Association between hyperuricemia and acute kidney injury in critically ill patients with sepsis.

BACKGROUND: Sepsis-related AKI is related to short-term mortality and poor long-term prognoses, such as chronic renal insufficiency, late development of end-stage renal disease, and long-term mortality. In this study, we aimed to investigate the association of hyperuricemia with acute kidney injury (AKI) in patients with sepsis. METHODS: The retrospective cohort study included 634 adult sepsis patients hospitalized in the intensive care unit (ICU) of the First Affiliated Hospital of Guangxi Medical University from March 2014 to June 2020 and the ICU of the Second Affiliated Hospital of Guangxi Medical University from January 2017 to June 2020. Based on the first serum uric acid level within 24 h of admission to the ICU, patients were divided into groups with or without hyperuricemia, and the incidence of AKI within seven days of ICU admission was compared between the two groups. The univariate analysis analyzed the effect of hyperuricemia on sepsis-related AKI, and the multivariable logistic regression model analysis was used. RESULTS: Among the 634 patients with sepsis, 163 (25.7%) developed hyperuricemia, and 324 (51.5%) developed AKI. The incidence of AKI in the groups with and without hyperuricemia was 76.7% and 42.3%, respectively, with statistically significant differences (2 = 57.469, P < 0.001). After adjusting for genders, comorbidities (coronary artery disease), organ failure assessment (SOFA) score on the day of admission, basal renal function, serum lactate, calcitonin, and mean arterial pressure, hyperuricemia was showed to be an independent risk factor for AKI in patients with sepsis (OR = 4.415, 95%CI 2.793 ~ 6.980, P < 0.001). For every 1 mg/dL increase in serum uric acid in patients with sepsis, the risk of AKI increased by 31.7% ( OR = 1.317, 95%CI 1.223 ~ 1.418, P < 0.001). CONCLUSION: AKI is a common complication in septic patients hospitalized in the ICU, and hyperuricemia is an independent risk factor for AKI in septic patients.

[Effects of C-reactive protein on the expression of transforming growth factor ß1 and receptors on human renal tubular epithelial cells].

OBJECTIVE: To explore the effect of C-reactive protein (CRP) on the expression of Fcγ receptors in human renal tubular epithelial cells and determine the role of Fcγ receptors in CRP-induced expression of transforming growth factor ß1 (TGFß1). METHODS: Human renal tubular epithelial cells (HK-2) were cultured and stimulated with recombinant human CRP. The mRNA expression of Fcγ receptors, including FcγRI (CD64), FcγRIIa (CD32a) and FcγRIII (CD16), was detected by real-time polymerase chain reaction (PCR). On the basis of real-time PCR results, CD32a was selected for further analysis: the CD32a expression in HK-2 cells incubated with 10 mg/L CRP for 24 h was determined by flow cytometry and Western blotting. HK-2 cells were preincubated with or without anti-CD32a IgG, followed by the addition of recombinant human CRP. Subsequently the biological effects of CRP were tested. TGFß1, type I collagen (ColI) and type IV collagen (ColIV) released into media were detected by enzyme-linked immunosorbent assay. And TGFß1 mRNA expression was measured by real-time PCR. RESULTS: On real-time PCR, CRP was found to significantly up-regulate the CD32a mRNA expression in HK-2 cells in a dose-dependent manner (P < 0.01). The peak up-regulation was observed at a dose of 10 mg/L. In contrast, mRNAs of CD16 and CD64 were not detected in HK-2 cells. Flow cytometry showed that CD32a expressed on HK-2 cells incubated with 10 mg/L recombinant human CRP for 24 h accounted for 23.35% ± 7.43%, significantly higher than that on non-CRP-treated cells (1.66% ± 0.28%, P < 0.01). Western blotting showed that CRP up-regulated CD32a expression in a dose-dependent manner. And 10 mg/L CRP induced the peak effect. Antibodies to CD32a inhibited the stimulatory effect of CRP on the generation of TGFß1, ColI and ColIV (all P < 0.05) and down-regulated the expression of TGFß1 mRNA (P < 0.01). CONCLUSION: The stimulation of CRP can significantly increase CD32a expression in renal tubular epithelial cells and up-regulate the expression of transforming growth factor TGFß1 through CD32a receptor.

Expression of soluble Toll-like receptors in pleural effusions.

BACKGROUND: The Toll-like receptors (TLRs) represent a group of single-pass transmembrane receptors expressed on sentinel cells that are central to innate immune responses.The aim of this study was to investigate the presence of soluble TLRs in pleural effusions, and the diagnostic values of TLRs for pleural effusion with various etiologies. METHODS: Pleural effusion and serum samples were collected from 102 patients (36 with malignant pleural effusion, 36 with tuberculous pleural effusion, 18 with bacterial pleural effusion, and 12 with transudative pleural effusion). The concentrations of TLR1 to TLR10 were determined in effusion and serum samples by enzyme linked immunosorbent assay. Four classical parameters (protein, lactate dehydrogenase, glucose and C-reactive protein (CRP)) in the pleural fluid were also assessed. Receiver-operating characteristic curves were used to assess the sensitivity and specificity of pleural fluid TLRs and biochemical parameters for differentiating bacterial pleural effusion. RESULTS: The concentrations of TLR1, TLR3, TLR4, TLR7 and TLR9 in bacterial pleural effusion were significantly higher than those in malignant, tuberculous, and transudative groups, respectively. Analysis of receiver operating characteristic curves revealed that the area under the curves of TLR1, TLR3, TLR4, TLR7 and TLR9 were 0.831, 0.843, 0.842, 0.883 and 0.786, respectively, suggesting that these TLRs play a role in the diagnosis of bacterial pleural effusion. Also, the diagnostic value of TLRs for bacterial pleural effusions was much better than that of biochemical parameters (protein, lactate dehydrogenase, glucose and CRP). CONCLUSIONS: The concentrations of TLR1, TLR3, TLR4, TLR7 and TLR9 appeared to be increased in bacterial pleural effusion compared to non-bacterial pleural effusions. Determination of these pleural TLRs may improve the ability of clinicians to differentiate pleural effusion patients of bacterial origin from those with other etiologies.

[Study on association of CTLA4 gene polymorphism with Grave's disease in Guangxi Zhuang nationality population].

OBJECTIVE: To investigate the relationship between the polymorphic (AT)n repeats in 3ountranslated region of exon 4 of CTLA4 gene [CTLA4(AT)n] and Graveso disease (GD) in Zhuang nationality population of Guangxi province. METHODS: The studied groups comprised 48 patients with GD and 44 normal controls. Amplification of target DNA was carried out by polymerase chain reaction (PCR). The amplified products were run by 8% polyacrylamide gel electrophoresis, and then followed by 0.1% silver staining. Some of amplified products were sequenced directly. RESULTS: Nineteen alleles of CTLA4 gene microsatellite polymorphism were found in Guangxi Zhuang nationality individuals. The 106 bp long allele was apparently increased in patients with GD of Zhuang nationality but not in healthy controls (P< 0.05). CONCLUSION: CTLA4 gene microsatellite polymorphism is strongly associated with Graveso disease in Zhuang nationality population of Guangxi province. CTLA4(AT)n 106 bp may be the susceptible gene in GD patients of Zhuang nationality in Guangxi; 19 alleles of CTLA4 gene microsatellite polymorphism were found in Guangxi Zhuang nationality individuals.