ABSTRACT
Objective:To investigate the risk factors of hyperuricemia (HUA) in non-dialysis diabetic nephropathy (DN) patients, and to observe the protective effect of febuxostat on kidney.Methods:The clinical data of 317 DN patients without dialysis in Affiliated Hospital of Hebei University from January 2018 to February 2021 were analyzed retrospectively. Among them, HUA occurred in 148 cases (HUA group), the incidence of HUA was 46.69%, and no HUA occurred in 169 cases (non-HUA group). In HUA group, 74 patients were treated with febuxostat (observation subgroup), and 74 patients with allopurinol (control subgroup). Multivariate Logistic regression analysis was used to analyze the independent risk factors of HUA in patients with DN; a nomogram model for predicting the occurrence of HUA in patients with DN was established by R 4.0.2 software, the predictive ability of the nomogram model was evaluated by receiver operating characteristic (ROC) curve, and the calibration and validity of the prediction model were verified by correction curve and deviation correction C-index.Results:There were no significant difference in gender composition and the incidence of diabetic retinopathy, diabetic peripheral neuropathy, diabetic foot between the two groups ( P>0.05); the age, body mass index (BMI), DN course>3 years rate, smoking rate, drinking rate, family history of diabetes rate, seafood consumption more than 2 times a week rate, and the incidences of hypertension, hyperlipidemia, coronary heart disease, nephrolithiasis, stroke in HUA group were significantly higher than those in non-HUA group: (57.96 ± 5.25) years old vs. (56.14 ± 4.71) years old, (24.18 ± 3.95) kg/m 2 vs. (23.06 ± 3.12) kg/m 2, 78.38% (116/148) vs. 30.77% (52/169), 84.46% (125/148) vs. 28.99% (49/169), 93.92% (139/148) vs. 40.24% (68/169), 62.84% (93/148) vs. 50.30% (85/169), 46.62% (69/148) vs. 15.38% (26/169), 41.89% (62/148) vs. 20.71% (35/169), 73.65% (109/148) vs. 45.56% (77/169), 39.86% (59/148) vs. 18.34% (31/169), 45.95% (68/148) vs. 26.04% (44/169) and 50.68% (75/148) vs. 8.28% (14/169), and there were statistical differences ( P<0.01 or <0.05). Multivariate Logistic regression analysis result showed that age, BMI, course of DN, smoking, drinking, hypertension, hyperlipidemia, coronary heart disease, nephrolithiasis, stroke and weekly seafood consumption were independent risk factors for HUA in patients with DN ( OR = 1.053, 1.062, 3.192, 3.638, 5.397, 1.371, 1.690, 1.404, 1.392, 2.295 and 2.581; 95% CI 1.028 to 1.078, 1.031 to 1.093, 2.517 to 3.867, 2.754 to 4.522, 4.169 to 6.625, 1.253 to 1.489, 1.482 to 1.898, 1.237 to 1.571, 1.284 to 1.501, 1.730 to 2.860 and 1.862 to 3.300; P<0.01), but the family history of diabetes was not related to the occurrence of HUA in DN patients ( P>0.05). A nomogram model was established based on age, BMI, course of DN, smoking, drinking, hypertension, hyperlipidemia, coronary heart disease, nephrolithiasis, stroke and weekly seafood consumption as predictors of HUA in patients with DN; the results of correction curve analysis show that the actual curve was consistent with the ideal curve, and the prediction of HUA in patients with DN by the nomogram model was consistent with the actual situation (C-index was 0.931, 95% CI 0.895 to 0.967). The results of ROC curve analysis show that the nomogram model had a strong ability to predict the occurrence of HUA in patients with DN (the area under the curve was 0.855, 95% CI 0.842 to 0.868). The total effective rate in observation subgroup was significantly higher than that in control subgroup: 93.24% (69/74) vs. 70.27% (52/74), the levels of uric acid, creatinine and urea nitrogen after treatment were significantly lower than those in control subgroup: (314 ± 65) μmol/L vs. (392 ± 75) μmol/L, (227 ± 46) μmol/L vs. (271 ± 53) μmol/L and (13.52 ± 2.47) mmol/L vs. (16.80 ± 3.05) mmol/L, and there were statistical differences ( P<0.01). Conclusions:The age, BMI, course of DN, smoking, drinking, hypertension, hyperlipidemia, coronary heart disease, nephrolithiasis, stroke and weekly seafood consumption are independent risk factors for HUA in patients with DN. Febuxostat can effectively protect the renal function of patients with DN complicated with HUA.
ABSTRACT
Objective:Hyperoxia is a necessary therapy in some neonatal diseases, and long-term therapeutic hyperoxia may induce severe damaging effects on intestinal epithelial cells.The aim of this study was to investigate whether hyperoxia could promote the expression of ASK1 and P38 in intestinal epithelial cells through ROS.Methods:The human colon adenocarcinoma cell line Caco-2 cells were treated with different concentrations of H 2O 2(100 μmol/L, 200 μmol/L and 400 μmol/L)and 85% oxygen in vitro.The expression of ASK1 was detected by immunofluorescence, and the expression of P38 and p-P38 were detected by Western Blot and Real-time PCR. Results:With the increase of H 2O 2 concentration, the fluorescence intensity of ASK1 increased.The fluorescence intensity of ASK1 in the hyperoxia group was significantly stronger than that of the control group and the H 2O 2 groups.With the increase of H 2O 2 concentration(100 μmol/L、200 μmol/L、400 μmol/L), the expression of P38 protein(0.21±0.02, 0.28±0.13, 0.44±0.07)and p-P38 protein(0.09±0.02, 0.19±0.03, 0.37±0.07)gradually increased.The expression of P38 mRNA in 200 μmol/L and 400 μmol/L H 2O 2 groups(4.03±0.68、3.94±0.71)was significantly higher than that in 100 μmol/L H 2O 2 group(3.05±0.47)( P<0.01). The expressions of P38 protein, p-P38 protein and P38 mRNA in the hyperoxia group were significantly higher than those in the H 2O 2 group( P<0.01). Compared with the control group, the expressions of P38 protein, p-P38 protein and p38 mRNA in the hyperoxia group and H 2O 2 groups increased significantly( P<0.01). Conclusion:The expression of ASK1 and P38 in intestinal epithelial cells increased significantly under hyperoxia, which indicated that hyperoxia might activate ASK1 and thereby regulate the expression of downstream P38 through ROS, resulting in intestinal epithelial cells damage.