Intradialytic systolic blood pressure variation can predict long-term mortality in patients on maintenance hemodialysis

International Urology and Nephrology - It is unclear which time-points of intradialytic blood pressure (BP) best predict prognosis. Thus, it is important to assess the association between different...     

Novel predictive biomarkers for acute injury superimposed on chronic kidney disease

Introduction and objectivesChronic kidney disease (CKD) is a risk factor for the development of acute kidney injury (AKI). Recent studies have revealed numerous biomarkers eligible for AKI prediction. However, the expression and performance of AKI biomarkers in acute injury superimposed on preexisting CKD (AonC) remain elusive. The aim of this study was to evaluate whether biomarkers which robustly expressed in acute kidney injury could predict acute injury based on CKD.Materials and methodsMice were classified into cohorts: AKI, CKD, AonC and sham. The AonC model mice were subjected to renal bilateral ischemia/reperfusion (I/R) injury fourteen days after intraperitoneally administrated with 20 mg/kg aristolochic acid. Severity of acute ischemic injury was stratified by clamping the dissected bilateral renal arteries with non-traumatic microvascular clips for 20 or 35 min. The AKI mice were induced with renal bilateral I/R injury and CKD mice were crafted with 20 mg/kg aristolochic acid administrated intraperitoneally. Histology, genetic and protein expression of biomarkers were measured in three cohorts.ResultsWe found that serum creatinine dramatically increased in severe (sAonC) but not in moderate (mAonC) injury mice. Upregulation of Kidney injury molecule-1 (KIM-1) mRNA, tissue inhibitor of metalloproteinase-2 (TIMP-2), Syndecan-1 (SDC-1) mRNA and insulin-like growth factor binding protein-7 (IGFBP7) protein indicated the onset of mAonC. An increase in neutrophil gelatinase-associated lipocalin (NGAL), rhomboid-like protein 2 (RHBDL2), Syndecan-1 (SDC-1) mRNA and protein, and a decrease in IGFBP7 protein were associated with sAonC.ConclusionsOur study revealed the variational expression of AKI biomarkers in AonC kidneys, and uncovered IGFBP7 protein can be used as a sensitive biomarker to predict and differentiate AonC severity. The performance of RHBDL2 and SDC-1 in predicting severe AonC was promising, providing new biomarkers for predicting AonC.     

Assessed value of high-sensitivity cardiac troponin T for cardiovascular disease among CKD patients

Objective To analyze the relationship between serum high-sensitivity cardiac troponin T (hs-cTnT) and cardiovascular disease (CVD) among non-dialysis chronic kidney disease (CKD) patients, and to further explore its value of evaluating and predicting CVD in this population. Methods Five hundred and fifty-seven non-dialysis CKD patients were involved in this cross-sectional study. The relationship between serum hs-cTnT and CVD was analyzed using comparison between groups and regression analysis, and its value on assessing cardiac structure and function was evaluated by ROC curves. Results Median level of hs-cTnT was 13 (7–29) ng/L, with 1.7% undetectable, 46.4% greater than 99th percentile of the general population. Multivariate analysis suggested that compared with the lowest quartile of hs-cTnT, the highest quartile was approximately six times as likely to develop into LVH (OR, 6.515; 95% CI, 3.478–12.206, p?<?0.05) and 18 times as likely to progress to left ventricular diastolic dysfunction(OR, 18.741; 95% CI, 2.422–145.017, p?<?0.05). And Ln cTnT level had a more modest association with LVEF (OR, ?1.117; 95% CI, ?5.839 to ?0.594; p?<?0.05). When evaluated as a screening test, the area under the curve of ROC curves for hs-cTnT was 0.718, 0.788 and 0.736, respectively (p?<?0.05). With a specificity of 90% as a diagnostic criterion, the value of hs-cTnT to evaluate LVH, LVEF?Conclusions In CKD non-dialysis population, hs-cTnT and NT-proBNP were valuable for evaluating LVH, left ventricular systolic dysfunction and left ventricular diastolic dysfunction.     

Multicenter study of the clinical features and mutation gene spectrum of Chinese children with Dent disease

Dent disease is a rare X-linked recessive inherited tubular disease. In this multicenter study, the clinical presentation and genetic background of Chinese children with Dent disease are studied to improve the cognition and diagnostic ability of pediatricians. In this prospective cohort, we described the genotype and phenotype of a national cohort composed of 45 pediatric probands with Dent disease belonging to 45 families from 12 different regions of China recruited from 2014 to 2018 by building up the multicenter registration system. The CLCN5 gene from 32 affected families revealed 28 different mutations. The OCRL gene from 13 affected families revealed 13 different mutations. The incidence of low-molecular-weight proteinuria (LMWP) in both Dent disease type 1 populations and Dent disease type 2 populations was 100.0%; however, the incidence of other manifestations was not high, which was similar to previously reported data. Therefore, LMWP is a key clinical feature that should alert clinicians to the possibility of Dent disease. A high amount of LMWP combined with positive gene test results can be used as the diagnostic criteria for this disease. The diagnostic criteria are helpful in reducing the missed diagnosis of this disease and are beneficial for protecting the renal function of these patients through early diagnosis and early intervention.     

Molecular mechanism of miR-382 in the pathogenesis of renal tubulointerstitial fibrosis

Objective To investigate the roles of microRNA-382 (miR-382) in the pathogenesis of renal tubulointerstitial fibrosis (TIF). Methods Human kidney epithelial cells (HK2)transfected with miR-382 inhibitor (antagomiR-382) were used to examine the effect of miR-382 abundance on cell polarity, as well as to test the complementary relationship between miR-382 and its predicted target gene heat shock protein 60 (HSPD1), which was further verified by 3′-untranslated region luciferase assay and site-directed mutagenesis. The role of miR-382 played in the development of renal interstitial fibrosis and redox regulation was examined in a mouse unilateral ureteral obstruction (UUO) model. Locked nucleic acid (LAN)-modified anti-miR-382 was intravenous delivered via tail vein 30 min prior to UUO, and repeated the dosage 24 h after the surgery. For clinical verification, renal biopsy specimens from 12 IgA nephropathy (IgAN) patients were collected, 6 patients with moderate to severe TIF and 6 patients without TIF. The relative abundance of miR-382 and HSPD1 protein was analyzed by using in situ hybridization and immunohistochemistry. Results HSPD1 was confirmed to be a new, direct target gene of miR-382 by in vitro 3′-untranslated region luciferase assay and site-directed mutagenesis. The development of epithelial transition in HK2 cells was accompanied with up-regulation of miR-382 [(6.54±0.96) vs (1.12±0.26), P＜0.05]. Blocking the expression of miR-382 could reversed the progression of epithelial transition partially. In UUO mice the abundance of miR-382 was up-regulated [(6.89±2.47) vs (1.00±0.42), P＜0.01] while HSPD1 and Trx were down-regulated compared with the sham group. Down-regulation of miR-382 was associated with significant decrease in TIF, but increase in HSPD1 and thioredoxin protein compared with UUO group [HSPD1: (0.34±0.10) vs (0.14±0.05); Trx: (0.79±0.18) vs (0.36±0.16); all P＜0.05]. The expression of miR-382 was up-regulated and HSPD1 was significantly down-regulated in IgAN patients with TIF. Conclusions miR-382 play an important role in renal tubulointerstitial fibrosis in human and mice. HSPD1 is one of the target genes of miR-382. The down-regulation of HSPD1 and the decrease ability of anti-oxidative stress may be the important mechanism of miR-382 involved in renal tubulointerstitial fibrosis.     

The relationship between indoxyl sulfate and left ventricular hypertrophy in hemodialysis patients

Objective To investigate the relationship between indoxyl sulfate (IS) and left ventricular hypertrophy (LVH) in hemodialysis patients. Methods For the eligible patients (age ≥18 years, dialysis duration > 6 months, without history of congestive heart failure within 3 months and comorbidity of cardiac aneurysm), clinical data were collected, biochemical measurements were completed, and echocardiographic examinations were performed. Plasma IS concentration was determined by high performance liquid chromatography electrospray tandem spectrometry (HPLC-ESI-MS/MS). Linear and Logistic regression models were employed to assess the associations of plasma IS and left ventricular mass index (LVMI) and LVH, respectively. Results Two hundred and ten hemodialysis patients (117 males) with mean age of（57.2 ± 14.3）years were enrolled. The prevalence of LVH was up to 64.0%. Univariate linear regression showed that plasma IS was positively correlated with LVMI (β=7.09, P=0.02). The result persisted after adjustment for all kinds of risk factors (β=4.16, P=0.03). Patients were categorized into two groups: LVH and non-LVH group. Logistic regression models were employed to assess the relationship of plasma IS and LVH. The result showed that plasma IS was independently associated with LVH after adjustment for other confounding risk factors (β=6.54, OR=1.13, 95%CI 1.09-1.44, P=0.03). Conclusions LVH is prevalent in hemodialysis patients. Plasma IS is significantly correlated with LVMI and the independent risk factor for LVH.     

Short sleep duration increases the risk of hyperuricemia among Chinese adults: findings from the China Health and Nutrition Survey

Study objectivesHyperuricemia is a growing public health problem with its increasing prevalence. Few studies have investigated the association between sleep duration and hyperuricemia. The objective of this study is to explore whether short sleep duration is an independent risk factor of hyperuricemia in Chinese adults.MethodsThe data we analyzed was extracted from the 2009 wave of the China Health and Nutrition Survey. The population we analyzed included 8289 participants aged 18 years or older with sleep of 5–10 h per 24 h. We categorized the population into three groups by sleep duration: 5–6 h (short sleeper),7–8 h (regular sleeper), and 9–10 h (long sleeper). Hyperuricemia was defined as serum uric acid ≥7 mg/dL in men and ≥6 mg/dL in women.ResultsAmong the three groups, 9.8% were short sleepers, 68.4% were regular sleepers and 21.8% were long sleepers. The prevalences of hyperuricemia were 19.5%,15.2% and 15.5% respectively. The risks of hyperuricemia in regular and long sleep groups were lower than short sleep group, and the association remained after adjusting for indexes including age, gender, chronic kidney disease, hypertension, diabetes mellitus, high low-density lipoprotein cholesterol (LDL-c), and obesity. In subgroup analysis, we found the association was still observed in participants without hypertension, diabetes mellitus or obesity.ConclusionsOur findings suggest that short sleep duration is associated with higher risk of hyperuricemia independently of cardiometabolic risk factors, especially in individuals without traditional hyperuricemia risk factors.