellitus Tipo 2/complicações , Adolescente , Criança , Proteinúria/fisiopatologia , Masculino , Feminino , Albuminúria/fisiopatologia , Proteínas Recombinantes de Fusão/uso terapêutico , Peptídeos Semelhantes ao Glucagon/análogos & derivados , Peptídeos Semelhantes ao Glucagon/uso terapêutico , Fragmentos Fc das Imunoglobulinas/uso terapêutico , Hipoglicemiantes/uso terapêutico , Nefropatias Diabéticas/fisiopatologia , Nefropatias Diabéticas/tratamento farmacológicoRESUMO
The Goldblatt model of hypertension (2K-1C) in rats is characterized by renal sympathetic nerve activity (rSNA). We investigated the effects of unilateral renal denervation of the clipped kidney (DNX) on sodium transporters of the unclipped kidneys and the cardiovascular, autonomic, and renal functions in 2K-1C and control (CTR) rats. The mean arterial pressure (MAP) and rSNA were evaluated in experimental groups. Kidney function and NHE3, NCC, ENaCß, and ENaCγ protein expressions were assessed. The glomerular filtration rate (GRF) and renal plasma flow were not changed by DNX, but the urinary (CTR: 0.0042 ± 0.001; 2K-1C: 0.014 ± 0.003; DNX: 0.005 ± 0.0013 mL/min/g renal tissue) and filtration fractions (CTR: 0.29 ± 0.02; 2K-1C: 0.51 ± 0.06; DNX: 0.28 ± 0.04 mL/min/g renal tissue) were normalized. The Na+/H+ exchanger (NHE3) was reduced in 2K-1C, and DNX normalized NHE3 (CTR: 100 ± 6; 2K-1C: 44 ± 14, DNX: 84 ± 13%). Conversely, the Na+/Cl- cotransporter (NCC) was increased in 2K-1C and was reduced by DNX (CTR: 94 ± 6; 2K-1C: 144 ± 8; DNX: 60 ± 15%). In conclusion, DNX in Goldblatt rats reduced blood pressure and proteinuria independently of GRF with a distinct regulation of NHE3 and NCC in unclipped kidneys.
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Rim , Trocador 3 de Sódio-Hidrogênio , Animais , Rim/inervação , Rim/metabolismo , Ratos , Masculino , Trocador 3 de Sódio-Hidrogênio/metabolismo , Taxa de Filtração Glomerular , Denervação , Isquemia/metabolismo , Pressão Sanguínea , Ratos Wistar , Hipertensão/metabolismo , Canais Epiteliais de Sódio/metabolismo , Modelos Animais de Doenças , Trocadores de Sódio-Hidrogênio/metabolismoRESUMO
We hypothesized that higher scores on the dietary inflammatory index (DII) would be associated with a lower glomerular filtration rate (GFR). This cross-sectional study included 2098 participants from Mexican Teachers Cohort Study, the Health Workers Cohort Study, and the Comitán Study belonging to the RenMex consortium. Energy-adjusted DII scores were estimated using a semi-quantitative food frequency questionnaire (FFQ). eGFR was estimated by the CKD Epidemiology Collaboration equation. Quantile regression models and ordered regression models were estimated to assess the associations of interest. Median age of study participants was 47 years, median eGFR was 102.9 mL/min/1.73m2, and the median energy-adjusted DII was 0.89 (range, -2.25, +4.86). The median eGFR was lower in participants in the highest percentile of DII compared to those in the lowest percentile (103.8 vs 101.4). We found that continuous and categorical energy-adjusted DII scores were associated with lower eGFR, especially at the lower percentiles. In adjusted ordered logistic regression, we found that the highest DII category was associated with 1.80 times the odds of belonging to the mildly decreased eGFR category or moderately decreased eGFR category compared lowest DII category (OR: 1.80, 95%CI 1.35, 2.40). A high DII score was associated with a lower eGFR among the Mexican population. Additional studies are crucial to validate these findings and explore potential strategies to reduce the consumption of pro-inflammatory foods as a preventive approach for chronic kidney disease (CKD).
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Dieta , Taxa de Filtração Glomerular , Inflamação , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , México/epidemiologia , Estudos Transversais , Adulto , Insuficiência Renal Crônica/epidemiologia , Estudos de Coortes , Fatores de RiscoRESUMO
OBJECTIVES: [51Cr]CrEDTA is used to measure the Glomerular Filtration Rate (GFR) in different clinical conditions. However, there is no consensus on the ideal number of blood samples to be taken and at what time points to measure its clearance. This study aimed to compare Slope Intercept (SI) and Single-Sample (SS) methods for measuring GFR in patients with solid tumors, stratified by age, GFR, and Body Mass Index (BMI). METHODS: 1,174 patients with cancer were enrolled in this prospective study. GFR was calculated by the SI method using blood samples drawn 2-, 4-, and 6-hours after [51Cr]CrEDTA injection (246-GFR). GFR was also measured using the SI method with samples at 2 and 4 hours (24-GFR) and at 4 and 6 hours (46-GFR), and SS methods according to Groth (4Gr-GFR) and Fleming (4Fl-GFR). Statistical analysis was performed to assess the accuracy, precision, and bias of the methods. RESULTS: Mean 246-GFR was 79.2 ± 21.9 mL/min/1.73 m2. ANOVA indicated a significant difference between 4Gr-GFR and the reference 246-GFR. Bias was lower than 5 mL/min/1.73 m2 for all methods, except for SS methods in subgroups BMI > 40 kg/m2; GFR > 105 or < 45. Precision was adequate and accuracy of 30 % was above 98% for all methods, except for SS methods in subgroup GFR < 45. CONCLUSION: 46-GFR and 246-GFR have high agreement and may be used to evaluate kidney function in patients with solid tumors. Single-sample methods can be adopted in specific situations, for non-obese patients with expected normal GFR.
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Taxa de Filtração Glomerular , Neoplasias , Humanos , Taxa de Filtração Glomerular/fisiologia , Feminino , Masculino , Estudos Prospectivos , Pessoa de Meia-Idade , Neoplasias/fisiopatologia , Neoplasias/sangue , Estudos Transversais , Idoso , Adulto , Radioisótopos de Cromo/farmacocinética , Índice de Massa Corporal , Reprodutibilidade dos Testes , Fatores de Tempo , Adulto Jovem , Idoso de 80 Anos ou mais , Valores de Referência , Fatores EtáriosRESUMO
BACKGROUND: Chronic kidney disease (CKD) is a global health problem with rising prevalence, morbidity, mortality, and associated costs. Early identification and risk stratification are key to preventing progression to kidney failure. However, there is a paucity of data on practice patterns of kidney function assessment to guide the development of improvement strategies, particularly in lower-income countries. METHODS: A retrospective observational analysis was conducted in a nationwide laboratory database in Brazil. We included all adult patients with at least one serum creatinine assessment between June 2018 and May 2021. Our primary objective was to determine the proportion of patients with estimated glomerular filtration rate (eGFR) evaluations accompanied by predicted levels of urinary albumin-to-creatinine ratio (pACR) assessments within 12 months. RESULTS: Out of 4,5323,332 serum creatinine measurements, 42% lacked pACR measurements within 12 months. Approximately 10.8% of tests suggested CKD, mostly at stage 3a. The proportion of serum creatinine exams paired with pACR assessment varied according to the CKD stage. Internal Medicine, Cardiology, and Obstetrics/Gynecology were the specialties requesting most of the creatinine tests. Nephrology contributed with only 1.1% of serum creatinine requests for testing. CONCLUSION: Our findings reveal that a significant proportion of individuals with a creatinine test lack an accompanying urinary albuminuria measurement in Brazil, contrary to the recommendations of the international guidelines. Non-Nephrologists perform most kidney function evaluations, even among patients with presumable advanced CKD. This highlights the urge to incorporate in clinical practice the early detection of CKD and to encourage more collaborative multidisciplinary care to improve CKD management.
Assuntos
Albuminúria , Creatinina , Taxa de Filtração Glomerular , Insuficiência Renal Crônica , Humanos , Brasil/epidemiologia , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/fisiopatologia , Creatinina/sangue , Estudos Retrospectivos , Feminino , Masculino , Medição de Risco/métodos , Pessoa de Meia-Idade , Bases de Dados Factuais , Adulto , Testes de Função Renal/métodos , IdosoRESUMO
Type 1 Diabetes Mellitus (T1DM) can generate severe complications, such as Diabetic Kidney Disease (DKD) or Diabetic Nephropathy (DN), with it emerging as the leading cause of terminal (end-stage) renal disease all over the world. For T1DM, the clinical evaluation of DKD uses markers like the Glomerular Filtration Rate (GFR) and the Urinary Albumin Excretion (UAE). However, early diagnosis of DKD is still a challenge. For this reason, investigating molecular markers, such as microRNAs (miRNAs), offers a promising perspective to an early diagnosis, highlighting the stability and the ability to reflect incipient molecular manifestations. Thus, here we investigated four miRNAs (hsa-let-7i-5p, hsa-miR-143-3p, hsa-miR-501-3p, and hsa-miR-100-5p) regarding nephropathy in patients with T1DM, considering the albuminuria (micro and macro) as a standard to evaluate the groups. As a result, we found a reduced expression of miR-100-5p in patients with MIC, indicating a protective role in nephropathy. Beyond that, expression levels between the groups (Non vs. UAE) were not significant when comparing the miRNAs miR-501-3p and miR-143-3p. Finally, miR-143-3p and miR-100-5p were linked to some target genes such as AKT1, MMP13, and IGF1R, that are connected to signal pathways and cellular metabolism.
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Biomarcadores , Diabetes Mellitus Tipo 1 , Nefropatias Diabéticas , MicroRNAs , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Albuminúria/genética , Biomarcadores/análise , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 1/complicações , Nefropatias Diabéticas/genética , Nefropatias Diabéticas/metabolismo , Regulação para Baixo/genética , Taxa de Filtração Glomerular , MicroRNAs/genética , Receptor IGF Tipo 1/genética , Receptor IGF Tipo 1/metabolismoRESUMO
INTRODUCTION: Identifying risk factors for autosomal dominant polycystic kidney disease (ADPKD) progression is important. However, studies that have evaluated this subject using a Brazilian sample is sparce. Therefore, the aim of this study was to identify risk factors for renal outcomes and death in a Brazilian cohort of ADPKD patients. METHODS: Patients had the first medical appointment between January 2002 and December 2014, and were followed up until December 2019. Associations between clinical and laboratory variables with the primary outcome (sustained decrease of at least 57% in the eGFR from baseline, need for dialysis or renal transplantation) and the secondary outcome (death from any cause) were analyzed using a multiple Cox regression model. Among 80 ADPKD patients, those under 18 years, with glomerular filtration rate <30 mL/min/1.73 m2, and/or those with missing data were excluded. There were 70 patients followed. RESULTS: The factors independently associated with the renal outcomes were total kidney length - adjusted Hazard Ratio (HR) with a 95% confidence interval (95% CI): 1.137 (1.057-1.224), glomerular filtration rate - HR (95% CI): 0.970 (0.949-0.992), and serum uric acid level - HR (95% CI): 1.643 (1.118-2.415). Diabetes mellitus - HR (95% CI): 8.115 (1.985-33.180) and glomerular filtration rate - HR (95% CI): 0.957 (0.919-0.997) were associated with the secondary outcome. CONCLUSIONS: These findings corroborate the hypothesis that total kidney length, glomerular filtration rate and serum uric acid level may be important prognostic predictors of ADPKD in a Brazilian cohort, which could help to select patients who require closer follow up.
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Progressão da Doença , Taxa de Filtração Glomerular , Rim Policístico Autossômico Dominante , Humanos , Rim Policístico Autossômico Dominante/complicações , Masculino , Feminino , Brasil/epidemiologia , Adulto , Pessoa de Meia-Idade , Fatores de Risco , Estudos de Coortes , Ácido Úrico/sangue , Estudos RetrospectivosRESUMO
Chronic kidney disease (CKD) has emerged as a significant global public health concern. Recent epidemiological studies have highlighted the link between exposure to fine particulate matter (PM2.5) and a decline in renal function. PM2.5 exerts harmful effects on various organs through oxidative stress and inflammation. Acute kidney injury (AKI) resulting from ischaemia-reperfusion injury (IRI) involves biological processes similar to those involved in PM2.5 toxicity and is a known risk factor for CKD. The objective of this study was to investigate the impact of PM2.5 exposure on IRI-induced AKI. Through a unique environmentally controlled setup, mice were exposed to urban PM2.5 or filtered air for 12 weeks before IRI followed by euthanasia 48 h after surgery. Animals exposed to PM2.5 and IRI exhibited reduced glomerular filtration, impaired urine concentration ability, and significant tubular damage. Further, PM2.5 aggravated local innate immune responses and mitochondrial dysfunction, as well as enhancing cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway activation. This increased renal senescence and suppressed the anti-ageing protein klotho, leading to early fibrotic changes. In vitro studies using proximal tubular epithelial cells exposed to PM2.5 and hypoxia/reoxygenation revealed heightened activation of the STING pathway triggered by cytoplasmic mitochondrial DNA, resulting in increased tubular damage and a pro-inflammatory phenotype. In summary, our findings imply a role for PM2.5 in sensitising proximal tubular epithelial cells to IRI-induced damage, suggesting a plausible association between PM2.5 exposure and heightened susceptibility to CKD in individuals experiencing AKI. Strategies aimed at reducing PM2.5 concentrations and implementing preventive measures may improve outcomes for AKI patients and mitigate the progression from AKI to CKD. © 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
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Injúria Renal Aguda , Camundongos Endogâmicos C57BL , Material Particulado , Traumatismo por Reperfusão , Animais , Injúria Renal Aguda/patologia , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/metabolismo , Traumatismo por Reperfusão/patologia , Material Particulado/efeitos adversos , Material Particulado/toxicidade , Camundongos , Masculino , Poluição do Ar/efeitos adversos , Modelos Animais de Doenças , Rim/patologia , Rim/metabolismo , Transdução de Sinais , Taxa de Filtração GlomerularRESUMO
INTRODUCTION/OBJECTIVES: The heterodimer exostosin-1/exostosin-2 (EXO-1/2) is a novel antigen observed in membranous nephropathy associated with systemic lupus erythematosus. This study aimed to evaluate the association between EXO-1/2 positivity in kidney biopsy and kidney outcomes. METHODS: The kidney biopsy tissue from 50 class 5 lupus nephritis (LN) and 55 mixed class 3/4 + 5 LN patients was stained for EXO-1/2. Baseline clinical and histological characteristics were compared between EXO-1/2 positive and EXO-1/2 negative patients. Time-to-event analyses were performed to compare rates of response to therapy, kidney flares, and progression to a 40% decline of the glomerular filtration rate (eGFR), doubling of serum creatinine, and kidney failure. RESULTS: Fourteen out of 50 (28%) of class 5 and 5 out of 55 (9%) of mixed class 3/4 + 5 LN stained positive for EXO-1/2. Patients with class 5 LN and EXO-1/2 positive stain were younger, with better kidney function at presentation, and lower scarring in the kidney biopsy analysis. Over a median follow-up of 100 months, patients with positive EXO-1/2 staining had significantly lower rates of progression in the full cohort. When analyzed separately in class 5 and mixed class LN subgroups, there were significantly lower rates of progression to a 40% decline of the eGFR and non-statistically significant trends for doubling of serum creatinine and kidney failure. CONCLUSION: EXO-1/2 is a novel antigen detected in class 5 LN and associated with a good prognosis of kidney function. The incorporation of EXO-1/2 staining in clinical practice can potentially modify the management of LN due to its prognostic implications. Key Points ⢠Exostosin-1/exostosin-2 antigen has been found in cases of membranous nephropathy associated with autoimmune diseases such as systemic lupus erythematosus. ⢠Exostosin-1/exostosin-2 staining in the kidney biopsy of class 5 or mixed class 3/4 + 5 lupus nephritis is associated with a good long-term prognosis of kidney function. ⢠The incorporation of exostosin-1/exostosin-2 staining into clinical practice can potentially modify management due to its prognostic implications.
Assuntos
Progressão da Doença , Taxa de Filtração Glomerular , Rim , Nefrite Lúpica , Humanos , Nefrite Lúpica/tratamento farmacológico , Nefrite Lúpica/metabolismo , Nefrite Lúpica/patologia , Feminino , Masculino , Adulto , Estudos Retrospectivos , Pessoa de Meia-Idade , Rim/patologia , Rim/fisiopatologia , Biópsia , Adulto Jovem , N-AcetilglucosaminiltransferasesRESUMO
BACKGROUND: Evidence on the effect of one-anastomosis gastric bypass (OAGB) on renal function is limited. OBJECTIVE: To compare the evolution of estimated renal function observed 1 year after OAGB and Roux-en-Y gastric bypass (RYGB) in individuals with obesity. DESIGN AND SETTING: Observational, analytical, and retrospective cohort study. Tertiary-level university hospital. METHODS: This study used a prospectively collected database of individuals who consecutively underwent bariatric surgery. Renal function was assessed by calculating the estimated glomerular filtration rate (eGFR), according to the Chronic Kidney Disease Epidemiology Collaboration. The one-year variation in the eGFR was compared between the procedures. RESULTS: No significant differences in age, sex, obesity-associated conditions, or body mass index were observed among individuals who underwent either OAGB or RYGB. OAGB led to a significantly higher percentage of total (P = 0.007) and excess weight loss (P = 0.026). Both OAGB and RYGB led to significantly higher values of eGFR (103.9 ± 22 versus 116.1 ± 13.3; P = 0.007, and 102.4 ± 19 versus 113.2 ± 13.3; P < 0.001, respectively). The one-year variation in eGFR was 11 ± 16.2% after OAGB and 16.7 ± 26.3% after RYGB (P = 0.3). Younger age and lower baseline eGFR were independently associated with greater postoperative improvement in renal function (P < 0.001). CONCLUSION: Compared with RYGB, OAGB led to an equivalent improvement in renal function 1 year after the procedure, along with greater weight loss.