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BACKGROUND: In patients with advanced chronic kidney disease (CKD), the effects of initiating treatment with an angiotensin-converting enzyme inhibitor (ACEi) or angiotensin-receptor blocker (ARB) on the risk for kidney failure with replacement therapy (KFRT) and death remain unclear. PURPOSE: To examine the association of ACEi or ARB treatment initiation, relative to a non-ACEi or ARB comparator, with rates of KFRT and death. DATA SOURCES: Ovid Medline and the Chronic Kidney Disease Epidemiology Collaboration Clinical Trials Consortium from 1946 through 31 December 2023. STUDY SELECTION: Completed randomized controlled trials testing either an ACEi or an ARB versus a comparator (placebo or antihypertensive drugs other than ACEi or ARB) that included patients with a baseline estimated glomerular filtration rate (eGFR) below 30 mL/min/1.73 m2. DATA EXTRACTION: The primary outcome was KFRT, and the secondary outcome was death before KFRT. Analyses were done using Cox proportional hazards models according to the intention-to-treat principle. Prespecified subgroup analyses were done according to baseline age (<65 vs. ≥65 years), eGFR (<20 vs. ≥20 mL/min/1.73 m2), albuminuria (urine albumin-creatinine ratio <300 vs. ≥300 mg/g), and history of diabetes. DATA SYNTHESIS: A total of 1739 participants from 18 trials were included, with a mean age of 54.9 years and mean eGFR of 22.2 mL/min/1.73 m2, of whom 624 (35.9%) developed KFRT and 133 (7.6%) died during a median follow-up of 34 months (IQR, 19 to 40 months). Overall, ACEi or ARB treatment initiation led to lower risk for KFRT (adjusted hazard ratio, 0.66 [95% CI, 0.55 to 0.79]) but not death (hazard ratio, 0.86 [CI, 0.58 to 1.28]). There was no statistically significant interaction between ACEi or ARB treatment and age, eGFR, albuminuria, or diabetes (P for interaction > 0.05 for all). LIMITATION: Individual participant-level data for hyperkalemia or acute kidney injury were not available. CONCLUSION: Initiation of ACEi or ARB therapy protects against KFRT, but not death, in people with advanced CKD. PRIMARY FUNDING SOURCE: National Institutes of Health. (PROSPERO: CRD42022307589).
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Antagonistas de Receptores de Angiotensina , Inibidores da Enzima Conversora de Angiotensina , Insuficiência Renal Crônica , Humanos , Antagonistas de Receptores de Angiotensina/uso terapêutico , Antagonistas de Receptores de Angiotensina/efeitos adversos , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Taxa de Filtração Glomerular , Ensaios Clínicos Controlados Aleatórios como Assunto , Insuficiência Renal Crônica/terapia , Terapia de Substituição Renal , Estudos RetrospectivosRESUMO
BACKGROUND: The sodium-glucose cotransporter type 2 inhibitor dapagliflozin reduces the risk of progressive kidney disease and cardiovascular events in patients with chronic kidney disease, with and without type 2 diabetes. Whether its effects are uniform across the spectrum of age and among men and women is unknown. OBJECTIVE: We performed a pre-specified analysis in DAPA-CKD to evaluate efficacy and safety of dapagliflozin according to baseline age and sex. DESIGN: Prospective randomized placebo-controlled trial. PARTICIPANTS: A total of 4304 adults with chronic kidney disease (estimated glomerular filtration rate (eGFR) 25-75 mL/min/1.73 m2; urinary albumin-to-creatinine ratio 200-5000 mg/g) with and without type 2 diabetes. INTERVENTION: Dapagliflozin 10 mg versus placebo once daily. MAIN MEASURES: Primary endpoint was a composite of ≥ 50% sustained eGFR decline, end-stage kidney disease, and kidney or cardiovascular death. Secondary endpoints included kidney composite endpoint (same as primary composite endpoint but without cardiovascular death), cardiovascular composite endpoint (hospitalized heart failure or cardiovascular death), and all-cause mortality. KEY RESULTS: Median follow-up was 2.4 years. Absolute risks of cardiovascular composite endpoint and all-cause mortality were higher in older patients. Absolute risk of kidney composite endpoint was highest in patients < 50 years (10.7 and 6.2 per 100 patient-years in the placebo and dapagliflozin groups, respectively) and lowest in patients ≥ 80 years (3.0 and 1.2 per 100 patient-years in the placebo and dapagliflozin groups, respectively). There was no evidence of heterogeneity of the effects of dapagliflozin on the primary or secondary endpoints based on age or sex. Neither age nor sex modified the effects of dapagliflozin on total or chronic eGFR slope. CONCLUSIONS: Dapagliflozin reduced the risks of mortality, cardiovascular events, and CKD progression in older patients, including in septuagenarians and octogenarians who comprised 25% of participants. Ageism and/or therapeutic nihilism should not discourage the use of dapagliflozin in older women and men who are likely to experience considerable benefit. TRIAL REGISTRY: clinicaltrials.gov NIH TRIAL REGISTRY NUMBER: NCT03036150.
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Compostos Benzidrílicos , Diabetes Mellitus Tipo 2 , Glucosídeos , Insuficiência Renal Crônica , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Glucosídeos/uso terapêutico , Glucosídeos/efeitos adversos , Compostos Benzidrílicos/uso terapêutico , Compostos Benzidrílicos/efeitos adversos , Masculino , Feminino , Insuficiência Renal Crônica/tratamento farmacológico , Pessoa de Meia-Idade , Idoso , Estudos Prospectivos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Fatores Etários , Fatores Sexuais , Taxa de Filtração Glomerular/efeitos dos fármacos , Adulto , Método Duplo-Cego , Resultado do Tratamento , Seguimentos , Idoso de 80 Anos ou maisRESUMO
BACKGROUND: Postoperative acute kidney injury (AKI) is a common condition after surgery, however, the available data about nationwide epidemiology of postoperative AKI in China from large and high-quality studies are limited. This study aimed to determine the incidence, risk factors and outcomes of postoperative AKI among patients undergoing surgery in China. METHODS: This was a large, multicentre, retrospective study performed in 16 tertiary medical centres in China. Adult patients (≥18 years of age) who underwent surgical procedures from 1 January 2013 to 31 December 2019 were included. Postoperative AKI was defined by the Kidney Disease: Improving Global Outcomes creatinine criteria. The associations of AKI and in-hospital outcomes were investigated using logistic regression models adjusted for potential confounders. RESULTS: Among 520 707 patients included in our study, 25 830 (5.0%) patients developed postoperative AKI. The incidence of postoperative AKI varied by surgery type, which was highest in cardiac (34.6%), urologic (8.7%) and general (4.2%) surgeries. A total of 89.2% of postoperative AKI cases were detected in the first 2 postoperative days. However, only 584 (2.3%) patients with postoperative AKI were diagnosed with AKI on discharge. Risk factors for postoperative AKI included older age, male sex, lower baseline kidney function, pre-surgery hospital stay ≤3 days or >7 days, hypertension, diabetes mellitus and use of proton pump inhibitors or diuretics. The risk of in-hospital death increased with the stage of AKI. In addition, patients with postoperative AKI had longer lengths of hospital stay (12 versus 19 days) and were more likely to require intensive care unit care (13.1% versus 45.0%) and renal replacement therapy (0.4% versus 7.7%). CONCLUSIONS: Postoperative AKI was common across surgery type in China, particularly for patients undergoing cardiac surgery. Implementation and evaluation of an alarm system is important for the battle against postoperative AKI.
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Injúria Renal Aguda , Complicações Pós-Operatórias , Humanos , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/epidemiologia , Masculino , Feminino , China/epidemiologia , Incidência , Estudos Retrospectivos , Fatores de Risco , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Idoso , Adulto , Mortalidade HospitalarRESUMO
OBJECTIVE: To examine the relationship between an accelerometer-derived "weekend warrior" pattern, characterized by achieving the most moderate to vigorous physical activity (MVPA) over 1-2 days, as opposed to more evenly distributed patterns, with risk of chronic kidney disease (CKD) and acute kidney injury (AKI). METHODS: 77,977 participants without prior kidney diseases and with usable accelerometer data (collected between 2013 and 2015) were included from the UK Biobank. Three physical activity patterns were compared: active weekend warrior pattern (achieving ≥150 min MVPA per week and accumulating ≥50 % of total MVPA in 1-2 days), active regular pattern (achieving ≥150 min MVPA but not meeting active weekend warrior criteria per week), and inactive pattern (<150 min MVPA per week). The study outcomes included incident CKD and AKI, ascertained through self-report data and data linkage with primary care, hospital admissions, and death registry records. RESULTS: During a median follow-up of 6.8 years, 1324 participants developed CKD and 1515 developed AKI. In multivariable-adjusted models, when compared with inactive participants, individuals with active weekend warrior pattern (CKD: hazard ratio [HR], 0.79, 95 % confidence interval [CI], 0.69-0.89; AKI: HR, 0.70, 95 %CI, 0.62-0.79) and those with active regular pattern (CKD: HR, 0.81, 95 %CI, 0.69-0.95; AKI: HR, 0.79, 95 %CI, 0.68-0.91) exhibited a similar and significantly lower risk of incident CKD and AKI. Similar findings were observed at the median threshold of ≥230.4 min of MVPA per week. CONCLUSION: Concentrated MVPA within 1 to 2 days is as effective as distributed ones in decreasing the risk of renal outcomes.
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BACKGROUND AND AIM: To date, few studies have investigated the association between dietary manganese intake and the risk of hypertension, so the prospective relationship of dietary manganese intake and new-onset hypertension remains uncertain. We aimed to investigate the association between dietary manganese intake and the risk of new-onset hypertension in the general Chinese population. METHODS AND RESULTS: This prospective cohort study included 12,177 participants who were free of hypertension at baseline from China Health and Nutrition Survey (CHNS). Dietary intake was measured by 3 consecutive 24-h dietary recalls combined with a household food inventory. The study outcome was new-onset hypertension, defined as systolic blood pressure ≥140 mm Hg or diastolic blood pressure ≥90 mm Hg or diagnosed by a physician or under antihypertensive treatment during the follow-up. During a median follow-up duration of 6.1 years, 4269 (44.9 per 1000 person-years) participants developed new-onset hypertension. Overall, there was a positive association between dietary manganese intake and new-onset hypertension. The adjusted HRs (95%CIs) of new-onset hypertension were 1.00 (reference), 0.97 (0.87, 1.08), 1.24 (1.10, 1.39) and 1.75 (1.52, 2.01) across the quartiles of dietary manganese intake, respectively. Accordingly, a significantly higher risk of new-onset hypertension (HR, 1.38; 95%CI: 1.27, 1.50) was found in participants in quartiles 3-4 of dietary manganese intake (≥6.0 mg/day), compared with those in quartiles 1-2 (<6.0 mg/day). CONCLUSIONS: In the general Chinese population, dietary manganese intake was positively associated with the risk of new hypertension, independent of sodium intake and other important covariates.
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Hipertensão , Manganês , Humanos , Manganês/efeitos adversos , Estudos Prospectivos , Estudos de Coortes , Hipertensão/induzido quimicamente , Hipertensão/diagnóstico , Hipertensão/epidemiologia , China/epidemiologiaRESUMO
OBJECTIVE: To examine the long-term association of objectively measured moderate-to-vigorous physical activity (MVPA) and its longitudinal changes with progression to chronic kidney disease (CKD) in patients with type 2 diabetes (T2D) and overweight/obesity. METHODS: This study included 1746 participants in the Look AHEAD trial with baseline estimated glomerular filtration rate (eGFR)≥60 mL/min/1.73 m2. MVPA was measured at baseline, year 1, year 4 and year 8 using an RT3 accelerometer. The outcome was progression to CKD, defined as eGFR<60 mL/min per 1.73 m2 with a drop of ≥30% or end-stage kidney disease. Cox hazards models were fitted to examine the association between MVPA and outcomes. RESULTS: Over a median follow-up of 12.0 years, 567 participants experienced progression to CKD. Overall, there was a linear inverse association of cumulative average total MVPA (per 100 min/week higher amount, HR: 0.91; 95% CI: 0.86 to 0.96) and MVPA accumulated in bouts of ≥10 min (per 100 minutes/week higher amount, HR: 0.81; 95% CI: 0.72 to 0.91) with progression to CKD. Moreover, an increase in total MVPA from baseline to year 4 (the fourth quartile, ≥63.2 min/week) was associated with a 33% lower risk of progression to CKD compared with the largest MVPA reduction (the first quartile, <-198.3 min/week). A lower risk of progression to CKD was also observed for increases in MVPA accumulated in bouts of both <10 min and ≥10 min. CONCLUSIONS: Longer MVPA time and increases in MVPA was associated with a reduced risk of progression to CKD in adults with overweight/obesity and T2D.
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Diabetes Mellitus Tipo 2 , Insuficiência Renal Crônica , Adulto , Humanos , Sobrepeso , Diabetes Mellitus Tipo 2/epidemiologia , Obesidade , Exercício Físico , Insuficiência Renal Crônica/epidemiologia , AcelerometriaRESUMO
SIGNIFICANCE STATEMENT: Serum creatinine is not a sensitive biomarker for neonatal AKI because it is confounded by maternal creatinine level, gestational age, and neonatal muscle mass. In this multicenter cohort study of 52,333 hospitalized Chinese neonates, the authors proposed serum cystatin C-related criteria (CyNA) for neonatal AKI. They found that cystatin C (Cys-C) is a robust and sensitive biomarker for identifying AKI in neonates who are at an elevated risk of in-hospital mortality and that CyNA detects 6.5 times as many cases as the modified Kidney Disease Improving Global Outcomes creatinine criteria. They also show that AKI can be detected using a single test of Cys-C. These findings suggest that CyNA shows promise as a powerful and easily applicable tool for detecting AKI in neonates. BACKGROUND: Serum creatinine is not a sensitive biomarker for AKI in neonates. A better biomarker-based criterion for neonatal AKI is needed. METHODS: In this large multicenter cohort study, we estimated the upper normal limit (UNL) and reference change value (RCV) of serum cystatin C (Cys-C) in neonates and proposed cystatin C-based criteria (CyNA) for detecting neonatal AKI using these values as the cutoffs. We assessed the association of CyNA-detected AKI with the risk of in-hospital death and compared CyNA performance versus performance of modified Kidney Disease Improving Global Outcomes (KDIGO) creatinine criteria. RESULTS: In this study of 52,333 hospitalized neonates in China, Cys-C level did not vary with gestational age and birth weight and remained relatively stable during the neonatal period. CyNA criteria define AKI by a serum Cys-C of ≥2.2 mg/L (UNL) or an increase in Cys-C of ≥25% (RCV) during the neonatal period. Among 45,839 neonates with measurements of both Cys-C and creatinine, 4513 (9.8%) had AKI detected by CyNA only, 373 (0.8%) by KDIGO only, and 381 (0.8%) by both criteria. Compared with neonates without AKI by both criteria, neonates with AKI detected by CyNA alone had an increased risk of in-hospital mortality (hazard ratio [HR], 2.86; 95% confidence interval [95% CI], 2.02 to 4.04). Neonates with AKI detected by both criteria had an even higher risk of in-hospital mortality (HR, 4.86; 95% CI, 2.84 to 8.29). CONCLUSIONS: Serum Cys-C is a robust and sensitive biomarker for detecting neonatal AKI. Compared with modified KDIGO creatinine criteria, CyNA is 6.5 times more sensitive in identifying neonates at elevated risk of in-hospital mortality.
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Injúria Renal Aguda , Cistatina C , Recém-Nascido , Humanos , Estudos de Coortes , Creatinina , Estudos Prospectivos , Mortalidade Hospitalar , BiomarcadoresRESUMO
Anemia is a common complication of chronic kidney disease with major option treatment of erythropoiesis-stimulating agents (ESAs). This study aimed to investigate the influencing factors of erythropoietin resistance index (ERI) and its association with mortality in maintenance hemodialysis (MHD) patients. Patients enrolled from China Dialysis Outcomes and Practice Patterns Study (DOPPS) 5 were included. ERI was calculated as follows: ESA (IU/week)/weight (kg, post-dialysis)/hemoglobin level (g/dL). The Cox regression model was used to analyze the influencing factors on survival outcomes. Stepwise multivariate logistic regression was used to identify the related risk factors, and subgroup analyses were performed. A total of 1270 MHD subjects (687 males and 583 females) were included, with an average age of 60 (49.0, 71.0) years. All subjects were divided into two groups by the median ERI of 14.03. Multivariate logistic regression showed that dialysis vintage (OR 0.957, 95% CI: 0.929-0.986), white blood cells (OR 0.900, 95% CI: 0.844-0.960), high flux dialyzer use (OR 0.866, 95% CI: 0.755-0.993), body mass index (OR 0.860, 95% CI: 0.828-0.892), males (OR 0.708, 95% CI: 0.625-0.801), and albumin (OR 0.512, 95% CI: 0.389-0.673) had a negative association with high ERI baseline (all p < 0.05). There were 176 (13.9%) deaths in total including 89 cardiac/vascular deaths during follow-up. Cox regression analysis showed that ERI was positively associated with all-cause mortality, especially in some subgroups. ERI was associated with increased all-cause mortality in MHD patients, indicating the possibility of death prediction by ERI. Patients with high ERI warrant more attention.
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Anemia , Eritropoetina , Hematínicos , Falência Renal Crônica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Anemia/etiologia , Epoetina alfa , Eritropoetina/uso terapêutico , Hematínicos/uso terapêutico , Falência Renal Crônica/complicações , Falência Renal Crônica/terapia , Diálise Renal/efeitos adversos , IdosoRESUMO
BACKGROUND: Patients with chronic kidney disease have a high risk of adverse kidney and cardiovascular outcomes. The effect of dapagliflozin in patients with chronic kidney disease, with or without type 2 diabetes, is not known. METHODS: We randomly assigned 4304 participants with an estimated glomerular filtration rate (GFR) of 25 to 75 ml per minute per 1.73 m2 of body-surface area and a urinary albumin-to-creatinine ratio (with albumin measured in milligrams and creatinine measured in grams) of 200 to 5000 to receive dapagliflozin (10 mg once daily) or placebo. The primary outcome was a composite of a sustained decline in the estimated GFR of at least 50%, end-stage kidney disease, or death from renal or cardiovascular causes. RESULTS: The independent data monitoring committee recommended stopping the trial because of efficacy. Over a median of 2.4 years, a primary outcome event occurred in 197 of 2152 participants (9.2%) in the dapagliflozin group and 312 of 2152 participants (14.5%) in the placebo group (hazard ratio, 0.61; 95% confidence interval [CI], 0.51 to 0.72; P<0.001; number needed to treat to prevent one primary outcome event, 19 [95% CI, 15 to 27]). The hazard ratio for the composite of a sustained decline in the estimated GFR of at least 50%, end-stage kidney disease, or death from renal causes was 0.56 (95% CI, 0.45 to 0.68; P<0.001), and the hazard ratio for the composite of death from cardiovascular causes or hospitalization for heart failure was 0.71 (95% CI, 0.55 to 0.92; P = 0.009). Death occurred in 101 participants (4.7%) in the dapagliflozin group and 146 participants (6.8%) in the placebo group (hazard ratio, 0.69; 95% CI, 0.53 to 0.88; P = 0.004). The effects of dapagliflozin were similar in participants with type 2 diabetes and in those without type 2 diabetes. The known safety profile of dapagliflozin was confirmed. CONCLUSIONS: Among patients with chronic kidney disease, regardless of the presence or absence of diabetes, the risk of a composite of a sustained decline in the estimated GFR of at least 50%, end-stage kidney disease, or death from renal or cardiovascular causes was significantly lower with dapagliflozin than with placebo. (Funded by AstraZeneca; DAPA-CKD ClinicalTrials.gov number, NCT03036150.).
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Compostos Benzidrílicos/uso terapêutico , Taxa de Filtração Glomerular/efeitos dos fármacos , Glucosídeos/uso terapêutico , Insuficiência Renal Crônica/tratamento farmacológico , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Idoso , Compostos Benzidrílicos/efeitos adversos , Compostos Benzidrílicos/farmacologia , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/prevenção & controle , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Nefropatias Diabéticas/tratamento farmacológico , Feminino , Glucosídeos/efeitos adversos , Glucosídeos/farmacologia , Humanos , Estimativa de Kaplan-Meier , Falência Renal Crônica/mortalidade , Masculino , Pessoa de Meia-Idade , Análise de Regressão , Insuficiência Renal Crônica/complicações , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Inibidores do Transportador 2 de Sódio-Glicose/farmacologiaRESUMO
BACKGROUND: The relations of the variety and quantity of different sources of dietary insoluble fibers and hypertension remain uncertain. We aimed to investigate the associations between the variety and quantity of insoluble fibers intake from six major food sources and new-onset hypertension, using data from the China Health and Nutrition Survey (CHNS). METHODS: Twelve thousand one hundred thirty-one participants without hypertension at baseline from CHNS were included. Dietary intake was measured by three consecutive 24-h dietary recalls combined with a household food inventory. The variety score of insoluble fiber sources was defined as the number of insoluble fiber sources consumed at the appropriate level, accounting for both types and quantities of insoluble fibers. The study outcome was new-onset hypertension, defined as blood pressure ≥ 140/90 mmHg, or physician-diagnosed hypertension or receiving antihypertensive treatments during the follow-up. RESULTS: During a median follow-up of 6.1 years, 4252 participants developed hypertension. There were L-shaped associations of dietary insoluble fibers derived from vegetables, beans, tubers, and fruits with new-onset hypertension; a reversed J-shaped association of whole grain-derived insoluble fiber with new-onset hypertension; and no obvious association of refined grain-derived insoluble fiber with new-onset hypertension. Therefore, refined grain was not included in the insoluble fiber variety score calculation. More importantly, a higher insoluble fiber variety score was significantly associated with lower risks of new-onset hypertension (per score increment, hazard ratio, 0.50; 95% CI, 0.45-0.55). CONCLUSIONS: There was an inverse association between the variety of insoluble fibers with appropriate quantity from different food sources and new-onset hypertension.
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Hipertensão , Humanos , Hipertensão/epidemiologia , Hipertensão/etiologia , Dieta/efeitos adversos , Verduras , Frutas , Inquéritos Nutricionais , Fibras na Dieta , Grão ComestívelRESUMO
RATIONALE & OBJECTIVE: Challenges in achieving valid risk prediction and stratification impede treatment decisions and clinical research design for patients with glomerular diseases. This study evaluated whether chronic histologic changes, when complementing other clinical data, improved the prediction of disease outcomes across a diverse group of glomerular diseases. STUDY DESIGN: Multicenter retrospective cohort study. SETTING & PARTICIPANTS: 4,982 patients with biopsy-proven glomerular disease who underwent native biopsy at 8 tertiary care hospitals across China in 2004-2020. NEW PREDICTORS & ESTABLISHED PREDICTORS: Chronicity scores depicted as 4 categories of histological chronic change, as well as baseline clinical and demographic variables. OUTCOME: Progression of glomerular disease defined as a composite of kidney failure or a ≥40% decrease in estimated glomerular filtration rate from the measurement at the time of biopsy. ANALYTICAL APPROACH: Multivariable Cox proportional hazard models. The performance of predictive models was evaluated by C statistic, time-dependent area under the receiver operating characteristic curve (AUROC), net reclassification index, integrated discrimination index, and calibration plots. RESULTS: The derivation and validation cohorts included 3,488 and 1,494 patients, respectively. During a median of 31 months of follow-up, a total of 444 (8.9%) patients had disease progression in the 2 cohorts. For prediction of the 2-year risk of disease progression, the AUROC of the model combining chronicity score and the Kidney Failure Risk Equation (KFRE) in the validation cohort was 0.76 (95% CI, 0.65-0.87); in comparison with the KFRE model (AUROC, 0.68 [95% CI, 0.56-0.79]), the combined model was significantly better (P = 0.04). The combined model also had a better fit, with a lower Akaike information criterion and a significant improvement in reclassification as assessed by the integrated discrimination improvements and net reclassification improvements. Similar improvements in predictive performance were observed in subgroup and sensitivity analyses. LIMITATIONS: Selection bias, relatively short follow-up, lack of external validation. CONCLUSIONS: Adding histologic chronicity scores to the KFRE model improved the prediction of kidney disease progression at the time of kidney biopsy in patients with glomerular diseases. PLAIN-LANGUAGE SUMMARY: Risk prediction and stratification remain big challenges for treatment decisions and clinical research design for patients with glomerular diseases. The extent of chronic changes is an important component of kidney biopsy evaluations in glomerular disease. In this large multicenter cohort including 4,982 Chinese adults undergoing native kidney biopsy, we evaluated whether histologic chronicity scores, when added to clinical data, could improve the prediction of disease prognosis for a diverse set of glomerular diseases. We observed that adding histologic chronicity scores to the kidney failure risk equation improved the prediction of kidney disease progression at the time of kidney biopsy in patients with glomerular diseases.
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Nefropatias , Insuficiência Renal Crônica , Insuficiência Renal , Adulto , Humanos , Estudos de Coortes , Estudos Retrospectivos , Progressão da Doença , Rim/patologia , Nefropatias/patologia , Insuficiência Renal/patologia , Taxa de Filtração Glomerular , Biópsia , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/patologiaRESUMO
AIMS: Visceral adiposity index (VAI) was a reliable marker for visceral adiposity accumulation and dysfunction. The association between VAI and nephropathy outcomes remains uncertain in patients with type 2 diabetes (T2DM). We aimed to evaluate the longitudinal relationships between VAI and incident nephropathy outcomes in T2DM patients. MATERIALS AND METHODS: Ten thousand one hundred and thirty two participants with T2DM from the ACCORD trial were included in the present study. Cumulative average VAI based on VAI measurements at baseline and follow-up was used to represent long-term VAI status. The primary outcome was the incident composite nephropathy outcome defined as: (1) serum creatinine doubling or >20 ml/min decrease in eGFR; or (2) development of macro-albuminuria; or (3) renal failure or end stage kidney disease (dialysis) or serum creatinine >3.3 mg/dl. RESULTS: During 26,168 person-years follow-up duration, 6094 (60.1%) participants developed the incident composite nephropathy outcome. When assessing cumulative average VAI as quartiles, compared with those in the 1-2 quartiles (<2.6), a significantly higher risk of incident composite nephropathy outcomes was observed among participants in the 3-4 quartiles (≥2.6, adjusted HR: 1.09, 95% CI: 1.01, 1.18). Moreover, the positive association was consistent in participants with or without single abnormal VAI components, including general obesity, abdominal obesity, elevated triglycerides, and low high-density lipoprotein cholesterol, or with different numbers of abnormal VAI components. Additionally, the positive association was stronger in participants with cumulative average systolic blood pressure <130 mmHg (vs. ≥130 mmHg; p-interaction < 0.001). CONCLUSIONS: In T2DM patients, higher cumulative average VAI was associated with a higher risk of incident composite nephropathy outcomes. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov, identifier: NCT00000620.
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Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/complicações , Obesidade Abdominal/complicações , Adiposidade , Creatinina , Obesidade/complicações , Índice de Massa Corporal , Fatores de RiscoRESUMO
BACKGROUND: The association between changes in estimated glomerular filtration rate (eGFR) over time and the risk of stroke remains inconclusive. We aimed to evaluate the relation of eGFR change during the China Stroke Primary Prevention Trial (CSPPT) with the risk of first stroke during the subsequent post-trial follow-up. METHODS: A total of 11,742 hypertensive participants with two eGFR measurements (median measure interval, 4.4; interquartile range, 4.2-4.6 years) and without a history of stroke from the CSPPT were included in this analysis. RESULTS: Over a median post-trial follow-up of 4.4 years, 729 first strokes were identified, of which 635 were ischemic, 88 were hemorrhagic, and 6 were uncertain types of strokes. Compared with those with 1 to <2% per year increase in eGFR (with the lowest stroke risk), those with an increase in eGFR of ≥4% per year had significantly increased risks of first stroke (adjusted hazard ratio [HR] 1.96; 95% confidence interval [CI], 1.10-3.50) and first ischemic stroke (adjusted HR 2.14; 95% CI, 1.17-3.90). Similarly, those with a decline in eGFR of ≥5% per year also had significantly increased first stroke (adjusted HR 2.13; 95% CI, 1.37-3.31) and first ischemic stroke (adjusted HR 1.89; 95% CI, 1.19-3.02) risk. However, there was no significant association between eGFR change and first hemorrhagic stroke. A similar result was found when the change in eGFR was quantified as an absolute annual change. CONCLUSION: In Chinese hypertensive patients, both the decline and increase of eGFR levels were independently associated with the risks of first stroke or first ischemic stroke.
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Hipertensão , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Taxa de Filtração Glomerular , Hipertensão/epidemiologia , AVC Isquêmico/complicações , Japão , Fatores de Risco , Acidente Vascular Cerebral/epidemiologiaRESUMO
The role of facility-level serum potassium (sK+) variability (FL-SPV) in dialysis patients has not been extensively studied. This study aimed to evaluate the association between FL-SPV and clinical outcomes in hemodialysis patients using data from the China Dialysis Outcomes and Practice Patterns Study (DOPPS) 5. FL-SPV was defined as the standard deviation (SD) of baseline sK+ of all patients in each dialysis center. The mean and SD values of FL-SPV of all participants were calculated, and patients were divided into the high FL-SPV (>the mean value) and low FL-SPV (≤the mean value) groups. Totally, 1339 patients were included, with a mean FL-SPV of 0.800 mmol/L. Twenty-three centers with 656 patients were in the low FL-SPV group, and 22 centers with 683 patients were in the high FL-SPV group. Multivariate logistic regression analysis showed that liver cirrhosis (OR = 4.682, 95% CI: 1.246-17.593), baseline sK+ (<3.5 vs. 3.5 ≤ sK+ < 5.5 mmol/L, OR = 2.394, 95% CI: 1.095-5.234; ≥5.5 vs. 3.5 ≤ sK+ < 5.5 mmol/L, OR = 1.451, 95% CI: 1.087-1.939), dialysis <3 times/week (OR = 1.472, 95% CI: 1.073-2.020), facility patients' number (OR = 1.088, 95% CI: 1.058-1.119), serum HCO3- level (OR = 0.952, 95% CI: 0.921-0.984), dialysis vintage (OR = 0.919, 95% CI: 0.888-0.950), other cardiovascular disease (OR = 0.508, 95% CI: 0.369-0.700), and using high-flux dialyzer (OR = 0.425, 95% CI: 0.250-0.724) were independently associated with high FL-SPV (all p < .05). After adjusting potential confounders, high FL-SPV was an independent risk factor for all-cause death (HR = 1.420, 95% CI: 1.044-1.933) and cardiovascular death (HR = 1.827, 95% CI: 1.188-2.810). Enhancing the management of sK+ of hemodialysis patients and reducing FL-SPV may improve patient survival.
Assuntos
Falência Renal Crônica , Diálise Renal , Humanos , População do Leste Asiático , Falência Renal Crônica/sangue , Falência Renal Crônica/mortalidade , Falência Renal Crônica/terapia , Potássio/sangue , Estudos Prospectivos , Diálise Renal/métodos , Diálise Renal/mortalidadeRESUMO
BACKGROUND: Dapagliflozin reduces the risk of end-stage renal disease in patients with chronic kidney disease. We examined the relative risk of cardiovascular and renal events in these patients and the effect of dapagliflozin on either type of event, taking account of history of cardiovascular disease. METHODS: In the DAPA-CKD trial (Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease), 4304 participants with chronic kidney disease were randomly assigned to dapagliflozin 10 mg once daily or placebo. The primary end point was a composite of sustained decline in estimated glomerular filtration rate ≥50%, end-stage kidney disease, or kidney or cardiovascular death. The secondary end points were a kidney composite outcome (primary end point, minus cardiovascular death), the composite of hospitalization for heart failure or cardiovascular death, and all-cause death. In a prespecified subgroup analysis, we divided patients into primary and secondary prevention subgroups according to history of cardiovascular disease. RESULTS: Secondary prevention patients (n=1610; 37.4%) were older, were more often male, had a higher blood pressure and body mass index, and were more likely to have diabetes. Mean estimated glomerular filtration rate and median urinary albumin-to-creatinine ratio were similar in the primary and secondary prevention groups. The rates of adverse cardiovascular outcomes were higher in the secondary prevention group, but kidney failure occurred at the same rate in the primary and secondary prevention groups. Dapagliflozin reduced the risk of the primary composite outcome to a similar extent in both the primary (hazard ratio, 0.61 [95% CI, 0.48-0.78]) and secondary (0.61 [0.47-0.79]) prevention groups (P-interaction=0.90). This was also true for the composite of heart failure hospitalization or cardiovascular death (0.67 [0.40-1.13] versus 0.70 [0.52-0.94], respectively; P-interaction=0.88), and all-cause mortality (0.63 [0.41-0.98] versus 0.70 [0.51-0.95], respectively; P-interaction=0.71). Rates of adverse events were low overall and did not differ between patients with and without cardiovascular disease. CONCLUSIONS: Dapagliflozin reduced the risk of kidney failure, death from cardiovascular causes or hospitalization for heart failure, and prolonged survival in people with chronic kidney disease, with or without type 2 diabetes, independently of the presence of concomitant cardiovascular disease. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03036150.
Assuntos
Compostos Benzidrílicos/uso terapêutico , Doenças Cardiovasculares/prevenção & controle , Glucosídeos/uso terapêutico , Insuficiência Renal Crônica/tratamento farmacológico , Idoso , Compostos Benzidrílicos/efeitos adversos , Compostos Benzidrílicos/farmacologia , Método Duplo-Cego , Feminino , Glucosídeos/efeitos adversos , Glucosídeos/farmacologia , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Diabetic kidney disease (DKD) is one of the most common and devastating complications of diabetic mellitus, and its prevalence is rising worldwide. Klotho, an anti-aging protein, is kidney protective in DKD. However, its large size, prohibitive cost and structural complexity hamper its potential utility in clinics. Here we report that Klotho-derived peptide 6 (KP6) mimics Klotho function and ameliorates DKD. In either an accelerated model of DKD induced by streptozotocin and advanced oxidation protein products in unilateral nephrectomized mice or db/db mice genetically prone to diabetes, chronic infusion of KP6 reversed established proteinuria, attenuated glomerular hypertrophy, mitigated podocyte damage, and ameliorated glomerulosclerosis and interstitial fibrotic lesions, but did not affect serum phosphorus and calcium levels. KP6 inhibited ß-catenin activation in vivo and blocked the expression of its downstream target genes in glomerular podocytes and tubular epithelial cells. In vitro, KP6 prevented podocyte injury and inhibited ß-catenin activation induced by high glucose without affecting Wnt expression. Co-immunoprecipitation revealed that KP6 bound to Wnt ligands and disrupted the engagement of Wnts with low density lipoprotein receptor-related protein 6, thereby interrupting Wnt/ß-catenin signaling. Mutated KP6 with a scrambled amino acid sequence failed to bind Wnts and did not alleviate DKD in db/db mice. Thus, our studies identified KP6 as a novel Klotho-derived peptide that ameliorated DKD by blocking Wnt/ß-catenin. Hence, our findings also suggest a new therapeutic strategy for the treatment of patients with DKD.
Assuntos
Diabetes Mellitus , Nefropatias Diabéticas , Podócitos , Animais , Diabetes Mellitus/metabolismo , Nefropatias Diabéticas/patologia , Camundongos , Peptídeos/farmacologia , Peptídeos/uso terapêutico , Podócitos/patologia , Via de Sinalização Wnt/fisiologia , beta Catenina/metabolismoRESUMO
OBJECTIVE: We aimed to investigate the prospective association between self-perceived psychological stress and first stroke, and to examine possible effect modifiers among adults with hypertension. METHODS: A total of 20,688 hypertensive adults with information on self-perceived psychological stress at baseline were included from the China Stroke Primary Prevention Trial. Participants were randomly assigned to a double-blind treatment of receiving a single tablet daily with either 10 mg enalapril and 0.8 mg folic acid or 10 mg enalapril alone. Follow-up visits occurred every 3 months after randomization. Psychological stress was measured with a one-item 3-point rating scale. The primary outcome was first stroke (fatal or nonfatal). RESULTS: The median treatment period was 4.5 years. Compared with participants with low levels of psychological stress, those with high psychological stress had a significantly higher risk of first stroke (adjusted hazard ratio = 1.40, 95% confidence interval = 1.01 to 1.94) or first ischemic stroke (adjusted hazard ratio = 1.45; 95% confidence interval = 1.01 to 2.09). Moreover, a stronger positive relationship between psychological stress and first stroke was found in participants with time-averaged mean arterial pressure <101 mm Hg (median; p-interaction = .004) during the treatment period. However, our study did not find a significant association between psychological stress and first hemorrhagic stroke. CONCLUSIONS: Higher psychological stress was associated with an increased risk of first stroke among treated hypertensive patients, especially in those with lower mean arterial pressure during the treatment period.
Assuntos
Hipertensão , Acidente Vascular Cerebral , Adulto , Anti-Hipertensivos/uso terapêutico , China , Método Duplo-Cego , Enalapril , Humanos , Hipertensão/complicações , Hipertensão/tratamento farmacológico , Hipertensão/epidemiologia , Estresse Psicológico/complicações , Acidente Vascular Cerebral/etiologiaRESUMO
BACKGROUND: Despite renin-angiotensin-aldosterone system blockade and immunosuppressive treatment, focal segmental glomerulosclerosis (FSGS) often progresses to kidney failure. The objective of this prespecified analysis of the dapagliflozin and prevention of adverse outcomes in chronic kidney disease trial (DAPA-CKD) was to assess efficacy and safety of dapagliflozin in a small subgroup of participants with FSGS confirmed by kidney biopsy. METHODS: In DAPA-CKD, patients with an estimated glomerular filtration rate (eGFR) 25-75 mL/min/1.73 m2 and urinary albumin:creatinine ratio (UACR) 200-5000 mg/g (22.6-565 mg/mol) were randomized to dapagliflozin 10 mg once daily or placebo as an adjunct to standard care and followed for median 2.4 years. The primary composite endpoint was sustained eGFR decline ≥50%, end-stage kidney disease, or kidney or cardiovascular death. The endpoint of interest for this analysis was eGFR slope (acute effects from baseline to Week 2 and chronic effects from Week 2 to end of treatment). RESULTS: Of 104 participants with biopsy-confirmed FSGS, 45 were randomized to dapagliflozin and 59 to placebo. Mean (standard deviation) age was 54.0 (14.3) years, mean eGFR 41.9 (11.5) mL/min/1.73 m2 and median (interquartile range) UACR 1248 (749-2211) mg/g. The primary outcome occurred in 4 (8.9%) and 7 (11.9%) participants randomized to dapagliflozin and placebo, respectively [hazard ratio 0.62, 95% confidence interval (95% CI) 0.17, 2.17]. Dapagliflozin led to a larger acute reduction (standard error) in eGFR compared with placebo (-4.5, 95% CI -5.9 to -3.1 versus -0.9, -2.1 to 0.4 mL/min/1.73 m2/2 weeks). Thereafter, mean rates of chronic eGFR decline with dapagliflozin and placebo were -1.9 (-3.0, -0.9) and -4.0 (-4.9, -3.0) mL/min/1.73 m2/year, respectively (difference 2.0, 95% CI 0.6 to 3.5, mL/min/1.73 m2/year). Adverse events leading to study drug discontinuation were similar in both groups; there were fewer serious adverse events with dapagliflozin. CONCLUSIONS: Among DAPA-CKD participants with FSGS, dapagliflozin reduced the rate of chronic decline of eGFR compared with placebo, although this difference was not statistically significant.
Assuntos
Diabetes Mellitus Tipo 2 , Glomerulosclerose Segmentar e Focal , Insuficiência Renal Crônica , Inibidores do Transportador 2 de Sódio-Glicose , Compostos Benzidrílicos/efeitos adversos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Taxa de Filtração Glomerular , Glomerulosclerose Segmentar e Focal/complicações , Glomerulosclerose Segmentar e Focal/tratamento farmacológico , Glucosídeos , Humanos , Pessoa de Meia-Idade , Insuficiência Renal Crônica/induzido quimicamente , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/tratamento farmacológico , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversosRESUMO
BACKGROUND: Studies suggested the association between blood flow rate (BFR) and mortality might be beyond dialysis adequacy. This study aimed to explore if BFR is an independent predictor of clinical outcomes in Chinese hemodialysis (HD) patients. METHODS: This study included data from patients in China Dialysis Outcomes and Practice Patterns Study (DOPPS) Phase 5. Patients with a record of BFR were included, and demographic data, comorbidities, hospitalization, and death records were collected. Associations between BFR and all-cause mortality and hospitalization were analyzed using Cox regression models. RESULTS: One thousand four hundred twelve (98.9%) patients were included. Most patients were with BFR < 300 ml/min. After full adjustment, each 10-ml/min increase of BFR was associated with a 6.4% decrease in all-cause mortality risk (HR: 0.936, 95% CI: 0.880-0.996) but not first hospitalization (HR: 0.987, 95% CI: 0.949-1.027). The impact of BFR on mortality may be more prominent in patients who were male gender, nondiabetic, albumin < 4.0 g/dl, and hemoglobin ≥ 9.0 g/dl. CONCLUSION: Increased BFR is independently associated with a lower risk of all-cause mortality within the range of BFR 200-300 ml/min. And this effect is more pronounced in patients who were male gender, nondiabetic, albumin < 4.0 g/dl, and hemoglobin ≥ 9.0 g/dl.
Assuntos
Falência Renal Crônica , Diálise Renal , Albuminas , Feminino , Hemoglobinas , Humanos , Falência Renal Crônica/complicações , Masculino , Diálise Renal/efeitos adversos , Fatores de RiscoRESUMO
NLRP3 (NOD-, LRR-, and pyrin domain-containing protein 3) inflammasome activation has emerged as a central mediator of kidney inflammation in diabetic kidney disease (DKD). However, the mechanism underlying this activation in DKD remains poorly defined. In this study, we found that kidney-enriched microRNA-10a and -10b (miR-10a/b), predominantly expressed in podocytes and tubular epithelial cells, were downregulated in kidney from diabetic mice and patients with DKD. High glucose decreased miR-10a/b expression in vitro in an osmolarity-independent manner. miR-10a/b functioned as negative regulators of the NLRP3 inflammasome through targeting the 3'untranslated region of NLRP3 mRNA, inhibiting assembly of the NLRP3 inflammasome and decreasing caspase-1-dependent release of pro-inflammatory cytokines. Delivery of miR-10a/b into kidney prevented NLRP3 inflammasome activation and renal inflammation, and it reduced albuminuria in streptozotocin (STZ)-treated mice, whereas knocking down miR-10a/b increased NLRP3 inflammasome activation. Restoration of miR-10a/b expression in established DKD ameliorated kidney inflammation and mitigated albuminuria in both db/db and STZ-treated mice. These results suggest a novel intervention strategy for inhibiting kidney inflammation in DKD by targeting the NLRP3 inflammasome.