A modified renal risk score for Chinese patients with antineutrophil cytoplasmic antibody-associated vasculitis.

BACKGROUND: The renal risk score (RRS) is a useful tool to predict end-stage renal disease (ESRD) in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). The current study aimed to validate the predictive performance of RRS and to further modify this model in Chinese AAV patients. METHODS: Two hundred and seventy-two patients diagnosed with AAV confirmed by renal biopsies were retrospectively enrolled from a single center. The RRS was calculated based on 3 categorical variables, i.e., the proportion of normal glomeruli, the proportion of interstitial fibrosis and tubular atrophy (IF/TA), and eGFR at biopsy, classifying these patients into low-, medium-, and high-risk groups. In addition, a modified model was developed based on the RRS and was further validated in another independent cohort of 117 AAV patients. The predictive performance of each model was evaluated according to discrimination and calibration. RESULTS: Patients were classified by the RRS into low- (26.5%), medium- (46.7%), and high-risk (26.8%) groups, with 120-month renal survival rates of 93.3%, 57.2%, and 18.4%, respectively (P < 0.001). The RRS showed good discrimination but less satisfactory calibration. Therefore, a modified model with improved discrimination and calibration was developed in Chinese AAV patients, with eGFR, proportion of normal glomeruli (both as continuous variables), and IF/TA (< 25%, 25-50%, > 50%) included. Internal and external validation of the modified model were performed. Finally, an online risk prediction tool was developed based on the modified model. CONCLUSIONS: The RRS was an independent predictor of ESRD of AAV patients. The modified model could predict the probability of ESRD for AAV patients with improved performance in Chinese AAV patients.

High-Quality Axions in a Class of Chiral U(1) Gauge Theories.

We show that there are many candidates for the quintessence and/or the QCD axions in a class of chiral U(1) gauge theories. Their qualities are high enough to serve as the dark energy and/or to solve the strong CP problem. Interestingly, the high quality of axion is guaranteed by the gauged U(1) and Z_{2N} symmetries and hence free from the nonperturbative quantum gravity corrections. Furthermore, our mechanism can be easily applied to the Fuzzy dark matter axion scenarios.

P38-DAPK1 axis regulated LC3-associated phagocytosis (LAP) of microglia in an in vitro subarachnoid hemorrhage model.

BACKGROUND: The phagocytosis and homeostasis of microglia play an important role in promoting blood clearance and improving prognosis after subarachnoid hemorrhage (SAH). LC3-assocaited phagocytosis (LAP) contributes to the microglial phagocytosis and homeostasis via autophagy-related components. With RNA-seq sequencing, we found potential signal pathways and genes which were important for the LAP of microglia. METHODS: We used an in vitro model of oxyhemoglobin exposure as SAH model in the study. RNA-seq sequencing was performed to seek critical signal pathways and genes in regulating LAP. Bioparticles were used to access the phagocytic ability of microglia. Western blot (WB), immunoprecipitation, quantitative polymerase chain reaction (qPCR) and immunofluorescence were performed to detect the expression change of LAP-related components and investigate the potential mechanisms. RESULTS: In vitro SAH model, there were increased inflammation and decreased phagocytosis in microglia. At the same time, we found that the LAP of microglia was inhibited in all stages. RNA-seq sequencing revealed the importance of P38 MAPK signal pathway and DAPK1 in regulating microglial LAP. P38 was found to regulate the expression of DAPK1, and P38-DAPK1 axis was identified to regulate the LAP and homeostasis of microglia after SAH. Finally, we found that P38-DAPK1 axis regulated expression of BECN1, which indicated the potential mechanism of P38-DAPK1 axis regulating microglial LAP. CONCLUSION: P38-DAPK1 axis regulated the LAP of microglia via BECN1, affecting the phagocytosis and homeostasis of microglia in vitro SAH model. Video Abstract.

Direct Detection Constraints on Blazar-Boosted Dark Matter.

We explore the possibility that relativistic protons in the extremely powerful jets of blazars may boost via elastic collisions the dark matter particles in the surroundings of the source to high energies. We concentrate on two sample blazars, TXS 0506+056, towards which IceCube recently reported evidence for a high-energy neutrino flux, and BL Lacertae, a representative nearby blazar. We find that the dark matter flux at Earth induced by these sources may be sizable, larger than the flux associated with the analogous process of dark matter boosted by galactic cosmic rays, and relevant to access direct detection for dark matter particle masses lighter than 1 GeV. From the null detection of a signal by XENON1T, MiniBooNE, and Borexino, we derive limits on dark matter-nucleus spin-independent and spin-dependent cross sections which, depending on the modelization of the source, improve on other currently available bounds for light dark matter candidates of 1 up to 5 orders of magnitude.

What is the impact of knee morphology on posterior cruciate ligament avulsion fracture in men and women: a case control study.

BACKGROUND: Several studies on the relationship between morphological parameters and traumatic diseases of the knee have already been conducted. However, few studies focused on the association between knee morphology and posterior cruciate ligament (PCL) avulsion fracture in adults. The objective of this study was to evaluate the impact of knee morphology on PCL avulsion fracture. METHODS: 76 patients (comprised 40 men and 36 women) with PCL avulsion fracture and 76 age- and sex-matched controls without PCL avulsion fracture were studied from 2012 to 2020. MRI measurements of the knee were acquired in the sagittal, coronal, and axial planes. The assessed measurements including intercondylar notch width index, coronal tibial slope, and medial/lateral posterior tibial slopes were compared between men and women, and between case and control groups respectively using independent sample t-tests. In addition, binary logistic regression analyses were used to identify independent risk factors of PCL avulsion fracture. RESULTS: Except notch width index (coronal) (p = 0.003) in the case groups, there was no statistical difference in the assessed measurements including notch width index (axial), coronal tibial slope, medial posterior tibial slope, and lateral posterior tibial slope between men and women in the case and control groups (p > 0.05). When female patients were analyzed, the notch width index (coronal) was significantly smaller (p = 0.0004), the medial posterior tibial slope (p = 0.018) and the lateral posterior tibial slope (p = 0.033) were significantly higher in the case group. The binary logistic regression analysis showed that the notch width index (coronal) (B = -0.347, OR = 0.707, p = 0.003) was found to be an independent factor of PCL avulsion fracture. However, none of the assessed measurements was found to have a statistical difference between the case and control groups in men (p > 0.05). CONCLUSIONS: Notch width index (coronal), medial posterior tibial slope, and lateral posterior tibial slope were found to affect PCL avulsion fracture in women, but no such measurements affected the PCL avulsion fracture in men. Furthermore, a smaller notch width index (coronal) in women was found to be a risk factor in PCL avulsion fracture.

Unstably controlled systolic blood pressure trajectories are associated with markers for kidney damage in prediabetic population: results from the INDEED cohort study.

BACKGROUND: The association between blood pressure change and kidney damage in patients with abnormal blood glucose remains unclear. The current study aimed to identify systolic blood pressure (SBP) trajectories among the prediabetic population and to determine their association with kidney damage after a long-term follow-up. METHODS: The incidence, development, and prognosis of diabetic kidney disease (INDEED) study is nested in the Kailuan cohort study with a focus on population with diabetes and prediabetes. We screened out people with prediabetes in 2006 and with more than three SBP records from 2006 to 2014 biennially. We used the latent mixture modeling to fit five groups of trajectories of SBP. In 2016, estimated glomerular filtration rate (eGFR), urinary albumin creatinine ratio (uACR), and urinary α1-microglobulin (α1MG), transferrin and α1-acid glycoprotein were measured, and the association between SBP trajectories and these markers was analyzed by linear regression and logistic regression models. RESULTS: Totally, 1451 participants with prediabetes and without kidney damage were identified in 2006. Five heterogeneous SBP trajectories were detected based on the longitudinal data from 2006 to 2014, as low-stable group (n = 323), moderate-stable group (n = 726), moderate-increasing group (n = 176), moderate-decreasing group (n = 181), and high-stable group (n = 45). Linear regression analysis showed that the moderate and high SBP groups had lower eGFR, higher uACR, higher urinary α1MG, higher transferrin, and higher α1-acid glycoprotein than the low-stable group. Multivariable analysis attenuated the association but did not change the statistical significance. CONCLUSIONS: Prediabetic patients with persistent high-level SBP trajectory or gradually increased SBP trajectory had severer kidney damage during follow-up.

Persistent Hematuria and Kidney Disease Progression in IgA Nephropathy: A Cohort Study.

RATIONALE & OBJECTIVE: Hematuria is the most typical presentation of immunoglobulin A nephropathy (IgAN); however, its role in disease progression is still controversial. This study aimed to evaluate the association of hematuria and progression of IgAN. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: A cohort of 1,333 patients with IgAN treated at a Chinese referral hospital with a median follow-up of 45 months. PREDICTORS: Microhematuria was evaluated in fresh urine using a fully automated urine particle analyzer (automated method) and urine sediment examination by a skilled examiner (manual method). Hematuria was characterized as a time-varying attribute; namely, average hematuria level was calculated for every 6-month period for each patient during follow-up. Remission was defined as average red blood cell count ≤5/high-power field (manual method) or ≤28 red blood cells/µL (automated method) during the first 6 months of follow-up. OUTCOMES: Composite event of 50% decline in estimated glomerular filtration rate or development of kidney failure. ANALYTICAL APPROACH: Multivariable cause-specific hazards models to analyze the relationship between hematuria and the composite kidney disease progression event. RESULTS: Time-varying hematuria during follow-up was an independent risk factor for the composite kidney disease progression event (HR, 1.46; 95% CI, 1.13-1.87; P = 0.003). Hematuria remission during the 6 months after diagnosis was associated with a significantly lower rate of the composite kidney disease progression event (HR, 0.41; 95% CI, 0.28-0.61; P < 0.001). A significant interaction was detected between remission of proteinuria and remission of hematuria during the first 6 months (P < 0.001). The association between remission of hematuria and kidney disease progression was detectable (HR, 0.46; 95% CI, 0.32-0.68) within the subpopulation with persistent proteinuria (protein excretion > 1.0 g/d during the first 6 months), but not among patients whose proteinuria had remitted (HR, 0.64; 95% CI, 0.31-1.29; P = 0.2). The 2 techniques for hematuria evaluation were strongly and significantly linearly correlated (r = 0.948; P < 0.001), and results using these 2 methods were consistent. LIMITATIONS: A single-center retrospective study. Proportional hazards regression incorporating time-varying covariates may create time-varying confounding. The predictive value of reductions in hematuria was not directly evaluated. CONCLUSIONS: Level of hematuria was independently associated with kidney disease progression, whereas hematuria remission was associated with improved kidney outcomes in IgAN among patients with persistent proteinuria. Additionally, to monitor IgAN progression, automated methods to evaluate hematuria hold promise as a replacement for manual evaluation of urinary sediment.

Soluble urokinase-type plasminogen activator receptor and incident end-stage renal disease in Chinese patients with chronic kidney disease.

BACKGROUND: Soluble urokinase-type plasminogen activator receptor (suPAR), a marker of immune activation, was shown to be associated with outcomes and kidney disease among various patient populations. The prognostic role of circulating suPAR levels in patients with chronic kidney disease (CKD) needs to be investigated in a cohort with large sample size of renal diseases. METHODS: We measured serum suPAR concentration in 2391 CKD patients in the multicenter Chinese Cohort Study of Chronic Kidney Disease, and investigated the association of serum suPAR with the prespecified endpoint event, end-stage renal disease (ESRD), using Cox proportional hazards regression model. RESULTS: Altogether, 407 ESRD events occurred during the median follow-up of 54.8 (interquartile range: 47.5-62.2) months. The higher levels of serum suPAR were independently associated with increased risk of incident ESRD after adjusting for potential confounders including the baseline estimated glomerular filtration rate categories, with the hazard ratios (HRs) of 1.53 [95% confidence intervals (CIs) 1.10-2.12] for the top tertile (≥3904 pg/mL) compared with the bottom tertile (<2532 pg/mL). When stratified by the etiologies of CKD, among patients with glomerulonephritis (GN), serum suPAR levels were also independently associated with the higher risk of ESRD, with an HR of 1.61 (95% CI 1.03-2.53) in the top tertile compared with the bottom tertile. CONCLUSIONS: Circulating suPAR level was independently associated with an increased risk of progression to ESRD in Chinese CKD patients, especially in those with an etiology of GN.

New 8-Hydroxybriaranes from the Gorgonian Coral Junceella fragilis (Ellisellidae).

Three new 8-hydroxybriaranes-fragilides R-T (1-3) were obtained from a sea whip gorgonian coral Junceella fragilis. The structures of briaranes 1-3 were elucidated by using spectroscopic methods, including 1D (1H and 13C NMR), 2D (COSY, HSQC, HMBC, and NOESY experiments) NMR studies, and (+)-HRESIMS. Fragilides S and T (2 and 3) are the only briaranes known to possess 8α-hydroxy and 17ß-methyl groups, respectively. Briarane 2 exerted an inhibition effect on iNOS release from RAW264.7; a macrophage cell line that originated from a mouse monocyte macrophage, stimulated with lipopolysaccharides.

Cognitive Changes in Peritoneal Dialysis Patients: A Multicenter Prospective Cohort Study.

RATIONALE & OBJECTIVE: Cognitive impairment is an independent predictor of technique failure and mortality in patients on peritoneal dialysis (PD) therapy. We investigated changes in cognitive function and factors associated with it in this population. STUDY DESIGN: Multicenter prospective cohort study. SETTING & PARTICIPANTS: 458 PD patients were enrolled and followed up for 2 years. PREDICTORS: Global and specific domains of cognitive function were measured at baseline and after 2 years. The Modified Mini-Mental State Examination (3MS) was used for assessment of global cognitive function; Trail-Making Tests A and B, for executive function; and subtests of the Battery for the Assessment of Neuropsychological Status, for immediate and delayed memory, visuospatial skill, and language ability. OUTCOMES: The primary outcome was change in cognitive function. Secondary outcomes included all-cause mortality, cardiovascular mortality, hospitalization, and transition to hemodialysis therapy. ANALYTICAL APPROACH: Multivariable linear regression models. RESULTS: The prevalence of cognitive impairment increased from 19.8% to 23.9%. 3MS scores significantly decreased (84.8 to 83.1), although executive function, immediate memory, and visuospatial skill improved over time. Delayed memory capacity and language ability were unchanged. Lower serum albumin level was associated with deteriorated delayed memory, visuospatial skill, and language ability, as well as with the decline in general cognitive function (ß values of 0.64, 0.90, 0.80, and 0.44, respectively). Advanced age, lower education, and depression were also correlated with deterioration in general and specific cognitive function. After multivariable adjustment, both global and specific cognitive impairment at baseline were associated with a greater rate of hospitalization, and memory dysfunction was associated with a lower dialysis modality survival rate. LIMITATIONS: A relatively short observation period, small number of deaths, and potential selection bias due to patients unavailable for the second assessment. CONCLUSIONS: In a PD population, global cognitive function declined over 2 years, though some specific cognitive domains improved. Besides well-recognized factors, hypoalbuminemia and depression were also risk factors for cognitive impairment.

Effects of Hydroxychloroquine on Proteinuria in Immunoglobulin A Nephropathy.

BACKGROUND: Hydroxychloroquine (HCQ) is a well-known immunomodulator that is useful as in the treatment for lupus because of its inhibitory effect on toll-like receptors and cytokines, which are speculated to play a role in the pathogenesis of Immunoglobulin A (IgA) nephropathy (IgAN). However, there was only one study that investigated the effect of HCQ on proteinuria in patients with IgAN. METHODS: Ninety patients with IgAN who received HCQ in addition to optimized dosage of renin-angiotensin-aldosterone system inhibitors (RAASi) were recruited for this study, and 90 matched historical controls who received RAASi alone were selected from our registry by the propensity score matching method. Their clinical data were compared at baseline and during follow-up till the termination of HCQ or addition of immunosuppressive agents. RESULTS: The median baseline proteinuria level of the 90 patients who received HCQ was comparable with the RAASi-alone group (1.5 [1.2, 2.1] vs. 1.5 [1.2, 1.9] g/day, p = 0.74). At 6 months post-study initiation, the median proteinuria level in the HCQ group was lower than that in the RAASi-alone group (0.8 [0.7, 1.2] vs. 1.2 [0.8, 1.8] g/day, p = 0.02). The percentage by which proteinuria was reduced in the HCQ group was significantly higher than that in the RAASi-alone group (-43% [-57, -12] vs. -19% [-46, 17], p = 0.01). No serious adverse effects were documented during treatment with HCQ. CONCLUSION: The addition of HCQ to RAASi resulted in a significant and safe reduction in proteinuria in patients with IgAN.

Prevalence and risk factors for cardiovascular disease among chronic kidney disease patients: results from the Chinese cohort study of chronic kidney disease (C-STRIDE).

BACKGROUND: Although a high incidence of cardiovascular disease (CVD) is observed among chronic kidney disease (CKD) patients in developed countries, limited information is available about CVD prevalence and risk factors in the Chinese CKD population. The Chinese Cohort of Chronic Kidney Disease (C-STRIDE) was established to investigate the prevalence and risk factors of CVD among Chinese CKD patients. METHODS: Participants with stage 1-4 CKD (18-74 years of age) were recruited at 39 clinical centers located in 28 cities from 22 provinces of China. At entry, the socio-demographic status, medical history, anthropometric measurements and lifestyle behaviors were documented, and blood and urine samples were collected. Estimated glomerular filtration rate (eGFR) was calculated by the CKD-EPI creatinine equation. CVD diagnosis was based on patient self-report and review of medical records by trained staff. A multivariable logistic regression model was used to estimate the association between risk factors and CVD. RESULTS: Three thousand four hundred fifty-nine Chinese patients with pre-stage 5 CKD were enrolled, and 3168 finished all required examinations and were included in the study. In total, 40.8% of the cohort was female, with a mean age of 48.21 ± 13.70 years. The prevalence of CVD was 9.8%, and in 69.1% of the CVD cases cerebrovascular disease was observed. Multivariable analysis showed that increasing age, lower eGFR, presence of hypertension, abdominal aorta calcification and diabetes were associated with comorbid CVD among CKD patients. The odds ratios and 95% confidence intervals for these risk factors were 3.78 (2.55-5.59) for age 45-64 years and 6.07 (3.89-9.47) for age ≥65 years compared with age <45 years; 2.07 (1.28-3.34) for CKD stage 3a, 1.66 (1.00-2.62) for stage 3b, and 2.74 (1.72-4.36) for stage 4 compared with stages 1 and 2; 2.57 (1.50-4.41) for hypertension, 1.82 (1.23-2.70) for abdominal aorta calcification, and 1.70 (1.30-2.23) for diabetes, respectively. CONCLUSIONS: We reported the CVD prevalence among a CKD patient cohort and found age, hypertension, diabetes, abdominal aorta calcification and lower eGFR were independently associated with higher CVD prevalence. Prospective follow-up and longitudinal evaluations of CVD risk among CKD patients are warranted.

[Causes of orchiectomy: An analysis of 291 cases].

OBJECTIVE: To study the causes of orchiectomy in different age groups. METHODS: We retrospectively reviewed the clinical data about 291 cases of orchiectomy performed between March 1993 and October 2014 and analyzed the causes of surgery and their distribution in different age groups. RESULTS: The main causes of orchiectomy were testicular torsion (45.8%), cryptorchidism (32.5%) and testicular tumor (16.9%) in the patients aged 0-25 years, testicular tumor (42.4%), cryptorchidism (25.9%) and tuberculosis (10.6%) in those aged 26-50 years. Prostate cancer was the leading cause in those aged 51-75 years (77.6%) or older (84.0%)), and testicular tumor was another cause in the 51-75 years old men (10.2%). Prostate cancer, testicular tumor, cryptorchidism, and testicular torsion were the first four causes of orchiectomy between 1993 and 2009. From 2010 to 2014, however, testicular tumor rose to the top while prostate cancer dropped to the fourth place. CONCLUSION: The causes of orchiectomy vary in different age groups. The proportion of castration for prostate cancer patients significantly reduced in the past five years, which might be attributed to the improvement of comprehensive health care service.

The impact of lipid-metabolizing genetic polymorphisms on body mass index and their interactions with soybean food intake: a study in a Chinese population.

OBJECTIVE: To evaluate the association of known polymorphisms in the lipid metabolic pathway with body mass index (BMI), and estimate their interactions with soybean food intake. METHODS: A community-based cross-sectional survey was conducted in a Chinese Han population. BMI, soybean food intake, and single nucleotide polymorphisms of rs599839, rs3846662, rs3846663, rs12916, rs174547, rs174570, rs4938303, and rs1558861 were measured in 944 subjects. A multivariate logistic regression was used to analyze the association of the studied polymorphisms with BMIs. The expectation-maximization algorithm was employed to evaluate the extent of linkage disequilibrium between pairwise polymorphisms. The gene-environment interaction was assessed in the general multifactor dimensionality reduction model. RESULTS: The polymorphisms of rs3846662 and rs3846663 were associated with 10% highest BMIs when comparing to the 10% lowest values both in individuals and haplotype-based association tests. Although no statistically significant gene-environment interactions were found, people with the haplotype composed of C allele in rs3846662 and T allele in rs3846663 and low frequency of soybean intake had significantly higher risk to overweight and obesity as compared with those with the haplotype consisting of T allele in rs3846662 and C allele in rs3846663 and highly frequent soybean food intake, with an odds ratio of 1.64 (95% confidence interval: 1.15-2.34, P<0.01) after adjusting for the common confounders. CONCLUSION: Our study has suggested that rs3846662 and rs3846663 may be the potential candidate polymorphisms for obesity, and their effect on the pathogenesis could be mediated by the frequency of soybean food intake.

Evaluation of the Risk Prediction Models in Predicting Kidney Outcomes in Antiglomerular Basement Membrane Disease.

Introduction: A previous study showed that the renal risk score (RRS) was transferrable to antiglomerular basement membrane (anti-GBM) disease and proposed a risk stratification according to the need of renal replacement therapy (RRT) and the percentage of normal glomeruli (N). Herein, we analyzed the risk factors associated with kidney outcomes in patients with biopsy-proven anti-GBM disease and evaluated these 2 prognosis systems. Methods: A total of 120 patients with biopsy-proven anti-GBM disease with complete clinicopathologic and outcome data were analyzed. Results: The median time to kidney biopsy was 41 days (interquartile range [IQR]: 22-63 days). RRT and N were the only independent predictors of end-stage kidney disease (ESKD). Patients with N ≥10% were more likely to achieve ESKD-free outcomes, even in the subcohort of patients who underwent posttreatment biopsies (P < 0.001). N and serum creatinine at presentation (cut-off values 750 µmol/l and 1300 µmol/l) were 2 independent factors for predicting kidney recovery. The RRS and the risk stratification tool exhibited predictive value for ESKD and could be transferred to patients with kidney biopsy following treatment (Harrell's C statistic [C] = 0.738 and C = 0.817, respectively). However, a cross-over of outcomes among groups was observed in the risk stratification tool in long-term follow-up, when patients with RRT and N ≥10% achieved better kidney outcomes than those without RRT but N <10%. Conclusion: Normal glomeruli percentage, even posttreatment, was a strong indicator for kidney outcomes, especially on long-term prognosis. Serum creatinine is a predictor for kidney recovery, independent of biopsy findings. The risk stratification tool for kidney survival was transferrable to patients with anti-GBM disease with biopsy following treatment in our cohort; however, this needs further validations for long-term outcomes.

[Association study between PDE4D gene polymorphism and ischemic stroke].

OBJECTIVE: To investigate the linkage and association between rs966221 (SNP 83) in PDE4D gene with stroke and related traits in ischemic stroke families. METHODS: Ischemic stroke families including ischemic stroke patients and their siblings and/or parents were recruited. Generalized estimating equation (GEE) was used to adjust for with-in family correlations and other potential confounding factors. Non-parameter linkage analysis and family based association test (FBAT) were applied to explore the relationship between rs966221 polymorphism and ischemic stroke together with its related traits. RESULTS: In the study 276 ischemic stroke families with totally 776 participants were enrolled. Apolipoprotein B (apoB), carotid intima media thickness (cIMT), high-density lipoprotein cholesterol and blood pressure were associated with ischemic stroke. In family based association test, after being adjusted for related chronic diseases, rs966221 C allele was found to be associated with cIMT in the dominant model (P=0.019), TT genotype (P=0.019) and CT genotype (P=0.007) were associated with cIMT significantly. After being adjusted for potential confounding factors, evidence of linkage was observed for rs966221 with apoB (P<0.001), high-sensitivity C-reactive protein (P=0.003) and systolic blood pressure (P=0.036). CONCLUSION: Abnormal serum lipid, blood pressure and increasing cIMT were associated with ischemic stroke, and linkage was observed for with apoB, high-sensitivity C-reactive protein, and systolic blood pressure; rs966221 C allele was probably associated with cIMT.

Clinicopathological Features of Kidney Injury Related to Immune Checkpoint Inhibitors: A Systematic Review.

(1) Background: Despite increasing recognition of immune checkpoint inhibitors (ICIs) and kidney immune-related adverse events (IRAEs), no large-sample studies have assessed the pathological characteristics and outcomes of biopsy-proven kidney IRAEs. (2) Methods: We comprehensively searched PubMed, Embase, Web of Science, and Cochrane for case reports, case series, and cohort studies for patients with biopsy-proven kidney IRAEs. All data were used to describe pathological characteristics and outcomes, and individual-level data from case reports and case series were pooled to analyze risk factors associated with different pathologies and prognoses. (3) Results: In total, 384 patients from 127 studies were enrolled. Most patients were treated with PD-1/PD-L1 inhibitors (76%), and 95% presented with acute kidney disease (AKD). Acute tubulointerstitial nephritis/acute interstitial nephritis (ATIN/AIN) was the most common pathologic type (72%). Most patients (89%) received steroid therapy, and 14% (42/292) required RRT. Among AKD patients, 17% (48/287) had no kidney recovery. Analyses of pooled individual-level data from 221 patients revealed that male sex, older age, and proton pump inhibitor (PPI) exposure were associated with ICI-associated ATIN/AIN. Patients with glomerular injury had an increased risk of tumor progression (OR 2.975; 95% CI, 1.176, 7.527; p = 0.021), and ATIN/AIN posed a decreased risk of death (OR 0.164; 95% CI, 0.057, 0.473; p = 0.001). (4) Conclusions: We provide the first systematic review of biopsy-proven ICI-kidney IRAEs of interest to clinicians. Oncologists and nephrologists should consider obtaining a kidney biopsy when clinically indicated.

Predictive Value of Leucine-Rich Alpha-2 Glycoprotein 1 in Cerebrospinal Fluid for the Prognosis of Aneurysmal Subarachnoid Hemorrhage: A Prospective Study.

OBJECTIVE: To determine whether leucine-rich alpha-2 glycoprotein 1 (LRG1) is a potential prognostic and severity biomarker in patients with aneurysmal subarachnoid hemorrhage (aSAH). METHODS: This observational and prospective study included 44 patients with aSAH from Nanjing Drum Tower Hospital from June to December 2020. Concentrations of LRG1 in the cerebrospinal fluid (CSF) were determined by enzyme-linked immunosorbent assay within 24 hours after aSAH. We further determined the relationship of CSF LRG1 levels with disease severity and prognosis 3 months after aSAH. RESULTS: Higher CSF LRG1 levels were associated with a higher Hunt-Hess grade (P < 0.05). Using univariate analysis, poor outcomes at 3 months were associated with higher World Federation of Neurological Surgeons scale grade, higher Hunt-Hess grade, higher CSF LRG1 levels, and higher Fisher grade. Logistic regression analysis revealed a significant impact of LRG1 on poor outcomes as well as after adjustment for confounding factors. CONCLUSIONS: These findings suggest an increase in CSF LRG1 levels in patients with aSAH, which may serve as a potential biomarker of unfavorable prognosis and disease severity.

Heat exposure and hospitalizations for chronic kidney disease in China: a nationwide time series study in 261 major Chinese cities.

BACKGROUND: Climate change profoundly shapes the population health at the global scale. However, there was still insufficient and inconsistent evidence for the association between heat exposure and chronic kidney disease (CKD). METHODS: In the present study, we studied the association of heat exposure with hospitalizations for cause-specific CKD using a national inpatient database in China during the study period of hot season from 2015 to 2018. Standard time-series regression models and random-effects meta-analysis were developed to estimate the city-specific and national averaged associations at a 7 lag-day span, respectively. RESULTS: A total of 768,129 hospitalizations for CKD was recorded during the study period. The results showed that higher temperature was associated with elevated risk of hospitalizations for CKD, especially in sub-tropical cities. With a 1 °C increase in daily mean temperature, the cumulative relative risks (RR) over lag 0-7 d were 1.008 [95% confidence interval (CI) 1.003-1.012] for nationwide. The attributable fraction of CKD hospitalizations due to high temperatures was 5.50%. Stronger associations were observed among younger patients and those with obstructive nephropathy. Our study also found that exposure to heatwaves was associated with added risk of hospitalizations for CKD compared to non-heatwave days (RR = 1.116, 95% CI 1.069-1.166) above the effect of daily mean temperature. CONCLUSIONS: Short-term heat exposure may increase the risk of hospitalization for CKD. Our findings provide insights into the health effects of climate change and suggest the necessity of guided protection strategies against the adverse effects of high temperatures.

Association between alkaline phosphatase/albumin ratio and the prognosis in patients with chronic kidney disease stages 1-4: results from a C-STRIDE prospective cohort study.

Background: The alkaline phosphatase-to-albumin ratio (APAR) has been demonstrated to be a promising non-invasive biomarker for predicting prognosis in certain diseases. However, the relationship between APAR and prognosis in non-dialysis chronic kidney disease (CKD) patients remains unclear. This study aims to identify the association between APAR and prognosis among CKD stages 1-4 in China. Methods: Patients with CKD stages 1-4 were consecutively recruited from 39 clinical centers in China from 2011 to 2016. New occurrences of end-stage kidney disease (ESKD), major adverse cardiovascular and cerebrovascular events, and all-cause deaths were the outcome events of this study. Subdistribution hazard competing risk and Cox proportional hazards regression models were adopted. Results: A total of 2,180 participants with baseline APAR values were included in the analysis. In the primary adjusted analyses, higher APAR level [per 1-standard deviation (SD) increase in natural logarithm transformed (ln-transformed) APAR] was associated with 33.5% higher risk for all-cause deaths [adjusted hazard ratio (HR) 1.335, 95% confidence interval (CI) 1.068-1.670]. In addition, there was evidence for effect modification of the association between APAR and ESKD by baseline estimated glomerular filtration rate (eGFR) (P interaction < 0.001). A higher APAR level (per 1-SD increase in ln-transformed APAR) was associated with a greater risk of ESKD among participants with eGFR ≥ 60 ml/min/1.73 m2 (adjusted SHR 1.880, 95% CI 1.260-2.810) but not in eGFR < 60 ml/min/1.73 m2. Conclusion: Higher APAR levels in patients with CKD stages 1-4 seemed to be associated with an increased risk of all-cause death. Thus, APAR appears to be used in risk assessment for all-cause death among patients with CKD stages 1-4.