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BACKGROUND: Older chronic kidney disease (CKD) patients frequently face unrecognized cognitive impairment and excess mortality. Physical activity (PA) reduces cognitive decline but whether PA modifies cognitive impairment-associated mortality remains unknown. METHODS: From 2005 to 2011, 30,561 older Taiwanese CKD patients were enrolled. Patients were divided into intact cognition (≥8 scores), mild (6-7 scores), and severe (≤5 scores) cognitive impairment groups by the Short Portable Mental Status Questionnaire (SPMSQ), and were also categorized into high-PA (≥60â¯min/week of moderate-intensity PA), low-PA (20-60â¯min/week) or inactive (<20â¯min/week) groups. Cox regression was conducted to evaluate the individual and joint associations of cognitive impairment and PA on all-cause and cardiovascular mortality. RESULTS: After a median follow-up of 4.52â¯years, the all-cause mortality were higher in CKD patients with severe (multivariable-adjusted hazard ratio [aHR] 2.31; 95â¯% confidence interval [CI] 2.05-2.60) and mild (aHR 1.74; CI 1.51-1.99) cognitive impairment than cognitively intact ones. Remarkably, decreased PA amount interacted and amplified the cognitive impairment-associated mortality risks. Notably, the high-PA status linked to lower overall mortality risks both in mild (aHR 0.65; CI 0.45-0.93) and severe (aHR 0.73; CI 0.54-0.99) cognitively-impaired patients as compared to inactivity. Survival tree analysis indicated the least mortality in those with high PA and >8 SPMSQ scores. Similar associations were found in the cardiovascular mortality. LIMITATIONS: Residual confounding and single ethnicity. CONCLUSIONS: Cognitive impairment defined by SPMSQ was progressively associated with higher mortality among elderly CKD. Higher PA linked to lower cognitive impairment-associated death risks, and could be promoted for longevity benefits.
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BACKGROUND: The adverse effects of sepsis-associated acute kidney injury (SA-AKI) highlight the need for new biomarkers. Signal Peptide-Complement C1r/C1s, Uegf, Bmp1-Epidermal Growth Factor-like Domain-Containing Protein 2 (SCUBE2), important for angiogenesis and endothelial integrity, has been linked to increased mortality in models of lipopolysaccharide-induced lung injury. This research aimed to assess the utility of plasma SCUBE2 levels as a prognostic indicator for SA-AKI in intensive care unit (ICU) patients. METHODS: Between September 2020 and December 2022, our study enrolled ICU patients diagnosed with stage 3 SA-AKI. We collected demographic information, illness severity indices, and laboratory data, including plasma SCUBE2 and sepsis-triggered cytokine levels. We employed receiver operating characteristic curves and DeLong tests to assess the predictive accuracy for survival, Kaplan-Meier curves to evaluate the relative risk of death, and multivariate logistic regression to identify independent mortality predictors. RESULTS: Among the total of 200 participants, the survivors had significantly higher plasma SCUBE2 levels (115.9 ng/mL) compared to those who died (35.6 ng/mL). SCUBE2 levels showed a positive correlation with the anti-inflammatory cytokine IL-10 and a negative correlation with the APACHE II score, SOFA score, C-reactive protein, and monocyte chemoattractant protein-1. Multivariate analysis revealed that elevated SCUBE2 and IL-10 levels were independently protective against mortality, and associated with the most favorable 30-day survival outcomes. CONCLUSIONS: In ICU patients with stage 3 SA-AKI, lower plasma levels of SCUBE2 were correlated with elevated pro-inflammatory factors, which impacted survival outcomes. This suggests that SCUBE2 could be a potential biomarker for predicting prognosis in patients with SA-AKI.
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Background: Fetuin-A is implicated in the pathogenesis of vascular calcification in chronic kidney disease (CKD); however, the relationship between fetuin-A, histopathologic lesions and long-term kidney outcomes in patients with various types of kidney disease remains unclear. Methods: We measured urinary fetuin-A levels in 335 individuals undergoing clinically indicated native kidney biopsy. The expressions of fetuin-A mRNA and protein in the kidney were assessed using RNA sequencing and immunohistochemistry. The association of urinary fetuin-A with histopathologic lesions and major adverse kidney events (MAKE), defined as a decline in estimated glomerular filtration rate (eGFR) of at least 40%, kidney failure or death, was analyzed. Results: Urinary fetuin-A levels showed a positive correlation with albuminuria (rs = 0.67, P < .001) and a negative correlation with eGFR (rs = -0.46, P < .001). After multivariate adjustment, higher urinary fetuin-A levels were associated with glomerular inflammation, mesangial expansion, interstitial fibrosis and tubular atrophy, and arteriolar sclerosis. Using a 1 transcript per million gene expression cutoff, we found kidney fetuin-A mRNA levels below the threshold in both individuals with normal kidney function and those with CKD. Additionally, immunohistochemistry revealed reduced fetuin-A staining in tubular cells of CKD patients compared with normal controls. During a median 21-month follow-up, 115 patients experienced MAKE, and Cox regression analysis confirmed a significant association between elevated urinary fetuin-A and MAKE. This association remained significant after adjusting for potential confounding factors. Conclusion: Urinary fetuin-A is associated with chronic histological damage and adverse clinical outcomes across a spectrum of biopsy-proven kidney diseases.
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BACKGROUND: Intensive care unit (ICU) mortality prediction helps to guide therapeutic decision making for critically ill patients. Several scoring systems based on statistical techniques have been developed for this purpose. In this study, we developed a machine-learning model to predict patient mortality in the very early stage of ICU admission. METHODS: This study was performed with data from all patients admitted to the intensive care units of a tertiary medical center in Taiwan from 2009 to 2018. The patients' comorbidities, co-medications, vital signs, and laboratory data on the day of ICU admission were obtained from electronic medical records. We constructed random forest and extreme gradient boosting (XGBoost) models to predict ICU mortality, and compared their performance with that of traditional scoring systems. RESULTS: Data from 12,377 patients was allocated to training (n = 9901) and testing (n = 2476) datasets. The median patient age was 70.0 years; 9210 (74.41%) patients were under mechanical ventilation in the ICU. The areas under receiver operating characteristic curves for the random forest and XGBoost models (0.876 and 0.880, respectively) were larger than those for the Acute Physiology and Chronic Health Evaluation II score (0.738), Sequential Organ Failure Assessment score (0.747), and Simplified Acute Physiology Score II (0.743). The fraction of inspired oxygen on ICU admission was the most important predictive feature across all models. CONCLUSION: The XGBoost model most accurately predicted ICU mortality and was superior to traditional scoring systems. Our results highlight the utility of machine learning for ICU mortality prediction in the Asian population.
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Estado Terminal , Unidades de Terapia Intensiva , Humanos , Idoso , Hospitais , Hospitalização , Aprendizado de MáquinaRESUMO
BACKGROUND: Identification of reliable biomarkers to assess kidney fibrosis severity is necessary for patients with CKD. Activin A, a member of the TGF- ß superfamily, has been suggested as a biomarker for kidney fibrosis. However, its precise utility in this regard remains to be established. METHODS: We investigated the correlation between plasma activin A levels, kidney fibrosis severity, and the incidence of major adverse kidney events in patients who underwent native kidney biopsies at a tertiary medical center. We performed RNA sequencing and histological analyses on kidney biopsy specimens to assess activin A expression. In vitro experiments were also conducted to explore the potential attenuation of TGF- ß -induced fibroblast activation through activin A inhibition. RESULTS: A total of 339 patients with biopsy-confirmed kidney diseases were enrolled. Baseline eGFR was 36 ml/min per 1.73 m 2 , and the urine protein/creatinine ratio was 2.9 mg/mg. Multivariable logistic regression analysis revealed a significant association between plasma activin A levels and the extent of tubulointerstitial fibrosis. Our RNA sequencing data demonstrated a positive correlation between kidney INHBA expression and plasma activin A levels. Furthermore, the histological analysis showed that myofibroblasts were the primary activin A-positive interstitial cells in diseased kidneys. During a median follow-up of 22 months, 113 participants experienced major adverse kidney events. Cox proportional hazards analysis initially found a positive association between plasma activin A levels and kidney event risk, but it became insignificant after adjusting for confounders. In cultured fibroblasts, knockdown of activin A significantly attenuated TGF- ß -induced fibroblast-myofibroblast conversion. CONCLUSIONS: Plasma activin A levels correlate with kidney fibrosis severity and adverse outcomes in various kidney disorders.
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BACKGROUND: Footbaths can be used to manage digital dermatitis (DD), a common cause of lameness in dairy cattle. Copper sulfate and chelated copper-zinc (CZS) solutions in footbaths are potentially harmful to the environment. HYPOTHESIS/OBJECTIVES: To determine if a quaternary ammonium salt-based disinfectant (QASD) footbath is as effective as a chelated CZS solution in controlling DD in dairy cows. ANIMALS: Fifty-one lactating Holstein cows were randomly assigned to one of two treatment groups, with DD status based on the M-stage scoring system and locomotion score balanced between treatment groups. MATERIALS AND METHODS: The groups were treated with a 1% QASD or a 2.5% chelated CZS. Footbaths were performed once per week for 15 weeks. Logistic regression was used to analyse clinical improvement. All cows received appropriate medical treatment for DD and other hoof diseases. RESULTS: Clinical improvement rates were 67% in the QASD group and 38% in the CZS group (p = 0.03). Logistic regression analysis showed that the odds (95% confidence interval) for clinical improvement rate in the CZS group were 0.30 (0.095-0.948) times that of the QASD group (p = 0.04). The M0 score in the QASD and CZS groups increased significantly (p < 0.05) at the end of the 15 week study period. In the QASD group, the proportion of M2, M3 and M4 scores were significantly decreased (p < 0.05). CONCLUSION AND CLINICAL RELEVANCE: Over a 15 week period, QASD for footbathing was associated with a lower prevalence of active DD lesions than when using CZS.
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Compostos de Amônio , Doenças dos Bovinos , Dermatite Digital , Desinfetantes , Feminino , Animais , Bovinos , Cobre/uso terapêutico , Desinfetantes/uso terapêutico , Dermatite Digital/tratamento farmacológico , Dermatite Digital/patologia , Lactação , Taiwan , Fazendas , Doenças dos Bovinos/tratamento farmacológico , Doenças dos Bovinos/patologia , Zinco/uso terapêutico , Compostos de Amônio/uso terapêuticoRESUMO
BACKGROUND: Hemodialysis (HD) patients are particularly vulnerable to severe coronavirus disease 2019 (COVID-19) due to their immunocompromised state and comorbid conditions. Timely vaccination could be the most effective strategy to reduce morbidity and mortality. However, data on the survival benefit of the COVID-19 vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and death among HD patients are limited, especially during the Omicron-dominant period. METHODS: In this prospective hospital-based cohort study, we identified HD patients from July 1, 2021, to April 29, 2022. The patients were divided into fully vaccinated and partially vaccinated groups. We compared the humoral response, risk of developing SARS-CoV-2 infection, and all-cause mortality between the two groups. RESULTS: Among the 440 HD patients included, 152 patients were fully vaccinated, and 288 patients were partially vaccinated. Patients in the fully vaccinated group exhibited higher anti-spike protein receptor-binding domain (S protein RBD) antibody levels and lower risks of all-cause mortality (adjusted hazard ratio, 0.35; 95% confidence interval, 0.17-0.73; p = 0.005) than the partially vaccinated group. However, the risk for SARS-CoV-2 infection did not significantly differ between the two groups. Irrespective of the number of vaccinations, the risk of all-cause mortality was lower in patients with anti-S protein RBD antibody levels in the higher tertile. CONCLUSION: A third dose of the COVID-19 vaccine was associated with a decreased risk of all-cause mortality among HD patients during the Omicron-dominant period. A higher post-vaccination anti-S protein RBD antibody level was also associated with a lower risk of mortality.
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Vacinas contra COVID-19 , COVID-19 , Humanos , COVID-19/prevenção & controle , Estudos Prospectivos , Estudos de Coortes , SARS-CoV-2 , Diálise Renal , Vacinação , Anticorpos AntiviraisRESUMO
Antibiotic therapy is the primary treatment for bovine mastitis, but the drawbacks of this strategy include poor cure rate and economic losses from the need to discard milk with antibiotic residues. Unfortunately, few other treatment options are currently available for mastitis. Failure of antibiotic treatments is often attributed to formation of bacterial biofilms and abscesses in the mammary gland tissue, which lead to chronic infections that are difficult to eradicate and drive recurrent disease. A major mastitis-causing pathogen (MCP) associated with biofilms in bovine mastitis is Staphylococcus aureus. In this study, we demonstrate that octanoic acid has broad-spectrum microbicidal activity against MCPs and effectively inhibits S. aureus biofilm formation in milk (>50% inhibition at 3.13 mM). Octanoic acid effectively clears biofilms (95% eradication at 1X minimum bactericidal concentration, MBC) and infrequently induces S. aureus small colony variants (SCVs) that may cause recurrent mastitis. Additionally, octanoic acid rapidly kills persistent biofilm cells and cells with antibiotic tolerance (within 4 h). In contrast, antibiotics treated at >100X MBC cannot eradicate biofilms but do induce SCVs and antibiotic-tolerant cells. These effects may accelerate the transition from biofilm to chronic infection. Thus, octanoic acid exhibits bactericidal action against S. aureus biofilms, and it is less likely than antibiotic therapy to induce persistent cells and pathogen tolerance. Moreover, octanoic acid acts additively with antibiotics against S. aureus, and it attenuates tetracycline-induced virulence factor gene expression in S. aureus cells. According to these data, octanoic acid may prevent the pathological progression of bovine mastitis and offer a new strategy for treating the condition.
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OBJECTIVES: Type 2 diabetes mellitus (T2DM) imposes a great burden on healthcare systems, and these patients experience higher long-term risks for developing end-stage renal disease (ESRD). Managing diabetic nephropathy becomes more challenging when kidney function starts declining. Therefore, developing predictive models for the risk of developing ESRD in newly diagnosed T2DM patients may be helpful in clinical settings. METHODS: We established machine learning models constructed from a subset of clinical features collected from 53,477 newly diagnosed T2DM patients from January 2008 to December 2018 and then selected the best model. The cohort was divided, with 70% and 30% of patients randomly assigned to the training and testing sets, respectively. RESULTS: The discriminative ability of our machine learning models, including logistic regression, extra tree classifier, random forest, gradient boosting decision tree (GBDT), extreme gradient boosting (XGBoost), and light gradient boosting machine were evaluated across the cohort. XGBoost yielded the highest area under the receiver operating characteristic curve (AUC) of 0.953, followed by extra tree and GBDT, with AUC values of 0.952 and 0.938 on the testing dataset. The SHapley Additive explanation summary plot in the XGBoost model illustrated that the top five important features included baseline serum creatinine, mean serum creatine within 1 year before the diagnosis of T2DM, high-sensitivity C-reactive protein, spot urine protein-to-creatinine ratio and female gender. CONCLUSIONS: Because our machine learning prediction models were based on routinely collected clinical features, they can be used as risk assessment tools for developing ESRD. By identifying high-risk patients, intervention strategies may be provided at an early stage.
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The transition dairy cows are challenged by various stresses such as decreased dry matter intake, liver dysfunction, increased inflammation, and oxidative stress, particularly in subtropical regions. These might increase the requirement for vitamin E and trace elements. To examine whether supplementation of vitamin E, selenium or copper, zinc, and manganese complex would help transition dairy cows to achieve greater reproduction performance by overcoming the immune function and postpartum disorders in subtropical Taiwan. A total of 24 Holstein Friesian dairy cows were enrolled in this study and divided into three groups (n = 8 cows/group): treatment 1 supplemented with organic selenium and vitamin E (SeE), treatment 2 supplemented with organic copper, zinc, and manganese complex (CZM) and control (CON). The results showed SeE supplementation improved immune function, reproductive performance, and milk yield, but not negative energy balance status. Supplementation of CZM improved milk yield and energy regulation through antioxidative capacity and immune function, but had no influence on reproductive performance.
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CONTEXT.: Galectin-9 reduces tissue damage in certain immune-mediated glomerular diseases. However, its role in structural and functional renal changes in patients with varying types of chronic kidney disease (CKD) is less clear. OBJECTIVE.: To investigate the association between plasma galectin-9 levels, proteinuria, tubulointerstitial lesions, and renal function in different CKD stages. DESIGN.: We measured plasma galectin-9 levels in 243 patients undergoing renal biopsy for determining the CKD etiology. mRNA and protein expression levels of intrarenal galectin-9 were assessed by quantitative real-time polymerase chain reaction and immunostaining. Relationships between plasma galectin-9, clinical characteristics, and tubulointerstitial damage were analyzed with logistic regression. We investigated galectin-9 expression patterns in vitro in murine J774 macrophages treated with differing stimuli. RESULTS.: To analyze the relationship between galectin-9 and clinical features, we divided the patients into 2 groups according to median plasma galectin-9 levels. The high galectin-9 group tended to be older and to have decreased renal function, higher proteinuria, and greater interstitial fibrosis. After multivariable adjustment, elevated plasma galectin-9 levels were independently associated with stage 3b or higher CKD. An analysis of gene expression in the tubulointerstitial compartment in the biopsy samples showed a significant positive correlation between intrarenal galectin-9 mRNA expression and plasma galectin-9 levels. Immunohistochemistry confirmed increased galectin-9 expression in the renal interstitium of patients with advanced CKD, and most galectin-9-positive cells were macrophages, as determined by double-immunofluorescence staining. In vitro experiments showed that galectin-9 expression in macrophages was significantly increased after interferon-γ stimulation. CONCLUSIONS.: Our findings suggest that plasma galectin-9 is a good biomarker for diagnosing advanced CKD.
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Rim , Insuficiência Renal Crônica , Humanos , Camundongos , Animais , Rim/patologia , Insuficiência Renal Crônica/diagnóstico , Galectinas/metabolismo , Biomarcadores , Proteinúria/metabolismo , Proteinúria/patologia , Biópsia , RNA MensageiroRESUMO
OBJECTIVE: Heart failure (HF) imposes a substantial burden and the prevalence of HF is high in patients with chronic kidney disease (CKD). HF results in multiple hospital admissions, but whether HF subtypes worsen long-term outcomes and renal function in patients with CKD remains inconclusive. METHODS: The study comprised 10 904 patients with CKD aged ≥20 years who underwent echocardiography between 1 January 2011 and 31 December 2018. The patients were stratiï¬ed into four groups: non-HF, HF with reduced ejection fraction (HFrEF), HF with mildly reduced ejection fraction (HFmrEF) and HF with preserved ejection fraction (HFpEF). The primary end points were all-cause mortality, major adverse cardiovascular events (MACEs) and adverse renal outcomes. RESULTS: In inverse probability of treatment weighting-adjusted method, the risk of all-cause mortality and MACEs relative to the non-HF group was greatest in the HFrEF group (HR 3.18 (95% CI 2.57 to 3.93) and HR 3.83 (95% CI 3.20 to 4.59)), followed by the HFmrEF (HR 2.75 (95% CI 2.22 to 3.42) and HR 3.08 (95% CI 2.57 to 3.69)) and HFpEF (HR 1.85 (95% CI 1.59 to 2.15) and HR 2.43 (95% CI 2.16 to 2.73) groups. In addition, the HFrEF group had the greatest risks of end-stage renal disease (HR 2.58 (95% CI 1.94 to 3.44)) compared with other groups. CONCLUSIONS: HF is associated with subsequent worse clinical outcomes, which may be more pronounced in patients with HFrEF, followed by those with HFmrEF and those with HFpEF relative to non-HF group.
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Insuficiência Cardíaca , Insuficiência Renal Crônica , Disfunção Ventricular Esquerda , Humanos , Insuficiência Cardíaca/diagnóstico por imagem , Insuficiência Cardíaca/epidemiologia , Volume Sistólico , Prognóstico , Disfunção Ventricular Esquerda/diagnóstico por imagem , Ecocardiografia , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/epidemiologia , Função Ventricular EsquerdaRESUMO
Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide synthase and plays a significant role in the pathogenesis of arteriovenous fistula (AVF) dysfunction. The aim of this study is to evaluate the effect of far-infrared (FIR) therapy on the maturation and patency of newly-created AVFs in patients with advanced diabetic kidney disease (DKD) as well as the concurrent change in plasma ADMA. The study enrolled 144 participants with advanced DKD where 101 patients were randomly allocated to the FIR therapy group (N = 50) and control group (N = 51). Patients receiving FIR therapy had a decreased AVF failure rate within 12 months (16% versus 35.3%; p = 0.027); decreased incremental change of ADMA concentration at the 3rd and 12th month; increased AVF blood flow at the 1st, 3rd, and 12th month; increased 3-month physiologic maturation rate (88% versus 68.6%; p = 0.034); increased 1-year unassisted AVF patency rate (84% versus 64.7%; p = 0.017); and increased clinical AVF maturation rate within 12 months (84% versus 62.7%; p = 0.029) compared to the control group. The study demonstrates that FIR therapy can reduce the incremental changes in plasma ADMA concentration, which may be associated with the improvement of AVF prognosis in patients with advanced DKD.
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Sepsis may lead to kidney function decline in patients with chronic kidney disease (CKD), and the deleterious effect may persist in patients who survive sepsis. We used a machine learning approach to predict the risk of end-stage renal disease (ESRD) in sepsis survivors. A total of 11,661 sepsis survivors were identified from a single-center database of 112,628 CKD patients between 2010 and 2018. During a median follow-up of 3.5 years, a total of 1366 (11.7%) sepsis survivors developed ESRD after hospital discharge. We adopted the random forest, extra trees, extreme gradient boosting, light gradient boosting machine (LGBM), and gradient boosting decision tree (GBDT) algorithms to predict the risk of ESRD development among these patients. GBDT yielded the highest area under the receiver operating characteristic curve of 0.879, followed by LGBM (0.868), and extra trees (0.865). The GBDT model revealed the strong effect of estimated glomerular filtration rates <25 mL/min/1.73 m2 at discharge in predicting ESRD development. In addition, hemoglobin and proteinuria were also essential predictors. Based on a large-scale dataset, we established a machine learning model computing the risk for ESRD occurrence among sepsis survivors with CKD. External validation is required to evaluate the generalizability of this model.
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Plasma galectin-3 (Gal-3) is associated with organ fibrosis, but whether urinary Gal-3 is a potential biomarker of kidney disease progression has never been explored. Between 2018 and 2021, we prospectively enrolled 280 patients who underwent renal biopsy and were divided into three groups based on their urinary Gal-3 levels (<354.6, 354.6−510.7, and ≥510.8 pg/mL) to assess kidney disease progression (defined as ≥40% decline in the estimated glomerular filtration rate or end-stage renal disease) and renal histology findings. Patients in the highest urinary Gal-3 tertile had the lowest eGFRs and highest proteinuria levels. In multivariate Cox regression models, patients in the highest tertile had the highest risk of kidney disease progression (adjusted hazard ratio, 4.60; 95% confidence interval, 2.85−7.71) compared to those in the lowest tertile. Higher urinary Gal-3 levels were associated with more severe renal fibrosis. Intrarenal mRNA expression of LGALS3 (Gal-3-encoded gene) was most correlated with the renal stress biomarkers (IGFBP7 and TIMB2), renal function biomarkers (PTGDS) and fibrosis-associated genes (TGFB1). The urinary Gal-3 level may be useful for the identification of patients at high risk of kidney disease progression and renal fibrosis, and for the early initiation of treatments for these patients.
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Background: Sepsis is known to cause renal function fluctuations during hospitalization, but whether these patients discharged from sepsis were still at greater risks of long-term renal adverse outcomes remains unknown. Methods: From 2011 to 2018, we included 1,12,628 patients with chronic kidney disease (CKD) aged ≥ 20 years. The patients with CKD were further divided into 11,661 sepsis group and 1,00,967 non-sepsis group. The following outcome of interest was included: all-cause mortality, readmission for acute kidney injury, estimated glomerular filtration rate decline ≥50% or doubling of serum creatinine, and end-stage renal disease. Results: After propensity score matching, the sepsis group was at higher risks of all-cause mortality [hazard ratio (HR) 1.39, 95% CI, 1.31-1.47], readmission for acute kidney injury (HR 1.67, 95% CI 1.58-1.76), eGFR decline ≥ 50% or doubling of serum creatinine (HR 3.34, 95% CI 2.78-4.01), and end-stage renal disease (HR 1.43, 95% CI 1.34-1.53) than non-sepsis group. Conclusions: Our study found that patients with CKD discharged from hospitalization for sepsis have higher risks of subsequent renal adverse events.
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The Taiwan Acute Kidney Injury (AKI) Task Force conducted a review of data and developed a consensus regarding nephrotoxins and AKI. This consensus covers: (1) contrast-associated AKI; (2) drug-induced nephrotoxicity; (3) prevention of drug-associated AKI; (4) follow up after AKI; (5) re-initiation of medication after AKI. Strategies for the avoidance of contrast media related AKI, including peri-procedural hydration, sodium bicarbonate solutions, oral N-acetylcysteine, and iso-osmolar/low-osmolar non-ionic iodinated contrast media have been recommended, given the respective evidence levels. Regarding anticoagulants, both warfarin and new oral anticoagulants have potential nephrotoxicity, and dosage should be reduced if renal pathology exam proves renal injury. Recommended strategies to prevent drug related AKI have included assessment of 5R/(6R) reactions - risk, recognition, response, renal support, rehabilitation and (research), use of AKI alert system and computerized decision support. In terms of antibiotics-associated AKI, avoiding concomitant administration of vancomycin and piperacillin-tazobactam, monitoring vancomycin trough level, switching from vancomycin to teicoplanin in high-risk patients, and replacing conventional amphotericin B with lipid-based amphotericin B have been shown to reduce drug related AKI. With respect to non-steroidal anti-inflammatory drug associated AKI, it is recommended to use these drugs cautiously in the elderly and in patients receiving renin-angiotensin-aldosterone system inhibitors/diuretics triple combinations.
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Injúria Renal Aguda , Vancomicina , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/tratamento farmacológico , Injúria Renal Aguda/prevenção & controle , Idoso , Anfotericina B/efeitos adversos , Antibacterianos/uso terapêutico , Anticoagulantes/uso terapêutico , Consenso , Meios de Contraste/efeitos adversos , Quimioterapia Combinada , Feminino , Humanos , Masculino , Piperacilina/efeitos adversos , Estudos Retrospectivos , TaiwanRESUMO
Sepsis survivors have a higher risk of long-term complications. Acute kidney injury (AKI) may still be common among sepsis survivors after discharge from sepsis. Therefore, our study utilized an artificial-intelligence-based machine learning approach to predict future risks of rehospitalization with AKI between 1 January 2008 and 31 December 2018. We included a total of 23,761 patients aged ≥ 20 years who were admitted due to sepsis and survived to discharge. We adopted a machine learning method by using models based on logistic regression, random forest, extra tree classifier, gradient boosting decision tree (GBDT), extreme gradient boosting, and light gradient boosting machine (LGBM). The LGBM model exhibited the highest area under the receiver operating characteristic curves (AUCs) of 0.816 to predict rehospitalization with AKI in sepsis survivors and followed by the GBDT model with AUCs of 0.813. The top five most important features in the LGBM model were C-reactive protein, white blood cell counts, use of inotropes, blood urea nitrogen and use of diuretics. We established machine learning models for the prediction of the risk of rehospitalization with AKI in sepsis survivors, and the machine learning model may set the stage for the broader use of clinical features in healthcare.
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OBJECTIVES: Substantial inconsistencies exist in current guidelines regarding recommendations of metformin usage with the administration of a contrast medium. We aimed to perform a meta-analysis to determine whether the risks of contrast-induced acute kidney injury (CI-AKI) and lactic acidosis increase with metformin use in diabetic patients receiving a contrast medium. METHODS: Studies were retrieved from databases from inception to May 15, 2021. Studies that compared the outcomes of using metformin with not using metformin during contrast medium administration were included. The primary outcomes were incidence of CI-AKI and lactic acidosis. The secondary outcomes were renal function changes from baseline. Data analysis was using risk ratio (RR) for dichotomous outcomes and mean differences (MD) with 95% confidence intervals (CI) for continuous outcomes. RESULTS: Analyses of two randomized controlled trials and four retrospective cohorts examining a total of 1459 patients revealed no significant differences in the incidence of CI-AKI (RR = 1.08; 95% CI, 0.72 to 1.63) and in changes in renal function measurements (serum creatinine: MD = 0.00 mg/dL, 95% CI, - 0.05 to 0.05; estimated glomerular filtration rate: MD = 0.22, 95% CI, - 2.47 to 2.91) after contrast medium administration between patients using and not using metformin. CONCLUSIONS: There is no evidence that continuing metformin during contrast medium administration is associated with a higher risk of CI-AKI, lactic acidosis, or renal function deterioration compared to patients who discontinued metformin or who were not metformin users. The limited quality of the included studies may compromise the strength of evidence provided in this meta-analysis. KEY POINTS: There is no need to discontinue metformin either before or after intravenous contrast medium exposure in patients with eGFR > 30 mL/min/1.73 m2. In patients receiving intra-arterial contrast medium with first-pass renal exposure, there is no need to withhold metformin if eGFR is above 60 mL/min/1.73 m2. For patients who have an eGFR level between 30 and 60 mL/min/1.73 m2 and are receiving intra-arterial contrast medium with first-pass renal exposure, no case of lactic acidosis was observed based on present data, but further evidence is needed to make a strong suggestion regarding its safety.
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Acidose Láctica , Injúria Renal Aguda , Metformina , Acidose Láctica/induzido quimicamente , Acidose Láctica/epidemiologia , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/epidemiologia , Feminino , Taxa de Filtração Glomerular , Humanos , Masculino , Metformina/efeitos adversos , Metformina/uso terapêutico , Estudos RetrospectivosRESUMO
AIMS: Physical activity has a protective effect against mortality and cardiovascular events in chronic kidney disease (CKD) patients. Nonetheless, how different levels of physical activity affect the health benefits in CKD remains unclear. This study aimed to investigate the dose-response effects of physical activity on mortality and major cardiorenal events in CKD. METHODS AND RESULTS: We evaluated a longitudinal cohort of 4508 Taiwanese CKD patients between 2004 and 2017. Physical activity was assessed by the NHANES questionnaire and quantified in metabolic equivalent-hours per week (MET-hour/week). Patients were categorized into highly active (≥7.5 MET-h/week), low-active (0.1 to <7.5 MET-h/week), or inactive (0 MET-h/week) groups. Cox regression and restricted cubic spline models were utilized to explore the association between physical activity and the risks of study outcomes, including all-cause mortality, end-stage renal disease (ESRD), and major adverse cardiovascular events (MACE, a composite of cardiovascular death, myocardial infarction, ischaemic stroke, and hospitalized heart failure). During a median follow-up of 686 days, 739 death, 1059 ESRD, and 521 MACE events occurred. Highly active group had the lowest chance of all study outcomes, followed by low-active and inactive groups (P < 0.001). Multivariable Cox regression showed that only highly active group was independently associated with lower risks for all-cause mortality [hazard ratio (HR) 0.62; 95% confidence interval (CI) 0.53-0.74], ESRD (HR 0.83, 95% CI 0.72-0.96), and MACE (HR 0.63, 95% CI 0.51-0.76) compared to the inactive group. The risks of MACE did not further decrease once physical activity surpassed 15 MET-h/week, indicating a U-shaped association. The results were consistent in the subgroup and sensitivity analyses. CONCLUSION: Physical activity of 7.5 to <15 MET-h/week is associated with lower risks of adverse cardiorenal outcomes and should be integrated into the care of CKD.