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Summary Observational studies on dietary or circulating magnesium and risk of cardiovascular disease (CVD) in Chronic Kidney Disease (CKD) stage 1–4 have reported no-to-modest inverse associations. 24 h Urinary magnesium concentration (24 h UMg), an indicator of intestinal magnesium absorption, may provide better insight into the connection of CKD progression. We examined 3179 participants aged 18–74 years with CKD stage 1–4 in the Chinese Cohort Study of Chronic Kidney Disease (C-STRIDE) study, a prospective population-based cohort study. Data were analysed using Spearman rank-order correlation coefficients for all comparisons. We also performed a time-to-event analysis of the data using the Kaplan–Meier survival model, Cox proportional hazard model and competing risk Fine and Gray subdistribution hazard model. During a median follow-up of 4.19 years (interquartile range, 3.43–5.09 years), when modelling end-stage renal disease (ESRD), CVD and death, 24 h UMg was associated with risk of CVD (HR, 1.612 (95% CI, 1.056–2.460)), while no significant association with ESRD and death endpoints could be detected. 24 h UMg risk variants display a modest association with CVD in CKD stage 1–4 patients. Trial registration ClinicalTrials.gov Identifier NCT03041987. Registered January 1, 2012. (retrospectively registered) ( https://www.clinicaltrials.gov/ct2/show/NCT03041987?term=Chinese+Cohort+Study+of+Chronic+Kidney+Disease+%28C-STRIDE%29&rank=1 ).

This study aimed to evaluate whether high-frequency oscillatory ventilation (HFOV) could reduce mortality and the incidence of bronchopulmonary dysplasia (BPD) of perinatal-onset neonatal acute respiratory distress syndrome (NARDS) compared with conventional mechanical ventilation (CMV). Medical records were collected and retrospectively analyzed. Among the 700 neonates with NARDS who needed invasive ventilation, 501 (71.6%) received CMV, while 199 (28.4%) received HFOV. One-to-one propensity score matching (127:127) was used to match the baseline characteristics of patients who received CMV and HFOV. The results showed that birth weight and oxygenation index (OI) were independently associated with mortality in the multivariate logistic regression. No significant differences were observed in mortality or the incidence of BPD between the two groups. The incidence of intraventricular hemorrhage (IVH) and ventilation-free days were significantly lower in the HFOV group than in the CMV group (3.9 vs 11.80%, p=0.02; 15.226 vs 20.967 days, p=0.01). There were no significant differences between the two groups regarding other secondary outcomes.Conclusion: HFOV was associated with a decreased incidence of IVH in infants with NARDS compared with CMV. However, there were significantly more VFDs in the CMV group than in the HFOV group, and HFOV did not appear to be superior to CMV in decreasing the mortality and incidence of BPD in infants with NARDS. What is Known: • The diagnostic criteria of neonatal acute respiratory distress syndrome (Montreux criteria) were established in 2017. • To date, studies comparing high-frequency oscillatory ventilation and conventional mechanical ventilation in the treatment of neonatal acute respiratory distress syndrome are insufficient. What is New: • High-frequency oscillatory ventilation did not appear to be superior to conventional mechanical ventilation in decreasing the mortality and incidence of bronchopulmonary dysplasia in infants with moderate-to-severe perinatal-onset neonatal acute respiratory distress syndrome. • High-frequency oscillatory ventilation was associated with a decreased incidence of intraventricular hemorrhage in infants with moderate-to-severe perinatal-onset acute respiratory distress syndrome compared with conventional mechanical ventilation.

Glucocorticoids are widely used in the treatment of nephritis, however, its dose-dependent side effects, such as the increased risk of infection and metabolic disturbances, hamper its clinical use. This study reports a visualized podocyte-targeting and focused ultrasound responsive glucocorticoid nano-delivery system (named as Dex/PFP@LIPs-BMS-α), which specific delivers dexamethasone (Dex) to podocyte targets and reduces systemic side effects. Methods: The glucocorticoid nano-delivery system was synthesized by a lipid thin film and a simple facile acoustic-emulsification method. This glucocorticoid nano-delivery system used BMS-470539 (BMS-α), a synthetic compound, as a "navigator" to specifically identify and target the melanocortin-1 receptor (MC-1R) on podocytes. The loaded perfluoropentane (PFP) realizes the directed "explosion effect" through ultrasound-targeted microbubble destruction (UTMD) technology under the coordination of low intensity focused ultrasound (LIFU) to completely release Dex. Results: Both in vitro and in vivo experiments have demonstrated that Dex/PFP@LIPs-BMs-α accurately gathered to podocyte targets and improved podocyte morphology. Moreover, in vivo, proteinuria and serum creatinine levels were significantly reduced in the group treated with Dex/PFP@LIPs-BMS-α, and no severe side effects were detected. Furthermore, Dex/PFP@LIPs-BMS-α, with capabilities of ultrasound, photoacoustic and fluorescence imaging, provided individualized visual guidance and the monitoring of treatment. Conclusion: This study provides a promising strategy of Dex/PFP@LIPs-BMS-α as effective and safe against immune-associated nephropathy.

Background It is unclear whether short‐term blood pressure variability is associated with renal outcomes in patients with chronic kidney disease. Methods and Results This study analyzed data from participants in the C‐ STRIDE (Chinese Cohort Study of Chronic Kidney Disease) who had chronic kidney disease stages 1 to 4. Short‐term blood pressure variability was measured by calculating the weighted SD (w‐ SD ) of systolic blood pressure ( SBP ). Renal outcomes were defined as dialysis initiation and/or transplantation. Risk factors associated with w‐ SD of SBP were evaluated by linear regression. Associations of short‐term SBP variability with renal outcomes were evaluated by Cox regression. In total, 1421 patients with chronic kidney disease were included in this study (mean age, 49.4±13.6 years; 56.2% men; estimated glomerular filtration rate, 50.5±29.3 mL/min per 1.73 m 2 ; proteinuria, 0.9 [0.3–2.0] g/d). Mean w‐ SD of SBP was 12.6±4.4 mm Hg. w‐ SD of SBP was independently associated with older age, 24‐hour SBP , blood pressure circadian pattern, and angiotensin II receptor blocker treatment. During a median follow‐up of 4.9 years, 237 patients developed renal outcomes (37.01 per 1000 patient‐years). The incidence rate increased across the quartiles of w‐ SD (log‐rank P =0.005). w‐ SD of SBP was associated with an increased risk of renal outcomes, both as a continuous variable (hazard ratio [HR], 1.47; 95% CI, 1.09–1.99) and as a categorical variable (quartile 4 versus quartile 1: HR, 1.60; 95% CI, 1.08–2.36), independent of 24‐hour SBP , daytime SBP , and nighttime SBP . Conclusions Short‐term SBP was independently associated with the risk of dialysis initiation and/or transplantation in patients with chronic kidney disease .

HIF-PHI (hypoxia-inducible factor prolyl hydroxylase inhibitor) was developed to improve renal anemia. This study was to evaluate the efficiency and safety of HIF-PHI in patients with non-dialysis-dependent chronic kidney disease (NDD-CKD). The literature was extracted from PubMed, EMBASE, the Cochrane Central Register of Controlled Trials, and the Wanfang database. Statistical tests and forest plots were depicted by Review Manager Version 5.3. The primary outcome was a change in hemoglobin level from baseline (ΔHb). Secondary outcomes were changes in ferritin (ΔFerritin), hepcidin (ΔHepcidin), and transferrin saturation from baseline (ΔTSAT), and adverse events (AEs). This study is registered with PROSPERO (registration number CRD42020199656). Ten trials were included. The results showed that HIF-PHI improved the ΔHb [SMD 3.03 (95% CI 2.10, 3.96), P < 0.00001] in NDD patients. HIF-PHI reduced hepcidin levels in the NDD patients [SMD − 1.44 (95% CI − 2.19–0.70), P = 0.0002]. ΔFerritin values were reduced significantly in the HIF-PHI group [SMD − 1.08 (95% CI − 1.63–0.53), P = 0.0001]. However, ΔTSAT values showed no significant difference in the HIF-PHI group compared to the placebo group [SMD − 0.23 (95% CI − 0.66–0.21), P = 0.31]. In the safety assessment, HIF-PHI did not increase adverse events significantly [RR 0.98 (95% CI 0.88–1.10), P = 0.74]. HIF-PHI improves renal anemia and iron utilization disorder in NDD-CKD patients, without significantly more adverse events.

BackgroundBile acids are important metabolites of intestinal microbiota, which have profound effects on host health. However, whether metabolism of bile acids is involved in the metabolic complications of end-stage renal disease (ESRD), and the effects of bile acids on the prognosis of ESRD remain obscure. Therefore, this study investigated the relationship between altered bile acid profile and the prognosis of ESRD patients.MethodsA targeted metabolomics approach based on ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was used to determine the changes in serum bile acids between ESRD patients (n= 77) and healthy controls (n= 30). Univariate and multivariate statistical analyses were performed to screen the differential proportions of bile acids between the two groups.ResultsSix differentially expressed bile acids were identified as potential biomarkers for differentiating ESRD patients from healthy subjects. The decreased concentrations of chenodeoxycholic acid, deoxycholic acid and cholic acid were significantly associated with dyslipidemia in ESRD patients. Subgroup analyses revealed that the significantly increased concentrations of taurocholic acid, taurochenodeoxycholic acid, taurohyocholic acid and tauro α-muricholic acid were correlated to the poor prognosis of ESRD patients.ConclusionsThe serum bile acid profile of ESRD patients differed significantly from that of healthy controls. In addition, the altered serum bile acid profile might contribute to the poor prognosis and metabolic complications of ESRD patients.

Netrin-1 has been found to protect kidneys from ischemia/reperfusion injury. In this study, we aimed to address whether the protective effects were mediated through suppression of oxidative stress and neuropeptide Y. Compared to sham-operated animals, animals after ischemia/reperfusion showed marked kidney damage and significantly increased levels of serum creatinine, blood urea nitrogen, malondialdehyde, and neuropeptide Y. Renal myeloperoxidase activity was elevated in animals with ischemia/reperfusion relative to sham-operated animals, whereas renal superoxide dismutase activity was reduced. Netrin-1 pretreatment attenuated ischemia/reperfusion-induced functional and pathological changes in the kidney. Moreover, the ischemia/reperfusion-induced changes in the oxidative stress biomarkers and neuropeptide Y were significantly counteracted by prior administration of netrin-1. Taken together, our data showed that netrin-1 pretreatment prevented renal ischemia/reperfusion injury, at least partially through reduction of oxidative stress and neuropeptide Y expression.