The Effects of Febuxostat on Urine NGAL and Urine KIM-1 in Patients with Hyperuricemia.

Retrospective analysis of the effects of febuxostat on urine neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) in patients with hyperuricemia was performed. From January 2018 to June 2018, there were 45 patients with asymptomatic hyperuricemia in the outpatient or inpatient of Changzhou Second People's Hospital, which were divided into the febuxostat group (25 cases) and the control group (20 cases). We collected the patients' baseline indicators and testing indicators after three months of treatment, including blood urea nitrogen, blood creatinine, blood uric acid, urine microalbumin, urine NGAL, urine KIM-1, and other indicators. The subjects in both groups were given lifestyle intervention, instructed to drink more water, and given a low-purine diet. The patients in the febuxostat group took febuxostat 40 mg/D or 80 mg/D. We used SPSS 25.0 statistical software for statistical analysis. Baseline indexes between the febuxostat group and the control group and indexes after treatment between two groups were both performed by independent sample t-test, and paired t-test was used for self-comparison between the groups before and after treatment. There was no significant difference in age, sex, body mass index (BMI), urea nitrogen, creatinine, uric acid, urine microalbumin/creatinine, urine NGAL/creatinine, and urine KIM-1/creatinine between the two groups before treatment (P > 0.05). Compared with before treatment, after 3 months of intervention, the levels of serum uric acid, urine microalbumin/creatinine, urine NGAL/creatinine, and urine KIM-1/creatinine were significantly decreased in the febuxostat group (P < 0.05), while the changes of blood urea nitrogen, serum creatinine, and epidermal growth factor receptor (eGFR) were not statistically significant (P > 0.05). After 3 months of intervention, the control group had no significant changes in blood urea nitrogen, creatinine, eGFR, uric acid, microalbumin/creatinine, urine NGAL/creatinine, and urine KIM-1/creatinine (P > 0.05). After 3 months of intervention, compared with the control group, the serum uric acid, microalbumin/creatinine, urine NGAL/creatinine, and urine KIM-1/creatinine were significantly decreased in the febuxostat group (P < 0.05), but there was no significant difference in blood urea nitrogen, creatinine, and eGFR (P > 0.05). Febuxostat can reduce urine NGAL/creatinine and urine KIM-1/creatinine levels in patients with hyperuricemia and has the protective effects on renal tubular injury caused by hyperuricemia, which can provide evidences for the early prevention and treatment of asymptomatic hyperuricemia.

Hydration Strategies for Preventing Contrast-Induced Acute Kidney Injury: A Systematic Review and Bayesian Network Meta-Analysis.

AIMS: Many previous studies have examined the effect of different hydration strategies on prevention of contrast-induced acute kidney injury (CI-AKI), but the optimal strategy is unknown. We performed a network meta-analysis (NWM) of these previous studies to identify the optimal strategy. METHODS AND RESULTS: Web of Science, PubMed, OVID Medline, and Cochrane Library were searched from their inception dates to September 30, 2018. Randomized controlled trials (RCTs) were selected based on strict inclusion criteria, and a Bayesian NWM was performed using WinBUGS V.1.4.3. We finally analyzed 60 eligible RCTs, which examined 21,293 patients and 2232 CI-AKI events. Compared to intravenous 0.9% sodium chloride (reference), intravenous sodium bicarbonate (OR [95% CI]: 0.74 [0.57, 0.93]), hemodynamic guided hydration (0.41 [0.18, 0.93]), and RenalGuard guided hydration (0.32 [0.14, 0.70]) significantly reduced the occurrence of CI-AKI. Oral hydration and intravenous 0.9% sodium chloride were each noninferior to no hydration in preventing CI-AKI. Intravenous 0.9% sodium chloride, sodium bicarbonate, and hemodynamic guided hydration were each noninferior to oral hydration in preventing CI-AKI. Based on surface under the cumulative ranking curve values, the RenalGuard system was best (0.974) and hemodynamic guided hydration was second best (0.849). CONCLUSION: There was substantial evidence to support the use of RenalGuard or hemodynamic guided hydration for preventing CI-AKI in high-risk patients, especially those with chronic kidney disease or cardiac dysfunction.

Sevoflurane induces neurotoxicity in the developing rat hippocampus by upregulating connexin 43 via the JNK/c-Jun/AP-1 pathway.

As one of the most popular anesthetics, sevoflurane is widely used in pediatric anesthesia. Unfortunately, an increasing number of studies have demonstrated that sevoflurane has potential neurotoxic effects on the developing brain and cognition, even in adolescence. Connexin 43 (Cx43) has been documented to contribute to cognitive dysfunction. The present study hypothesized that Cx43 may participate in sevoflurane-induced neuroinjury and investigated the underlying mechanisms in young Sprague Dawley (SD) rats. Seven-day-old SD rats (P7) were exposed to 3% sevoflurane for 4 h. The levels of Cx43,mitogen-activated protein kinase (MAPK) signaling pathway components(including total and phosphorylated p38, extracellular signal-regulated kinase (ERK), and c-Jun n-terminal kinase (JNK) and activator protein 1(AP-1) transcription factors (including total and phosphorylated c-Fos, and c-Jun) were assessed by Western blot analysis. Neuronal apoptosis was detected using immunohistochemistry (IHC). The Morris water maze (MWM) was performed to evaluate cognitive function from P28 to P33. The results showed that anesthesia with 3% sevoflurane for 4 h increased Cx43 levels in the rat hippocampus from 6 h to 3 d, and compared with sevoflurane exposure in the control group rats, exposure in P7 SD rats also increased the ratios of phosphorylated JNK to JNK and, phosphorylated c-Jun to c-Jun in the hippocampus from 6 h to 3 d. All these effects could be alleviated by pretreatment with the JNK inhibitor SP600125 (10 mg/kg). Neuroapoptosis was similarly increased from 6 h to 1 d after inhaled sevoflurane exposure. Finally, the MWM indicated that sevoflurane could increase the escape latency and, decrease the number of platform crossings from P28 to P33. Overall, our findings suggested that sevoflurane increased Cx43 expression and induced to apoptosis by activating the JNK/c-Jun signaling pathway in the hippocampus of P7 rats. This finding may reveal a new strategy for preventing sevoflurane-induced neuronal dysfunction.

A novel anti-human ICOSL monoclonal antibody that enhances IgG production of B cells.

ICOSL, a newly identified member of the B7 superfamily, plays a major role in immune responses. In this study, a functional anti-human ICOSL monoclonal antibody (MAb) 3B3 was obtained and characterized by means of flow cytometry, Western blot, and competition assay. This MAb could specifically recognize a distinct epitope of the ICOSL molecule. As a functional antibody, MAb 3B3 could inhibit the proliferation of T lymphocytes stimulated by ICOSL-L929 transfectants. Furthermore, it could enhance IgG production of PWM-driven B cells. The results indicate that the ICOS-ICOSL signal is critically involved in specific humoral immunity.