Evaluation of serum cysteine-rich protein 61 and cystatin C levels for assessment of acute kidney injury after cardiac surgery

Objective The occurrence of acute kidney injury (AKI) after cardiopulmonary bypass (CPB) can lead to morbidity and mortality. We hypothesized that cysteine-rich protein 61 (CYR61) and cystatin C (CysC) may be potential novel biomarkers of AKI after cardiopulmonary bypass. Methods Patients were classified into AKI and non-AKI group depending on serum creatinine. Levels of creatinine, CysC, and CYR61 were measured at five time-points before and within 48?h after the surgery. Results Fifty patients were included in the study. Serum creatinine pre-operative values were 74.0?±?43.3?μmol/L in AKI group vs. 64.8?±?17.9?μmol/L in non-AKI group. During 48?h, the values increased to 124.6?±?67.2?μmol/L in AKI group (p?<?0.001) but in non-AKI group they did not change significantly. Serum CysC values were significantly increased already 2?h after CBP in AKI group (949?±?557?μg/L, p?<?0.05) compared to non-AKI group (700?±?170?μg/L). Pre-operative serum CYR61 tended to be lower in AKI group (12.4?μg/L) than in non-AKI group (20.3?μg/L), but 24?h after the surgery, the levels in AKI group tended to be higher than non-AKI group. Conclusion Serum CYR61 does not seem to be an early predictor of AKI in patients after cardiac surgery with CPB, but it might possibly identify patients at risk of developing more severe kidney injury. Serum CysC could be a promising biomarker of AKI, differentiating patients at risk of developing AKI after cardiac surgery as early as 2?h after surgery.     

The postreperfusion syndrome is associated with acute kidney injury following donation after brain death liver transplantation

Acute kidney injury (AKI) is frequently observed after donation after brain death (DBD) liver transplantation (LT) and associated with impaired recipient survival and chronic kidney disease. Hepatic ischemia/reperfusion injury (IRI) is suggested to be an important factor in this process. The postreperfusion syndrome (PRS) is the first manifestation of severe hepatic IRI directly after reperfusion. We performed a retrospective study on the relation between hepatic IRI and PRS and their impact on AKI in 155 DBD LT recipients. Severity of hepatic IRI was measured by peak postoperative AST levels and PRS was defined as >30% decrease in MAP ≥1 min within 5 min after reperfusion. AKI was observed in 39% of the recipients. AKI was significantly more observed in recipients with PRS (53% vs. 32%; P = 0.013). Median peak AST level was higher in recipients with PRS (1388 vs. 771 U/l; P < 0.001). Decrease in MAP after reperfusion correlated well with both severity of AKI (P = 0.012) and hepatic IRI (P < 0.001). Multiple logistic regression identified PRS as an independent factor for postoperative AKI (OR 2.28; 95% CI 1.06–4.99; P = 0.035). In conclusion, PRS reflects severe hepatic IRI and predicts AKI after DBD LT. PRS immediately after reperfusion is an early warning sign and creates opportunities to preserve postoperative renal function.     

Sclerosing Encapsulating Peritonitis in an Anti-HCV-Positive Patient on Chronic Ambulatory Peritoneal Dialysis

We investigated the role of neutrophil gelatinase-associated lipocalin (NGAL) on renal tubular epithelial cell in the renal ischemia/reperfusion injury (IRI) rats. Male Sprague–Dawley rats were randomly assigned to three groups. The control group (n = 5) underwent left nephrectomy. The ischemia/reperfusion (I/R) + normal saline (NS) (n = 5) and I/R + NGAL groups (n = 5) were subjected to 45 min right renal ischemia followed by 48 h of reperfusion after left nephrectomy. The pathological changes of kidney tissues were investigated using hematoxylin–eosin staining; renal tubular epithelial cell apoptosis was detected using terminal dUTP nick-labeling method; expression of apoptosis-regulating protein Fas and Bcl-2 was measured using real-time polymerase chain reaction, Western blot, and immunohistochemical staining. Compared with I/R + NS group, kidney tissues from I/R + NGAL group revealed reduced histological damage and a decreased number of renal tubular epithelial cell apoptosis (9.2 ± 2.53 nuclei or 4.0 ± 0.7 per high-power field vs. 20.3 ± 3.7 nuclei or 8.1 ± 0.3 per high-power field); rats with NGAL showed downregulated fas mRNA (2.34 ± 0.51 vs. 6.84 ± 2.34), fas protein (0.65 ± 0.05 vs. 0.95 ± 0.08), and upregulated bcl-2 protein (0.33 ± 0.05 vs. 0.24 ± 0.03). The results had statistical significance (p < 0.05). We think NGAL could protect against renal IRI and might be related to decreasing tubular epithelial cell apoptosis via adjusting the expression of apoptosis-regulating proteins.     

纤维蛋白肽Bβ15～42对大鼠缺血再灌注损伤肾脏局部炎性反应的影响

目的 观察纤维蛋白肽Bβ15～42(the fibrin-derived peptide Bβ15-42,FgBβ15～42肽)对大鼠肾脏缺血再灌注损伤(IRI)后肾脏局部炎性反应的影响并探讨其机制.方法 将SD大鼠随机分成假手术组(Sham组)、IRI组、阴性治疗组和FgBβ15 ～ 42肽治疗组.Sham组:分离肾动脉后关闭腹腔;IRI组:采用双侧肾动脉夹闭的方法制作肾脏IRI模型;阴性治疗组:于肾脏再灌注后立即尾静脉注射随机肽段3.6 mg/kg; FgBβ15～42肽治疗组:于肾脏再灌注后立即尾静脉注射FgBβ15～ 42肽3.6 mg/kg.后3组按照再灌注24h、48 h分为两个亚组,Sham组与各亚组均为8只大鼠.常规生化法检测肾功能;HE、PAS染色观察肾脏组织学改变;免疫组化、实时荧光定量PCR法及Western印迹检测肾组织白细胞介素1β(IL-1β)、细胞间黏附分子1(ICAM-1)的mRNA及蛋白表达.结果 与Sham组相比,IRI组的Scr和BUN水平均显著增加(均P ＜0.05),肾小管及间质病理损伤显著,以再灌注48 h更为明显;与IRI组相比,FgBβ15～ 42肽治疗组Scr和BUN显著下降(均P＜0.05),小管间质损伤程度明显减轻(P＜0.05).与Sham组相比,IRI组IL-1β和ICA M-1的mRNA和蛋白水平于再灌注24h显著上升,48 h稍微下降,但仍维持在较高水平;FgBβ15～ 42肽治疗组大鼠肾组织IL-1β和ICAM-1的表达于再灌注24h、48 h显著低于同时间点的IRI组(均P＜0.05),但仍明显高于Sham组.上述各指标在阴性治疗组和IRI组之间的表达差异无统计学意义.结论 FgBβ15～42肽对肾脏IRI具有保护作用,其作用机制可能与其减少炎性因子IL-1β、黏附分子ICAM-1的表达有关.     

A Role for galectin‐3 in renal tissue damage triggered by ischemia and reperfusion injury

Ischemic‐reperfusion injury (IRI) triggers an inflammatory response involving neutrophils/macrophages, lymphocytes and endothelial cells. Galectin‐3 is a multi‐functional lectin with a broad range of action such as promotion of neutrophil adhesion, induction of oxidative stress, mastocyte migration and degranulation, and production of pro‐inflammatory cytokines. The aim of this study was evaluate the role of galectin‐3 in the inflammation triggered by IRI. Galectin‐3 knockout (KO) and wild type (wt) mice were subjected to 45 min of renal pedicle occlusion. Blood and kidney samples were collected at 6, 24, 48 and 120 h. Blood urea was analyzed enzymatically, while MCP‐1, IL‐6 and IL‐1β were studied by real‐time PCR. Reactive oxygen species (ROS) was investigated by flow cytometry. Morphometric analyses were performed at 6, 24, 48 and 120 h after reperfusion. Urea peaked at 24 h, being significantly lower in knockout animals (wt = 264.4 ± 85.21 mg/dl vs. gal‐3 KO = 123.74 ± 29.64 mg/dl, P = 0.001). Galectin‐3 knockout animals presented less acute tubular necrosis and a more prominent tubular regeneration when compared with controls concurrently with lower expression of MCP‐1, IL‐6, IL‐1β, less macrophage infiltration and lower ROS production at early time points. Galectin‐3 seems to play a role in renal IRI involving the secretion of macrophage‐related chemokine, pro‐inflammatory cytokines and ROS production.     

Expression and function of Erbin protein in renal ischemia-reperfusion injury

Objective To investigate the expression of ErbB2 interacting protein (Erbin) in renal ischemia-reperfusion injury (IRI) in vivo and in vivo, and the effect of Erbin over-expression on IRI. Methods (1) In vivo, the model of renal IRI was constructed in mice, and set up sham group and reperfusion 3, 6, 12, 24 and 48 h IRI group. BUN and Scr were detected and PAS staining was used to observe the pathology change of renal tissues. Cell apoptosis was detected by TUNEL staining. Erbin and NF-κB expression in renal tissue was detected by Western blotting, and immunohistochemistry was used to detect the distribution of Erbin. (2) In vivo, IRI model in HK2 cells was constructed and cells were harvested after culturing in normal medium for 3, 6, 12 and 24 h. Erbin expression was detected by Western blotting. Flow cytometry and ELISA were used to evaluate the level of cell apoptosis and inflammatory cytokine secretion respectively. HK2 cells were transiently transfected with Prk5-myc-Erbin plasmid via lipofectamine 2000, and were divided into control group, IRI group, Erbin group and Erbin+IRI group. The protein expression of Erbin and NF-κB, cell apoptosis and inflammatory cytokine secretion was detected. Results (1) Compared with sham group, serum BUN and Scr were dramatically increased in IRI model, especially in 24 h after reperfusion (P＜0.05). Moreover, PAS staining showed that a lot of renal tubular epithelial cells were necrosis and fell off, and many protein cast were formed, renal injury score and apoptotic index were higher in 6 h, 12 h, 24 h, 48 h IRI model than those in sham group (all P＜0.05). The expression of Erbin, which was expressed in renal tubules, and nuclear NF-κB in 24 h IRI model were significantly increased, as compared with sham group (all P＜0.05). (2) Compared to those in control group, nuclear NF-κB expression, apoptosis and inflammatory cytokine secretion were significantly increased in IRI group. Meanwhile, Erbin expression was also induced and peaked at 24 h (P＜0.05). Compared to those in IRI group, cell apoptosis, the expression of nuclear NF-κB, inflammatory cytokine IL-6 and TNF-α were decreased in Erbin+IRI group (all P＜0.05). Conclusions Erbin expression is up-regulated in renal IRI, and over-expression of Erbin can partly inhibit NF-κB activation, cell apoptosis and inflammatory cytokine secretion in IRI group, which indicates Erbin may playing a protective role in renal IRI.     

Assessment of fractional excretion of urea for early diagnosis of cardiac surgery associated acute kidney injury

Abstract

Background: Acute kidney injury (AKI) is a common complication after cardiac surgery (CS). Recently, neutrophil gelatinase-associated lipocalin (NGAL) was shown to predict AKI development earlier than serum creatinine, but it is not widely used in clinical practice. Fractional excretion of urea (FeU) has been referred to as a useful tool to discriminate between prerenal and established AKI. The aim of our study is to evaluate the sensitivity and specificity of FeU, in the early diagnosis of AKI in patients undergoing CS. Methods: We performed a prospective study on adults undergoing CS. AKI was defined by AKIN criteria. Individuals suffering from CKD, were excluded. Sensitivity and specificity of FeU, fractional excretion of sodium (FeNa) and urine NGAL, measured at 1, 6 and 24?h following CS, were assessed. Results: We included 66 patients (26% female) aging 68?±?11 years. AKI prevalence was 24% and mortality was 3.28%. Patients with AKI had a significantly lower FeU compared to those without AKI (23.89?±?0.67% vs. 34.22?±?0.58%; p?<?0.05) 6?h after CS, but not at the 1- and 24-h time points. NGAL was also statistically significant between both groups. FeU showed a 75% sensitivity and 79.5% specificity; the AUC was 0.786. ROC analysis of FeU and NGAL yielded similar values (p?=?NS). Conclusion: FeU is useful as an early biomarker to predict AKI after CS and it is comparable to the new biomarker NGAL.     

大鼠肾脏缺血再灌注损伤中垂体中叶素及降钙素受体样受体的表达

目的 观察垂体中叶素（IMD）及其受体降钙素受体样受体（CRLR）在大鼠肾脏缺血再灌注损伤中的表达变化。 方法 将健康雄性Wistar大鼠随机分为假手术组和手术组,夹闭大鼠双侧肾动脉制作肾脏缺血再灌注损伤（IRI）模型,于缺血再灌注后0、6、12、24、48、72 h 6个时间点各取6只大鼠,留取血清及肾组织标本,对肾脏病理损伤评分并行半定量分析; Western印迹法半定量分析肾组织IMD及其受体CRLR的表达变化;放射免疫法检测血浆中IMD的表达变化。 结果 手术组大鼠发生了急性肾小管坏死（ATN）,以缺血再灌注48 h时病理损伤最重。与假手术组比较,IMD及CRLR在缺血再灌注12、24、48、72 h表达显著增高（均P < 0.01）;血浆中IMD在缺血再灌注12、48、72 h表达显著增高（均P < 0.05）。 结论 IMD及受体CRLR在大鼠肾脏缺血再灌注损伤中表达增加,血浆中IMD表达上调,提示其可能在肾脏缺血再灌注损伤病理生理过程中发挥作用。     

CD44 expression in renal ischemia-reperfusion injury in rats

Renal ischemia-reperfusion injury (IRI) is an invariable consequence of transplantation. The tubuloepithelial expression of CD44 is markedly enhanced in autoimmune renal injuries. The aim of this experimental study was to evaluate the effect of IRI on the expression of CD44 in rat kidney. Thirty male Sprague-Dawley rats were used. The rats were divided into three groups. The rats in group 1 (n = 10) underwent laparotomy and left nephrectomy (Sham surgery). The rats in group 2 (n = 10) underwent laparotomy, 1 h renal ischemia, followed by 1 h of reperfusion and then left nephrectomy was performed. The rats in group 3 (n = 10) underwent laparotomy, 1 h renal ischemia, followed by 24 h of reperfusion and then left nephrectomy was performed. Histopathological findings and the immunohistochemical expression of CD44 in ischemic and reperfused rat kidneys were investigated. In histopathologic evaluation, non-specific changes were observed in group 2 and early phase of IRI were present in group 3. CD44 was expressed in both group 2 and 3 but not in group 1. The mean immunohistochemical staining percentages of rat kidneys in group 1, 2, and 3 were 0.00 ± 0.00, 39.90 ± 5.53, and 26.20 ± 8.38, respectively. The immunohistochemical staining pattern was more dense in group 2 than in group 3 (P < 0.001). In conclusion, the expression of CD44 in renal tubuloepithelial cells was significantly increased after IRI. The increase in CD44 expression was more prominent during the early phase of IRI and started to decline after 24 h of reperfusion.     

Acute kidney injury in the elderly hospitalized patients

Objective: We aimed to evaluate acute kidney injury (AKI), occurrence of recovery and risk factors associated with permanent kidney injury and mortality in the elderly individuals. Design: Evidence for this study was obtained from retrospective cohort study from our center. Patients: A total of 193 patients (>65 years, mean age: 79.99?±?6.93) with acute kidney injury were enrolled in this study between 2011 and 2012. Patients with kidney failure or renal replacement therapy (RRT) history at admission were excluded. Intervention: Main outcome measurements: serum creatinine (SCr), estimated GFR (with CKD-Epi) and complete blood counts were evaluated at baseline and daily basis thereafter. The AKI was defined based on Kidney Disease Improving Global Outcomes (KDIGO) classification. Results: Among 193 patients, 43 (22%) patients required RRT. Mortality rate was 18% (n?=?36) SCr levels were restored within 9.9?±?6.7days on average (8–39 days). Sixteen patients (12.7%) required RRT after discharge. The mean hospital stay was 10.1?±?8.6 days (7–41 days). Mortality rate of patients who have no renal recovery was higher (44.8% vs. 4.8%) than renal recovery group (p?0.01). Conclusion: The AKI represents a frequent complication in the elderly patients with longer hospital stay and increased mortality and morbidity. Our results show that dialytic support requirement is an independent predictor of permeant kidney injury in the elderly AKI patients. Older age, low diastolic blood pressure, high CRP and low hemoglobin levels were independent risk factors for mortality.     

Metformin alleviated EMT and fibrosis after renal ischemia–reperfusion injury in rats

Purpose The purpose of this study is to assess the potential effects of metformin on the development of EMT and tubulointerstitial fibrosis 12 weeks after acute renal ischemia–reperfusion. Methods Male Sprague–Dawley rats were randomly assigned to four groups: Sham, IRI, transient administration of metformin (TAM), and continuous administration of metformin (CAM). Metformin was administered i.p. at a dose of 125?μg kg?^??1 d^???1 3 d prior to suffering from IRI (TAM), or from 3 d before suffering from IRI to 12 weeks after reperfusion (CAM). Renal function, histology, and expressions of IL-6, TNF-α, α-SMA, TGF-β1, Vimentin, and E-cadherin were analyzed. Results Tubulointerstitial fibrosis worsened further in IRI, accompanied by the increased expressions of interleukin-6, TNF-α, α-SMA, TGF-β1, Vimentin, and loss of E-cadherin. Although there were no significant differences between IRI and TAM (p?>?0.05). Compared with the IRI, expressions of IL-6, TNF-α, α-SMA, TGF-β1, and Vimentin were reduced and the expression of E-cadherin was restored in CAM (p?0.05). CAM also significantly promoted activation of AMPK (p?0.05), which showed no difference among Sham, IRI, and TAM (p?>?0.05). Conclusions CAM significantly attenuated tubulointerstitial fibrosis and EMT in rats, potentially via activation of AMPK and down-regulation of TGF-β1.     

Involvement of peroxisome proliferator–activated receptor gamma in vitamin D–mediated protection against acute kidney injury in rats

Background

Vitamin D has been reported as renoprotective agents in various studies. Recently, a few in vitro studies highlighted cross talk between vitamin D and peroxisome proliferator–activated receptor gamma (PPAR-γ). The present study investigated the activation of PPAR-γ as novel mechanism in vitamin D–mediated protection against ischemia reperfusion–induced acute kidney injury (AKI) in rats.

Materials and methods

The AKI was induced by clamping renal pedicles for 40 min followed by reperfusion for 24 h. The AKI was assessed by measuring creatinine clearance, serum urea, uric acid level, and lactate dehydrogenase activity. Moreover, serum potassium, calcium level, fractional excretion of sodium, and microproteinuria were measured in rats. The oxidative stress in renal tissues was assessed by quantification of thiobarbituric acid–reactive substances, superoxide anion generation, reduced glutathione level, and catalase and myeloperoxidase activities. The hematoxylin-eosin staining was carried out to observe histopathologic changes in renal tissues. Vitamin D (0.25, 0.5, and 1 μg/kg) was administered for 7 d before subjecting rats to renal ischemia reperfusion injury (IRI).

Results

The renal IRI in rats induced significant changes in serum, urinary, and oxidative stress parameters in renal tissues. Moreover, hematoxylin-eosin staining revealed marked damage produced by IRI in renal tissues. The administration of vitamin D at 0.5 μg/kg dose afforded maximum protection against renal IRI. The prior treatment with PPAR-γ antagonist bisphenol A diglycidyl ether significantly attenuated protective effect of vitamin D, thus confirming involvement of PPAR-γ in vitamin D–mediated renoprotection.

Conclusions

It is concluded that activation of PPAR-γ significantly contributes toward vitamin D–mediated protection against ischemia reperfusion–induced AKI.     

低氧诱导因子1α高表达对小鼠急性缺血性肾损伤的影响

目的 探讨低氧预处理诱导低氧诱导因子1α（HIF-1α）高表达对小鼠肾缺血再灌注损伤（IRI）的影响及其可能机制。 方法 雄性C57BL/6N小鼠35只，随机分为健康对照组、氯化钴（CoCl2）组和8%O2组，每组10只；预处理12 h后，以上3组各取5只，分为缺血再灌注（IR）组、CoCl2＋IR组、8%O2＋IR组；另设5只作为假手术对照组。采用夹闭双侧肾蒂30 min的方法建立肾缺血动物模型，观察CoCl2和8％O2预处理对小鼠IR 24 h后肾功能、肾组织病理和相关肾损伤指标的影响及与CoCl2和8％O2诱导HIF-1α及其保护性靶基因血红素氧化酶1（HO-1）表达之间的关系。 结果 CoCl2＋IR组小鼠的肾功能[BUN (35.2±12.2) mmol/L，Scr (34.0±9.7) μmol/L]和8%O2＋IR组小鼠的肾功能[BUN (31.8±9.1) mmol/L，Scr (41.6±10.6) μmol/L]均较IR组[BUN (65.8±2.6) mmol/L，Scr (229.5±11.2) μmol/L]显著改善（P < 0.01）；与此相一致，CoCl2＋IR组和8%O2＋IR组的病理学改变、细胞凋亡程度和波形蛋白的表达均明显低于IR组。另外，CoCl2组和8%O2组中HIF-1α及其靶基因HO-1的表达明显高于健康对照组。 结论 低氧预处理可上调体内HIF-1α表达，对小鼠IRI肾脏具有良好保护效果     

Low levels of high-density lipoproteins are associated with acute kidney injury following revascularization for chronic limb ischemia

Abstract

Objectives: Perioperative acute kidney injury (AKI) is not uncommon, following revascularization. HDL has been shown to reduce organ injury in animal models. The aim of the study is to examine the association of HDL on AKI in patients undergoing revascularization for chronic limb ischemia. Methods: All patients who underwent revascularization between June 2001 and December 2009 were analyzed. Patients on dialysis and with incomplete data were excluded. Patients were grouped for HDL < or ≥40?mg/dL. Univariate and multivariate analysis were used to identify factors associated with AKI. Results: A total of 684 patients were included. Eighty-two (12.0%) patients developed postoperative AKI (15.7% in low HDL group vs. 6.3% in high HDL group, p?<?0.001). The AKI group were more likely to be older (71.5?±?10.1 vs. 68.0?±?10.8, p?=?0.01), ASA 4 class (26% vs. 14%, p?<?0.001), to have albumin <3?g/dL (59% vs. 32%, p?<?0.001), low HDL levels (79% vs. 58%, p?<?0.001), DM (61% vs. 44%, p?=?0.005), CAD (67% vs. 55%, p?=?0.003), preoperative chronic kidney disease (CKD) stage III–IV (55% vs.39%, p?<?0.001), to present with critical limb ischemia (82% vs. 63%, p?=?0.001), and to be on ACEI (67% vs. 51%, p?=?0.006). Multivariate logistic regression analysis showed low HDL (Odds Ratio (OR) 1.66 [1.23–2.24]) and serum albumin levels <3?g/dL (OR 1.66 [1.29–2.13], p?<?0.001) were independently associated with increased odds for developing AKI. Propensity score analyses showed low HDL was independently associated with increased odds of AKI (OR 2.4 (1.4–4.2)). Conclusions: AKI following revascularization is not uncommon (12.0%), and lower concentrations of HDL and serum albumin are associated with increased odds of postoperative AKI. There was also a trend of higher prevalence of AKI among those with pre-existing CKD.     

Implications of dynamic changes in miR-192 expression in ischemic acute kidney injury

Purpose

Ischemia–reperfusion injury (IRI) is a major cause of acute kidney injury (AKI) with poor outcomes. While many important functions of microRNAs (miRNAs) have been identified in various diseases, few studies reported miRNAs in acute kidney IRI, especially the dynamic changes in their expression and their implications during disease progression.

Methods

The expression of miR-192, a specific kidney-enriched miRNA, was assessed in both the plasma and kidney of IRI rats at different time points after kidney injury and compared to renal function and kidney histological changes. The results were validated in the plasma of the selected patients with AKI after cardiac surgery compared with those matched patients without AKI. The performance characteristics of miR-192 were summarized using area under the receiver operator characteristic (ROC) curves (AUC-ROC).

Results

MiRNA profiling in plasma led to the identification of 42 differentially expressed miRNAs in the IRI group compared to the sham group. MiR-192 was kidney-enriched and chosen for further validation. Real-time PCR showed that miR-192 levels increased by fourfold in the plasma and decreased by about 40% in the kidney of IRI rats. Plasma miR-192 expression started increasing at 3 h and peaked at 12 h, while kidney miR-192 expression started decreasing at 6 h and remained at a low level for 7 days after reperfusion. Plasma miR-192 level in patients with AKI increased at the time of ICU admission, was stable for 2 h and decreased after 24 h. AUC-ROC was 0.673 (95% CI: 0.540–0.806, p = 0.014).

Conclusions

Plasma miR-192 expression was induced in a time-dependent manner after IRI in rats and patients with AKI after cardiac surgery, comparably to the kidney injury development and recovery process, and may be useful for the detection of AKI.

     

Preoperative serum cystatin C combined with dipstick proteinuria predicts acute kidney injury after cardiac surgery

Background: Acute kidney injury (AKI) is common following cardiac surgery and is associated with poor outcomes. However, the detection of those preoperative patients who will develop AKI is still difficult. In this study, we compared serum cystatin C combined with dipstick proteinuria as early markers to predict AKI available before surgery. Methods: We prospectively followed 616 patients undergoing cardiac surgery and identified 179 that developed AKI, defined as an increase in serum creatinine (SCr) of ≥?0.3?mg/dL or ≥?50% increase in creatinine level. Preoperative values for cystatin C were categorized into quartiles. We defined proteinuria, measured with a dipstick, as mild (trace to 1+) or heavy (2?+?to 4+). Univariate as well as multivariate regression was performed. Cystatin C combined with dipstick proteinuria before surgery was assessed for its' predictive value of AKI using receiver operating characteristic (ROC) curves. Results: The final cohort consisted of 616 patients aged 60.7?±?13.2 years, and baseline SCr was 75.8?±?26.4?μmol/L, estimated glomerular filtration rate (eGFR) 96.3?±?29.0?mL/min/1.73?m² and cystatin C 1.05?±?0.33?mg/L. Patients in higher cystatin C quartiles were older (p?p?=?0.021), hyperuricemia (p?p?p?=?0.002). Those with heavy proteinuria were more often to have diabetes mellitus (p?=?0.010), hyperuricemia (p?=?0.043), worse cardiac function (p?p?p?p?p?p?p?p?Conclusion: These data suggest that preoperative serum cystatin C combined with dipstick proteinuria may improve prediction of AKI among patients undergoing cardiac surgery.     

Role of ERK1/2 and JNK phosphorylation in iodine contrast agent-induced apoptosis in diabetic rat kidneys

Abstract

Background: The risk of contrast-induced acute kidney injury (CIAKI) is significantly increased in patients with diabetes mellitus. This study aimed to investigate molecular mechanisms of contrast media-induced apoptosis in diabetic rat kidneys, especially the involvement of ERK1/2 and JNK signal pathways. Methods: Diabetic Sprague–Dawley rats were induced by intraperitoneal injection of streptozotocin. Ten weeks later the normal and diabetic rats were administered high-osmolar contrast media (HOCM; meglumine diatrizoate) or normal saline (10?mL/kg) injection for 2 consecutive days. At 24?h after the operation, the rats were sacrificed, the blood samples were collected for examining serum creatinine and the kidneys were collected for determining the expression of caspase-3 by immunohistochemistry and the expression of Bcl-2, Bax, upstream signal molecule p-JNK, and p-ERK1/2 by western blotting. Results: The serum creatinine was significantly increased in diabetes + contrast media group (DC group) after operation compared with in the diabetic group (D group; 103.89?±?9.01?μmol/L vs. 71.52?±?7.03?μmol/L, p?<?0.05). While creatinine clearance rate (Ccr) was significantly decreased in DC group after operation (1.49?±?0.33?mL/min vs. 2.60?±?0.54?mL/min, p?<?0.05). Especially, in the diabetic kidney, the expression of caspase-3 was also significantly increased after intravenous injection of HOCM compared with normal saline. The expression level of upstream signal molecule p-JNK protein was apparently increased, but p-ERK1/2 protein was significantly decreased (both p?<?0.05). Conclusions: The ionic HOCM-induced renal cells apoptosis in diabetic rats through activating the caspase-3 apoptotic pathway, which might be mediated by upstream MAPK (inhibiting p-ERK1/2 expression and promoting p-JNK expression) signal pathways.     

Effects of acute kidney injury on clinical outcomes in patients with upper gastrointestinal bleeding

Aim Upper gastrointestinal bleeding (UGIB) is a very frequently encountered condition that has a high morbidity and which increases treatment costs. Duration of hospital stay and mortality increases in patients with UGIB complicated by acute kidney injury (AKI). The aim of this study was to reveal risk factors in patients with UGIB developing AKI and to compare clinical outcomes and hospital costs between patients with UGIB developing AKI and those with UGIB not developing AKI.

Material and methods This retrospective study included 245 patients admitted to the emergency unit and the intensive care unit for internal diseases at Ankara Numune Education and Research Hospital, Turkey. Results The difference in mortality rates between the patients with AKI and those without AKI was significant (p?0.001). The mean duration of intensive care unit stay was 0.2?±?1.1 days in the patients without AKI (n?=?143) and 2.5?±?5.6 days in the patients with AKI. It was significantly higher in the patients with AKI (p?0.001). Hospital stay was significantly longer in the patients with AKI than those without AKI, and as severity of AKI increased, hospital stay became considerably longer (p?0.001). Hospital costs were significantly higher in the patients with AKI than those without AKI, and as severity of AKI increased, hospital costs considerably rose (p?0.001). Conclusion AKI is a condition that lengthens hospital stay, increases hospital costs and creates a burden on health care systems. Detect kidney injury earlier and administering an appropriate treatment can improve clinical outcomes in patients with UGIB developing AKI.