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OBJECTIVE To investigate the effects of echinacoside (ECH) on renal injury in uremia (URE) rats and its mechanism. METHODS URE model of the rat was established by 5/6 nephrectomy. Successfully modeled rats were grouped into uremia group (URE group), ECH low-dose [10 mg/(kg·d)] group, ECH medium-dose [20 mg/(kg·d)] group, ECH high-dose [40 mg/(kg·d)] group, ECH high-dose+anisomycin [p38 mitogen-activated protein kinase (p38 MAPK) pathway activator] group [ECH-H+Ani group, 40 mg/(kg·d) ECH +2 mg/(kg·d) anisomycin], with a sham operation group, 12 mice in each group. Each drug group was given corresponding ECH intragastrically, while ECH-H+Ani group was further injected with anisomycin via the tail vein, once a day, for 8 consecutive weeks. The serum levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-6, blood urea nitrogen (BUN), β2-microglobulin (β2-MG), serum creatinine (Scr), neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), cystatin C (Cys-C) and 24 h urine protein (24 h UP) as well as the levels of malondialdehyde (MDA) and superoxide dismutase (SOD) activity in renal tissue were all detected; pathological changes of renal tissue were observed; the rate of positive expression of α-smooth muscle protein (α-SMA) and E-cadherin, and the phosphorylation of p38 MAPK and nuclear factor-κB (NF-κB) p65 were determined in renal tissue of rats. RESULTS Compared with URE group, glomerular swelling, damage and necrosis of renal tubular epithelial cells and inflammatory cell infiltration were relieved significantly in ECH groups. The renal injury score, levels of TNF-α, IL-1β, IL-6, BUN, Scr, β2-MG, 24 h UP, NGAL, KIM- 1, Cys-C and MDA, the positive expression rate of α-SMA in renal tissue, the phosphorylation of p38 MAPK and NF-κB p65 were decreased in dose-dependent manner, while SOD activity and the positive expression rate of E-cadherin were obviously increased in dose-dependent manner (P<0.05). Anisomycin significantly attenuated the improvement effect of high-dose ECH on renal injury in URE rats (P<0.05). CONCLUSIONS ECH may inhibit inflammation and oxidative stress, enhance renal function, and improve renal injury in uremic rats by inhibiting the activation of p38 MAPK/NF-κB signaling pathway.
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Objective To explore the mechanism and management of acute kidney injury induced by the interaction be-tween voriconazole and nifedipine.Methods A patient with acute kidney injury was treated with nifedipine controlled-release tablets and voriconazole tablets at the same time.Pharmacists analyzed drug interactions and drug characteristics during diagnosis and treatment and proposed treatment recommendations,discontinued suspected drugs(cefotaxime and voriconazole),and deter-mined subsequent treatment based on the analysis results.Results The doctor accepted the advice and the patient gradually re-covered from acute kidney injury.Conclusion Drug-drug interactions,especially those based on the interaction of liver drug enzyme CYP450,should be paid attention to in clinical diagnosis and treatment,to improve efficacy and reduce adverse reactions.
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Background The burden of chronic kidney diseases (CKD) is continuously increasing in the globe. Environmental factors are one of the trigger factors for chronic kidney diseases of unknown etiology (CKDu). However, the current toxicological evidence on the renal effects induced by environmental high concentrations of multiple ions in drinking water and high temperature exposure is very limited. Objective To preliminary investigate the renal effects of exposure to drinking water with environmental high concentrations of fluoride, calcium, sodium, and bromide ions alone or in combination with high temperature in mice. Methods A mouse drinking water exposure model was established using ICR male mouse (8 weeks old) with exposure to 3 mg·L−1 fluoride ions, 250 mg·L−1 calcium ions, 400 mg·L−1 sodium ions, and 1 mg·L−1 bromide ions (to mimic the high concentration of ions in the groundwater in the areas with a high prevalence rate of CKDu in Sri Lanka) and high temperature of 32 ℃. ICR male mice were randomly divided into a mixed fluoride-calcium-sodium-bromide ion and high temperature exposure group, exposure groups of each ion and high temperature alone, a fluoride-calcium-sodium ion exposure group, and a fluoride-calcium-sodium-bromide ion exposure group. In the control group, the animals were given normal purified water at room temperature of (23±2) ℃. After 12 consecutive weeks of exposure, body weights and liver (kidney) organ coefficients were determined. Assessment of renal histopathologic damage was performed by hematoxylin-eosin staining and pathology scoring. At the end of the 12-week exposure period, 24 h urine samples were collected for the measurements of creatinine (UCr), albumin (ALB), neutrophil gelatinase-associated lipocalin (NGAL), and β2-microglobulin (β2-MG) levels. Cell apoptosis was assessed by TUNEL assay. Results The mice in the mixed exposure group showed a significant decrease in body weight and marked increases in the scores of renal histopathological injuries and the urinary levels of β2-MG compared to those of the control mice (P<0.05). Compared with the control group, the differences in body weight and urinary renal injury indexes of the mice in the fluoride-calcium-sodium and the fluoride-calcium-sodium-bromide ion groups (except for the decrease of the β2-MG levels in urinary in the latter group) were not statistically significant (P>0.05), but the renal histopathological injury scores were significantly increased (P<0.05). By contrast, body weights, liver (kidney) organ coefficient, and renal histopathological injury scores were comparable in the control mice and the mice fed with drinking water containing high levels of a single ion alone or housed at high temperature alone (P>0.05). Furthermore, the renal histopathological injury score showed no significant differences between the fluoride-calcium-sodium ion exposure group and the fluoride-calcium-sodium-bromide ion exposure group (P>0.05). The interaction between bromide ions and fluoride-calcium-sodium ions on renal tissue pathological damage was not statistically significant (P>0.05). Results from the TUNEL assay showed a significant increase in renal cell apoptosis in the fluoride-calcium-sodium ion exposure group (P<0.05). Conclusions Environmental high levels of mixed fluoride, calcium, and sodium ions in drinking water induce renal pathological damage in mice, which are exacerbated in combination with high temperature environment. High temperature exposure alone does not affect the pathological damage of renal tissue,
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OBJECTIVE To investigate the effect of dioscin on renal injury in septic rats and its possible mechanism. METHODS The septic rat model was induced by using cecal ligation and puncture. Sixty model rats were randomly divided into model group (0.5% sodium carboxymethyl cellulose solution), dioscin low-dose, medium-dose and high-dose groups (30, 60, 120 mg/kg) and dexamethasone group (positive control, 10 mg/kg), with 12 rats per group; another 12 rats were selected as the sham operation group (0.5% sodium carboxymethyl cellulose solution). After 15 minutes of modeling, rats in each group were injected with medicine/0.5% sodium carboxymethyl cellulose solution via the tail vein. Twenty-four hours after administration, the levels of creatinine (Cr), blood urea nitrogen (BUN), neutrophil gelatinase associated lipocalin (NGAL), kidney injury molecule-1 (KIM- 1), interleukin 6 (IL-6), IL-1β and tumor necrosis factor-α (TNF-α) in serum and malondialdehyde (MDA) in renal tissue, superoxide dismutase (SOD) activity and the protein expressions of nuclear factor E2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), NOD-like receptor protein 3 (NLRP3) were detected; renal histomorphology was observed. RESULTS Compared with model group, pathological injury of renal tissue was improved significantly in dioscin low-dose, medium-dose and high-dose groups; the levels of Cr, BUN, NGAL, KIM-1, IL-6, IL-1β and TNF-α in serum, MDA level and protein expression of NLRP3 in renal tissue were decreased significantly (P<0.05); SOD activity in renal tissue, protein expressions of Nrf2 and HO-1 were increased significantly (P<0.05), in a dose-dependent manner (P<0.05). The pathological damage of renal tissue in the dioscin high-dose group was similar to dexamethasone group, and there was no statistically significant difference in the levels of the above indicators (P>0.05). CONCLUSIONS Dioscin can activate the Nrf2/HO-1 signaling pathway to inhibit NLRP3 inflammasome, and realize the inhibition of inflammatory factors and oxidative stress, so as to protect the kidney injury in sepsis.
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OBJECTIVE To investigate the effect of dioscin on renal injury in septic rats and its possible mechanism. METHODS The septic rat model was induced by using cecal ligation and puncture. Sixty model rats were randomly divided into model group (0.5% sodium carboxymethyl cellulose solution), dioscin low-dose, medium-dose and high-dose groups (30, 60, 120 mg/kg) and dexamethasone group (positive control, 10 mg/kg), with 12 rats per group; another 12 rats were selected as the sham operation group (0.5% sodium carboxymethyl cellulose solution). After 15 minutes of modeling, rats in each group were injected with medicine/0.5% sodium carboxymethyl cellulose solution via the tail vein. Twenty-four hours after administration, the levels of creatinine (Cr), blood urea nitrogen (BUN), neutrophil gelatinase associated lipocalin (NGAL), kidney injury molecule-1 (KIM- 1), interleukin 6 (IL-6), IL-1β and tumor necrosis factor-α (TNF-α) in serum and malondialdehyde (MDA) in renal tissue, superoxide dismutase (SOD) activity and the protein expressions of nuclear factor E2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), NOD-like receptor protein 3 (NLRP3) were detected; renal histomorphology was observed. RESULTS Compared with model group, pathological injury of renal tissue was improved significantly in dioscin low-dose, medium-dose and high-dose groups; the levels of Cr, BUN, NGAL, KIM-1, IL-6, IL-1β and TNF-α in serum, MDA level and protein expression of NLRP3 in renal tissue were decreased significantly (P<0.05); SOD activity in renal tissue, protein expressions of Nrf2 and HO-1 were increased significantly (P<0.05), in a dose-dependent manner (P<0.05). The pathological damage of renal tissue in the dioscin high-dose group was similar to dexamethasone group, and there was no statistically significant difference in the levels of the above indicators (P>0.05). CONCLUSIONS Dioscin can activate the Nrf2/HO-1 signaling pathway to inhibit NLRP3 inflammasome, and realize the inhibition of inflammatory factors and oxidative stress, so as to protect the kidney injury in sepsis.
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Tenofovir disoproxil fumarate (TDF) is a first-line treatment for chronic hepatitis B. With increasing use worldwide, the adverse events of renal injury caused by this drug have also attracted industry attention. This article reports a 61- year-old patient with liver cancer complicated with hepatitis B virus (HBV) infection. The patient started using TDF in mid-March 2022 and developed kidney injury after 2 months of treatment, during which he received 2 courses of donafenib combined with sintilimab chemotherapy and irregular administration of diclofenac for pain relief. In this paper, Naranjo’s assessment scale was used to evaluate the drugs that may be associated with renal injury, including TDF and sintilimab, and the drugs that are suspected to be associated with renal injury are donafenib and diclofenac. The renal injury caused by TDF can be judged according to the changes in the patient’s condition, the incidence of drug-induced renal injury, clinical manifestations, occurrence time, occurrence mechanism, drug combination, and high-risk factors. The changes of serum creatinine in patients with liver cancer complicated with HBV infection after TDF should be dynamically monitored in the clinic, and the dose of antiviral drugs should be adjusted if necessary and other antiviral drugs with less impact on renal function can be selected, to provide individualized medication recommendations for tumor patients, reduce the incidence of TDF-related renal injury.
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Objective:To analyze the relationship between plasma uranium concentration and renal injury.Methods:A case-control study was conducted in Hunan province, involving 102 renal injury cases and 102 matched controls. The association between plasma uranium concentration and renal injury was analyzed using conditional logistic regression models, and the dose-response relationship was analyzed through restricted cubic spline regression. The linear regression model and Spearman correlation were used to analyze the association between plasma uranium concentration and renal injury indicators.Results:The median of plasma uranium concentration was 8.94 ng/L in all subjects and 10.19 ng/L in the case group. The plasma uranium may be a risk factor for renal injury, with a dose-response relationship between the both representing nonlinear association ( χ2=5.15, P<0.05). The risk of renal injury was 4.21 times higher in the group exposed to highest uranium concentration than that in the group exposed to lowest uranium concentration. Plasma uranium concentration was closely related to glomerular filtration rate, serum creatinine and β 2-microglobulin ( r=0.211, -0.142, 0.195, P<0.05). Conclusions:The plasma uranium concentration is significantly associated with the renal injury, which may provide epidemiology evidence for the prevention of renal injury.
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Objective To explore the influencing factors of renal injury in elderly patients with cor pulmonale, and to provide information for the prevention of renal injury in patients with cor pulmonale. Methods A total of 309 elderly patients with cor pulmonale over 60 years old treated in our hospital from June 2019 to December 2020 were included in the study. According to the patients with renal injury , they were divided into cor pulmonale renal injury group (case group) and cor pulmonale non renal injury group (control group). The basic information of the two groups and the influencing factors of potential renal injury in the past were collected, The influencing factors of renal injury in elderly patients with cor pulmonale were analyzed by univariate analysis and regression model. Results The single factor analysis of the case group was higher than that of the control group, with a male age of 80 years, smoking history, family history of diabetes, concurrent infection, diabetes mellitus and left ventricular ejection fraction (LVEF) 80 years old (or = 3.142), smoking history (or=2.115) , concurrent infection (or=4.263) , and excessive systolic blood pressure (or=2.279) were the risk factors potentially increasing the risk of renal injury, which were statistically significant (P < 0.05). Conclusion Elderly patients with cor pulmonale over 80 years old , with smoking history and abnormal blood pressure , as well as those complicated with infection , have an increased risk of renal injury. It is worthy of clinical attention and relevant preventive measures to improve the prognosis of patients.
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OBJECTIVE To establish a method for the determination of polymyxin B concentration in plasma and apply it to clinical practice. METHODS After precipitated with 5% trichloroacetic acid solution, using polymyxin E2 as internal standard, the concentrations of polymyxin B1 and B2 in plasma sample were determined by UPLC-MS/MS. The determination was performed on BEH C18 chromatographic column with water (0.1% formic acid)-acetonitrile (0.1% formic acid) as mobile phase (gradient elution) at the flow rate of 0.5 mL/min. The sample size was 10 µL. The detection was accomplished with electrospray ionization operated in positive ion scanning by multi-reaction monitoring mode. The ion pairs for quantitative analysis were m/z 603.2→101.2 (polymyxin B1), m/z 595.7→101.1 (polymyxin B2) and m/z 578.5→101.1 (internal standard). The plasma concentration of polymyxin B in 79 critically ill patients was measured by the above method, the occurrence of acute renal injury (AKI) was recorded and the relationship of polymyxin B concentration in plasma with AKI was analyzed. RESULTS The linear ranges of polymyxin B1 and polymyxin B2 were 200-20 000, 50-5 000 ng/mL (r>0.995), and the lower limits of quantification were 200 and 50 ng/mL, respectively. RSDs of intra‐day and inter‐day precision tests were not higher than 12.06%, the average extraction recovery was 103.04%-117.44%, and RSDs of matrix effect test and stability test were all not higher than 7.42%. Steady state trough and peak plasma concentration were (2.54±2.52) and (8.17±5.20) mg/L for 79 clinical patients using polymyxin B. Eighteen patients out of 27 included patients developed AKI, with an incidence of 66.67%. The peak concentration of polymyxin B of patients without AKI was significantly lower than that of patients with AKI (P<0.05), but there was no significant difference in the trough concentration between two groups (P>0.05). CONCLUSIONS The established UPLC-MS/MS has the advantages of simple operation and high sensitivity, and can be used to monitor the plasma concentration of polymyxin B in patients. The occurrence of AKI is correlated with the peak concentration of polymyxin B.
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ObjectiveTo observe the protective effect and mechanism of Tianhuang formula (THF) against renal injury in hyperuricemia nephropathy (HN) mice through network pharmacology. MethodAll mice were randomly divided into a normal group, a model group, a febuxostat group (5 mg·kg-1), a low-dose THF group (L-THF, 60 mg·kg-1), and a high-dose THF group (H-THF, 120 mg·kg-1). The mice in the normal group were treated with 0.5% sodium carboxymethylcellulose (CMC-Na) by gavage daily. The HN model was induced by oral administration of 500 mg·kg-1 hypoxanthine and intraperitoneal injection of 200 mg·kg-1 oteracil potassium in mice except for those in the blank group. The mice in the groups with drug intervention were treated with corresponding drugs by gavage for three weeks. The levels of serum uric acid, creatinine, urea nitrogen, and 24-h albuminuria were measured. The renal injury was observed by hematoxylin-eosin (HE) staining and PAS staining, and renal fibrosis was observed by Sirius red staining. The effects and molecular mechanism of THF in HN mice were analyzed by Western blot, network pharmacology, and molecular docking. ResultBiochemical results indicated that compared with model group, BUN and 24 h urinary protein levels were significantly decreased in L-THF group (P<0.05), SUA and SCr levels were significantly decreased (P<0.01), and SUA, BUN, SCr and 24 h urinary protein levels in H-THF group were significantly decreased (P<0.01). The results of pathological staining showed that the kidney injury and interstitial fibrosis were improved in different doses of THF groups (P<0.05). Western blot results showed that the Nod-like receptor heat protein domain associated protein 3 (NLRP3) inflammatorome, interleukin-1β (IL-1β), fibronectin (FN), uric acid transporter 1 (URAT1), phosphorylated p65 (p-p65) and phosphorylated nuclear transcription factor (NF) -κB were inhibited in the H-THF group The expression of protein-producing α (p-IκBα) was reduced to the normal level (P<0.01), but the expression of IL-1β, URAT1 and p-IκBα in HN mice was not affected in the L-THF group. ConclusionTHF ameliorates renal inflammation and fibrosis by inhibiting the activation of NF-κB and NLRP3 inflammasomes to alleviate HN
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Objective To investigate the effect of Yinchenhao decoction on renal oxidative stress injury in rats with obstructive jaundice and its association with the regulation of the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and nuclear translocation. Methods A total of 32 male Sprague-Dawley rats were randomly divided into sham-operation group (S group), model group (O group), low-dose Yinchenhao decoction group (LY group), and high-dose Yinchenhao decoction group (HY group), with 8 rats in each group. For the rats in the S group, the upper common bile duct was isolated without ligation, and for those in the other groups, double ligation of the middle and upper 1/3 of the common bile duct was performed to establish a model of obstructive jaundice. After 7 days, the rats in the LY group and the HY group were given Yinchenhao decoction by gavage at a dose of 6.3 and 18.9 mL/kg, respectively, while those in the S and O groups were given an equal volume of distilled water by gavage every day for 7 consecutive days, and the rats were treated on day 14. ELISA was used to measure the serum levels of total bilirubin (TBil), direct bilirubin (DBil), alanine aminotransferase (ALT), gamma-glutamyl transpeptidase (GGT), blood urea nitrogen (BUN), and creatinine (Cr); spectrophotometry was used to measure the activity of the oxidative stress factors superoxide dismutase (SOD) and malondialdehyde (MDA) in renal tissue; quantitative real- time PCR and Western blotting were used to measure the mRNA and protein expression levels of Nrf2, Kelch-like ECH-associated protein 1 (Keap1), and NAD(P)H quinone dehydrogenase 1 (NQO1) in renal tissue; immunohistochemistry was used to measure observe the nuclear translocation of Nrf2 protein in renal tissue. A one-way analysis of variance was used for comparison of continuous data between multiple groups, and the least significant difference t -test was used for further pairwise comparison within groups. Results Compared with the S group, the O group had significant increases in the levels of TBil, DBil, ALT、GGT, BUN, and Cr, a significant reduction in the activity of SOD, and a significant increase in the level of MDA (all P 0.05). Compared with the S group, the O group had a significant reduction in the positive rate of Nrf2 in cell nucleus in renal tissue ( P < 0.05), and compared with the O group, the LY group and the HY group had a significant increase in the positive rate of Nrf2 in cell nucleus ( P < 0.05). Conclusion Yinchenhao decoction can effectively alleviate renal injury caused by obstructive jaundice, possibly by upregulating the protein expression of Nrf2 in renal tissue and regulating the nuclear translocation of Nrf2 protein, so as to mediate the protein expression of downstream NQO1, regulate oxidative stress response caused by obstructive jaundice, and thereby alleviate renal injury in rats.
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ObjectiveTo investigate the effect of alcohol extract of Oroxylum indicum (MHD-80) on reducing uric acid (UA) and protecting the kidney in the hyperuricemia (HUA) model in vivo. MethodPotassium oxazine (350 mg·kg-1) and adenine (80 mg·kg-1) were used to construct an HUA model of mice in vivo to evaluate the mechanism related to UA reduction and the protective effect of renal function of MHD-80. Seventy male ICR mice were randomly divided into seven groups, including the normal group, model group, allopurinol group (5 mg·kg-1), febusotan group (5 mg·kg-1), and MHD-80 low-, medium-, and high-dose groups (3, 6, 12 mg·kg-1), with 10 in each group. Except for the normal group, the other groups were given intragastric administration of potassium oxazine and adenine for 14 consecutive days to establish the HUA model. On the 8th to 14th day after modeling, each group was given corresponding drugs by intragastric administration, once a day. 1 h after the last administration, blood was collected from the eyeballs, and kidney and liver tissues of mice were collected. Serum levels of UA, urea nitrogen (BUN), and creatinine (Cr) and liver activity of xanthine oxidase (XOD) were determined by enzyme colorimetry. Serum contents of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were determined by enzyme-linked immunosorbent assay (ELISA). Hematoxilin-eosin (HE) staining was used to observe the pathological changes in kidney tissues. The protein expression levels of ATP-binding box transporter G2 (ABCG2) and glucose-facilitating transporter 9 (GLUT9) in kidney tissues were detected by Western blot. ResultIn vivo experiment shows that compared with the normal group, the serum levels of UA, Cr, BUN, inflammatory factors TNF-α, IL-1β, and liver XOD activity in the serum of mice in the model group were significantly increased (P<0.05, P<0.01), and the expression of GLUT9 in kidney tissues was significantly up-regulated (P<0.05). ABCG2 protein expression was significantly down-regulated (P<0.05), and renal injury was obvious. Compared with the model group, the levels of UA, BUN, Cr, TNF-α, IL-1β, and liver XOD activity in the serum of mice in the high-dose group of MHD-80 were decreased to different degrees (P<0.05, P<0.01), GLUT9 protein expression was significantly down-regulated (P<0.01), ABCG2 protein expression was significantly up-regulated (P<0.05) in the high-dose group of MHD-80, and the degree of renal injury was reduced. ConclusionMHD-80 has certain uric acid reduction, anti-inflammatory, and anti-renal injury effects, which are related to inhibiting XOD activity and regulating the expression of ABCG2 and GLUT9 uric acid transporter.
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Objective To elucidate the mechanism of dl-3-N-butylphthalide (NBP) on renal ischemia-reperfusion injury (IRI) in rat models. Methods Forty SD rats were randomly divided into the sham operation group (Sham group), model group (IRI group), NF-κB inhibitor pyrrolidine dithiocarbamate group (PDTC group), low-dose NBP group (NBP-L group) and high-dose NBP group (NBP-H group), with 8 rats in each group. Serum creatinine (Scr), serum cystatin C(Cys-C), blood urea nitrogen (BUN) and serum interleukin (IL)-1β and IL-18 levels were detected in all groups. Pathological injury of renal tissues in each group was observed by Hematoxylin-eosin (HE) staining. The expression levels of inflammatory factors and nuclear factor (NF)-κB signaling pathway and cell pyroptosis-related proteins in renal tissues were measured by Western blot and immunohistochemical staining. Results Compared with the Sham group, renal tissue injury was more severe, and the levels of Scr, Cys-C, BUN and serum IL-1β and IL-18 were all up-regulated in the IRI group. Western blot showed that the relative expression levels of NOD-like receptor protein (NLRP3), Gasdermin D(GSDMD), cysteinyl aspartate specific proteinase (Caspase)-1, IL-18, IL-1β, NF-κB p65 and p-NF-κB p65 proteins were all up-regulated, and immunohistochemical staining revealed that the expression levels of NF-κB p65 and p-NF-κB p65, IL-1β, IL-18 and NLRP3 proteins were all up-regulated in the IRI group. Compared with the IRI group, renal tissue injury was alleviated, and the levels of Scr, Cys-C, BUN and serum IL-18 and IL-1β were down-regulated in the PDTC, NBP-L and NBP-H groups. Western blot showed that the expression levels of NLRP3, GSDMD, Caspase-1, IL-1β, IL-18, NF-κB p65 and p-NF-κB p65 proteins were down-regulated, and immunohistochemical staining indicated that the expression levels of NF-κB p65, p-NF-κB p65, IL-1β, IL-18 and NLRP3 proteins were down-regulated in the PDTC, NBP-L and NBP-H groups, respectively. Compared with the NBP-L group, renal tissue injury was mitigated, and the levels of Scr, Cys-C, BUN, serum IL-18 and IL-1β were all down-regulated in the NBP-H group. Western blot showed the expression levels of NLRP3, GSDMD, Caspase-1, IL-1β, IL-18, NF-κB p65 and p-NF-κB p65 proteins were down-regulated in the NBP-H group. Immunohistochemical staining indicated that the expression levels of NF-κB p65, p-NF-κB p65, IL-1β, IL-18 and NLRP3 proteins were down-regulated in the NBP-H group. Conclusions NBP may down-regulate the activity of NF-κB/NLRP3 signaling pathway and reduce the expression levels of cell pyroptosis-related proteins and inflammatory factors after renal IRI, thereby suppressing cell pyroptosis and alleviating renal IRI.
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Objective To investigate the effect of the fusion of leader peptide on the structure of human manganese superoxide dismutase (SOD2) and anti-cisplatin (DDP)-induced renal injury. Methods The effect of mitochondrion targeting sequence (MTS) on the structure and activity of SOD2 was analyzed by structure prediction and superoxide dismutase (SOD) specific-activity determination. The DDP injury model of Kunming (KM) mice was established, and amifostine (AMFT) was set as a positive control. Indicators such as kidney index, renal function, kidney antioxidant capacity, and appearance and pathology changes of mice kidney were used to evaluate the effect of MTS-SOD2 against DDP-induced kidney injury. Results The MTS leader peptide seemed to change the secondary and tertiary structures of SOD2 to some extent, but it also increased the specific activity of the MTS-SOD2 protein. Pre-administration of a medium dose of MTS-SOD2 (0.84 mg/kg) before the use of DDP significantly reduced the level of renal malondialdehyde and increased the SOD activity and total antioxidant capacity (T-AOC) in the kidney, thereby reducing the renal pathological damage and consequently maintaining renal function. The overall protective effect of MTS-SOD2 was comparable to or even better than that of 200 mg/kg AMFT. Conclusion The MTS leader peptide enhances the activity of SOD2 and confers it with an excellent anti-DDP-induced renal-injury effect because of its transmembrane function.
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This paper analyzed the clinical data, diagnosis and treatment of 4 asymptomatic patients with ureteral calculi without hydrops in our hospital from October 2018 to January 2019, and comprehensively discussed the previous literature. The 4 patients in this group had no obvious clinical symptoms, no positive stones were found in the B-ultrasound of the urinary system, and no hydroureter and hydroureter of the affected side was found. Urinary CT scan confirmed ureteral stones. They were all located in the lower ureter, and the stones obstructed the lumen. The stones were round and smooth, and there was no obvious hyperplasia and edema in the surrounding mucosa. The lithotripsy was completed in the first-stage operation, and the DJ catheter was left behind for one month after the operation. Based on the clinical diagnosis and treatment process of the 4 cases of asymptomatic calculi in this group and the analysis of previous studies, these patients were mostly detected by imaging examinations or other systematic imaging examinations during the regular review of urinary calculi. Ureteral stones with obstruction did not necessarily have stone-related symptoms. The onset of renal colic involved an increase in intraluminal pressure, related stimulation of nerve endings, smooth muscle spasms caused by stretching of the ureteral wall, and systemic changes in cytokines and related hormones. Cascade reactions, etc., were associated with the movement of stones down. Ureteral stones without hydrops were mostly located in the lower ureter, which had a certain buffering effect on obstructive pressure. Asymptomatic ureteral calculi could also induce irreversible damage to renal function, and the proportion of damage increased with the diameter of the stone. Patients with a history of urinary calculi, especially those with asymptomatic stones for the first time, should be paid attention to during clinical follow-up. At present, there are few research reports on asymptomatic and non-accumulating ureteral calculi. We analyze the clinical diagnosis and treatment process and characteristics of this group of patients combined with previous literature to provide a reference for the diagnosis and treatment of such patients.
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Humanos , Cálculos Ureterales/terapia , Cálculos Urinarios/terapia , Uréter , Litotricia/métodos , Edema/terapia , Cálculos Renales/terapiaRESUMEN
Objective:To analyze the risk factors of Henoch-Schonlein purpura complicated by renal injury.Methods:Ninety patients with Henoch-Schonlein purpura admitted to The First Affiliated Hospital of Anhui Medical University from May 2019 to March 2022 were included in this study. A retrospective cohort study was conducted, and patients were divided into a non-renal injury group and a renal injury group based on whether they were complicated by renal injury. Clinical data were collected from the two groups. Univariate and multivariate logistic regression analyses were performed to identify the relevant risk factors for Henoch-Schonlein purpura complicated by renal injury.Results:There were no significant differences in sex, infection history, abdominal pain, arthralgia, gastrointestinal bleeding, prothrombin time, hemoglobin, albumin, activated partial thromboplastin, fibrinogen, blood lipids, and immunoglobulin levels between the two groups (all P > 0.05). The age of patients in the renal injury group was 49.5 (25, 65.25) years, which was significantly higher than 19 (10, 30.75) in the non-renal injury group ( Z = -4.17, P < 0.05). The incidence of previous purpura in the renal injury group was 36.2% (21/58), which was significantly higher than 9.4% (3/32) in the non-renal injury group ( χ2 = 7.59, P < 0.05). The white blood cell count in the renal injury group was 9.66 (6.80, 14.21) × 10 9/L, which was significantly higher than 7.78 (6.01, 10.53) × 10 9/L in the non-renal injury group ( Z = -2.00, P < 0.05). The platelet count in the renal injury group was 222.50 (189.75, 291.75) × 10 9/L, which was significantly lower than 274.50 (233.00, 322.50) × 10 9/L in the non-renal injury group ( Z = -2.71, P < 0.05). Logistic regression analysis showed that age ( OR = 1.055, 95% CI: 1.026-1.084) and previous purpura ( OR = 6.610, 95% CI: 1.653-26.428) were independent risk factors for Henoch-Schonlein purpura complicated by renal injury ( P < 0.05). Conclusion:The occurrence of Henoch-Schonlein purpura complicated by renal injury is associated with patient age, history of purpura, white blood cell count, and platelet level.
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Globally, cardiac arrest (CA) is a leading cause of death and disability. Asphyxial CA (ACA)-induced kidney damage is a crucial factor in reducing the survival rate. The purpose of this study was to investigate the role of antioxidant enzymes in histopathological renal damage in an ACA rat model at different time points. A total of 88 rats were divided into five groups and exposed to ACA except for the sham group. To evaluate glomerular function and oxidative stress, serum levels of blood urea nitrogen (BUN) and creatinine (Crtn) and malondialdehyde (MDA) levels in renal tissues were measured. To determine histopathological damage, hematoxylin and eosin staining, periodic acid-Schiff staining, and Masson's trichrome staining were performed. Expression levels of antioxidant enzymes including superoxide dismutase-1 (SOD-1), superoxide dismutase-2 (SOD-2), catalase (CAT), and glutathione peroxidase (GPx) were measured by immunohistochemistry (IHC). Survival rate of the experimental rats was reduced to 80% at 6 h, 55% at 12 h, 42.9% at 1 day, and 33% at 2 days after return of spontaneous circulation. Levels of BUN, Crtn, and MDA started to increase significantly in the early period of CA induction. Renal histopathological damage increased markedly from 6 h until two days post-CA. Additionally, expression levels of antioxidant enzymes were significantly decreased at 6 h, 12 h, 1 day, and 2 days after CA. CA-induced oxidative stress and decreased levels of antioxidant enzymes (SOD-1, SOD-2, CAT, GPx) from 6 h to two days could be possible mediators of severe renal tissue damage and increased mortality rate.
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SUMMARY OBJECTIVE: Intervention in chronic total occlusion lesions involves long procedure time, a serious contrast load, and complex procedures. In this study, we aimed to investigate mortality rate of patients who had procedural coronary angiography done for chronic total occlusion lesions in coronary angiography series and who developed contrast-induced nephropathy. METHODS: A total of 218 patients with chronic total occlusion lesion in at least one coronary artery, from three different medical centers, who underwent procedural coronary angiography were recruited for the study. Patient population was divided into two groups: those who developed contrast-induced nephropathy and those who did not. Mortality due to all causes was investigated between both groups throughout a 100-month follow-up. RESULTS: Mean age of patients with incidence of contrast-induced nephropathy was 66.7±11.8, and 23.8% of them were comprised by female. We found a significantly higher mortality in long-term follow-up in the patient group with contrast-induced nephropathy (42.9 vs. 57.1%, p≤0.001). According to Kaplan-Meier analysis performed additionally, survival during follow-up was significantly shorter in this group and, in logistic regression analysis, it was an independent predictor of mortality (OR 3.02; 95%CI 1.41-6.45, p=0.004). CONCLUSION: We identified that the development of contrast-induced nephropathy is associated with long-term mortality. It might be possible to reduce adverse events with prophylactic approaches before the procedure and close follow-up of such patients after the procedure.
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ABSTRACT BACKGROUND: Acute kidney injury (AKI) is a frequent complication during the postoperative period following liver transplantation. Occurrence of AKI in intensive care unit (ICU) patients is associated with increased mortality and higher costs. OBJECTIVE: To evaluate occurrences of moderate or severe AKI among patients admitted to the ICU after liver transplantation and investigate characteristics associated with this complication. DESIGN AND SETTING: Single-center retrospective cohort study in a public hospital, Belo Horizonte, Brazil. METHODS: Forty-nine patients admitted to the ICU between January 2015 and April 2017 were included. AKI was defined from a modified Kidney Disease Improving Global Outcomes (KDIGO) score (i.e. based exclusively on serum creatinine levels). RESULTS: Eighteen patients (36.7%) developed AKI KDIGO 2 or 3; mostly KDIGO 3 (16 out of the 18 patients). Lactate level within the first six hours after ICU admission (odds ratio, OR: 1.3; 95% confidence interval, CI: 1.021-1.717; P = 0.034) and blood transfusion requirement within the first week following transplantation (OR: 8.4; 95% CI: 1.687-41.824; P = 0.009) were independently associated with development of AKI. Patients with AKI KDIGO 2 or 3 underwent more renal replacement therapy (72.2% versus 3.2%; P < 0.01), had longer hospital stay (20 days versus 15 days; P = 0.001), higher in-hospital mortality (44.4% versus 6.5%; P < 0.01) and higher mortality rate after one year (44.4% versus 9.7%; P = 0.01). CONCLUSION: Need for blood transfusion during ICU stay and hyperlactatemia within the first six postoperative hours after liver transplantation are independently associated with moderate or severe AKI. Developing AKI is apparently associated with poor outcomes.