Incidence, risk factors and outcome of postoperative acute kidney injury in China.

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.

Effect of DPP-4i inhibitors on renal function in patients with type 2 diabetes mellitus: a systematic review and meta-analysis of randomized controlled trials.

AIMS: About 20-40% patients with type 2 diabetes mellitus (T2DM) had an increased risk of developing diabetic nephropathy (DN). Dipeptidyl peptidase-4 inhibitors (DPP-4i) were recommended for treatment of T2DM, while the impact of DPP-4i on renal function remained unclear. This study aimed to explore the effect of DPP-4i on renal parameter of estimated glomerular filtration rate (eGFR) and albumin-to-creatinine ratio (ACR) in T2DM. METHODS: A systematic search was performed across PubMed, Embase and Cochrane Library. A fixed or random-effects model was used for quantitative synthesis according to the heterogeneity, which was assessed with I2 index. Sensitivity analysis and publication bias were performed with standard methods, respectively. RESULTS: A total of 17 randomized controlled trials were identified. Administration of DPP-4i produced no significant effect on eGFR (WMD, -0.92 mL/min/1.73m2, 95% CI, -2.04 to 0.19) in diabetic condition. DPP-4i produced a favorable effect on attenuating ACR (WMD, -2.76 mg/g, 95% CI, -5.23 to -0.29) in patients with T2DM. The pooled estimate was stable based on the sensitivity test. No publication bias was observed according to Begg's and Egger's tests. CONCLUSIONS: Treatment with DPP-4i preserved the renal parameter of eGFR in diabetic condition. Available evidences suggested that administration of DPP-4i produced a favorable effect on attenuating ACR in patients with T2DM. INTERNATIONAL PROSPECTIVE REGISTER FOR SYSTEMATIC REVIEW (PROSPERO) NUMBER: CRD.42020144642.

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.

Gut microbiota in the association between obesity and kidney function decline: a metagenomics-based study in a rat model.

OBJECTIVES: Obesity can induce dysbiosis in the gut microbiota and is considered a separate risk factor for kidney function decline. Nonetheless, the precise function of intestinal microorganisms in facilitating the connection between obesity and kidney function decline remains uncertain. Hence, the objective of this study was to investigate the alterations in the gut microbiota composition that take place during obesity and their correlations with renal function utilizing a rat model. METHODS: For 20 weeks, 25 Sprague-Dawley rats were fed either a high-fat diet (HFD) or a normal-fat normal diet (ND). Physiological indices, peripheral plasma, kidney tissue, and colon contents were collected for comparison between groups. Metagenomic analysis of intestinal flora was performed. RESULTS: The HFD group demonstrated significantly increased levels of creatinine and urea nitrogen in the peripheral blood. Additionally, the HFD rats exhibited a significantly larger glomerular diameter compared to the ND group, accompanied by the presence of glomerulosclerosis, tubular vacuolar transformation, and other pathological changes in certain glomeruli. Metagenomics analysis revealed a notable rise in the prevalence of the Firmicutes phylum within the HFD group, primarily comprising the Rumenococcus genus. Functional analysis indicated that the gut microbiota in the HFD group primarily correlated with infectious diseases, signal transduction, and signaling molecules and interactions. CONCLUSIONS: This study provides evidence that the consumption of a HFD induces modifications in the composition and functionality of the gut microbiome in rats, which may serve as a potential mechanism underlying the relationship between obesity and the progression of kidney function decline.

Features of cardiovascular magnetic resonance native T1 mapping in maintenance hemodialysis patients and their related factors.

PURPOSE: Increased myocardial T1 values on cardiovascular MRI (CMRI) have been shown to be a surrogate marker for myocardial fibrosis. The use of CMRI in patients on hemodialysis (HD) remains limited. This research aimed to explore the characteristics of native T1 values in HD patients and identify factors related to T1 values. METHODS: A total of thirty-two patients on HD and fourteen healthy controls were included in this study. All participants underwent CMRI. Using modified Look-Locker inversion recovery (MOLLI) sequence, native T1 mapping was achieved. Native CMRI T1 values were compared between the two groups. In order to analyze the relationship between T1 values and clinical parameters, correlation analysis was performed in patients on HD. RESULTS: Patients on HD exhibited elevated global native T1 values compared to control subjects. In the HD group, the global native T1 value correlated positively with intact parathyroid hormone (iPTH) (r = 0.418, p = 0.017) and negatively with triglycerides (r= -0.366, p = 0.039). Moreover, the global native T1 value exhibited a positive correlation with the left ventricular end-diastolic volume indexed to body surface area (BSA; r = 0.528, p = 0.014), left ventricular end-systolic volume indexed to BSA (r = 0.506, p = 0.019), and left ventricular mass indexed to BSA (r = 0.600, p = 0.005). A negative correlation was observed between the global native T1 value and ejection fraction (r = 0.-0.551, p = 0.010). CONCLUSION: The global native T1 value was prolonged in HD patients compared with controls. In the HD group, the global T1 value correlated strongly with iPTH, triglycerides, and cardiac structural and functional parameters.

COF-based membranes for liquid phase separation: Preparation, mechanism and perspective.

Covalent organic frameworks (COFs) are a new kind of crystalline porous materials composed of organic molecules connected by covalent bonds, processes the characteristics of low density, large specific surface area, adjustable pore size and structure, and easy to functionalize, which have been widely used in the field of membrane separation technology. Recently, there are more and more researches focusing on the preparation methods, separation application, and mechanism of COF membranes, which need to be further summarized and compared. In this review, we primarily summarized several conventional preparation methods, such as two-phase interfacial polymerization, in-situ growth on substrate, unidirectional diffusion method, layer-by-layer assembly method, mixed matrix membranes, and so on. The advantages and disadvantages of each method are briefly summarized. The application potential of COF membrane in liquid separation are introduced from four aspects: dyeing wastewater treatment, heavy metal removal, seawater desalination and oil-water separation. Then, the mechanisms including pore structure, hydrophilic/hydrophobic, electrostatic repulsion/attraction and Donnan effect are introduced. For the efficient removal of different kind of pollutions, researchers can select different ligands to construct membranes with specific pore size, hydrophily, salt or organic rejection ability and functional group. The ideas for the design and preparation of COF membranes are introduced. Finally, the future direction and challenges of the next generation of COF membranes in the field of separation are prospected.

Variants within the LPL gene confer susceptility to diabetic kidney disease and rapid decline in kidney function in Chinese patients with type 2 diabetes.

AIM: To examine the association between lipoprotein lipase (LPL) polymorphisms and susceptibility to diabetic kidney disease (DKD) and early renal function decline in Chinese patients with type 2 diabetes (T2D). METHODS: The association of eight LPL single nucleotide polymorphisms (SNPs) with DKD was analysed in 2793 patients with T2D from the third China National Stroke Registry. DKD was defined as either an urine albumin-to-creatinine ratio (UACR) of 30 mg/g or higher at baseline and 3 months, or an estimated glomerular filtration rate (eGFR) of less than 60 mL/min/1.73 m2 at baseline and 3 months. Rapid decline in kidney function (RDKF) was defined as a reduction in the eGFR of 3 mL/min/1.73 m2 or greater per year. Logistic regression models were used to evaluate the association of LPL SNP and DKD with an additive model. RESULTS: The SNPs rs285 C>T (OR = 1.40, P = .0154), rs328 C>G (OR = 2.24, P = .0104) and rs3208305 A>T (OR = 1.85, P = .0015) were identified to be significantly associated with DKD defined by eGFR. Among 1241 participants with follow-up data, 441 (35.5%) showed RDKF over a mean follow-up period of 1 year, and the rs285 C allele was associated with higher odds of RDKF (OR = 1.31, 95% CI 1.04-1.66; P = .025) after adjustment for multiple variables. CONCLUSIONS: These results suggest that LPL-related SNPs are new candidate factors for conferring susceptibility to DKD and may promote rapid loss of renal function in Chinese patients with T2D.

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.

Dipping Pattern and 1-year stroke functional outcome in ischemic stroke or transient ischemic attack.

AIMS: This study aimed to explore whether a relationship exists between dipping patterns and 1-year functional outcome in patients with acute ischemic stroke (IS) or transient ischemic attack (TIA). METHODS: Data from the Blood Pressure and Clinical Outcome in TIA or Ischemic Stroke Study (BOSS), a nationwide, hospital-based, longitudinal cohort study, was used for this study. Patients with acute IS or TIA were recruited within 7 days after onset and ambulatory blood pressure monitoring was performed during hospitalization. Patients were defined as dippers if nocturnal systolic blood pressure fell by ≥10%, non-dippers if 0-10%, and reverse dippers if < 0%. Poor functional outcome was defined as a modified Rankin Scale (mRS) score of 3-5. Logistic regression analysis was used to test the association between dipping patterns and 1-year functional outcome. RESULTS: Among the 1808 IS/TIA patients, 19.19% were dippers, 53.21% were non-dippers, and 27.60% were reverse dippers. Poor functional outcome occurred in 22.44% of reverse dippers, which was significantly higher than that of dippers (16.14%) and non-dippers (16.53%) (P = .014). A univariate analysis revealed that reverse dipping was a risk factor for poor functional outcome (Odds ratio 1.504, 95% confidence interval 1.055-2.145, P = .024). However, this significance disappeared after adjusting for confounders. CONCLUSIONS: Reverse dipping was prevalent in patients with IS/TIA. The higher incidence of 1-year poor functional outcome in reverse dippers warrants further investigation.

Coherent Doppler wind lidar signal denoising adopting variational mode decomposition based on honey badger algorithm.

Coherent Doppler wind lidar (CDWL) is used to measure wind velocity distribution by using laser pulses. However, the echo signal is easily affected by atmospheric turbulence, which could decrease the effective detection range of CDWL. In this paper, a variation modal decomposition based on honey badger algorithm (VMD-HBA) is proposed and demonstrated. Compared with conventional VMD-based methods, the proposed method utilizes a newly developed HBA to obtain the optimal VMD parameters by iterating the spectrum fitness function. In addition, the Correlation Euclidean distance is applied to identify the relevant mode and used to reconstruct the signal. The simulation results show that the denoising performance of VMD-HBA is superior to other available denoising methods. Experimentally, this combined method was successfully realized to process the actual lidar echo signal. Under harsh detection conditions, the effective detection range of the homemade CDWL system is extended from 13.41 km to 20.61 km.

Association between serum uric acid to serum creatinine ratio and poor functional outcomes in patients with acute ischemic stroke.

BACKGROUND AND PURPOSE: The role of serum uric acid (SUA) in prognosis is controversial because SUA levels largely depend on renal clearance function. This study aimed to investigate the association between renal function-normalized SUA (SUA to serum creatinine [SCr] ratio [SUA/SCr ratio]) and poor functional outcomes in patients with acute ischemic stroke (AIS). METHODS: All patients were recruited from the Third China National Stroke Registry. Poor functional outcomes were defined by modified Rankin Scale (mRS) scores of 3-6 or 2-6 at 3 months and 1 year. RESULTS: Among 8169 enrolled patients, the median (interquartile range) SUA/SCr ratio was 4.19 (3.47-5.08). Compared with patients in the fourth quintile group, those in the first quintile group had higher proportions of mRS scores 3-6 (odds ratio [OR] 1.55, 95% confidence interval [CI] 1.24-1.93) and mRS scores 2-6 (OR 1.28, 95% CI 1.08-1.53) at 3 months. The addition of SUA/SCr ratio to the conventional risk model had a greater incremental value than the addition of either SUA or SCr alone. Subgroup analysis showed that the association was only significant in patients with normal kidney function (p for interaction<0.05). Similar results were found for outcomes at 1 year. CONCLUSIONS: A lower SUA/SCr ratio was associated with poor functional outcomes in patients with AIS at 3 months and at 1 year, suggesting the potential use of SUA/SCr ratio in clinical practice as a preferable marker for stroke outcomes.

The Association between Baseline and 3-Month Albuminuria and 1-Year Prognosis of Ischemic Stroke.

INTRODUCTION: The association between the changes in albuminuria levels and the clinical prognosis of stroke is unknown. The present study aimed to explore the relationships between changes in albuminuria and the risk of adverse stroke outcomes. METHODS: The patients with ischemic stroke or transient ischemic attack from the Third China National Stroke Registry (CNSR-III) who had the urinary albumin-to-creatinine ratio (ACR) detected at baseline and 3-month were recruited. They were classified into 4 groups according to baseline and 3-month ACR and followed up for 1 year. RESULTS: A total of 5,311 patients were finally included in the study. There were 3,738 (70.4%), 483 (9.1%), 451 (8.5%), and 639 (12.0%) patients with no albuminuria, baseline albuminuria, 3-month albuminuria, and persistent albuminuria, respectively. After adjustment for confounding variables, persistent albuminuria was independently associated with all-cause death (hazard ratio [HR], 2.23; 95% CI, 1.17-4.25; p = 0.02), stroke recurrence (HR, 1.55; 95% CI, 1.02-2.36; p = 0.04), and poor functional outcome (OR, 2.22; 95% CI, 1.66-2.96; p < 0.001). Baseline albuminuria was independently associated with poor functional outcome (OR, 1.65; 95% CI, 1.19-2.28; p = 0.003), while 3-month albuminuria was independently associated with stroke recurrence (HR, 1.68; 95% CI, 1.06-2.65; p = 0.03). CONCLUSIONS: Changes in albuminuria can predict adverse 1-year outcomes in Chinese ischemic stroke patients. In particular, persistent albuminuria was independently associated with 1-year all-cause death, stroke recurrence, and poor functional outcome.

Association of Urine Albumin-Creatinine Ratio and Cystatin C-Based Estimated GFR with Outcomes in Patients with Ischemic Stroke.

BACKGROUND/AIMS: Data about the independent and combined effects of cystatin C-based estimated glomerular filtration rate (eGFRcys) and albuminuria on the risk of poor outcome in stroke patients are limited. The aim was to elucidate how these two renal markers affect the clinical outcomes after ischemic stroke separately and jointly. METHODS: The study subjects consisted of 10,197 patients with ischemic stroke from the third China National Stroke Registry. The study outcomes were all-cause mortality, poststroke disability, recurrence of stroke, and cardiocerebral vascular disease (CVD) composite events. Cox proportional hazard models and multivariable logistic regression model were applied to evaluate the effects of eGFRcys and urine albumin-creatinine ratio (ACR) on these outcomes. RESULTS: Both reduced eGFRcys and increased ACR were independently associated with higher incidences of all-cause death and poststroke disability (p < 0.01). Mildly decreased eGFRcys (60-89 mL/min/1.73 m2) is associated with increased risk of all-cause death and poststroke disability in the presence of high-normal ACR (10-29 mg/g). Patients with both eGFRcys <45 mL/min/1.73 m2 and ACR ≥30 mg/g at baseline had a 6.8-fold risk for all-cause mortality and 3.6-fold risk for poststroke disability, compared with patients with eGFRcys of 90-119 mL/min/1.73 m2 and ACR <10 mg/g. In addition, increased ACR was associated with recurrent stroke and CVD composite event, while reduced eGFRcys showed no relationship with these outcomes. CONCLUSIONS: Both decreased eGFRcys and albuminuria are independent risk factors for all-cause death and poststroke disability. Combining the two markers is useful for improving risk stratification even in those without chronic kidney disease.

A prospective study on tryptophan immunoadsorption in AQP4 antibody-positive neuromyelitis optica spectrum disorders.

INTRODUCTION: Neuromyelitis optica spectrum disorders (NMOSD) is a rare inflammatory demyelinating disease of the central nervous system. NMOSD pathogenesis is mainly mediated by antibodies directed against aquaporin4 (AQP4 antibody). Immunoadsorption (IA) could specifically remove pathogenic antibody to alleviate the disease. Until now, prospective studies concerning the efficacy of IA on NMOSD are scarce. This study aims to prospectively evaluate the efficacy and safety of IA in the treatment of NMOSD. PATIENTS AND METHODS: We included patients with AQP4 antibody-positive NMOSD who were hospitalized from September 2019 to September 2020, with no significant improvement in symptoms after 1 week of high-dose intravenous steroid therapy. Tryptophan IA therapy was initiated with five sessions on alternate days. Expanded Disability Status Scale (EDSS), visual acuity, and laboratory values were measured before and after IA, with a follow-up of 6 months. Spinal magnetic resonance imaging (MRI) characteristics were collected. Related side effects were recorded. RESULTS: Seven patients were enrolled in the present study. After five IA, the patients' EDSS decreased from 5.71 ± 2.04 to 4.64 ± 2.29, P = .006. The visual acuity of the three visually impaired patients was improved. AQP4-IgG decreased significantly from 80.00 (interquartile range [IQR], 21.00-80.00) (U/mL) to 9.72 (IQR, 5.21-55.57) (U/mL) (P = .018). MRI of the spinal cord showed the scope of the myelopathy was narrowed and no significant enhancement was observed on postcontrast T1-weighted image at 90 days after treatment. Only one patient had transient hypotension. CONCLUSIONS: Tryptophan IA therapy effectively and safely improved neurological function and visual acuity, and reduced the AQP4 antibody concentration in patients with NMOSD.

Association of acute kidney disease with the prognosis of ischemic stroke in the Third China National Stroke Registry.

BACKGROUND: Acute kidney disease (AKD) evolves a spectrum of acute and subacute kidney disease requiring a global strategy to address. The present study aimed to explore the impact of AKD on the prognosis of ischemic stroke. METHODS: The Third China National Stroke Registry (CNSR-III) was a nationwide registry of ischemic stroke or transient ischemic attack between August 2015 and March 2018. As a subgroup of CNSR-III, the patients who had serum creatinine (sCr) and serum cystatin C (sCysC) centrally tested on admission and at 3-month, and with 1-year follow-up data were enrolled. Modified AKD criteria were applied to identify patients with AKD during the first 3 months post stroke according to the guidelines developed by the Kidney Disease: Improving Global Outcomes in 2012. The primary clinical outcome was 1-year all-cause death, and secondary outcomes were stroke recurrence and post stroke disability. RESULTS: Five thousand sixty-five patients were recruited in the study. AKD was identified in 3.9%, 6.7%, 9.9% and 6.2% of the patients by using sCr, sCr-based estimated glomerular filtration rate (eGFRsCr), sCysC-based eGFR (eGFRsCysC), and combined sCr and sCysC-based eGFR (eGFRsCr+sCysC) criteria, respectively. AKD defined as sCr or eGFRsCr criteria significantly increased the risk of all-cause mortality (adjusted HR 2.67, 95% CI: 1.27-5.61; adjusted HR 2.19, 95% CI: 1.17-4.10) and post stroke disability (adjusted OR 1.60, 95% CI: 1.04-2.44; adjusted OR 1.51, 95% CI: 1.08-2.11). AKD diagnosed by eGFRsCysC or eGFRsCr+sCysC criteria had no significant impact on the risk of all-cause death and post stroke disability. AKD, defined by whichever criteria, was not associated with the risk of stroke recurrence in the adjusted model. CONCLUSIONS: AKD, diagnosed by sCr or eGFRsCr criteria, were independently associated with 1-year all-cause death and post stroke disability in Chinese ischemic stroke patients.

Long-term and short-term duration of thienopyridine therapy after coronary stenting in patients with chronic kidney disease a meta-analysis of literature studies.

The study aimed to compare the efficacy and safety outcome associated with a short and a prolonged duration of thienopyridine therapy in patients with chronic kidney disease (CKD) after coronary stenting. We systematically searched PubMed, EMBASE and the Cochrane Library from their inception to 1 January 2019 for studies comparing short and prolonged thienopyridine therapy in patients with CKD. Ischemic and bleeding events were considered as the clinical endpoints in this analysis. Odds Ratios (OR) with 95% confidence intervals (CIs) were used as estimates of effect size in random-effect models. Seven studies comprising a total of 17,628 CKD patients were included in the evaluation. Prolonged duration of thienopyridine use, when compared to short-term thienopyridine, was associated with reduced risk of all-cause mortality (odds ratio 0.75, 95% confidence interval: 0.70-0.81, P< .001) and stent thrombosis (OR: 0.54, 95% CI 0.32 to 0.89; P< .001), but the odds of myocardial infarction (OR: 0.91, 95% CI: 0.77-1.07; P = .23) and stroke (OR: 0.91, 95% CI 0.73 to 1.13; P = .38) did not differ according to different duration of thienopyridine. As for bleeding events, long-term thienopyridine therapy did not significantly increase the bleeding (OR: 0.95, 95% CI 0.79 to 1.14; P = .58). In these patients with CKD following PCI, prolonged thienopyridine therapy compared with short-term therapy, was associated with reduced all-cause mortality and stent thrombosis, without any significant difference in myocardial infarction, stroke, and bleeding. Thienopyridine prolongation decisions for CKD patients should be individualized after careful consideration of the benefit-risk balance.

High on-clopidogrel platelet reactivity and chronic kidney disease: a meta-analysis of literature studies.

BACKGROUND: The efficacy of clopidogrel is often attenuated in the setting of renal impairment. High on-treatment platelet reactivity (HPR) is an independent correlate of adverse event. Here we performed a quantitative evaluation of the prevalence and impact of HPR in patients with chronic kidney disease (CKD). METHODS: We systematically searched PubMed, EMBASE and the Cochrane Library from their inception to 1 March 2018 for cohort studies assessing the risk ratio (RR) of prevalence of HPR in CKD versus non-CKD patients and association of cardiovascular outcome with HPR in CKD patients treated with clopidogrel. Outcome measures included major adverse cardiac event, myocardial infarction and stent thrombosis. RRs and 95% confidence intervals (CIs) were used as estimates of effect size in random-effect models. RESULTS: Ten studies comprising a total of 3028 CKD patients and 11138 non-CKD patients were included in the evaluation. Compared to patients with normal renal function, patients with CKD had a significantly higher risk of HPR (OR: 1.34, 95% CI: 1.23-1.46). In CKD patients, HPR was associated with increased risk of MACE (RR 2.99, 95% CI 1.19 to 7.53; p < 0.00001), myocardial infarction (RR1.74, 95% CI 1.29 to 2.33; p = 0.0002), and stent thrombosis (RR 2.98, 95% CI 1.42 to 6.26; p = 0.004). CONCLUSIONS: Based on pooled analysis, CKD appeared correlated with HPR and this association had prognostic significance. Further studies with standardised laboratory methods and specifically defined protocols are required to validate the clinical relevance of such response variability to clopidogrel in CKD patients.

Astragaloside IV protects against diabetic nephropathy via activating eNOS in streptozotocin diabetes-induced rats.

BACKGROUND: Astragaloside IV (AS-IV) was reported to play a role in improving diabetic nephropathy (DN), however, the underlying mechanisms still remain unclear. The aim of the present study is to investigate whether AS-IV ameliorates DN via the regulation of endothelial nitric oxide synthase (eNOS). METHODS: DN model was induced in Sprague-Dawley (SD) male rats by intraperitoneal injection of 65 mg/kg streptozotocin (STZ). Rats in the AS-IV treatment group were orally gavaged with 5 mg/kg/day or 10 mg/kg/day AS-IV for eight consecutive weeks. Body weight, blood glucose, blood urea nitrogen (BUN), Serum creatinine (Scr), proteinuria and Glycosylated hemoglobin (HbA1c) levels were measured. Hematoxylin-Eosin (HE) and Periodic Acid-Schiff (PAS) staining were used to detect the renal pathology. The apoptosis status of glomerular cells was measured by TUNEL assay. The phosphorylation and acetylation of eNOS were detected by western blot. The effects of AS-IV on high-glucose (HG)-induced apoptosis and eNOS activity were also investigated in human renal glomerular endothelial cells (HRGECs) in vitro. RESULTS: Treatment with AS-IV apparently reduced DN symptoms in diabetic rats, as evidenced by reduced BUN, Scr, proteinuria, HbA1c levels and expanding mesangial matrix. AS-IV treatment also promoted the synthesis of nitric oxide (NO) in serum and renal tissues and ameliorated the phosphorylation of eNOS at Ser 1177 with decreased eNOS acetylation. Moreover, HG-induced dysfunction of HRGECs including increased cell permeability and apoptosis, impaired eNOS phosphorylation at Ser 1177, and decreased NO production, were all reversed by AS-IV treatment. CONCLUSIONS: These novel findings suggest that AS-IV ameliorates functional abnormalities of DN through inhibiting acetylation of eNOS and activating its phosphorylation at Ser 1177. AS-IV could be served as a potential therapeutic drug for DN.

Impact of CYP2C19 polymorphism in prognosis of minor stroke or TIA patients with declined eGFR on dual antiplatelet therapy: CHANCE substudy.

Clopidogrel resistance is prevalent in chronic kidney disease (CKD) patients. Genetic polymorphism is considered to be the most important factor that influences clopidogrel resistance. Limited data exist as to the role of pharmacogenetics in prognosis of stroke patients with impaired renal function on clopidogrel. We sought to explore whether decreased kidney function alters the association between CYP2C19 genetic variants and clinical outcome in patients with minor stroke or transient ischemic attack (TIA) receiving clopidogrel therapy. A total of 1476 participants on clopidogrel-aspirin treatment with genotyping results in High-Risk Patients with Acute Nondisabling Cerebrovascular Events (CHANCE) trial were categorized by quintiles of renal function estimated by estimated glomerular filtration rate (eGFR), and were stratified according to the possession of CYP2C19 loss-of-function (LOF) alleles: carriers and non-carriers. Patients were followed up and clinical outcomes were evaluated. The primary efficacy outcome was new stroke. The secondary efficacy outcome was combined vascular events (ischemic stroke, hemorrhagic stroke, myocardial infarction, or vascular death). The safety outcome was bleeding event. CYP2C19 LOF carriers had higher odds of new stroke than non-carriers (10.4% versus 2.4 %, hazard ratio [HR], 5.30; 95% CI, 1.51-18.3, P = 0.009) in the lowest quintile of renal function group with eGFR < 75 ml/min/1.73 m2 but not in the other four higher quintiles. Similar results were observed for the ischemic stroke and combined vascular events. There was no significant difference in the individual outcomes of bleeding in carriers compared with non-carriers in any renal function group. Among patients with minor stroke or TIA taking clopidogrel-aspirin treatment, CYP2C19 LOF carrier state was associated with higher risk of new stroke in those with eGFR < 75 ml/min/1.73 m2. This observation supports that the evaluation of CYP2C19 LOF carrier state may be useful for identification of the patients with kidney impairment with greater likelihood of having worse outcomes.

Insulin Resistance Index from Oral Glucose Tolerance Test Predicts Ischemic Stroke Outcomes in Non-Diabetic Patients with Different Estimated Glomerular Filtration Rate Strata.

BACKGROUND: Insulin resistance is associated with cardiovascular morbidity and mortality in the general population. However, the relationship between insulin resistance and health outcomes is controversial in patients with impaired renal function. Our study aimed to investigate the association between insulin resistance and prognosis in a cohort of non-diabetic stroke patients with different estimated glomerular filtration rate (eGFR) strata. METHODS: Data were derived from Abnormal Glucose Regulation in Patients with Acute Stroke across China (ACROSS-China) registry. Ischemic stroke patients without history of diabetes were included. Fasting and oral glucose tolerance test (OGTT)-derived measures of insulin resistance were calculated along with homeostasis model assessment of insulin resistance (HOMA-IR) and composite insulin sensitivity index (ISI). Insulin resistance was defined by the highest HOMA-IR quartile (Q4) and the lowest composite ISI quartile (Q1). RESULTS: Among 1,196 patients, HOMA-IR Q4 (insulin resistance) vs. Q1-3 was associated with increased 1-year mortality (adjusted hazards ratio [HR] 1.83, 95% CI 1.07-3.13) and poor functional outcome (adjusted OR 1.97, 95% CI 1.32-2.95) only in participants with an eGFR ≥90 mL/min/1.73 m2. By comparison, composite ISI Q1 (insulin resistance) vs. Q2-4 was associated with higher risks of 1-year mortality (adjusted HR 3.64, 0.90-14.78; 2.50, 1.19-5.26; and 1.99, 1.17-3.39, respectively) and poor functional outcome (adjusted OR 3.62, 1.08-12.19; 1.51, 0.85-2.70; and 2.25, 1.42-3.57, respectively) in all 3 subgroups with eGFR < 60, 60-89, and ≥90 mL/min/1.73 m2. CONCLUSIONS: An OGTT-derived estimate of insulin resistance with the composite ISI, but not HOMA-IR, was independently associated with increased risks of 1-year mortality and poor functional outcome in non-diabetic ischemic stroke patients with different eGFR strata.