Incidence, risk factors, and outcomes of acute liver injury in hospitalized adults with acute kidney injury: a large multicenter study.

BACKGROUND: Acute kidney injury (AKI) and acute liver injury (ALI) were associated with poor outcomes during hospitalization, respectively. However, the clinical outcome of AKI combined with ALI (AKI-ALI) remains unknown. The current study aimed to describe AKI-ALI's incidences, risk factors, and outcomes. METHODS: The study population included patients aged 18-99 years with enough serum creatinine and liver testing hospitalized at 19 medical centers throughout China between 2000 and 2021. AKI was defined by Kidney Disease Improving Global Outcomes and ALI was defined by the change of liver enzymes based on Asia Pacific Association of Study of Liver consensus guidelines. Cox proportional hazard model was used to identify risk factors for AKI-ALI, and a time-dependent Cox proportional hazard regression model was used to estimate the association between AKI-ALI and in-hospital mortality. RESULTS: Among the 18,461 patients with AKI, 1689 (9.1%) combined with ALI. Male patients or those who have used nonsteroidal anti-inflammatory drugs or vasopressors, and who have heart failure or shock, with higher AST or GGT values, were associated with an increased risk of AKI-ALI. Compared with AKI-nonALI, patients with AKI-ALI were at higher risk of in-hospitalized mortality (hazard ratio [HR] 1.76, 95% confidence interval [CI] 1.54, 2.00). In addition, a stronger association between AKI-ALI and in-hospital mortality was found in those with lower AKI grades (p for interaction = 0.037). CONCLUSIONS: ALI was not uncommon among patients with AKI, especially in patients who used vasopressors and had shock. This study highlights the association between AKI-ALI and a significantly increased risk of mortality. It suggests that dynamic monitoring of liver function is essential, particularly in patients with AST and GGT exceeding the normal upper limit, to improve the in-hospital prognosis of AKI patients.

Post-treatment level of LDL cholesterol and all-cause mortality in patients with atherosclerotic cardiovascular disease: evidence from real-world setting.

AIMS: This study aimed to evaluate the safety of the currently recommended target of LDL cholesterol (LDL-C) control on mortality in patients with atherosclerotic cardiovascular disease (ASCVD). METHODS AND RESULTS: Using deidentified electronic health record data, we conducted a multicentre retrospective cohort study involving individuals with documented ASCVD who had received statin treatment for at least 3 months across China. The primary outcomes assessed encompassed all-cause mortality, CV mortality, and non-CV mortality. Relationships between post-treatment LDL-C concentrations and outcomes were evaluated using restricted cubic spline curves based on Cox proportional hazards regression analyses. Additionally, competitive risk models were employed to explore associations between LDL-C levels and cause-specific mortality. Among 33 968 participants, we identified nearly linear associations of post-treatment LDL-C level with all-cause mortality and CV mortality during a median follow-up of 47 months. Notably, patients who achieved the recommended target of LDL-C (<1.4 mmol/L) were at significantly lower risks of all-cause mortality [hazard ratio (HR), 0.77; 95% confidence interval (CI), 0.69-0.86] and CV mortality (subdistribution HR, 0.68; 95% CI, 0.58-0.79), compared with those with LDL-C ≥ 3.4 mmol/L. This survival benefit was consistent in patients with different intensities of LDL-C reduction and other subgroup analyses. And no correlation was found between post-treatment LDL-C concentration and non-CV mortality. CONCLUSION: Our findings supported the safety of currently recommended target of LDL-C control and the 'lower is better' principle in patients with ASCVD.

Intensive control of LDL cholesterol (LDL-C) has been widely recommended for cardiovascular (CV) protection in patients with atherosclerotic CV disease. Nevertheless, a U-shaped association between LDL-C levels and all-cause mortality has been noted in several general population studies, prompting concerns regarding the safety of intensive lipid control. In this multicentre cohort comprising 33 968 patients at the highest CV risk, we found that patients with lower post-treatment LDL-C level were at lower risk of both all-cause and CV mortality, and this survival benefit was unaffected by intensity of LDL-C reduction, types of lipid-lowering agents, and other clinical characteristics.

Epidemiology and outcomes of post-AKI proteinuria.

Background: Acute kidney injury (AKI) has been associated with increased risks of new-onset and worsening proteinuria. However, epidemiologic data for post-AKI proteinuria was still lacking. This study aimed to determine the incidence, risk factors and clinical correlations of post-AKI proteinuria among hospitalized patients. Methods: This study was conducted in a multicenter cohort including patients aged 18-100 years with hospital-acquired AKI (HA-AKI) hospitalized at 19 medical centers throughout China. The primary outcome was the incidence of post-AKI proteinuria. Secondary outcomes included AKI recovery and kidney disease progression. The results of both quantitative and qualitative urinary protein tests were used to define post-AKI proteinuria. Cox proportional hazard model with stepwise regression was used to determine the risk factors for post-AKI proteinuria. Results: Of 6206 HA-AKI patients without proteinuria at baseline, 2102 (33.9%) had new-onset proteinuria, whereas of 5137 HA-AKI with baseline proteinuria, 894 (17.4%) had worsening proteinuria after AKI. Higher AKI stage and preexisting CKD diagnosis were risk factors for new-onset proteinuria and worsening proteinuria, whereas treatment with renin-angiotensin system inhibitors was associated with an 11% lower risk of incident proteinuria. About 60% and 75% of patients with post-AKI new-onset and worsening proteinuria, respectively, recovered within 3 months. Worsening proteinuria was associated with a lower incidence of AKI recovery and a higher risk of kidney disease progression. Conclusions: Post-AKI proteinuria is common and usually transient among hospitalized patients. The risk profiles for new-onset and worsening post-AKI proteinuria differed markedly. Worsening proteinuria after AKI was associated with adverse kidney outcomes, which emphasized the need for close monitoring of proteinuria after AKI.

Statin initiation and risk of incident kidney disease in patients with diabetes.

BACKGROUND: The role of statin therapy in the development of kidney disease in patients with type 2 diabetes mellitus (DM) remains uncertain. We aimed to determine the relationships between statin initiation and kidney outcomes in patients with type 2 DM. METHODS: Through a new-user design, we conducted a multicentre retrospective cohort study using the China Renal Data System database (which includes inpatient and outpatient data from 19 urban academic centres across China). We included patients with type 2 DM who were aged 40 years or older and admitted to hospital between Jan. 1, 2000, and May 26, 2021, and excluded those with pre-existing chronic kidney disease and those who were already on statins or without follow-up at an affiliated outpatient clinic within 90 days after discharge. The primary exposure was initiation of a statin. The primary outcome was the development of diabetic kidney disease (DKD), defined as a composite of the occurrence of kidney dysfunction (estimated glomerular filtration rate [eGFR] < 60 mL/min/1.73 m2 and > 25% decline from baseline) and proteinuria (a urinary albumin-to-creatinine ratio ≥ 30 mg/g and > 50% increase from baseline), sustained for at least 90 days; secondary outcomes included development of kidney function decline (a sustained > 40% decline in eGFR). We used Cox proportional hazards regression to evaluate the relationships between statin initiation and kidney outcomes, as well as to conduct subgroup analyses according to patient characteristics, presence or absence of dyslipidemia, and pattern of dyslipidemia. For statin initiators, we explored the association between different levels of lipid control and outcomes. We conducted analyses using propensity overlap weighting to balance the participant characteristics. RESULTS: Among 7272 statin initiators and 12 586 noninitiators in the weighted cohort, statin initiation was associated with lower risks of incident DKD (hazard ratio [HR] 0.72, 95% confidence interval [CI] 0.62-0.83) and kidney function decline (HR 0.60, 95% CI 0.44-0.81). We obtained similar results to the primary analyses for participants with differing patterns of dyslipidemia, those prescribed different statins, and after stratification according to participant characteristics. Among statin initiators, those with intensive control of high-density lipoprotein cholesterol (LDL-C) (< 1.8 mmol/L) had a lower risk of incident DKD (HR 0.51, 95% CI 0.32-0.81) than those with inadequate lipid control (LDL-C ≥ 3.4 mmol/L). INTERPRETATION: For patients with type 2 DM admitted to and followed up in academic centres, statin initiation was associated with a lower risk of kidney disease development, particularly in those with intensive control of LDL-C. These findings suggest that statin initiation may be an effective and reasonable approach for preventing kidney disease in patients with type 2 DM.

Association between mean arterial pressure and clinical outcomes among patients with heart failure.

AIMS: Mean arterial pressure (MAP) is widely used for evaluating organ perfusion, but its impact on clinical outcomes in patients with heart failure (HF) remains poorly understood. The aim of this study is to investigate the relationship between MAP and all-cause mortality and readmission in patients with HF. METHODS AND RESULTS: We retrospectively analysed data from PhysioNet, involving 2005 patients with HF admitted to Zigong Fourth People's Hospital between 2016 and 2019. The primary outcomes were composite outcomes of all-cause mortality and readmission at 3 and 6 months. The secondary outcomes were readmission at 3 and 6 months. Multivariate-adjusted Cox regression models, restricted cubic spline curves (RCS), and propensity score matching (PSM) were used to explore the relationship between MAP and clinical outcomes. Among 2005 patients with HF [≥70 years, 1460 (72.8%); male, 843 (42.0%)], the incidence of primary outcome at 3 months was 33.4% (223/668), 24.4% (163/668), and 22.7% (152/669), and at 6 months, it was 47.5% (317/668), 38.5% (257/668), and 38.0% (254/669) across MAP tertiles [from Tertile 1 (T1) to Tertile 3 (T3)], respectively. The RCS showed an 'L-shaped' relationship between MAP and primary or secondary endpoints. Multivariate-adjusted Cox models showed that a higher MAP was significantly associated with a lower risk of composite endpoints at 3 months [adjusted hazard ratio (aHR) 0.75, 95% confidence interval (CI) 0.61-0.92, P = 0.006, Tertile 2 (T2); aHR 0.69, 95% CI 0.56-0.86, P = 0.001, T3] and 6 months (aHR 0.79, 95% CI 0.67-0.93, P = 0.005, T2; aHR 0.77, 95% CI 0.64-0.91, P = 0.003, T3) compared with T1. After 1:1 PSM, the effect of maintaining a relatively higher MAP was slightly attenuated. Threshold analyses indicated that per 10 mmHg increase in MAP, there was a 21% and 14% decrease in composite endpoints at 3 and 6 months, respectively (aHR 0.79, 95% CI 0.69-0.91, P = 0.001), and 6 months (aHR 0.86, 95% CI 0.77-0.97, P = 0.013) in patients with MAP ≤ 93 mmHg. The associations were consistent in readmission (secondary outcomes), various subgroups, and sensitivity analysis. CONCLUSIONS: A higher MAP was associated with a lower risk of a composite of all-cause mortality and readmission. Maintaining a relatively higher MAP could potentially improve the clinical prognosis for patients with HF.

Detecting Neonatal AKI by Serum Cystatin C.

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.

Positive association of triglyceride-glucose index with new-onset hypertension among adults: a national cohort study in China.

BACKGROUND: Previous studies showed that the triglyceride-glucose (TyG) index was a better predictor of adverse cardiovascular events than triglycerides or fasting blood glucose alone. However, few studies have focused on new-onset hypertension. We aimed to explore the association of TyG index with new-onset hypertension in Chinese adults. METHODS: A total of 4,600 participants who underwent at least 2 rounds of visits from 2009 to 2015 in the China Health and Nutrition Survey were enrolled in this study. Our outcome of interest was new-onset hypertension. Multivariate Cox hazard regression models and restricted cubic spline were performed to explore the relationship between TyG index and new-onset hypertension. RESULTS: The mean (standard deviation, SD) age of the study population was 48.1 (13.6) years, and 2058 (44.7%) of the participants were men. The mean (SD) TyG index level was 8.6 (0.7). A total of 1,211 (26.3%) participants developed new-onset hypertension during a median (interquartile range) follow-up duration of 6.0 (2.0-6.1) years. The incidences of new-onset hypertension were 18.1%, 25.3%, 28.5%, and 33.4% by quartiles of TyG index [from quartile 1 (Q1) to Q4], respectively. The Cox model showed that high levels of TyG index were significantly associated with increased risk of new-onset hypertension (adjusted hazard ratio [aHR]: 1.29, 95% confidence interval [CI] 1.07-1.55, Q2; aHR, 1.24, 95% CI 1.03-1.49, Q3; aHR, 1.50, 95% CI 1.22-1.84, Q4) compared with Q1. Consistently, as a continuous variable, for every 1.0 increase in TyG index, there was a 17% increase in the risk of new-onset hypertension (aHR, 1.17; 95% CI 1.04-1.31). The associations were consistent in various subgroups and sensitivity analysis. The dose-response curve indicated a positive, linear association between TyG index and the risk of new-onset hypertension. CONCLUSIONS: High TyG index was significantly associated with an increased risk of new-onset hypertension among Chinese adults. Our findings suggest that maintaining a relatively low level of TyG index might be effective in the primary prevention of hypertension.

Loop Diuretics Are Associated with Increased Risk of Hospital-Acquired Acute Kidney Injury in Adult Patients: A Retrospective Study.

Background: The association between loop diuretics and acute kidney injury (AKI) remains unclear. Methods: The population studied was selected from the Epidemiology of AKI in Chinese Hospitalized patients (EACH) study. Exposure to loop diuretics was defined as any filled prescription prior to the date when AKI was detected in patients with HA-AKI, and prior to the last date of SCr testing in those without AKI. The outcome was AKI, defined by the Kidney Disease Improving Global Outcomes criteria. Associations between loop diuretics and HA-AKI were examined by Cox proportional hazards models adjusted for baseline and time-dependent covariates. Results: Of the 150,020 patients, 16,437 (11.0%) were prescribed loop diuretics, and 5717 (3.8%) experienced HA-AKI events. The crude rates of HA-AKI in patients who were and were not prescribed loop diuretics were 1632 (9.9%) and 3262 (2.8%), respectively. A multivariate cox proportional hazards analysis showed that exposure to loop diuretics was associated with significantly increased risks of HA-AKI compared with non-users (hazard ratio (HR), 1.61; 95% CI (confidence interval), 1.55-1.67), other diuretics (HR, 1.09; 95% CI, 1.03-1.15), and osmotic diuretics (HR, 1.30; 95% CI, 1.20-1.42). Compared with other diuretics, the use of loop diuretics was associated with higher risks of HA-AKI in women, in patients without hypertension, in patients without heart failure, in patients without liver cirrhosis, and in patients not requiring surgery. Conclusions: Loop diuretics are widely used and are associated with increased risks of HA-AKI in hospitalized adults. Renal function should be more closely monitored during the use of loop diuretics.

Association of Ibuprofen Prescription With Acute Kidney Injury Among Hospitalized Children in China.

Importance: Ibuprofen is widely used in children worldwide, especially in those with cancer, fever, or trauma. However, large and high-quality studies of the association between ibuprofen and acute kidney injury (AKI) in children have been lacking. Objective: To examine the association between the use of ibuprofen and the risk of hospital-acquired AKI in hospitalized children in China. Design, Setting, and Participants: This cohort study analyzed the cohort of the Epidemiology of AKI in Chinese Hospitalized Patients (EACH) study, a large, multicenter retrospective study of 3 044 023 patients who were admitted to 1 of 25 academic medical centers in China between January 1, 2013, and December 31, 2015. Patient-level data were obtained from the electronic health record system of the participating centers. Hospitalized children aged 1 month to 18 years who had prescriptions and a certain number of serum creatinine (SCr) tests were included. Children with end-stage renal disease, community-acquired AKI, low baseline SCr level (<10 µmol/L), high standardized baseline SCr level (>4 times the sex- and age-specific reference value), or missing diagnosis code were excluded. Data analysis was conducted from January 1, 2020, to August 30, 2020. Exposures: Exposure to ibuprofen was coded as a time-dependent dichotomous variable. Main Outcomes and Measures: Baseline SCr level was calculated for each patient as the mean of all available SCr values between the 30 days prior to admission and the first SCr testing within the first 3 days of hospitalization. Acute kidney injury was defined as an increase in SCr level of 26.5 µmol/L or higher within 48 hours or by 50% or more over the baseline value, according to the Kidney Disease: Improving Global Outcomes guidelines. Results: Among the 50 420 children (mean [SD] age, 5.0 [5.2] years; 30 640 boys [60.8%]) included in this study, 5526 (11.0%) used ibuprofen and 3476 (6.9%) developed hospital-acquired AKI during hospitalization. Ibuprofen use was associated with a statistically significantly increased risk of hospital-acquired AKI (hazard ratio [HR], 1.23; 95% CI, 1.14-1.34) after adjusting for confounders. Ibuprofen use was associated with a greater hazard in children who had chronic kidney disease vs those without (HR, 2.31 [95% CI, 1.73-3.10] vs 1.19 [95% CI, 1.09-1.29]), required intensive care vs those without this need (HR, 1.47 [95% CI, 1.24-1.75] vs 1.18 [95% CI, 1.07-1.29]), or were older vs younger (>10 years and >1 year to 10 years vs 1 month to 1 year) (HR, 1.64 [95% CI, 1.32-2.05]; 1.36 [95% CI, 1.23-1.52] vs 0.99 [95% CI, 0.86-1.13]). Dose-response analysis suggested that the association of ibuprofen with the risk of hospital-acquired AKI was dose-dependent. Conclusions and Relevance: This study found that ibuprofen was widely used and associated with an increased risk of hospital-acquired AKI in hospitalized children in China. The judicious use of ibuprofen and close monitoring of kidney function in children are needed.