ABSTRACT
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.
ABSTRACT
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.
ABSTRACT
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.
ABSTRACT
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.
ABSTRACT
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.
ABSTRACT
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.
ABSTRACT
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.
ABSTRACT
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.
ABSTRACT
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.
ABSTRACT
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
ABSTRACT
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.
ABSTRACT
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.
ABSTRACT
Introduction: rhabdomyolysis is a clinical and paraclinical syndrome characterized by the presence of skeletal muscle necrosis that leads to the consequent release of intracellular muscle components with a variable clinical presentation and complications that put life at risk such as acute kidney injury. Methods: we present a case report of a patient with rhabdomyolysis with severe elevation of muscle enzymes and secondary acute kidney injury who was subsequently documented (initial Total CK 189,000 u/L) after extreme physical activity (CrossFit), who developed multiple complications and the need for support in the Intensive Care Unit (ICU) with satisfactory outcome. Results: Patient with kidney failure, receiving renal therapy with a favorable evolution and survival at discharge from the intensive care unit of a third-level hospital in the city of Pereira, Risaralda, Colombia. Conclusions: Rhabdomyolysis is a clinical and paraclinical syndrome characterized by the presence of skeletal muscle necrosis. The main cause is severe direct traumatic injury or crushes injuries; however, other conditions such as infections, intoxication, muscle ischemia, neuroleptic malignant syndrome, malignant hyperthermia, metabolic disorders, and genetic pathologies can also cause it, and particularly, extended rest, immobilization or strenuous exercise. The clinical presentation and complications are variable.
Introducción: la rabdomiólisis es un síndrome clínico y paraclínico caracterizado por la presencia de necrosis del músculo esquelético que lleva a la liberación de componentes musculares intracelulares, con una presentación clínica variable y complicaciones que ponen en riesgo la vida,como la insuficiencia renal aguda. Métodos: presentamos un caso clínico de un paciente con rabdomiólisis con elevación severa de enzimas musculares y lesión renal aguda secundaria que posteriormente se documentó (CK Totalinicial189.000u/L) luego de actividad física extrema (CrossFit), quien desarrolló múltiples complicaciones y la necesidad de apoyo en la Unidad de Cuidados Intensivos (UCI) con evolución satisfactoria. Resultados: Paciente con insuficiencia renal, que recibe terapia renal con una evolución favorable y supervivencia al egreso de la unidad de cuidados intensivos de un hospital de tercer nivel de la ciudad de Pereira, Risaralda, Colombia. Conclusiones: La rabdomiólisis es un síndrome clínico y paraclínico caracterizado por la presencia de necrosis del músculo esquelético. La causa principal son las lesiones traumáticas directas severas o las lesiones por aplastamiento; sin embargo, otras condiciones como las infecciones, la intoxicación, la isquemia muscular, el síndrome neuroléptico maligno, la hipertermia maligna, los trastornos metabólicos y las patologías genéticas también pueden causarla, y en particular, el reposo prolongado, la inmovilización o el ejercicio extenuante. La presentación clínica y las complicaciones son variables.
ABSTRACT
Chemotherapy agents have some undesirable and non-selective cytostatic effects. Considering that kidneys are vulnerable to drug-induced toxicity, this study evaluated renal injury caused by vincristine sulfate (VS) in 12 female dogs diagnosed with transmissible venereal tumor (TVT). The animals were treated with VS (0.025 mg/kg IV) every 7 days for 4 weeks. During treatment, the animals were subjected to clinical examination, blood count, serum measurement of symmetric dimethylarginine (SDMA), blood urea nitrogen (BUN), creatinine, alanine aminotransferase, and alkaline phosphatase. In addition, urinalysis and urinary gamma-glutamyl transferase (GGT) measurements were performed. All parameters were determined three times: before beginning the treatment (T0), after 14 days (T1), and after 28 days (T2). During the study period, there were no changes in serum urea or creatinine levels, urine specific gravity, or persistent proteinuria. Furthermore, urinary GGT measurement did not indicate tubular lesions, and consistent elevation of SDMA was found in only one patient above the reference range. The results showed that weekly therapy with VS as a single agent for 28 days does not induce renal injury in most cases.(AU)
Os agentes quimioterápicos possuem efeitos citostáticos indesejáveis e não seletivos. Considerando a vulnerabilidade renal à toxicidade induzida por drogas, este estudo avaliou a lesão renal causada pelo sulfato de vincristina (VS) em 12 cadelas com diagnóstico de tumor venéreo transmissível (TVT). Os animais foram tratados com VS (0,025 mg / kg IV) a cada sete dias, durante quatro semanas. No transcurso do tratamento, os animais foram submetidos a exame clínico, hemograma, dosagem sérica de dimetilarginina simétrica (SDMA), nitrogênio ureico sanguíneo (BUN), creatinina, alanina aminotransferase e fosfatase alcalina. Além disso, foram realizadas análises de urina e medições de gama-glutamil transferase (GGT) urinária. Todos os parâmetros foram mensurados em três tempos, antes do início do tratamento (T0), aos 14 dias (T1) e aos 28 dias (T2). Durante o período do estudo, não houve alterações nas concentrações de ureia ou creatinina séricas, na gravidade específica da urina ou proteinúria persistente. Além disso, a medição de GGT urinária não indicou lesões tubulares, e elevação consistente de SDMA foi encontrada em apenas um paciente acima do intervalo de referência. Os resultados mostraram que a terapia semanal com VS como agente único por 28 dias não induz lesão renal na maioria dos casos.(AU)
Subject(s)
Animals , Female , Dogs , Venereal Tumors, Veterinary/drug therapy , Vincristine/adverse effects , Renal Insufficiency, Chronic/veterinary , Medical Examination , Dogs/injuriesABSTRACT
Objective:To establish an early prediction Nomogram model for severe acute pancreatitis(SAP) complicated with acute renal injury (AKI), and evaluate the prediction efficiency of the model.Methods:The clinical data of 295 SAP patients hospitalized in Zhejiang Rongjun Hospital from July 2017 to June 2021 were retrospectively analyzed, and the patients were divided into AKI group ( n=61) and non-AKI group ( n=234) according to whether complicated with AKI. The common characters, clinical data and laboratory examination results were compared. The risk factors for SAP complicated with AKI was analyzed by multivariate logistic regression analysis, and a nomogram prediction model was established by R software. The receiver operating characteristic (ROC) curve was drawn and the area under the curve (AUC) was calculated to evaluate its prediction performance. Results:The acute physiology and chronic health assessment Ⅱ (APACHEⅡ) and Ranson score, the incidence of abdominal compartment syndrome (ACS) and systemic inflammatory response syndrome (SIRS), the cases of shock and mechanical ventilation, and the levels of blood lactic acid (BLA), blood creatinine (Scr), urea nitrogen (BUN), C-reactive protein (CRP), procalcitonin (PCT) and cystatin C(Cys C) in peripheral blood were significantly higher in AKI group than those in non-AKI group, while the levels of blood calcium were lower than those in non-AKI group, and the differences were statistically significant (all P value <0.05). Multivariate logistic regression analysis showed that APACHEⅡ score ( OR=1.185, 95% CI 1.074-1.308, P=0.001), Ranson score ( OR=12.668, 95% CI 5.102-31.456, P<0.001), Scr ( OR=1.028, 95% CI 1.002-1.054, P=0.034), PCT ( OR=4.298, 95% CI 1.379-13.395, P<0.001) and Cys C ( OR=38738.38, 95% CI 43.190-347459.41, P<0.001) were independent risk factors for SAP complicated AKI. Serum calcium ( OR=0.0001, 95% 0.000-0.048, P<0.001) was an independent protective factor for SAP complicated AKI. A Nomogram prediction model based on the six factors above were established, and its AUC, sensitivity and specificity to predict AKI were 0.987, 99.0% and 98.5% in the training set, and were 0.976, 98.6% and 94.2% in the validation set. Conclusions:This study successfully established an early prediction model with high predict value for SAP complicated with AKI, which can efficiently predict the risk of SAP with concurrent AKI.
ABSTRACT
Objective:To study the risk factors of acute kidney injury in patients with diabetic nephropathy and the prognostic value of urinary neutrophil gelatinase associated lipocalin (NGAL) .Methods:The data of 80 patients with diabetic nephropathy in the First Hospital of Shanxi Medical University from Mar. 2016 to Dec. 2020 were retrospectively studied. According to the random selection of numbers + artificial arrangement, they were divided into observation group and control group according to the presence or absence of acute kidney injury (AKI) . The observation group included patients with diabetic nephropathy complicated by acute kidney injury, and the control group included patients with diabetic nephropathy. The urinary albumin/creatinine ratio (ACR) , blood routine, left ventricular ejection fraction (LVEF) , NGAL, etc. were compared between the two groups. The correlation and influencing factors of acute kidney injury in patients with diabetic nephropathy and age, eGFR, severe infection, antibiotics, heart failure, respiratory failure, ACR, LVEF, and NGAL were studied. At the same time, the prognostic value of urinary NGAL was analyzed.Results:Single factor screening: There was no significant difference in gender or body weight between the two groups ( P>0.05) . However, there were differences in age, epidermal growth factor receptor (eGFR) , severe infection, antibiotics, heart failure, respiratory failure, ACR, LVEF, and NGAL ( P<0.05) . Correlation: Acute kidney injury in patients with diabetic nephropathy was very weakly correlated with gender, age, and body weight, moderately correlated with eGFR, heart failure, respiratory failure, ACR, and LVEF, and highly correlated with NGAL, severe infection, and antibiotics. Risk factors: The independent risk factors for acute kidney injury in patients with diabetic nephropathy included severe infection, eGFR, antibiotics, ACR, LVEF, and NGAL. The prognostic value of urinary NGAL: AUC=0.967, standard error 0.021, Youden index 0.967, sensitivity 0.967, specificity 1, and zero cutoff point 30.00. Conclusion:The main influencing factors of DN complicated with AKI are severe infection, eGFR, antibiotics, ACR, LVEF, NGAL, and urinary NGAL has prognostic value for DN complicated with AKI, and it is worthy of clinical application.
ABSTRACT
Objective:To investigate the significant effects of enhanced whole-body computed tomography (EWBCT) and non-enhanced whole-body computed tomography (N-EWBCT) on the missed diagnosis rate, renal function and prognosis of patients with severe trauma.Methods:Clinical data of trauma patients admitted from January 1, 2017 to December 31, 2020 were collected from the trauma database of the Trauma Center of the Second Affiliated Hospital of Soochow University. All patients included in this study were divided into the EWBCT group and N-EWBCT group according to whether they underwent enhanced whole-body computed tomography examination. The differences in baseline data, missed diagnosis rate, renal function and prognosis of the two groups of patients were compared.Results:A total of 459 patients were included in this study, including 184 patients in the EWBCT group and 275 patients in the N-EWBCT group. The missed diagnosis rate of the N-EWBCT group was significantly higher than that of the EWBCT group (18% vs. 5%, P < 0.01). The risk ratio of acute kidney injury (AKI) in the EWBCT group and N-EWBCT group was 9% and 7%, respectively, and there was no statistical difference between the two groups ( P >0.05). The mortality rate of patients in the N-EWBCT group was higher than that in the EWBCT group (23% vs. 12%, P=0.002). Conclusions:Compared with N-EWBCT, EWBCT does not significantly increase the risk of renal damage in patients with severe trauma. For patients with severe trauma, early EWBCT can reduce the missed diagnosis rate and improve the clinical prognosis.
ABSTRACT
ObjectiveTo observe the effect of Hedysarum polysaccharides （HPS） on the Wnt/β-catenin signal pathway in db/db mice with diabetic nephropathy. MethodFifty db/db mice were randomly divided into model group， irbesartan group， and high， middle， and low-dose HPS experimental groups according to their body mass， with 10 mice in each group， and another 10 C57BL/6 mice were selected as a normal group. The normal group and the model group were given 5 mL·kg-1·d-1 distilled water， the irbesartan group was given 22.75 mg·kg-1·d-1 irbesartan suspension， and the high， middle， and low-dose HPS experimental groups were given 200， 100， and 50 mg·kg-1·d-1 HPS suspensions， respectively. The mice in the 6 groups were given intragastric administration once a day for 12 weeks. The general state， blood glucose （GLU）， 24 h urine protein （UTP）， blood creatinine （SCr）， and urea nitrogen （BUN） of mice in each group were determined. The pathological changes in the kidney tissue were observed by hematoxylin-eosin staining （HE）. The protein and mRNA expression levels of Wnt1， β-catenin， glycogen synthesis kinase-3β （GSK-3β）， and phosphorylated GSK-3β （p-GSK-3β） in the kidney were detected by Western blot and real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. ResultAfter treatment for 12 weeks， as compared with the normal group， the general state of mice in the model group was worse and the pathological ultrastructural lesions of kidney tissues were obvious. The levels of GLU， 24 h UTP， SCr， and BUN in the model group increased （P<0.01）. As compared with the model group， the general state and renal pathological ultrastructure of mice in the high and middle-dose HPS groups were improved to some extent， and the levels of SCr， BUN， and 24 h UTP in the high and middle-dose HPS groups decreased （P<0.05，P<0.01）. As compared with the normal group， the expression levels of Wnt1， β-catenin， GSK-3β， and p-GSK-3β protein and mRNA in the model group were higher （P<0.01）， while the expression levels of Wnt1， β-catenin， GSK-3β， and p-GSK-3β protein and mRNA in the high and middle-dose HPS groups were lower than those in the model group （P<0.05，P<0.01）. ConclusionHPS can alleviate the renal injury of diabetic nephropathy to some extent， and its mechanism may be related to the inhibition of the activation of the Wnt/β-catenin signal pathway.
ABSTRACT
OBJECTIVES@#Farnesoid X receptor (FXR) is a member of the nuclear receptor superfamily of ligand activated transcription factors and belongs to bile acid receptor. Studies have shown that the expression of FXR in renal tissue can reduce renal injury via regulation of glucose and lipid metabolism, inhibition of inflammatory response, reduction of oxidative stress and renal fibrosis. However, it is unclear whether FXR is involved in autophagy in renal diseases. This study aims to investigate the role of FXR in cisplatin-induced acute renal injury and whether its mechanism is related to autophagy regulation.@*METHODS@#Twelve male WT or FXR-KO mice at 12 weeks were randomly divided into a WT group, a WT+cisplatin group, a FXR-KO group, and a FXR-KO+cisplatin group, with 6 mice in each group. The WT+cisplatin group and the FXR-KO+cisplatin group were intraperitoneally injected with cisplatin (20 mg/kg), and the WT group and the FXR-KO group were intraperitoneally injected with equal volume of cisplatin solvent. Seventy-two hours later, the mice were killed and blood and renal tissue samples were collected. The levels of SCr and BUN were detected by immunoturbidimetry. After the staining, the pathological changes of renal tissue were observed under optical microscope. The protein levels of LC3 and p62 were detected by Western blotting and immunohistochemistry. The clearance of damaged mitochondria and the accumulation of lysosomal substrate were observed under electron microscope. The apoptosis of renal tubular epithelial cells was detected by TUNEL.@*RESULTS@#Compared with the WT group or the FXR-KO group, both SCr and BUN levels in the WT+cisplatin group or the FXR-KO+cisplatin group were significantly increased (P<0.01 or P<0.001), and SCr and BUN levels in the FXR-KO+cisplatin group were significantly higher than those in the WT+cisplatin group (both P<0.05). Under the light microscope, there were no obvious pathological changes in the renal tissue of mice in the WT group and the FXR-KO group. Both the WT+cisplatin group and the FXR-KO+cisplatin group had vacuolar or granular degeneration of renal tubular epithelial cells, flat cells, lumen expansion, brush edge falling off, and even exposed basement membrane and tubular formation. The scores of renal tubular injury in the WT+cisplatin group and the FXR-KO+cisplatin group were significantly higher than those in the WT group and the FXR-KO group, respectively (both P<0.001), and the score in the FXR-KO+cisplatin group was significantly higher than that in the WT+cisplatin group (P<0.05). Under the transmission electron microscope, the mitochondria of mouse tubular epithelial cell in the WT+cisplatin group and the FXR-KO+cisplatin group was swollen, round, vacuolated, cristae broken or disappeared; the lysosome was uneven and high-density clumps, and the change was more obvious in the FXR-KO+cisplatin group. Western blotting showed that the ratio of LC3-II to LC3-I was decreased and the expression of p62 was increased in the WT+cisplatin group compared with the WT group and the FXR-KO+cisplatin group compared with FXR-KO group (P<0.05 or P<0.01); compared with the FXR-KO group, the ratio of LC3-II to LC3-I was decreased and the expression of p62 was increased significantly in the FXR-KO+cisplatin group (both P<0.05). Immunohistochemistry results showed that the expression of total LC3 and p62 in renal cortex of the WT+cisplatin group and the FXR-KO+cisplatin group was increased significantly, especially in the FXR-KO+cisplatin group. TUNEL results showed that the mice in the WT group and the FXR-KO group had negative staining or only a few apoptotic tubular epithelial cells, and the number of apoptotic cells in the WT+cisplatin group and the FXR-KO+cisplatin group were increased. The apoptosis rates of renal tubular epithelial cells in the WT+cisplatin group and the FXR-KO+cisplatin group were significantly higher than those in the WT group and the FXR-KO group, respectively (both P<0.001), and the apoptosis rate in the FXR-KO+cisplatin group was significantly higher than that in the WT+cisplatin group (P<0.05).@*CONCLUSIONS@#Knockout of FXR gene aggravates cisplatin induced acute renal injury, and its mechanism may be related to inhibiting autophagy and promoting apoptosis.