Association between inflammatory biomarkers and postoperative acute kidney injury after cardiac surgery in patients with preoperative renal dysfunction: a retrospective pilot analysis.

BACKGROUND: Acute kidney injury (AKI) represents a significant post-cardiac surgery complication, particularly prevalent among individuals with pre-existing renal dysfunction. Chronic kidney disease (CKD) is frequently accompanied by persistent, low-grade inflammation, which is known to exacerbate systemic stress responses during surgical procedures. This study hypothesizes that these inflammatory responses might influence the incidence and severity of postoperative acute kidney injury (AKI), potentially serving as a protective mechanism by preconditioning the kidney to stress. METHODS: This retrospective study enrolled patients with preoperative renal dysfunction (eGFR between 15 and 60 ml/min/1.73 m²) who underwent cardiac surgery between January 2020 and December 2022. Preoperative inflammatory biomarkers were evaluated. The primary outcome was the incidence of postoperative AKI, as defined by the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Multivariate regression models and sensitivity analyses were conducted to ascertain the relationship between inflammatory biomarkers and AKI. Restricted cubic spines (RCS) was conducted to explore nonlinear associations between inflammatory biomarkers and AKI. RESULTS: AKI occurred in 53.4% (392/734) of patients, accompanied by significant mortality and length of hospital stay increases in cases of AKI (P < 0.005). After full adjustment of confounders, neutrophil percentage-to-albumin ratio (OR = 0.28), systemic inflammation response index (OR = 0.70), systemic immune inflammation index (OR = 0.69), neutrophil-to-lymphocyte ratio (OR = 0.70), monocyte/high-density lipoprotein cholesterol ratio (OR = 0.53), neutrophil/high-density lipoprotein cholesterol ratio (OR = 0.43) demonstrated an inverse association with AKI. Sensitivity analyses revealed that patients in the highest quartile of these biomarkers exhibited a significantly lower prevalence of AKI compared to those in the lowest quartile (p for trend < 0.05). The RCS analysis suggested an "Inverted U-shaped" association of both LnNPAR and LnSIRI with AKI. CONCLUSIONS: This study identified an inverse association between preoperative inflammatory biomarkers and postoperative AKI in patients with preoperative renal dysfunction. The findings implied that preoperative inflammation may play a protective role against postoperative AKI in this patient population undergoing cardiac surgery.

Protective effect of reduced glutathione on acute kidney injury in lung cancer patients treated with cisplatin: a retrospective cohort study.

BACKGROUND: Cisplatin is a common cause of acute kidney injury (AKI) during chemotherapy for lung cancer, and the nephrotoxicity limits its clinical use. Reduced glutathione (GSH) is a major component of the cellular antioxidant defense system and performs important physiological functions. The aim of this study was to analyze the protective effect of GSH on AKI in lung cancer patients treated with cisplatin. METHODS: The clinical data were retrospectively collected from lung cancer patients treated with cisplatin at our hospital between 1 January and 31 December 2019. The patients were divided into AKI group and non-AKI group based on whether AKI occurred, and into GSH group and non-GSH group based on whether GSH was used. Univariate and multivariate logistic regressions were used to analyze the risk factors for AKI. RESULTS: A total of 1372 lung cancer patients treated with cisplatin were enrolled. Of these patients, 231 patients (16.8%) developed AKI. The incidence of AKI was lower in the GSH group compared with the non-GSH group (10.6% vs. 18%, p = 0.009). Multivariate logistic regression analysis indicated that older age (OR = 1.045, 95% CI 1.025-1.065, p < 0.001), anemia (OR = 2.436, 95% CI 1.800-3.298, p < 0.001), higher SUA levels (OR = 1.002, 95% CI 1.000-1.004, p = 0.012), higher total amount of cisplatin per cycle (OR = 1.015, 95% CI 1.004-1.025, p = 0.005), and combination with paclitaxel (OR = 2.099, 95% CI 1.435-3.070, p < 0.001) were independent risk factors for AKI in lung cancer patients treated with cisplatin, whereas GSH (OR = 0.573, 95% CI 0.353-0.931, p = 0.025) and mannitol (OR = 0.229, 95% CI 0.055-0.963, p = 0.044) reduced the risk of AKI. CONCLUSION: GSH was an independent protective factor against AKI in lung cancer patients treated with cisplatin and could be considered for clinical use in these patients to better protect renal function.

Serum soluble interleukin-2 receptor alpha may predict tubulointerstitial inflammatory cell infiltration and short-term disease progression in immunoglobin A nephropathy.

This study aims to explore the relationship between serum soluble interleukin-2 receptor alpha (sIL-2Rα) levels and histologic features in immunoglobin A nephropathy (IgAN), and evaluate its predicting values on disease progression and remission status. IgAN patients were included retrospectively. Lee classification, Oxford classification and histological scoring were evaluated. Patients' estimated filtration rate (eGFR) and proteinuria remission status were collected during 6-month follow-up. Logistic regression was used to determine the risk factors and predicting value. Receiver operating characteristic (ROC) curve were used to determine the predicting value for outcome. One hundred seventy-two subjects were included in this study. Individuals in moderate-to-severe tubulointerstitial inflammatory cell infiltration group manifested with significantly elevated serum sIL-2Rα levels than those in non-to-mild group. Serum sIL-2Rα levels were positively correlated with infiltration scores. Serum sIL-2Rα was an independent risk factor for moderate-to-severe inflammatory cell infiltration [sIL-2Rα: OR 1.29 (1.015-1.640, p = 0.038)]. ROC curve analysis regarding predictive value for moderate-to-severe inflammatory cell infiltration of sIL-2Rα suggested area under curve was 0.859 (0.801-0.918, p = 0.000) when sIL-2Rα combined with eGFR < 60 mL/(min·1.73 m2), 24-h proteinuria excretion > 1.0 g, and hemoglobin. It showed good sensitivity (71.6%) and specificity (87.6%). Additionally, sIL-2Rα levels at kidney biopsy were strong predictive factor for kidney function loss 6 months after kidney biopsy [OR 4.161 (1.013-17.088, p = 0.048)]. High serum sIL-2Rα was significantly associated with serious inflammatory cell infiltration in IgAN, and it showed strong predictive value for disease prognosis. Serum sIL-2Rα could be a useful noninvasive biomarker to evaluate the extent of histological injury and disease prognosis in IgAN.

Assessing the predictive value of elevated postoperative syndecan-1 levels for progressive acute kidney injury and kidney replacement therapy necessity in adult cardiac surgery patients.

BACKGROUND: The development of acute kidney injury (AKI) post-cardiac surgery significantly increases patient morbidity and healthcare costs. Prior researches have established Syndecan-1 (SDC-1) as a potential biomarker for endothelial injury and subsequent acute kidney injury development. This study assessed whether postoperative SDC-1 levels could further predict AKI requiring kidney replacement therapy (AKI-KRT) and AKI progression. METHODS: In this prospective study, 122 adult cardiac surgery patients, who underwent valve or coronary artery bypass grafting (CABG) or a combination thereof and developed AKI within 48 h post-operation from May to September 2021, were monitored for the progression to stage 2-3 AKI or the need for KRT. We analyzed the predictive value of postoperative serum SDC-1 levels in relation to multiple endpoints. RESULTS: In the study population, 110 patients (90.2%) underwent cardiopulmonary bypass, of which thirty received CABG or combined surgery. Fifteen patients (12.3%) required KRT, and thirty-eight (31.1%) developed progressive AKI, underscoring the severe AKI incidence. Multivariate logistic regression indicated that elevated SDC-1 levels were independent risk factors for progressive AKI (OR = 1.006) and AKI-KRT (OR = 1.011). The AUROC for SDC-1 levels in predicting AKI-KRT and AKI progression was 0.892 and 0.73, respectively, outperforming the inflammatory cytokines. Linear regression revealed a positive correlation between SDC-1 levels and both hospital (ß = 0.014, p = 0.022) and ICU stays (ß = 0.013, p < 0.001). CONCLUSION: Elevated postoperative SDC-1 levels significantly predict AKI progression and AKI-KRT in patients following cardiac surgery. The study's findings support incorporating SDC-1 level monitoring into post-surgical care to improve early detection and intervention for severe AKI.

Clinicopathological features of kidney injury in patients receiving immune checkpoint inhibitors (ICPi) combined with anti-vascular endothelial growth factor (anti-VEGF) therapy.

BACKGROUND: Immune checkpoint inhibitor (ICPi) combined with anti-vascular endothelial growth factor (VEGF) therapy has increasingly become a promising strategy in various malignancies. However, the combination might be associated with increased risk of nephrotoxicity. METHODS: We retrospectively recruited patients who suffered kidney injury and received renal biopsy after anti-VEGF/ICPi mono- or combination therapy and divided them into three groups: anti-VEGF monotherapy, ICPi monotherapy and combination therapy. Clinical and histopathological features of three groups were analysed. All patients were followed-up for 3 months after biopsy, with or without glucocorticoid treatment, and renal outcome were compared. RESULTS: A total of 46 patients were enrolled. Eighteen patients received anti-VEGF monotherapy, 12 received ICPi monotherapy and 16 received combined treatment of anti-VEGF and ICPi. Proteinuria level of anti-VEGF group, ICPi group and combination group were 4.07±3.17 g/day, 0.60±0.61 g/day and 2.05±2.50 g/day, respectively (p=0.002). The peak serum creatinine level of combination group (1.75±0.77 mg/dL) was also in between ICPi group (2.79±0.90 mg/dL) and anti-VEGF group (1.34±0.60 mg/dL) (p<0.001). Multiple histopathological patterns involving glomerulus, tubulointerstitium and vessel existed in the majority of cases in combination group (68.8%). Renal complete and partial recovery rate of combination therapy were also in between monotherapy (57.1% vs 40.0% in anti-VEGF group, 100.0% in ICPi group, respectively). CONCLUSIONS: Kidney injury in patients treated with combination therapy of ICPi and anti-VEGF shows hybrid pathological patterns and intermediate clinical features compared with monotherapy. Cohorts with larger sample and better design, as well as basic research, are needed to elucidate the mechanism of 'protection' effect of combination anti-cancer therapy to renal function.

Serum Insulin-Like Growth Factor-Binding Protein 7 Deriving from Spleen and Lung Could Be Used for Early Recognition of Cardiac Surgery-Associated Acute Kidney Injury.

INTRODUCTION: The utility of arithmetic product of urinary tissue metalloproteinase inhibitor 2 (TIMP2) and insulin-like growth factor-binding protein 7 (IGFBP7) concentrations has been widely accepted on early diagnosis of acute kidney injury (AKI). However, which organ is the main source of those two factors and how the concentration of IGFBP7 and TIMP2 changed in serum during AKI still remain to be defined. METHODS: In mice, gene transcription and protein levels of IGFBP7/TIMP2 in the heart, liver, spleen, lung, and kidney were measured in both ischemia-reperfusion injury (IRI)- and cisplatin-induced AKI models. Serum IGFBP7 and TIMP2 levels were measured and compared in patients before cardiac surgery and at inclusion (0 h), 2 h, 6 h, and 12 h after intensive care unit (ICU) admission, and compared with serum creatinine (SCr), blood urea nitrogen (BUN), estimated glomerular filtration rate (eGFR), and serum uric acid (UA). RESULTS: In mouse IRI-AKI model, compared with the sham group, the expression levels of IGFBP7 and TIMP2 did not change in the kidney, but significantly upregulated in the spleen and lung. Compared with patients who did not develop AKI, the concentration of serum IGFBP7 at as early as 2 h after ICU admission (sIGFBP7-2 h) was significantly higher in patients who developed AKI. The relationships between sIGFBP7-2 h in AKI patients and log2 (SCr), log2 (BUN), log2 (eGFR), and log2 (UA) were statistically significant. The diagnostic performance of sIGFBP7-2 h measured by the macro-averaged area under the receiver operating characteristic curve was 0.948 (95% CI, 0.853-1.000; p < 0.001). CONCLUSION: The spleen and lung might be the main source of serum IGFBP7 and TIMP2 during AKI. The serum IGFBP7 value demonstrated good predictive accuracy for AKI following cardiac surgery within 2 h after ICU admission.

Effect of angiography timing on acute kidney injury after cardiac surgery in patients with preoperative renal dysfunction.

BACKGROUND: Cardiac surgery-associated acute kidney injury (AKI) is one of the common complications of cardiac surgery. Preoperative angiography helps assess heart disease but may increase the risk of AKI. Although more and more patients with preoperative renal dysfunction can undergo cardiac surgery with the advances in surgical techniques, there is little research on the effect of angiography on postoperative AKI in these patients. This study investigates whether angiography increases the risk of AKI after cardiac surgery in patients with preoperative renal dysfunction (15 ≤ eGFR < 60 ml/min/1.73m2). METHODS: Patients with preoperative renal dysfunction (15 ≤ eGFR < 60 ml/min/1.73m2) who underwent angiography and cardiac surgery successively from January 2015 to December 2020 were retrospectively enrolled in this study. The primary outcome was postoperative AKI, defined as the Kidney Disease: Improving Global Outcomes Definition and Staging (KDIGO) criteria. Univariate analysis and multivariate regression were performed to identify the association between angiography timing and AKI. RESULTS: A total of 888 consecutive eligible patients with preoperative renal dysfunction (15 ≤ eGFR < 60 ml/min/1.73m2) were enrolled in this study. The incidence of AKI was 48.31%. Male (OR = 1.903), the interval between angiography and surgery (0-2d OR = 2.161; 3-6d OR = 3.291), cross-clamp duration (OR = 1.009), were identified as predictors for AKI. The interval between angiography and surgery was also associated with AKI in the patients with 15 ≤ eGFR < 30ml/min/1.73m2 (0-2d OR = 4.826; 3-6d OR = 5.252), 30 ≤ eGFR < 45 ml/min/1.73m2 (0-2d OR = 2.952; 3-6d OR = 3.677), but not associated with AKI in patients with 45 ≤ eGFR < 60 ml/min/1.73m2. CONCLUSIONS: In patients with preoperative renal dysfunction, the interval between angiography and cardiac surgery (0-2d and 3-6d) was associated with AKI. For patients with poorer preoperative renal function, the interval between angiography and cardiac surgery is of great concern.

Proteinuria is a risk factor for acute kidney injury after cardiac surgery in patients with stages 3-4 chronic kidney disease: a case control study.

BACKGROUND: Acute kidney injury (AKI) is a common complication after cardiac surgery, and preoperative renal dysfunction is an important risk factor. Proteinuria indicates renal structural damage, but there are few studies on proteinuria and the risk of AKI after cardiac surgery in patients with renal dysfunction. This study aimed to elucidate whether proteinuria can predict AKI after cardiac surgery in patients with renal dysfunction. METHODS: Patients with stages 3-4 chronic kidney disease (CKD) who underwent cardiac surgery were included in this retrospective study. AKI was defined according to the KDIGO criteria. The association between proteinuria and AKI in patients with CKD stages 3-4 was investigated. RESULTS: The incidence of AKI in the entire cohort (n = 1546) was 53.55%. The in-hospital mortality of patients with was higher than patients without AKI (AKI vs. no AKI, 4.7 vs. 0.8%, P < 0.001). Multivariate logistic regression analysis showed that proteinuria was an independent risk factor for AKI (trace to 1+ OR 2.37; 2+ -3+ OR 5.16) and AKI requiring renal replacement therapy (AKI-RRT) (trace to 1+ OR 3.64; 2+-3+ OR 5.71). Mild proteinuria (trace to 1+ OR 2.59) was also an independent risk factor for in-hospital death. In patients with diabetes mellitus, mild proteinuria (OR 1.925), instead of severe proteinuria (2-3+), was a risk factor of AKI in patients with kidney dysfunction and diabetes. CONCLUSIONS: In the population of patients with renal dysfunction, the incidence of AKI was high, which significantly compromised renal and overall prognosis. As a simple and inexpensive routine test, preoperative proteinuria still has value in predicting AKI in patients with impaired renal function.

Clec7a expression in inflammatory macrophages orchestrates progression of acute kidney injury.

Acute kidney injury (AKI) is associated with high risk of mortality, post-disease renal fibrosis, kidney dysfunction and renal failure. Renal macrophages play a key role in the pathogenesis (M1 subpopulation), healing and remodeling (M2 subpopulation) in AKI and, thus, have been a promising target for clinical treatment of AKI. Here, in a mouse renal ischemia/reperfusion injury (IRI) model for AKI, we showed that renal macrophages could be further classified into Clec7a+ M1 macrophages, Clec7a- M1 macrophages, Clec7a+ M2 macrophages and Clec7a- M2 macrophages, representing distinct macrophage populations with different functionality. Interestingly, Clec7a+ M1 macrophages exhibited potent pro-inflammatory and phagocytic effects compared to Clec7a- M1 macrophages, while Clec7a- M2 macrophages exhibited better proliferating and migrating potential, which is critical for their role in tissue repairing after injury. These data from mice were further strengthened by bioinformatics analyses using published database. In vivo, combined expression of Clec7a in M1 macrophages and depletion of Clec7a in M2 macrophages significantly improved the renal function after IRI-AKI. Together, our data suggest that Clec7a is crucial for the fine regulation of macrophage phenotype during AKI and could be a novel target for boosting clinical therapy.

Effects of hyperuricaemia, with the superposition of being overweight and hyperlipidaemia, on the incidence of acute kidney injury following cardiac surgery: a retrospective cohort study.

OBJECTIVES: Acute kidney injury (AKI) is a common complication of cardiac surgery. This study aimed to explore the effects of hyperuricaemia, being overweight and hyperlipidaemia as risk factors for AKI in patients following cardiac surgery (cardiac surgery-associated acute kidney injury (CSA-AKI)). DESIGN: Retrospective observational study. SETTING: University teaching, grade-A tertiary hospital in Shanghai, China. PARTICIPANTS: Patients who underwent cardiac surgery from July 2015 to December 2015 in Zhongshan Hospital, Fudan University. MAIN OUTCOME MEASURES: We investigated the effect of hyperuricaemia, in combination with being overweight and hyperlipidaemia, on the risk of CSA-AKI. RESULTS: A total of 1420 patients were enrolled. The AKI incidence in the highest uric acid group was 44.4%, while that in the lowest uric acid group was 28.5% (p<0.001). Patients in the higher uric acid quartiles were more likely to be overweight and hyperlipidaemic at the same time (p<0.001). Multivariate logistic regression analysis showed that hyperuricaemia was an independent risk factor for AKI (OR=1.237, 95% CI 1.095 to 1.885; p=0.009); being overweight or hyperlipidaemia alone was not an independent risk factor, but the combination of being overweight and hyperlipidaemia was (OR=1.544, 95% CI 1.059 to 2.252; p=0.024). In the final model, the OR value increased to 3.126 when hyperuricaemia was combined with being overweight and hyperlipidaemia, and the Hosmer-Lemeshow test showed that all three models fit well (p=0.433, 0.638 and 0.597, respectively). CONCLUSIONS: The combination of being overweight and having hyperlipidaemia was an independent risk factor, but being overweight or having hyperlipidaemia alone was not. The combination of hyperuricaemia, being overweight and hyperlipidaemia further increased the risk of CSA-AKI.

Suppressing Syndecan-1 Shedding to Protect Against Renal Ischemia/Reperfusion Injury by Maintaining Polarity of Tubular Epithelial Cells.

ABSTRACT: Syndecan-1 (SDC-1), a type of heparan sulfate proteoglycan on the surface of epithelial cells, is involved in maintaining cell morphology. Loss of cell polarity constitutes the early stage of ischemic acute kidney injury (AKI). This study investigated the role of SDC-1 shedding in I/R-induced AKI and the underlying mechanisms. Levels of the shed SDC-1 in the serum were measured with ELISA 12 and 24 h after reperfusion in renal I/R model mice. Na+/K+-ATPase-α1 expression was evaluated using western blotting in vivo and immunofluorescence in hypoxia/reoxygenation (H/R) cysts. Renal tubular epithelial cell apoptosis was measured using TUNEL in vivo and flow cytometry in vitro. Furthermore, plasma syndecan-1 (pSDC-1) levels were measured in patients at the time of anesthesia resuscitation after cardiac surgery. We found that shed SDC-1 levels increased and Na+/K+-ATPase-α1 expression decreased after H/R in the three-dimensional (3D) tubular model, and this state was exacerbated with extended period of hypoxia. After the inhibition of SDC-1 shedding by GM6001, SDC-1 and Na+/K+-ATPase-α1 expression was restored, while H/R-induced apoptosis was decreased. In vivo, SDC-1 shedding was induced by renal I/R and was accompanied with a loss of renal tubular epithelial cell polarity and increased apoptosis. GM6001 pretreatment protected against I/R injury by alleviating the disruption of cell polarity and apoptosis. pSDC-1 levels were significantly higher in AKI patients than in non-AKI patients. ROC curve showed that the accuracy of pSDC-1 for AKI prediction was 0.769. In conclusion, inhibition of I/R-induced SDC-1 shedding could contribute to renal protection by restoring the loss of cell polarity and alleviating apoptosis in tubular epithelial cells.

Association Between Syndecan-1, Fluid Overload, and Progressive Acute Kidney Injury After Adult Cardiac Surgery.

Background: Acute kidney injury (AKI) is a common complication after cardiac surgery and the prognosis of AKI worsens with the increase in AKI severity. Syndecan-1(SDC-1) is a biomarker of endothelial glycocalyx degradation. Fluid overload (FO) is associated with poor outcomes in AKI patients and may be related to the damage of endothelial function. This study aimed at demonstrating the association between elevated SDC-1, FO, and AKI progression. Methods: In this prospective study, we screened patients who underwent cardiac surgery and enrolled patients who experienced an AKI within 48 h after surgery from December 1, 2018 to January 31, 2019. Blood and urine samples were collected at the time of AKI diagnosis for plasma SDC-1 (pSDC-1) and urine SDC-1 (uSDC-1) measurements. Fluid balance (FB) = accumulated [fluid intake (L) - fluid output (L)]/body weight (kg) × 100%. FO was defined as FB > 5%. The primary endpoint was progressive AKI, defined as AKI progression from a lower to a higher stage. The patients were divided into progressive AKI group vs. non-progressive AKI group. Results: The quartiles of pSDC-1 concentration (117.3 [67.4, 242.3] ng/mL) showed a graded association with the incidence of progressive AKI, ranging from 5.0, 11.9, 32.6 to 52.4% (p for trend < 0.001). Multivariate logistic regression showed that increased pSDC-1 was an independent risk factor for progressive AKI. The AUC-ROC area of pSDC-1 concentration in predicting AKI progression was 0.847. Linear regression showed a positive correlation between FB and pSDC-1 concentration (R 2 = 0.384, p < 0.001). In patients with FO, the progressive AKI incidence was significantly higher in the high pSDC-1 (≥117.3 ng/mL) subgroup than in the low pSDC-1 subgroup (58.3 vs. 17.6%, OR = 9.167, P = 0.005). In patients without FO, the progressive AKI incidence was also significantly higher in the high pSDC-1 subgroup with a lower odds ratio (30.4 vs. 7.4%, OR = 6.714, P = 0.002). Conclusion: Elevated pSDC-1 concentration was associated with progressive AKI after cardiac surgery and showed good predictive ability for progressive AKI. FB was related to the increase of pSDC-1. The interaction between pSDC-1 and FB may further aggravate the progression of AKI.

The Association of Syndecan-1, Hypercoagulable State and Thrombosis and in Patients With Nephrotic Syndrome.

The aim of this study is to investigate whether Syndecan-1 (SDC-1), an indicator of endothelial glycocalyx injury, would increase the risk of hypercoagulable state and thrombosis in patients with nephrotic syndrome (NS). The prospective study was conducted among patients undergoing renal biopsy in the Department of Nephrology in our hospital from May to September 2018. We enrolled in patients with NS as the experimental group and patients with normal serum creatinine and proteinuria less than 1 g as the control group. Patients' characteristics including age, sex, laboratory test results and blood samples were collected for each patient. The blood samples were taken before the renal biopsy. The samples were immediately processed and frozen at -80°C for later measurement of Syndecan-1. One hundred and thirty-six patients were enrolled in the study. Patients with NS and hypercoagulability had a higher level of SDC-1 compared with control group. Patients with membranous nephropathy occupied the highest SDC-1 level (P = 0.012). Logistic regression showed that highly increased level of SDC-1 (>53.18 ng/ml) was an independent predicator for predicting hypercoagulable state. The elevated level of SDC-1 indicated that endothelial injury, combined with its role of accelerating hypercoagulable state, might be considered of vital importance in the pathophysiological progress of thrombosis formation in patients with NS.

Urinary Soluble CD163 Levels Predict IgA Nephropathy Remission Status.

Noninvasive biomarkers of disease activity are needed to predict disease remission status in patients with IgA nephropathy (IgAN). Soluble CD163 (sCD163), shed by monocytes and macrophages, is a potential biomarker in diseases associated with excessive macrophage activation. We investigated the association of urinary sCD163 (u-sCD163) with histopathological activity and clinical manifestations in 349 patients with biopsy-diagnosed IgAN. U-sCD163 was measured via enzyme-linked immunosorbent assay. In patients with IgAN, higher u-sCD163 levels were associated with histological lesions of greater severity, as well as more proteinuria and poorer renal function. Additionally, u-sCD163 was correlated with infiltration of tubulointerstitial CD163+ macrophages. High u-sCD163 levels (>3.57 ng/mg Cr) were associated with a 2.66-fold greater risk for IgAN remission failure in adjusted analyses. Adding u-sCD163 levels to the model containing clinical data at biopsy and MEST-C score significantly improved the risk prediction of IgAN remission status (AUC 0.788). Together, our results suggest that u-sCD163 may be a useful noninvasive biomarker to evaluate disease severity and remission status of IgAN.

The Effect of Admission Serum Magnesium on the Acute Kidney Injury Among Patients with Malignancy.

PURPOSE: This study aimed to explore the relationship between serum magnesium (Mg) levels and incidence of acute kidney injury (AKI) in patients with malignancy. PATIENTS AND METHODS: Hospitalized patients with malignancy between October 1, 2014 and September 30, 2015 in Zhongshan Hospital were recruited. All relevant data were extracted from the electronic database. RESULTS: All 99,845 patients were enrolled and 16,082 eligible patients were divided into three groups according to admission serum Mg levels in this study. Among them, 2383 (14.8%) cases were diagnosed as AKI. The incidence of AKI showed a V trend with the increase of serum Mg level. The effect of low serum Mg level on the onset of AKI seems to be greater than high serum Mg level. Patients with low serum Mg level spent a longer time in the hospital than those with normal serum Mg level and high serum Mg level. Further, multivariate logistic regression model was used to assess the importance of serum Mg level to influence AKI incidence. There was a higher AKI incidence in patients with magnesium level 0.66mmol/L or less (aOR=2.438, 95% CI=1.696, 3.505). CONCLUSION: Low serum Mg level might be a independent risk factor for AKI in patients with malignancy. Appropriate clinical intervention for serum Mg disorder may contribute to decreasing the incidence of AKI and the possibility of poor outcomes in cancer patients.

LncRNA GAS5 promotes apoptosis as a competing endogenous RNA for miR-21 via thrombospondin 1 in ischemic AKI.

Mounting evidence has indicated that long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) played important roles in renal ischemia/reperfusion (I/R) injury. However, the involvement of lncRNA growth arrest specific 5 (GAS5) in acute kidney injury (AKI) remained largely unexplored. This study aimed to determine possible mechanisms of GAS5 in the renal I/R process. We found that GAS5, noticeably upregulated by renal I/R injury, was further suppressed by delayed IPC while knockdown of miR-21 in vivo before IPC could significantly increased the GAS5 levels. Concurrently, TSP-1 was negatively regulated by miR-21 in vivo and vitro. Additionally, Reciprocal repression of GAS5 and miR-21 was identified. Knockdown of miR-21 in H6R0.5 treated HK-2 cells promoted apoptosis. Co-transfection of miR-21 mimic and pcDNA-GAS5 or pcDNA-Vector were performed, results of which showed that inhibition of miR-21 on TSP-1 could be rescued by overexpression of GAS5. This study suggested that GAS5 facilitated apoptosis by competitively sponging miR-21, which negatively regulated TSP-1 in renal I/R injury. This novel regulatory axis could act as a therapeutic target for AKI in the future.

Evaluation of five different renal recovery definitions for estimation of long-term outcomes of cardiac surgery associated acute kidney injury.

BACKGROUND: The commonly used recommended criteria for renal recovery are not unequivocal. This study compared five different definitions of renal recovery in order to evaluate long-term outcomes of cardiac surgery associated acute kidney injury (CSA-AKI). METHODS: Patients who underwent cardiac surgery between April 2009 and April 2013 were enrolled and divided into acute kidney injury (AKI) and non-AKI groups. The primary endpoint was 3-year major adverse events (MAEs) including death, new dialysis and progressive chronic kidney disease (CKD). We compared five criteria for complete renal recovery: Acute Renal Failure Trial Network (ATN): serum creatinine (SCr) at discharge returned to within baseline SCr + 0.5 mg/dL; Acute Dialysis Quality Initiative (ADQI): returned to within 50% above baseline SCr; Pannu: returned to within 25% above baseline SCr; Kidney Disease: Improving Global Outcomes (KDIGO): eGFR at discharge ≥60 mL/min/1.73 m2; Bucaloiu: returned to ≥90% baseline estimated glomerular filtration rate (eGFR). Multivariate regression analysis was used to compare risk factors for 3-year MAEs. RESULTS: The rate of complete recovery for ATN, ADQI, Pannu, KDIGO and Bucaloiu were 84.60% (n = 1242), 82.49% (n = 1211), 60.49% (n = 888), 68.60% (n = 1007) and 46.32% (n = 680). After adjusting for confounding factors, AKI with complete renal recovery was a risk factor for 3-year MAEs (OR: 1.69, 95% CI: 1.20-2.38, P <  0.05; OR: 1.45, 95% CI: 1.03-2.04, P <  0.05) according to ATN and ADQI criteria, but not for KDIGO, Pannu and Bucaloiu criteria. We found that relative to patients who recovered to within 0% baseline SCr or recovered to ≥100% baseline eGFR, the threshold values at which significant differences in 3-year MAEs were observed were > 30% or > 0.4 mg/dL above baseline SCr or < 70% of baseline eGFR. CONCLUSIONS: ADQI or ATN-equivalent criteria may overestimate the extent of renal recovery, while KDIGO, Pannu and Bucaloiu equivalent criteria may be more appropriate for clinical use. Our analyses revealed that SCr at discharge > 30% or > 0.4 mg/dL of baseline, or eGFR < 70% of baseline led to significant 3-year MAE incidence differences, which may serve as hints for new definitions of renal recovery.

Preoperative hidden renal dysfunction add an age dependent risk of progressive chronic kidney disease after cardiac surgery.

BACKGROUND: To study different value of estimated glomerular filtration rate with normal serum creatinine whether is a risk factor for hidden renal function of cardiac surgery outcomes. METHODS: A total of 1744 cardiac surgery patients with serum creatinine ≤1.2 mg/dL (female)/1.5 mg/dL (male) were divided into 3 groups: estimated glomerular filtration rate ≥ 90 mL/min/1.73 m2 (no renal dysfunction, n = 829), 60 ≤ estimated glomerular filtration rate < 90 mL/min/1.73 m2 (hidden renal dysfunction, n = 857), estimated glomerular filtration rate < 60 mL/min/1.73 m2 (known renal dysfunction, n = 58) and followed up for 3 years. Multivariate regression analyses for risk factors of postoperative acute kidney injury. RESULTS: The proportion of preoperative hidden renal dysfunction was 67.1% among patients ≥  65 years old and 44.1% among patients < 65 years old. Multivariate Cox regression analyses showed that for patients < 65 years, known renal dysfunction was a risk factor for postoperative acute kidney injury (P <  0.01) and progressive chronic kidney disease (P = 0.018), while hidden renal dysfunction was a risk factor for progressive chronic kidney disease (P = 0.024). For patients ≥  65 years, only known renal dysfunction was a risk factors for 3-year mortality (P = 0.022) and progressive chronic kidney disease (P <  0.01). CONCLUSION: Hidden renal dysfunction was common in patients with normal serum creatinine for cardiac surgery, with a prevalence of 49.1%. For patients < 65 years old, hidden renal dysfunction was an independent risk factor for progressive chronic kidney disease.

Delayed Ischemic Preconditioning Attenuated Renal Ischemia-Reperfusion Injury by Inhibiting Dendritic Cell Maturation.

BACKGROUND/AIMS: Even though delayed ischemic preconditioning (DIPC) has been reported to produce renal protection, the underlying mechanism remains poorly understood. We reported that a 15-minute renal ischemic preconditioning (IPC) 4 days before subsequent ischemia-reperfusion attenuated renal injury Kidney dendritic cells (DCs) are abundant in the renal tubulointerstitium and, depending on their status, can induce immune activation or tolerance. The aim of the present study was to investigate the role of DCs in IPC of the kidney. METHODS: Mouse kidneys were challenged by transient brief episodes of sublethal ischemia followed by subsequent prolonged ischemia. DC abundance and maturation in the spleen and kidney were measured by flow cytometry and immunohistochemical staining. To confirm the function of mature DCs in the renoprotective effect of IPC on renal ischemia-reperfusion injury the A2 adenosine receptor (A2AR) antagonist SCH58261 was administered to stimulate DC maturation prior to assessment of renal functional and histological injury and the inflammatory reaction. RESULTS: Compared with sham-operated animals, preconditioned mice had a reduced injury with less CD11c+ cells, lower levels of the pro-inflammatory cytokine IL-17 and reduced expression of the mature DC marker CCR7. Preconditioned mice also produced more of the anti-inflammatory cytokine IL-10. Both renal cells and splenocytes from these mice had more DCs (CD45+/CD11c+/F4/80-), but fewer of these DCs were mature (CD45+/CD11c+/ F4/80-/MHC-II+/CD80+) compared with those from sham-treated animals, suggesting that the immunomodulatory effect of renal ischemic preconditioning is both local and systemic. Additionally, injection of the A2AR antagonist SCH58261 reversed IPC-induced inhibition of DC maturation and mitigated the protective effect of preconditioning, suggesting that DC maturation contributes to immune cell-mediated ischemic preconditioning. CONCLUSION: Our results show that DIPC of the kidney provides local and systemic immunosuppression by inhibiting DC maturation and hence mediates a renal protective effect.