Advances in oxidative stress and NOD-like/toll-like receptors in acute renal injury

Acute Kidney Injury(AKI)is a clinical syndrome characterized by rapid renal deterioration with high morbidity and mortality.Renal reperfusion(IRI),renal toxicity and sepsis are the main causes of AKI.IRI is one of the main causes of acute kidney injury in clinic,accounting for 75%of all the causes of AKI[1].The fatality rate of AKI caused by IRI is high,and the surviving patients may leave chronic renal impairment with different degrees[2].A number of studies have shown that ischemia-reperfusion injury leading to renal dysfunction is directly related to oxidative stress,and the inhibition of oxidative stress through nod-like/toll-like signaling pathway can reduce acute renal injury.This review summarizes the research progress in regulating oxidative stress and the relationship between innate immune receptors and acute renal injury.

Relationship between hemoglobin A1c and contrast-induced acute renal injury in patients with type 2 diabetes mellitus undergoing cardiac catheterization

Background There were few studies to explore the relationship between hemoglobin Alc （HbAlc）and contrast-induced acute renal injury （CI-AKI）in patients with type 2 diabetes mellitus （T2DM）. Methods Two hundred seventy-nine patients with T2DM undergonging elective cardiac catheterization from Dongguan Kanghua Hospital were recruited. Patients were classified into quartiles based on HbAlc （ 〈 6.30%, 6.30- 6.70%, 6.71-7.70, and 〉 7.70%）. Baseline data, CI-AKI incidence and in-hospital outcomes were compared between the groups. Logistic regression was used to assess the relationship between HbAlc and CI-AKI. Results CI-AKI occurred in 26 （9.3%）patients. CI-AKI incidences of HbAlc quartiles were 4.6 %（3/65）, 2.8%（2/71）, 12.3%（9/73） and 17.1%（12/70） （P = 0.003）, respectively. There were no significant differences in in-hospital death or required renal replacement therapy among the four groups. Univariate logistic analysis showed that HbAlc was related with CI-AKI （OR = 1.319, 95%CI： 1.078-1.615, P = 0.007）. Multivariate analysis found that after adjusting eGFR 〈 60 ml/min/1.73 m2, age 〉 70 years and anemia, I-IbAlc 〉17% was still a significant independent risk factor for CI-AKI in patients with T2DM. Conclusions HbAlc is significantly associated with CI-AKI. HbAlc ≥ 7% may increase the risk of CI-AKI in patients with T2DM undergoing elective cardiac catheterization.

Risk factors of acute renal injury in patients with acute left heart failure

Objective To investigate the risk factors of acute renal injury(acute kidney injury)in patients with acute left heart failure.Methods Clinical data of 188 patients with acute left heart failure who were admitted to our hospital were retrospectively analyzed.Logistic regression analysis was used to assess the risk factors for AKI.

Changes of Apoptosis in Rats of Acute Ischemic Renal Injury under Treatment of Tetrandrine

ObjectiveTo elucidate the effect of tetrandrine on acute ischemic renal injury and its relation with apoptosis. MethodsA model for bilateral post ischemic renal injury in rats was developed by clamping renal pedicles for 45 min. Renal tissular DNA fragmentation analysis and renal tissular HE staining were used. Also quantitative analysis of apoptosis in injured renal tubular epithelium was carried out by using TdT mediated dUTP nick and labeling (TUNEL). ResultsApoptosis of renal tubular epithelium increased in acute ischemic renal injury. Tetrandrine could remarkably decrease the level of apoptosis in injured renal tubule while protecting renal tissue against the ischemic injuries. ConclusionTetrandrine could adjust the level of apoptosis in renal tubular epithelium and alleviate renal tissular injury.

Prognosis of Acute Renal Failure of the Child during Severe Malaria in Niamey-Niger

Introduction: In malaria-endemic areas, acute renal failure (ARF) is one of the most serious complications, it occurs in 40% of severe forms of malaria in adults and is linked to 75% of deaths, especially when extra-renal cleaning is not available. In children, studies of ARF during malaria are limited. We have no published studies on this topic in Niger. The main objective of our study is to evaluate the prognosis of ARF during severe malaria in children. Patients and Method: This is a one-year prospective study (January 1, 2016 to December 31, 2016) conducted in the resuscitation unit of the pediatric department of the National Lamordé Hospital of Niamey (Niger). We included in the study children aged 0 to 15 years hospitalized for severe malaria with impaired renal function. Patients who had chronic renal failure or who had acute renal failure with a thick negative drop were excluded from the study. Acute renal failure is defined according to Kidney Disease Improving Global Outcomes (KDIGO) criteria basing on creatinine clearance. Results: The incidence of ARF was 12.60%. The mean age of the patients was 4.25 ± 1.3 years [8 months - 15 years]. The mean hemoglobin level was 8.2 ± 2.7 g/dl. In 54.02% of cases, the hemoglobin level is ≤5 g/dl. Mean serum creatinine was 543.7 ± 69.5 μmol/l [107 - 2500 μmol/l] and mean azotemia was 27.5 ± 3.5 mmol/l. Severe anemia (54.02%) were more related to the occurrence of ARF(with p = 0.014). According to the RIFLE classification, 55 patients (63.22%) were in the Risk stage, 18 patients (20.69%) were in the injury stage and 14 patients (16.09%) in the failure stage. All patients were placed on injectable Artesunate. The average length of hospital stay was 8.6 ± 4.5 days [5 to 22 days]. Dialysis was reported in 15/87 (17.24%). For technical and financial reasons only 8 patients were hemodialysed. Indications for dialysis were severe uremic syndrome 7 cases (8.04%), fluid overload 5 cases (5.75%) and severe hyperkalemia 3 cases (3.45%). Conclusion: The etiological factors of ARI in malaria were massive hemoglobinuria, severe anemia and shock. Adequate management of simple cases of malaria and the early transfer of severe cases to resuscitation services can prevent certain complications such as acute renal failure.

Effect of oleic acid-induced acute lung injury and conventional mechanical ventilation on renal function in piglets

Background Animal models that demonstrate changes of renal function in response to acute lung injury （ALl） and mechanical ventilation （MV） are few. The present study was performed to examine the effect of ALl induced by oleic acid （OA） in combination with conventional MV strategy on renal function in piglets. Methods Twelve Chinese mini-piglets were randomly divided into two groups： the OA group （n=6）, animals were ventilated with a conventional MV strategy of 12 ml/kg and suffered an ALl induced by administration of OA, and the control group （n=6）, animals were ventilated with a protective MV strategy of 6 ml/kg and received the same amount of stedle saline. Results Six hours after OA injection a severe lung injury and a mild-moderate degree of renal histopathological injury were seen, while no apparent histological abnormalities were observed in the control group. Although we observed an increase in the plasma concentrations of creatinine and urea after ALl, there was no significant difference compared with the control group. Plasma concentrations of neutrophil gelatinase-associated lipocalin （NGAL） and cystatin C increased （5.6＋1.3） and （7.4＋1.5） times in the OA group compared to baseline values, and were significantly higher than the values in the control group. OA injection in combination with conventional MV strategy resulted in a dramatic aggravation of hemodynamic and blood gas exchange parameters, while these parameters remained stable during the experiment in the control group. The plasma expression of TNF-a and IL-6 in the OA group were significantly higher than that in the control group. Compared with high expression in the lung and renal tissue in the OA group, TNF-a and IL-6 were too low to be detected in the lung and renal tissue in the control group. Conclusions OA injection in combination with conventional MV strategy not only resulted in a severe lung injury but also an apparent renal injury. The potential mechanisms involved a cytokine response of TNF-a and IL-6 in plasma, lung and renal tissues.

Role of adult resident renal progenitor cells in tubular repair after acute kidney injury

Acute kidney injury is a serious global health problem and determinant of morbidity and mortality. Recent advancements in the fi eld of stem cell research raise hopes for stem cell-based regenerative approaches to treat acute kidney diseases. In this review, the authors summarized the latest research advances of the adult resident renal progenitor cells（ARPCs） on kidney repair, the role of ARPCs on tubular regeneration after acute kidney injury, the current understanding of the mechanisms rela ted to ARPC activation and modulation, as well as the challenges that remain to be faced.

Effects of Fufang Shenhua Tablet(复方肾华片) on the Expression of Toll-Like Receptors during Acute Kidney Injury Induced by Ischemia-Reperfusion in Rats

Objective： To investigate the impact of a traditional Chinese medicinal compound known as Fufang Shenhua Tablet （复方肾华片, SHP） on the expression of Toll-like receptors （TLRs） during renal ischemia-reperfusion injury （IRI）-induced acute kidney injury （AKI） in rats. Methods： A total of 28 Wistar rats were randomly divided into five groups： （1） pseudo-operation control group, （2） ischemia-reperfusion model group, （3） Astragaloside group, （4） high-dose SHP group, and （5） low-dose SHP group. There were four rats in the pseudo-operation group and six rats in each of the other groups. The accepted ischemia-reperfusion model was established after a 7-day gavage intervention, and pathological changes and renal function were observed, using an enzyme-linked immunosorbent assay （ELISA） to detect interleukin 8 （IL-8） and interferon gamma （IFN-r） levels, as well as immunohistochemical staining to detect altered levels of TLR2 and TLR4 expression in renal tissue. Results： After 24 h, renal pathological damage and the expression levels of serum creatinine （Scr）, IL-8, IFN- r, TLR2, and TLR4 were significantly higher in the model group as compared with the pseudo-operation group （P〈0.05）. In addition, at 24 h the above indicators decreased significantly in the Astragaloside group, high- dose SHP group and low-dose SHP group as compared with the ischemia-reperfusion model group （P〈0.05）. TLR2 and TLR4 expression levels were significantly reduced in the SHP treatment and Astragaloside group as compared with the pseudo-operation group （P〈0.05）. Further, the high-dose SHP group showed significantly less renal damage score and decreased levels of TLR expression than those of low-dose SHP group and Astragaloside group （all P〈0.05）. Conclusion： SHP can alleviate the renal structural and functional damage caused by IRI-induced AKI in rats by reducing the damage of renal pathology, which may reduce inflammatory cytokine levels by downregulating the expression of TLRs in renal tissue in a dose-dependent manner.

Optimization of central venous pressure during the perioperative period is associated with improved prognosis of high-risk operation patients

Background:While central venous pressure(CVP)measurement is used to guide fluid management for high-risk surgical patients during the perioperative period,its relationship to patient prognosis is unknown.Methods:This single-center,retrospective observational study enrolled patients undergoing high-risk surgery from February 1,2014 to November 31,2020,who were admitted to the surgical intensive care unit(ICU)directly after surgery.Patients were divided into the following three groups according to the first CVP measurement(CVP1)after admission to the ICU:low,CVP1<8 mmHg;moderate,8 mmHg≤CVP1≤12 mmHg;and high,CVP1>12 mmHg.Perioperative fluid balance,28-day mortality,length of stay in the ICU,and hospitalization and surgical complications were compared across groups.Results:Of the 775 high-risk surgical patients enrolled in the study,228 were included in the analysis.Median(interquartile range)positive fluid balance during surgery was lowest in the low CVP1 group and highest in the high CVP1 group(low CVP1:770[410,1205]mL;moderate CVP1:1070[685,1500]mL;high CVP1:1570[1008,2000]mL;all P<0.001).The volume of positive fluid balance during the perioperative period was correlated with CVP1(r=0.336,P<0.001).The partial arterial pressure of oxygen(PaO 2)/fraction of inspired oxygen(FiO 2)ratio was significantly lower in the high CVP1 group than in the low and moderate CVP1 groups(low CVP1:400.0[299.5,443.3]mmHg;moderate CVP1:362.5[330.0,434.9]mmHg;high CVP1:335.3[254.0,363.5]mmHg;all P<0.001).The incidence of postoperative acute kidney injury(AKI)was lowest in the moderate CVP1 group(low CVP1:9.2%;moderate CVP1:2.7%;high CVP1:16.0%;P=0.007).The proportion of patients receiving renal replacement therapy was highest in the high CVP1 group(low CVP1:1.5%;moderate CVP1:0.9%;high CVP1:10.0%;P=0.014).Logistic regression analysis showed that intraoperative hypotension and CVP1>12 mmHg were risk factors for AKI within 72 h after surgery(adjusted odds ratio[aOR]=3.875,95%confidence interval[CI]:1.378–10.900,P=0.010 and aOR=1.147,95%CI:1.006–1.309,P=0.041).Conclusions:CVP that is either too high or too low increases the incidence of postoperative AKI.Sequential fluid therapy based on CVP after patients are transferred to the ICU post-surgery does not reduce the risk of organ dysfunction caused by an excessive amount of intraoperative fluid.However,CVP can be used as a safety limit indicator for perioperative fluid management in high-risk surgical patients.