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BACKGROUND: Diabetic kidney disease (DKD) stands as the predominant cause of chronic kidney disease and end-stage kidney disease. Its diverse range of manifestations complicates the treatment approach for patients. Although kidney biopsy is considered the gold standard for diagnosis, it lacks precision in predicting the progression of kidney dysfunction. Herein, we addressed whether the presence of glomerular crescents is linked to the outcomes in patients with biopsy-confirmed type 2 DKD. METHODS: We performed a retrospective evaluation, involving 327 patients diagnosed with biopsy-confirmed DKD in the context of type 2 diabetes, excluding cases with other glomerular diseases, from nine tertiary hospitals. Hazard ratios (HRs) were calculated using a Cox regression model to assess the risk of kidney disease progression, defined as either ≥ 50% decrease in estimated glomerular filtration rates or the development of end-stage kidney disease, based on the presence of glomerular crescents. RESULTS: Out of the 327 patients selected, ten patients had glomerular crescents observed in their biopsied tissues. Over the follow-up period (median of 19 months, with a maximum of 18 years), the crescent group exhibited a higher risk of kidney disease progression than the no crescent group, with an adjusted HR of 2.82 (1.32-6.06) (P = 0.008). The presence of heavy proteinuria was associated with an increased risk of developing glomerular crescents. CONCLUSION: The presence of glomerular crescents is indeed linked to the progression of type 2 DKD. Therefore, it is important to determine whether there is an additional immune-mediated glomerulonephritis requiring immunomodulation, and it may be prudent to monitor the histology and repeat a biopsy.
Assuntos
Diabetes Mellitus Tipo 2 , Nefropatias Diabéticas , Progressão da Doença , Glomérulos Renais , Humanos , Nefropatias Diabéticas/patologia , Estudos Retrospectivos , Masculino , Feminino , Pessoa de Meia-Idade , Diabetes Mellitus Tipo 2/complicações , Glomérulos Renais/patologia , Idoso , Taxa de Filtração Glomerular , Estudos de Coortes , Biópsia , Falência Renal Crônica , Fatores de RiscoRESUMO
Background: Kidney volume is used as a predictive and therapeutic marker for several clinical conditions. However, there is a lack of large-scale studies examining the relationship between kidney volume and various clinicodemographic factors, including kidney function, body composition and physical performance. Methods: In this observational study, MRI-derived kidney volume measurements from 38 526 UK Biobank participants were analysed. Major kidney volume-related measures included body surface area (BSA)-adjusted total kidney volume (TKV) and the difference in bilateral kidneys. Multivariable-adjusted linear regression and cubic spline analyses were used to explore the association between kidney volume-related measures and clinicodemographic factors. Cox or logistic regression was used to identify the risks of death, non-kidney cancer, myocardial infarction, ischaemic stroke and chronic kidney disease (CKD). Results: The median of BSA-adjusted TKV and the difference in kidney volume were 141.9 ml/m2 [interquartile range (IQR) 128.1-156.9] and 1.08-fold (IQR 1.04-1.15), respectively. Higher BSA-adjusted TKV was significantly associated with higher estimated glomerular filtration rate {eGFR; ß = 0.43 [95% confidence interval (CI) 0.42-0.44]; P < .001}, greater muscle volume [ß = 0.50 (95% CI 0.48-0.51); P < .001] and greater mean handgrip strength [ß = 0.15 (95% CI 0.13-0.16); P < .001] but lower visceral adipose tissue volume [VAT; ß = -0.09 (95% CI -0.11 to -0.07); P < .001] in adjusted models. A greater difference in bilateral kidney volumes was associated with lower eGFR, muscle volume and physical performance but with higher proteinuria and VAT. Higher BSA-adjusted TKV was significantly associated with a reduced risk of CKD [odds ratio (OR) 0.7 (95% CI 0.63-0.77); P < .001], while a greater difference in kidney volume was significantly associated with an increased risk of CKD [OR 1.13 (95% CI 1.07-1.20); P < .001]. Conclusion: Higher BSA-adjusted TKV and lower differences in bilateral kidney volumes are associated with higher kidney function, muscle volume and physical performance and a reduced risk of CKD.
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BACKGROUND: Further study is warranted to determine the association between estimated glomerular filtration rate (eGFR) or albuminuria and the risk of death from diverse causes. METHODS: We screened >10 million general health screening examinees who received health examinations conducted in 2009 using the claims database of Korea. After the exclusion of those previously diagnosed with renal failure and those with missing data, 9,917,838 individuals with available baseline kidney function measurements were included. The primary outcome was mortality and cause-specific death between 2009 and 2019 identified through death certificates based on the diagnostic codes of International Classification of Diseases, 10th revision. Multivariable Cox regression analysis adjusted for various clinicodemographic and social characteristics was used to assess mortality risk. RESULTS: The hazard ratio of death was significantly high in both the eGFR <60 mL/min/1.73 m2 and in the eGFR ≥120 mL/ min/1.73 m2 groups in univariable and multivariable regression analyses when compared to those within the reference range (eGFR of 90-120 mL/min/1.73 m2). The results were similar for death by cardiovascular, cancer, infection, endocrine, respiratory, and digestive causes. We also found that albuminuria was associated with higher risk of death regardless of eGFR range, and those in the higher categories of dipstick albuminuria showed higher risk. CONCLUSION: We reconfirmed the significant association between eGFR, albuminuria, and mortality. Healthcare providers should keep in mind that albuminuria and decreased eGFR as well as kidney hyperfiltration are independent predictors of mortality.
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Intestinal microbiota and their metabolites affect systemic inflammation and kidney disease outcomes. Here, we investigated the key metabolites associated with the acute kidney injury (AKI)-to chronic kidney disease (CKD) transition and the effect of antibiotic-induced microbiota depletion (AIMD) on this transition. In 61 patients with AKI, 59 plasma metabolites were assessed to determine the risk of AKI-to-CKD transition. An AKI-to-CKD transition murine model was established four weeks after unilateral ischemia-reperfusion injury (IRI) to determine the effects of AIMD on the gut microbiome, metabolites, and pathological responses related to CKD transition. Human proximal tubular epithelial cells were challenged with CKD transition-related metabolites, and inhibitory effects of NADPH oxidase 2 (NOX2) signals were tested. Based on clinical metabolomics, plasma trimethylamine N-oxide (TMAO) was associated with a significantly increased risk for AKI-to-CKD transition [adjusted odds ratio 4.389 (95% confidence interval 1.106-17.416)]. In vivo, AIMD inhibited a unilateral IRI-induced increase in TMAO, along with a decrease in apoptosis, inflammation, and fibrosis. The expression of NOX2 and oxidative stress decreased after AIMD. In vitro, TMAO induced fibrosis with NOX2 activation and oxidative stress. NOX2 inhibition successfully attenuated apoptosis, inflammation, and fibrosis with suppression of G2/M arrest. NOX2 inhibition (in vivo) showed improvement in pathological changes with a decrease in oxidative stress without changes in TMAO levels. Thus, TMAO is a key metabolite associated with the AKI-to-CKD transition, and NOX2 activation was identified as a key regulator of TMAO-related AKI-to-CKD transition both in vivo and in vitro.
Assuntos
Injúria Renal Aguda , Antibacterianos , Modelos Animais de Doenças , Microbioma Gastrointestinal , Metilaminas , NADPH Oxidase 2 , Estresse Oxidativo , Insuficiência Renal Crônica , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/microbiologia , Injúria Renal Aguda/prevenção & controle , Injúria Renal Aguda/patologia , Injúria Renal Aguda/tratamento farmacológico , Metilaminas/sangue , Metilaminas/metabolismo , Animais , NADPH Oxidase 2/antagonistas & inibidores , NADPH Oxidase 2/metabolismo , Humanos , Masculino , Microbioma Gastrointestinal/efeitos dos fármacos , Insuficiência Renal Crônica/microbiologia , Insuficiência Renal Crônica/complicações , Pessoa de Meia-Idade , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Antibacterianos/efeitos adversos , Antibacterianos/farmacologia , Camundongos Endogâmicos C57BL , Feminino , Traumatismo por Reperfusão/prevenção & controle , Idoso , Apoptose/efeitos dos fármacos , Progressão da DoençaRESUMO
Health risks due to climate change are emerging, particularly from high-temperature exposure. The perceived temperature is an equivalent temperature based on the complete heat budget model of the human body. Therefore, we aimed to analyze the effect of perceived temperature on overall mortality among patients with chronic kidney disease. In total, 32,870 patients with chronic kidney disease in Seoul participated in this retrospective study (2001-2018) at three medical centers. The perceived temperature during the summer season was calculated using meteorological factors, including the air temperature near the automated weather station, dew point temperature, wind velocity, and total cloud amount. We assessed the association between perceived temperature using Kriging spatial interpolation and mortality in patients with CKD in the time-varying Cox proportional hazards model that was adjusted for sex, age, body mass index, hypertension, diabetes mellitus, estimated glomerular filtration rate, smoking, alcohol consumption, and educational level. During the 6.14 ± 3.96 years of follow-up, 3863 deaths were recorded. In multivariable analysis, the average level of perceived temperature and maximum level of perceived temperature demonstrated an increased risk of overall mortality among patients with chronic kidney disease. The concordance index for mortality of perceived temperature was higher than temperature, discomfort index, and heat index. When stratified by age, diabetes mellitus, and estimated glomerular filtration rate, patients with chronic kidney disease with young age (age <65 years) showed higher hazard ratio for mortality (interaction P = 0.049). Moreover, the risk of death in the winter and spring seasons was more significant compared to that of the summer and autumn seasons. Therefore, long-term exposure to high perceived temperature during summer increases the risk of mortality among patients with chronic kidney disease.