Dl-3-N-butylphthalide alleviates renal ischemia-reperfusion injury by down-regulating NF-κB signaling pathway and inhibiting cell pyroptosis in rat models / 器官移植

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.

Determination of polymyxin B concentration in plasma and its application in critically ill patients / 中国药房

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.

Relationship between contrast-induced nephropathy and long-term mortality after percutaneous coronary intervention in patients with chronic coronary total occlusion

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.

Risk factors for acute kidney injury after liver transplantation in intensive care unit: a retrospective cohort study

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.

Rabdomiolisis causada por ejercicio

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.

Knockout of farnesoid X receptor gene aggravates cisplatin-induced kidney injury / 中南大学学报(医学版)

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.

Construction and evaluation of early prediction model for severe acute pancreatitis complicated with acute renal injury / 中华胰腺病杂志

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.

Risk factors of acute kidney injury in patients with diabetic nephropathy and the prognostic value of urine NGAL / 中华内分泌外科杂志

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.

The clinical value of enhanced whole-body CT in the early treatment of severe trauma / 中华急诊医学杂志

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.

Nephrotic syndrome associated with primary atypical hemolytic uremic syndrome / Síndrome nefrótica associada à síndrome hemolítico-urêmica atípica primária

Abstract Primary atypical hemolytic-uremic syndrome is a rare disease characterized by non-immune microangiopathic hemolytic anemia, thrombocytopenia, and renal dysfunction; it is related to alterations in the regulation of the alternative pathway of complement due to genetic mutations. The association with nephrotic syndrome is unusual. We present here a pediatric patient diagnosed with primary atypical hemolytic-uremic syndrome associated with nephrotic syndrome who responded to eculizumab treatment.

Resumo A síndrome hemolítico-urêmica atípica primária é uma doença rara, caracterizada por anemia hemolítica microangiopática não-imune, trombocitopenia e disfunção renal; está relacionado a alterações na regulação da via alternativa do complemento devido a mutações genéticas. A associação com a síndrome nefrótica é incomum. Apresentamos aqui um paciente pediátrico com diagnóstico de síndrome hemolítico-urêmica atípica primária associada à síndrome nefrótica que respondeu ao tratamento com eculizumab.

Impacto da hemodiálise em pacientes críticos com insuficiência renal em um hospital no Distrito Federal / Impact of hemodialysis in critical patients with renal insufficiency in a hospital in the Federal District

Introdução: Tempo de início da hemodiálise (HD) desempenha um papel importante nos desfechos dos pacientes. Objetivo: Analisar as consequências de um tempo prolongado para início da realização de HD, em pacientes críticos com lesão renal. Métodos: Quantitativo, analítico e retrospectivo, por meio de coleta de dados em prontuários eletrônicos de pacientes. Resultados: Cerca de 41,66% (n= 70) dos pacientes aguardaram um período maior que 24 horas para hemodiálise. O risco de óbito antes da realização da HD é 5.15 vezes maior quando o tempo até a hemodiálise é posterior a 24 horas. Conclusão: É preciso evitar tais mortes com uma nova forma de repensar a gestão de recursos de saúde.

Introduction: Hemodialysis (HD) initiation time play an important role in patientsoutcomes. Objective: To analyze the consequences of prolonged time to the start of HD in critically ill patients. Methods: Quantitative, analytical and retrospective, through the collection of data in the electronic medical records of hospitalized patients. Results: About 41.66% (n=70) of the patients waited for a longer period than 24 hours for HD. The risk of death before HD is 5.15 times higher when the time until performing HD is after 24 hours. Conclusion: It is necessary to avoid this deaths with a new way to rethinking the management of health resources.

Renal artery involvement: independent risk factors of KDIGO stage 3 in acute renal injury after moderate hypothermic circulatory arrest in acute Stanford type A aortic dissection / 中华胸心血管外科杂志

Objective:To explore whether renal artery involvement is an independent risk factor of acute renal injury (AKI) KDIGO stage 3 after moderate hypothermic circulatory arrest in patients with acute Stanford type A aortic dissection.Methods:From December 2015 to October 2017, 492 consecutive patients with acute Stanford A-type aortic dissection received surgical treatment, 486 of them were included in the study. All patients underwent aortic CTA to determine the extent of aortic dissection and renal artery involvement. According to the standard of Improving Global Outcomes (KDIGO), the renal function of patients after operation was graded. The risk factors of AKI KDIGO stage 3 were analyzed.Renal artery involvement and other risk factors were included in univariate analysis, and significant variables in univariate analysis were included in multivariate logistic regression analysis.Results:In 492 patients, 40 (8.13%) died in hospital, of which 6 died of severe bleeding during operation or failed to wean from cardiopulmonary bypass which lead to unable to leave the Weaning from cardiopulmonary bypass and these 6 patients were excluded in the research. Among 486 patients included in the study, 251 (51.64%) had AKI. Among them, 83 (17.08%) were in the KDIGO stage 1, 56 (11.52%) in stage 2 and 112 (23.05%) in stage 3.The results of univariate analysis showed that there were significant differences in renal artery involvement, age, time from onset to operation, D-dimer, leukocytes and platelets in peripheral blood, creatinine clearance rate, time of cardiopulmonary bypass during operation and aortic cross-clamping time( P>0.05). The above risk factors were included in multivariate logistic regression. The results showed that preoperative renal artery involvement ( OR=1.94, P=0.02), age ( OR=1.03, P=0.02), creatinine clearance rate<85 ml/min ( OR=2.28, P=0.001), and intraoperative cardiopulmonary bypass time ( OR=1.01, P=0.02) were independent risk factors. The incidence of AKI in patients with renal artery involvement was 54.65%, significantly higher than 41.98% in patients without renal artery involvement ( P>0.05). Conclusion:Renal artery involvement is an independent risk factor of AKI KDIGO stage 3 after moderate deep hypothermic circulatory arrest of acute Stanford type A aortic dissection.

Effect of dexmedetomidine on pyroptosis in mice with acute renal injury induced by endotoxin and the relationship with miRNA-223-3p / 中华麻醉学杂志

Objective:To evaluate the effect of dexmedetomidine on pyroptosis in mice with acute renal injury induced by endotoxin and the relationship with miRNA-223-3p.Methods:Thirty-two clean-grade healthy male ICR mice, aged 8-12 weeks, weighing 20-25 g, were divided into 4 groups ( n=8 each) using the random number table method: control group (group C), lipopolysaccharide (LPS) group (group L), LPS plus dexmedetomidine group (group LD), and LPS plus dexmedetomidine plus atipamezole group (group LDT). The model of acute renal injury induced by endotoxin was established by intraperitoneal injection of LPS 400 μg/kg, followed by intraperitoneal injection of LPS 10 mg/kg 8 h later.Dexmedetomidine 40 μg/kg was intraperitoneally injected once every 2 h for 3 times in total starting from 30 min after establishing the model in group LD.Atipamezole 750 μg/kg was intraperitoneally injected immediately after establishing the model, and 30 min later dexmedetomidine 40 μg/kg was intraperitoneally injected once every 2 h for 3 times in total in group LDT.The equal volume of normal saline was intraperitoneally injected in group C. Blood samples were collected from the heart at 24 h after establishing the model, and serum creatinine (Cr) and blood urea nitrogen (BUN) concentrations were measured with an automatic biochemical analyzer.The animals were sacrificed and the left kidney tissues were obtained for microscopic examination of pathological changes after HE staining (with a light microscope) and for determination of the expression of caspase-1 p20, NOD-like receptor thermoprotein structural domain-related protein 3 (NLRP3) and ASC protein and mRNA (by quantitative real-time polymerase chain reaction and Western blot), contents of interleukin-1beta (IL-1β) and IL-18 (by enzyme-linked immunosorbent assay), and rate of pyroptosis in renal cortical cells (by TUNEL). Results:Compared with group C, the concentrations of serum Cr and BUN were significantly increased, the expression of NLRP3, caspase-1 p20 and ASC protein and mRNA in the renal tissues was up-regulated, the contents of IL-1β and IL-18 were increased, the rate of pyroptosis in renal cortical cells was increased ( P<0.05), no significant change was found in the expression of miRNA-223-3p ( P>0.05), and pathological changes of kidney were accentuated in group L. Compared with group L, the concentrations of serum Cr and BUN were significantly decreased, the expression of NLRP3, caspase-1 p20 and ASC protein and mRNA in the renal tissues was down-regulated, the contents of IL-1β and IL-18 were decreased, the rate of pyroptosis in renal cortical cells was decreased, the expression of miRNA-223-3p was up-regulated ( P<0.05), and pathological changes of kidney were attenuated in group LD.Compared with group LD, the concentrations of serum Cr and BUN were significantly increased, the contents of IL-1β and IL-18 were increased, the expression of NLRP3, caspase-1 p20 and ASC protein and mRNA in the renal tissues was up-regulated, the rate of pyroptosis in renal cortical cells was increased, the expression of miRNA-223-3p was down-regulated ( P<0.05), and the pathological changes of kidney were accentuated in group LDT. Conclusion:The mechanism by which dexmedetomidine reduces acute renal injury may be related to up-regulating the expression of miRNA-223-3p and inhibiting pyroptosis in mice.

Protective mechanism of tea polyphenols in potassium dichromate-induced acute renal injury in mice / 中国职业医学

OBJECTIVE: To explore the protective effect of tea polyphenols and its mechanism in potassium dichromate(PD)-induced acute renal injury in mice. METHODS: The specific pathogen free weaned Kunming mice were divided into control group, model group and low-, middle-and high-dose tea polyphenols groups, with 12 mice in each group. Mice in the control group were given 0.9% sodium chloride solution, and mice in other four groups were given PD solution with 4.275 mg/kg body weight every morning by intragastric administration. Then, mice in the control group and model group were given 0.9% sodium chloride solution in the afternoon, while mice in the low-, middle-and high-dose tea polyphenols groups were given 0.3 mL tea polyphenols solution with a dose of 200, 400 or 600 mg/kg body weight, respectively by gavage, once a day for two consecutive weeks. The body mass of mice was weighed during the experiment. At the end of the experiment, the mice were sacrificed. The kidneys were removed and weighed. The kidney organ coefficients were calculated. The levels of urea nitrogen and creatinine in serum were determined by two-point method, the activities of catalase(CAT) and glutathione peroxidase(GSH-Px) in serum of mice were detected by colorimetry. The pathological change of kidney in mice was observed. RESULTS: The body weight of mice in the model group decreased(P<0.05), while the kidney mass, renal organ coefficient, serum levels of urea nitrogen and creatinine increased(all P<0.05), and the serum activities of CAT and GSH-Px decreased(all P<0.05) compared with the control group. The body weight of mice in the three tea polyphenols groups increased(all P<0.05), while the kidney mass, renal organ coefficient, urea nitrogen and creatinine levels in serum decreased(all P<0.05), and the activities of CAT and GSH-Px in serum increased with the increasing intervention dose of tea polyphenols(all P<0.05) compared with the model group. The change of acute renal injury was mainly caused by renal tubular injury in the model group. The pathological changes of renal tissue in the three tea polyphenols intervention groups were improved compared to that in the model group, and the improvement showed a dose-effect relationship with the intervention of tea polyphenols. CONCLUSION: Tea polyphenols have a protective effect on PD-induced acute renal injury with a dose-effect relationship. Its mechanism of action is related to the fact that tea polyphenols can reduce or reverse oxidative stress and inflammation in the kidney.

Terapias de reemplazo renal contínuas (TRRC) en pacientes críticos inmunosuprimidos / Continuous renal replacement therapies (CRRT) in critically ill immunosuppressed patients

La injuria renal aguda (IRA) se caracteriza por un abrupto deterioro de la función renal asociado a lteraciones hidroelectrolíticas y metabólicas. La misma es frecuente en la unidad de cuidados intensivos (UCI) pediátricos y tiene un impacto significativo en la morbilidad y mortalidad. Las principales indicaciones de terapia de reemplazo renal (TRR) incluyen la corrección de los trastornos metabólicos y el manejo de la sobrecarga de fluidos. Varios modos de TRR pueden ser utilizadas en la UCI: hemodiálisis intermitente, diálisis peritoneal y las terapias de reemplazo renal continuas (TRRC). Las terapias de reemplazo renal continuas han ganado un rol preponderante en Cuidados Críticos ya que posibilitan dializar a pacientes hemodinámicamente inestables. Del total de pacientes admitidos en la UCI (n:1506) desde enero 2012 hasta diciembre 2018, requirieron TRRC el 6,7% (n: 102). La mortalidad predicha por el Score PIM3 fue de 19,53%, la mediana de edad en meses fue de 60 (RIC 25-75: 12-144), no hubo diferencias en cuanto al sexo. Los diagnósticos más frecuentes fueron trasplantados de órganos sólidos 33%, seguidos de trasplante de células progenitoras hematopoyéticas (TCPH) el 26%. La mediana de los días de internación fue de 16 (RIC 25-75: 7-29) y de días de requerimiento de una TRRC 5 (RIC 25-75 3-9). La técnica dialítica más utilizada fue CVVHD, en el 87% de los pacientes. La mortalidad global fue del 75%, presentando los pacientes con TCPH mayor mortalidad con respecto a otros diagnósticos. Se debe reconocer y categorizar precozmente a los pacientes con mayor riesgo de desarrollar IRA y aplicar medidas de nefroprotección para mejorar su sobrevida (AU)

Acute renal injury (IRA) is characterized by sudden deterioration of kidney function associated with hydroelectrolytic and metabolic disturbances. IRA is common in the pediatric intensive care unit (ICU) and has a significant impact on morbidity and mortality. The main indications for renal replacement therapy (RRT) include correction of the metabolic disorders and management of fluid overload. Different types of RRT may be used in the ICU: intermittent hemodialysis, peritoneal dialysis, and continuous renal replacement therapies (CRRT). Continuous renal replacement therapies have gained a major role in critical care as they allow for dialysis in hemodynamically unstable patients. Of all patients admitted to the ICU (n:1506) between January 2012 and December 2018, 6.7% required CRRT (n: 102). Predicted mortality rate according to the PIM3 score was 19.53%. Median age was 60 months (IQR 25-75: 12-144). No differences in sex were observed. The most common diagnoses were solid organ transplantation in 33%, followed by hematopoietic stem cell transplantation (HSCT) in 26%. Median length of hospital stay was 16 days (IQR 25-75: 7-29) and median days on CTTT was 5 (IQR 25-75 3-9). The most common dialysis technique was CVVHD, used in 87% of the patients. Overall mortality rate was 75%, with a higher mortality in HSCT patients compared to others. Patients at a higher risk of developing IRA should be timely recognized and categorized and nephroprotective measures should be started early to improve survival (AU)

Bases teóricas sobre la infección por coronavirus-2 en el sistema renal / Theoretical bases on coronavirus-2 infection in the renal system

RESUMEN Introducción: La infección por coronavirus-2, que causa la enfermedad conocida como COVID-19, afecta la función renal en muchos de los pacientes. Objetivo: Ofrecer un referente teórico para contribuir a la preparación de estudiantes de Medicina y médicos generales respecto a la influencia de la infección por coronavirus-2 en el sistema renal. Método: En el Hospital General Docente "Dr. Agostinho Neto", entre marzo y julio de 2020, se hizo una revisión narrativa sobre este tema a través de una búsqueda en diferentes bases de datos bibliográficas: Pubmed/Medline, Science Direct y SciELO. Resultados: La información se estructuró en: aspectos generales de la COVID-19, fisiopatología, manifestaciones, bases terapéuticas, pronóstico e impacto social de la nefropatía causada por COVID-19; también, se identificaron aspectos irresueltos respecto al fallo renal causado por esta pandemia. Conclusiones: El pronóstico del paciente con COVID-19 se agrava por la presencia de fallo renal agudo, no obstante, en la fisiopatología, las manifestaciones clínicas y el pronóstico en los pacientes con esta complicación no es del todo conocida. Su aparición es más común en los pacientes con antecedente de enfermedad renal crónica, diabetes mellitus e hipertensión arterial sistémica, lo que legitima la necesidad de la preparación profesional para ser capaz de una evaluación precisa del sistema renal para la prevención y control de esta complicación.

ABSTRACT Introduction: The infection for coronavirus-2, which causes the infectious disease known as COVID-19, often affects the renal function in many of the patients. Objective: To offer a theoretical referent, to contribute on the preparation of medicine students and general doctors about the influence of the infection for coronavirus-2 on the renal system. Method: In the Hospital Dr. Agostinho Neto, between March and June of 2020, a narrative review about this topic was made through a search in the bibliographical databases Pubmed/Medline, Science Direct and SciELO. Results: The information was structured as: general aspects of the COVID-19, physiopathology, symptoms, therapeutic bases, prognosis, and social impact of the nephropathy caused by COVID-19. Unsettled aspects regarding the renal failure caused by this pandemic were also identified. Conclusions: The patient's prognostic with COVID-19 is worsened by the presence of acute renal failure; nevertheless, in the physiopathology, the clinical manifestations and patient prognosis on this complication are not completely known. Its appearance is more common in patients with an antecedent of chronic kidney failure, diabetes mellitus and systemic arterial hypertension which legitimates the necessity of professional preparation to be capable of a precise evaluation of the renal system for prevention and control of this complication.

Nefritis tubulointersticial aguda. Revisión bibliográfica / Acute interstitial nephritis. Literature review

RESUMEN La nefritis tubulointersticial aguda hace referencia a un tipo de daño renal que afecta principalmente el intersticio y ocasiona la lesión renal aguda, potencialmente reversible. Su curso puede ser subclínico, con deterioro progresivo hasta evolucionar hacia la insuficiencia renal crónica. La nefritis tubulointersticial aguda tiene múltiples etiologías, las más frecuentes son los medicamentos, productos herbales, las infecciones y las enfermedades autoinmunes. Las principales manifestaciones clínicas son la poliuria, polaquiuria, nocturia, dolor lumbar, microhematuria y leucocituria, aunque puede ser totalmente asintomática. El tratamiento depende de la causa de base y los esteroides juegan un papel importante cuando la condición es de origen medicamentoso o autoinmune. El pronóstico generalmente es bueno, si el problema se identifica de forma oportuna y se trata adecuadamente.

SUMMARY Acute tubulointerstitial nephritis is a kidney lesion that mainly affects the interstitium and can lead to a reversible acute kidney injury. It can progress subclinically, with progressive development towards chronic renal failure. Acute tubulointerstitial nephritis has several causes, being the most common medications, herbal products, infections and autoimmune diseases. The main clinical manifestations are polyuria, polaquiuria, nycturia, lumbar pain, microhematuria, leukocyturia, although the patients also can be completely asymptomatic. Treatment is determined by the underlying cause. Steroids play an important role when tubulointerstitial nephritis is caused by medication or autoimmune diseases. The prognosis is usually good if the problem is detected early and treated properly.

Possible association between dysnatremias and mortality during hospitalization in patients undergoing acute hemodialysis: analysis from a Peruvian retrospective cohort / Possível associação entre distúrbios do sódio e mortalidade hospitalar em pacientes submetidos a hemodiálise aguda: análise de uma coorte retrospectiva peruana

Abstract Objective: To evaluate the association between dysnatremias or dyschloremias and mortality during hospitalization in patients with acute kidney injury (AKI) or chronic kidney disease (CKD) undergoing acute hemodialysis. Methods: We carried out a retrospective cohort study on adult patients undergoing acute hemodialysis with AKI or CKD diagnosis at a public hospital in Lima, Peru. Dysnatremias were categorized as hyponatremia (Na < 135mmol/L) or hypernatremia (Na > 145mmol/L), and dyschloremias were defined as hypochloremia (Cl < 98 mmol/L) or hyperchloremia (Cl > 109mmol/L). The outcome of interest was mortality during hospitalization. We performed generalized lineal Poisson family models with bias-corrected and accelerated non-parametric bootstrap to estimate the risk ratios at crude (RR) and adjusted analysis (aRR) by gender, age, HCO3 (for all patients) and Liaño score (only for AKI) with CI95%. Results: We included 263 patients (mean age: 54.3 years, females: 43%): 191 with CKD and 72 with AKI. Mortality was higher in patients with AKI (59.7%) than in patients with CKD (14.1%). In overall, patients with hypernatremia had a higher mortality during hospitalization compared to those who had normal sodium values (aRR: 1.82, 95% CI: 1.17-2.83); patients with hyponatremia did not have different mortality (aRR: 0.19, 95% CI: 0.69-2.04). We also found that hyperchloremia (aRR: 1.35, 95% CI: 0.83-2.18) or hypochloremia (aRR: 0.66, 95% CI: 0.30-14.78) did not increase mortality in comparison to normal chloride values. No association between dysnatremias or dyschloremias and mortality during hospitalization was found in CKD and AKI subgroups. Conclusions: In our exploratory analysis, only hypernatremia was associated with mortality during hospitalization among patients with AKI or CKD undergoing acute hemodialysis.

Resumo Objetivo: Avaliar a associação entre distúrbios do sódio ou do cloro e mortalidade hospitalar de pacientes com insuficiência renal aguda (IRA) ou doença renal crônica (DRC) submetidos a hemodiálise aguda. Métodos: O presente estudo de coorte retrospectiva incluiu pacientes adultos submetidos a hemodiálise aguda com diagnóstico de IRA ou DRC em um hospital público de Lima, Peru. Os distúrbios do sódio foram classificados como hiponatremia (Na < 135mmol/L) ou hipernatremia (Na > 145mmol/L), enquanto os distúrbios do cloro foram classificados como hipocloremia (Cl < 98 mmol/L) ou hipercloremia (Cl > 109mmol/L). O desfecho de interesse foi mortalidade hospitalar. Utilizamos modelos de Poisson da família de modelos lineares generalizados com bootstrap não-paramétrico e correção de viés acelerado para estimar os riscos relativos na análise bruta (RR) e ajustada (RRa) para sexo, idade, HCO3 (para todos os pacientes) e escore de Liaño (apenas para IRA) com IC 95%. Resultados: Foram incluídos 263 pacientes (idade média 54,3 anos; 43% do sexo feminino), 191 com DRC e 72 com IRA. A mortalidade foi mais elevada nos pacientes com IRA (59,7%) do que nos indivíduos com DRC (14,1%). No geral, os pacientes com hipernatremia tiveram mortalidade hospitalar mais elevada do que os indivíduos com valores normais de sódio (RRa: 1,82; IC 95%: 1,17-2,83). Os pacientes com hiponatremia não apresentaram mortalidade diferente (RRa: 0,19; IC 95%: 0,69-2,04). Também identificamos que hipercloremia (RRa: 1,35; IC 95%: 0,83-2,18) e hipocloremia (RRa: 0,66; IC 95%: 0,30-14,78) não elevaram a mortalidade em comparação a indivíduos com níveis normais de cloro. Não foi encontrada associação entre distúrbios do sódio ou do cloro e mortalidade hospitalar nos subgrupos com DRC e IRA. Conclusões: Em nossa análise exploratória, apenas hipernatremia apresentou associação com mortalidade hospitalar em pacientes com IRA ou DRC submetidos a hemodiálise aguda.

Procalcitonina como biomarcador de daño renal agudo en pacientes con sepsis y choque séptico / Procalcitonin as a biomarker for acute kidney injury in patients with sepsis and septic shock

Resumen Introducción: hasta el 60 % de los pacientes con sepsis desarrollan daño renal agudo. La procalcitonina indica la presencia de sepsis y puede predecir un daño renal agudo. Objetivos: determinar los valores de procalcitonina como biomarcador predictor de daño renal agudo y sus complicaciones en el espectro de sepsis. Métodos: estudio transversal. Se midió procalcitonina durante las 24 horas de hospitalización. Se determinó el área bajo la curva, el error estándar, la sensibilidad y especificidad de los valores de procalcitonina relacionado con daño renal agudo. Resultados: un total de 72 pacientes con edad de 51 años (rango 18 -79); 35 (48,6 %) casos eran hombres, 44 (61,1 %) presentaron sepsis, 14 (19,4 %) choque séptico, 11 (15,3 %) sepsis severa y 3 (4,2 %) hipotensión inducida por sepsis. Encontramos una elevación de procalcitonina (≥0,5 ng/mL) en 54 (75 %) pacientes; presentaron daño renal agudo 42 (58,3 %) casos; estadio KDIGO 1 en 19 (45,2 %), KDIGO 2 en 12 (28,6 %) y KDIGO 3 en 11 (26,2 %) pacientes; de ellos 37 (88,1 %) presentaron procalcitonina ≥0,5 ng/mL (OR 5,65, IC 95 % 1,73 - 18,42; p<0,01). El área debajo de la curva 0,75 (IC 95 % 0,63 - 0,86 p <0,0001); el valor de procalcitonina de 2,565 ng/mL tuvo la mayor validez prediciendo daño renal agudo, con sensibilidad de 61,9 %, especificidad de 80 %, un valor predictivo positivo de 44,52 %, valor predictivo negativo de 56,18 %, LR+ de 0.80 y un LR- de 0.77. Conclusión: en el espectro de sepsis, el nivel de procalcitonina ≥2,565 ng/mL al ingreso hospitalario predice daño renal agudo.

Abstract Introduction: Up to 60% of patients with sepsis develop acute kidney injury. Procalcitonin indicates the presence of sepsis and could predict acute kidney injury. Objectives: To determine the values of procalcitonin as a predictive biomarker of acute renal injury and its complications in the sepsis spectrum. Methods: Cross-sectional study. Procalcitonin was measured during the 24 hours of hospitalization. We determined the area under the curve, standard error, sensitivity and specificity of procalcitonin values related to acute renal injury. Results: A total of 72 patients aged 51 years (range 18-79); 35 (48.6%) were male, 44 (61.1%) presented sepsis, 14 (19.4%) had septic shock, 11 (15.3%) severe sepsis and 3 (4.2%) sepsis-induced hypotension. We found an elevation of procalcitonin (≥0.5 ng / mL) in 54 (75%) patients; presented acute renal injury 42 (58.3%) cases; KDIGO 1 in 19 (45.2%), KDIGO 2 in 12 (28.6%) and KDIGO 3 in 11 (26.2%) patients; of them 37 (88.1%) had procalcitonin ≥0.5 ng / mL (OR 5.65, 95% CI 1.73-18.42, p <0.01). The area under the curve 0.75 (95% CI 0.63 - 0.86 p <0.0001); the value of procalcitonin of 2,565 ng / mL had the highest validity predicting acute renal injury, with sensitivity of 61.9%, specificity of 80%, a positive predictive value of44.52%, negative predictive value of 56.18%, LR + of 0.80 and an LR - 0.77. Conclusion: In the sepsis spectrum, the level of procalcitonin ≥2,565 ng / mL at hospital admission predicts acute kidney injury.