Syndecan-1 shedding destroys epithelial adherens junctions through STAT3 after renal ischemia/reperfusion injury.

Adherens junctions between tubular epithelial cells are disrupted in renal ischemia/reperfusion (I/R) injury. Syndecan-1 (SDC-1) is involved in maintaining cell morphology. We aimed to study the role of SDC-1 shedding induced by renal I/R in the destruction of intracellular adherens junctions. We found that SDC-1 shedding was increased while the expression of E-cadherin was decreased. This observation was accompanied by the activation of STAT3 in the kidneys. Inhibiting the shedding of SDC-1 induced by I/R could alleviate this effect. Mild renal I/R could induce more severe renal injury, lower E-cadherin expression, damaged cell junctions, and activated STAT3 in knockout mice with the tubule-specific deletion of SDC-1 mice. The results in vitro were consistent with those in vivo. Inhibiting the shedding of SDC-1 could alleviate the decreased expression of E-cadherin and damage of cell adherens junctions through inhibiting the activation of STAT3 during ischemic acute kidney injury.

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.

Risk Factors and Prognosis of Acute Kidney Injury after Cardiac Surgery in Patients with Chronic Kidney Disease.

INTRODUCTION: Cardiac surgery-associated acute kidney injury (CSA-AKI) is one of the most prevalent complications of cardiac surgery, while the renal and overall prognoses of chronic kidney disease (CKD) patients with CSA-AKI are extremely poor. However, there is little published information on the occurrence of CSA-AKI in patients with CKD. The purpose of this study was to investigate the risk factors and prognostic factors of cardiac surgery-related AKI in patients with CKD. METHODS: A retrospective study was performed on CKD patients who underwent cardiac surgery at a tertiary referral teaching hospital. CSA-AKI was defined based on the KDIGO criteria. The risk factors for CSA-AKI and the factors affecting renal function recovery at discharge or death in patients with AKI were investigated. RESULTS: Among 1638 CKD patients enrolled, the incidence of CSA-AKI was 50.55%. AKI patients' in-hospital mortality was higher than patients without AKI (AKI vs. no AKI, 4.7 vs. 0.9%, p < 0.001). Multivariate logistic regression analysis showed that male (odds ratio [OR] 1.479), preoperative hypertension (OR 1.548), preoperative hemoglobin <110 g/L (OR 2.389), and aortic clamping time >58 min (OR 1.567) were independent risk factors for AKI after cardiac surgery in patients with CKD. Factors affecting renal function recovery of AKI patients included preoperative diabetes mellitus (OR 0.306), hyperchloremia (OR 0.927), estimate of the glomerular filtration rate (OR 1.034), and AKI progression. Compared with patients with AKI stage 1, the rate of renal function recovery in patients with AKI stage 2 and stage 3 was reduced by 78.9% and 82.3%, respectively. CONCLUSIONS: In the population of patients with CKD, the incidence of CSA-AKI was high, which significantly affected renal and overall prognosis. The prompt intervention of modifiable factors may help improve the prognosis of patients with CKD.

Improvement of cardiac function after coronary artery bypass grafting surgery reduces the risk of postoperative acute kidney injury.

BACKGROUND: Pre-existing renal dysfunction is an independent risk factor for cardiac surgery-associated acute kidney injury (AKI). We aimed to investigate whether the improvement of postoperative cardiac function after coronary artery bypass grafting (CABG) surgery would affect the risk of AKI in patients with different levels of baseline renal function. METHODS: Data were collected from patients who underwent CABG surgery from January 2018 to April 2019. Patients were divided into normal (GFR ≥ 90 ml/min/1.73 m2 ), non-CKD (60≤GFR < 90 ml/min/1.73 m2 ), and CKD (GFR < 60 ml/min/1.73 m2 ) groups. Improvement in cardiac function was defined as △LVEF (postoperative LVEF-preoperative LVEF) ≥ 10% preoperative LVEF. Patients were further divided into subgroups according to postoperative cardiac function improvement. RESULTS: A total of 1365 patients were enrolled, including 793 (58.1%) in the normal group, 476 (34.9%) in the non-CKD group, and 96 (7.0%) in the CKD group. The AKI incidence in the normal, non-CKD, and CKD groups was 22.2%, 28.4%, and 40.6%, respectively. Patients with improved cardiac function in the non-CKD and CKD groups had significantly lower AKI incidence than those without improved cardiac function (22.8% vs. 36.9%, p = .002% and 32.8% vs. 54.3%, p = .037, respectively). For non-CKD patients with improved cardiac function, the serum creatinine at discharge was significantly lower than its preoperative serum creatinine (0.8 ± 0.5 vs 1.2 ± 0.9 mg/dl, p = .002). Multivariate logistic regression analysis showed that the improvement in cardiac function could reduce the risk for postoperative AKI in non-CKD patients but not in CKD patients. CONCLUSIONS: For patients with renal dysfunction and mildly reduced eGFR (60≤GFR < 90 ml/min/1.73 m2 ), improved cardiac function after CABG surgery can reduce the serum creatinine level and reduce the risk for postoperative AKI.

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.

Risk Scoring Systems Including Electrolyte Disorders for Predicting the Incidence of Acute Kidney Injury in Hospitalized Patients.

INTRODUCTION: Electrolyte disorders are common among hospitalized patients with acute kidney injury (AKI) and adversely affect the outcome. This study aimed to explore the potential role of abnormal electrolyte levels on predicting AKI and severe AKI. METHODS: In this retrospective, observational study, we included all hospitalized patients in our hospital in China from October 01, 2014, to September 30, 2015. Since only a few patients had arterial blood gas analysis (ABG), all subjects involved were divided into two groups: patients with ABG and patients without ABG. Severe AKI was defined as AKI stage 2 or 3 according to KDIGO guideline. RESULTS: A total of 80,091 patients were enrolled retrospectively and distributed randomly into the test cohort and the validation cohort (2:1). Logistic regression was performed in the test cohort to analyze risk factors including electrolyte disorders and elucidate the association. The test data (derivation cohort) led to AUC values of 0.758 (95% CI: 0.743-0.773; AKI with ABG), 0.751 (95% CI: 0.740-0.763; AKI without ABG), 0.733 (95% CI: 0.700-0.767; severe AKI with ABG), 0.853 (95% CI: 0.824-0.882; severe AKI without ABG). Application of the scoring system in the validation cohort led to AUC values of 0.724 (95% CI: 0.703-0.744; AKI with ABG), 0.738 (95% CI: 0.721-0.755; AKI without ABG), 0.774 (95% CI: 0.732-0.815; severe AKI with ABG), 0.794 (95% CI: 0.760-0.827; severe AKI without ABG). Hosmer-Lemeshow tests revealed a good calibration. CONCLUSION: The risk scoring systems involving electrolyte disorders were established and validated adequately efficient to predict AKI and severe AKI in hospitalized patients. Electrolyte imbalance needs to be carefully monitored and corrections should be made on time to avoid further adverse outcome.

Novel predictive biomarkers for acute injury superimposed on chronic kidney disease / Novedosos biomarcadores predictivos para lesiones agudas superpuestas a una enfermedad renal crónica

INTRODUCTION AND OBJECTIVES: Chronic kidney disease (CKD) is a risk factor for the development of acute kidney injury (AKI). Recent studies have revealed numerous biomarkers eligible for AKI prediction. However, the expression and performance of AKI biomarkers in acute injury superimposed on preexisting CKD (AonC) remain elusive. The aim of this study was to evaluate whether biomarkers which robustly expressed in acute kidney injury could predict acute injury based on CKD. MATERIALS AND METHODS: Mice were classified into cohorts: AKI, CKD, AonC and sham. The AonC model mice were subjected to renal bilateral ischemia/reperfusion (I/R) injury fourteen days after intraperitoneally administrated with 20 mg/kg aristolochic acid. Severity of acute ischemic injury was stratified by clamping the dissected bilateral renal arteries with non-traumatic microvascular clips for 20 or 35 min. The AKI mice were induced with renal bilateral I/R injury and CKD mice were crafted with 20mg/kg aristolochic acid administrated intraperitoneally. Histology, genetic and protein expression of biomarkers were measured in three cohorts. RESULTS: We found that serum creatinine dramatically increased in severe (sAonC) but not in moderate (mAonC) injury mice. Upregulation of Kidney injury molecule-1 (KIM-1) mRNA, tissue inhibitor of metalloproteinase-2 (TIMP-2), Syndecan-1 (SDC-1) mRNA and insulin-like growth factor binding protein-7 (IGFBP7) protein indicated the onset of mAonC. An increase in neutrophil gelatinase-associated lipocalin (NGAL), rhomboid-like protein 2 (RHBDL2), Syndecan-1 (SDC-1) mRNA and protein, and a decrease in IGFBP7 protein were associated with sAonC. CONCLUSIONS: Our study revealed the variational expression of AKI biomarkers in AonC kidneys, and uncovered IGFBP7 protein can be used as a sensitive biomarker to predict and differentiate AonC severity. The performance of RHBDL2 and SDC-1 in predicting severe AonC was promising, providing new biomarkers for predicting AonC

INTRODUCCIÓN Y OBJETIVOS: La enfermedad renal crónica (ERC) es un factor de riesgo para el desarrollo de una lesión renal aguda (LRA). Estudios recientes han revelado numerosos biomarcadores para la predicción de LRA. No obstante, la expresión y el rendimiento de los biomarcadores de LRA en lesiones agudas superpuestas a una ERC preexistente (AonC, en inglés) siguen siendo imprecisos. El objetivo de este estudio fue evaluar si los biomarcadores que se encuentran muy expresados en la lesión renal aguda podrían predecir una lesión aguda superpuesta a una ERC. MATERIALES Y MÉTODOS: Se dividieron ratones en cohortes (LRA, ERC, AonC y grupo de referencia). A los ratones del modelo de AonC se les indujo una lesión renal bilateral por isquemia/reperfusión (I/R) 14 días después de la administración intraperitoneal de 20 mg/kg de ácido artistolóquico. La gravedad de la lesión isquémica aguda se estratificó pinzando las arterias renales bilaterales diseccionadas con horquillas microvasculares no traumáticas durante 20 o 35 min. A los ratones de LRA se les indujo una lesión renal bilateral por I/R y a los ratones de ERC se les administraron 20mg/kg de ácido artistolóquico por vía intraperitoneal. Se determinaron la histología, la genética y la expresión de proteínas en las tres cohortes. RESULTADOS: Observamos que la creatinina sérica aumentaba drásticamente en los ratones con lesiones graves (AonCg) pero no en aquellos con lesiones moderadas (AonCm) El aumento del ARNm de la molécula1 de lesión renal (KIM-1), del inhibidor tisular de metaloproteinasas 2 (TIMP-2), del ARNm de sindecán 1 (SDC-1) y de la proteína de unión al factor de crecimiento insulinoide 7 (IGFBP7) fue indicativo de aparición de AonCm. El incremento de la lipocalina asociada a la gelatinasa de neutrófilos (NGAL), la proteína romboidal 2 (RHBDL2) y el ARNm y la proteína de sindecán 1 (SDC-1), así como la reducción de la proteína IGFBP7, se asociaron a una AonCg. CONCLUSIONES: Nuestro estudio mostró la variación de la expresión de los biomarcadores de LRA en riñones con AonC y descubrió que la proteína IGFBP7 puede emplearse como biomarcador sensible para la predicción y la diferenciación de la gravedad de la AonC. El rendimiento de RHBDL2 y SDC-1 en la predicción de AonC graves resultó prometedor, lo que ofrece nuevos biomarcadores para la predicción de AonC

Hemodilution is associated with underestimation of serum creatinine in cardiac surgery patients: a retrospective analysis.

BACKGROUND: Fluid overload is related to the development and prognosis of cardiac surgery-associated acute kidney injury (CSA-AKI). The study is to investigate the influence of serum creatinine (SCr) corrected by fluid balance on the prognosis of patients with cardiac surgery. METHODS: A retrospective study was conducted in 1334 patients who underwent elective cardiac surgery from January 1 to December 31, 2015. Kidney Disease: Improving Global Outcomes (KDIGO) criteria for AKI were applied to identify CSA-AKI. SCr was measured every 24 h during ICU period and was accordingly adjusted for cumulative fluid balance. Changes in SCr, defined as ∆Crea, were determined by difference between before and after adjustment for cumulative fluid balance. All patients were then divided into three groups: underestimation group (∆Crea ≥ P75), normal group (P25 < ∆Crea < P75) and overestimation group (∆Crea ≤ P25). RESULTS: The incidence of AKI increased from 29.5% to 31.8% after adjustment for fluid balance. Patients in underestimation group showed prolonged length of ICU stay compared with normal group and overestimation group (3.2 [1.0-4.0] vs 2.1 [1.0-3.0] d, P < 0.001; 3.2  [1.0-4.0] vs 2.3 [1.0-3.0] d, P < 0.001). Length of hospital stay and mechanical ventilation dependent days in underestimation group were significantly longer than normal group (P < 0.001). Multivariate analysis showed age, baseline SCr and left ventricular ejection fraction were independently associated with underestimation of creatinine. CONCLUSIONS: Cumulative fluid balance after cardiac surgery disturbs accurate measurement of serum creatinine. Patients with underestimation of SCr were associated with poor prognosis.

Novel predictive biomarkers for acute injury superimposed on chronic kidney disease.

INTRODUCTION AND OBJECTIVES: Chronic kidney disease (CKD) is a risk factor for the development of acute kidney injury (AKI). Recent studies have revealed numerous biomarkers eligible for AKI prediction. However, the expression and performance of AKI biomarkers in acute injury superimposed on preexisting CKD (AonC) remain elusive. The aim of this study was to evaluate whether biomarkers which robustly expressed in acute kidney injury could predict acute injury based on CKD. MATERIALS AND METHODS: Mice were classified into cohorts: AKI, CKD, AonC and sham. The AonC model mice were subjected to renal bilateral ischemia/reperfusion (I/R) injury fourteen days after intraperitoneally administrated with 20mg/kg aristolochic acid. Severity of acute ischemic injury was stratified by clamping the dissected bilateral renal arteries with non-traumatic microvascular clips for 20 or 35min. The AKI mice were induced with renal bilateral I/R injury and CKD mice were crafted with 20mg/kg aristolochic acid administrated intraperitoneally. Histology, genetic and protein expression of biomarkers were measured in three cohorts. RESULTS: We found that serum creatinine dramatically increased in severe (sAonC) but not in moderate (mAonC) injury mice. Upregulation of Kidney injury molecule-1 (KIM-1) mRNA, tissue inhibitor of metalloproteinase-2 (TIMP-2), Syndecan-1 (SDC-1) mRNA and insulin-like growth factor binding protein-7 (IGFBP7) protein indicated the onset of mAonC. An increase in neutrophil gelatinase-associated lipocalin (NGAL), rhomboid-like protein 2 (RHBDL2), Syndecan-1 (SDC-1) mRNA and protein, and a decrease in IGFBP7 protein were associated with sAonC. CONCLUSIONS: Our study revealed the variational expression of AKI biomarkers in AonC kidneys, and uncovered IGFBP7 protein can be used as a sensitive biomarker to predict and differentiate AonC severity. The performance of RHBDL2 and SDC-1 in predicting severe AonC was promising, providing new biomarkers for predicting AonC.

Erythrocyte transfusion limits the role of elevated red cell distribution width on predicting cardiac surgery associated acute kidney injury.

BACKGROUND: Acute kidney injury (AKI) is one of the more serious complications after cardiac surgery. Elevated red cell distribution width (RDW) was reported as a predictor for cardiac surgery associated acute kidney injury (CSAKI). However, the increment of RDW by erythrocyte transfusion makes its prognostic role doubtful. The aim of this study is to elucidate the impact of erythrocyte transfusion on the prognostic role of elevated RDW for predicting CSAKI. METHODS: A total of 3207 eligible patients who underwent cardiac surgery during 2016-2017 were enrolled. Changes of RDW was defined as the difference between preoperative RDW and RDW measured 24 h after cardiac surgery. The primary outcome was CSAKI which was defined by the Kidney Disease: Improving Global Outcomes Definition and Staging (KDIGO) criteria. Univariate and multivariate analysis were performed to identify predictors for CSAKI. RESULTS: The incidence of CSAKI was 38.07% and the mortality was 1.18%. CSAKI patients had higher elevated RDW than those without CSAKI (0.65% vs. 0.39%, p < 0.001). Multivariate regression showed that male, age, New York Heat Association classification 3-4, elevated RDW, estimated glomerular filtration rate < 60 mL/min/1.73 m2, cardiopulmonary bypass time > 120 min and erythrocyte transfusion were associated with CSAKI. Subgroup analysis showed elevated RDW was an independent predictor for CSAKI in the non-transfused subset (adjusted odds ratio: 1.616, p < 0.001) whereas no significant association between elevated RDW and CSAKI was found in the transfused patients (odds ratio: 1.040, p = 0.497). CONCLUSIONS: Elevated RDW is one of the independent predictors of CSAKI in the absence of erythrocyte transfusion, which limits the prognostic role of the former on predicting CSAKI.

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.

Novel predictive biomarkers for acute injury superimposed on chronic kidney disease.

INTRODUCTION AND OBJECTIVES: Chronic kidney disease (CKD) is a risk factor for the development of acute kidney injury (AKI). Recent studies have revealed numerous biomarkers eligible for AKI prediction. However, the expression and performance of AKI biomarkers in acute injury superimposed on preexisting CKD (AonC) remain elusive. The aim of this study was to evaluate whether biomarkers which robustly expressed in acute kidney injury could predict acute injury based on CKD. MATERIALS AND METHODS: Mice were classified into cohorts: AKI, CKD, AonC and sham. The AonC model mice were subjected to renal bilateral ischemia/reperfusion (I/R) injury fourteen days after intraperitoneally administrated with 20mg/kg aristolochic acid. Severity of acute ischemic injury was stratified by clamping the dissected bilateral renal arteries with non-traumatic microvascular clips for 20 or 35min. The AKI mice were induced with renal bilateral I/R injury and CKD mice were crafted with 20mg/kg aristolochic acid administrated intraperitoneally. Histology, genetic and protein expression of biomarkers were measured in three cohorts. RESULTS: We found that serum creatinine dramatically increased in severe (sAonC) but not in moderate (mAonC) injury mice. Upregulation of Kidney injury molecule-1 (KIM-1) mRNA, tissue inhibitor of metalloproteinase-2 (TIMP-2), Syndecan-1 (SDC-1) mRNA and insulin-like growth factor binding protein-7 (IGFBP7) protein indicated the onset of mAonC. An increase in neutrophil gelatinase-associated lipocalin (NGAL), rhomboid-like protein 2 (RHBDL2), Syndecan-1 (SDC-1) mRNA and protein, and a decrease in IGFBP7 protein were associated with sAonC. CONCLUSIONS: Our study revealed the variational expression of AKI biomarkers in AonC kidneys, and uncovered IGFBP7 protein can be used as a sensitive biomarker to predict and differentiate AonC severity. The performance of RHBDL2 and SDC-1 in predicting severe AonC was promising, providing new biomarkers for predicting AonC.

The Effect of Postoperative Fluid Balance on the Occurrence and Progression of Acute Kidney Injury After Cardiac Surgery.

OBJECTIVES: In addition to the association between positive fluid balance (FB) and acute kidney injury (AKI) after cardiac surgery reported by former studies, this study examined the relationship between FB and progressive AKI. DESIGN: A retrospective, observational study. SETTING: University teaching, grade A tertiary hospital in Shanghai, China. PARTICIPANTS: Adult patients after cardiac surgery from July-December 2016. INTERVENTIONS: Perioperative data relating to postoperative fluid intake and output were collected. AKI progression was defined as a worsening of AKI stage. FB was calculated as (fluid intake [L] - fluid output [L]/body weight [kg] × 100%). MEASUREMENTS AND MAIN RESULTS: The study comprised 1,522 patients. The incidences of AKI and progressive AKI were 33.1% (n = 504) and 18.1% (n = 91), respectively. There was an exponential increase between 24-hour FB and AKI occurrence, and an approximate "U"-shape association between 48-hour FB and AKI progression. Multivariate logistic regression showed that 24-hour FB ≥5% was an independent risk factor for AKI incidence (odds ratio [OR] 3.976; p < 0.001) and 48-hour FB <-5% or ≥3% was associated with an increase of AKI progression (FB <-5%, OR 7.078 [p = 0.031]; FB 3%-5%, OR 6.598 [p = 0.020]; FB ≥5%, OR 16.453 [p < 0.001]). CONCLUSIONS: An exponential increase was found between 24-hour FB and AKI occurrence and a "U"-shape association between 48-hour FB and AKI progression. Both excessively negative and positive accumulative 48-hour FB increased the risk of AKI progression, suggesting cautious monitoring and application of fluid load in clinical practice.

Volume-associated hemodynamic variables for prediction of cardiac surgery-associated acute kidney injury.

BACKGROUND: Delayed diagnosis of acute kidney injury (AKI) is common because the changes in renal function markers often lag injury. We aimed to find optimal non-invasive hemodynamic variables for the prediction of postoperative AKI and AKI renal replacement therapy (RRT). METHODS: The data were collected from 1,180 patients who underwent cardiac surgery in our hospital between March 2015 and Feb 2016. Postoperative central venous pressure (CVP), mean arterial pressure (MAP), heart rate, PaO2, and PaCO2 on ICU admission and daily fluid input and output (calculated as 24 h PFO) were monitored and compared between AKI vs. non-AKI and RRT vs non-RRT cases. RESULTS: The AKI and AKI-RRT incidences were 36.7% (n = 433) and 1.2% (n = 14). Low cardiac output syndromes (LCOSs) occurred significantly more in AKI and RRT than in non-AKI or non-RRT groups (13.2% vs. 3.9%, P < 0.01; 42.9% vs. 7.1%, P < 0.01). CVP on ICU admission was significantly higher in AKI and RRT than in non-AKI and non-RRT groups (11.5 vs. 9.0 mmHg, P < 0.01; 13.3 vs. 9.9 mmHg, P < 0.01). 24 h PFO in AKI and RRT cases were significantly higher than in non-AKI or non-RRT patients (1.6% vs. 0.9%, P < 0.01; 3.9% vs. 0.8%, P < 0.01). The areas under the ROC curves to predict postoperative AKI by CVP on ICU admission (> 11 mmHg) + LCOS + 24 h PFO (> 5%) and to predict AKI-RRT by CVP on ICU admission (> 13 mmHg) + LCOS + 24 h PFO (> 5%) were 0.763 and 0.886, respectively. CONCLUSION: The volume-associated hemodynamic variables, including CVP on ICU admission, LCOS, and 24 h PFO after surgery could predict postoperative AKI and AKI-RRT.

A novel machine learning algorithm, Bayesian networks model, to predict the high-risk patients with cardiac surgery-associated acute kidney injury.

BACKGROUND: Cardiac surgery-associated acute kidney injury (CSA-AKI) is a well-recognized complication with an ominous outcome. HYPOTHESIS: Bayesian networks (BNs) not only can reveal the complex interrelationships between predictors and CSA-AKI, but predict the individual risk of CSA-AKI occurrence. METHODS: During 2013 and 2015, we recruited 5533 eligible participants who underwent cardiac surgery from a tertiary hospital in eastern China. Data on demographics, clinical and laboratory information were prospectively recorded in the electronic medical system and analyzed by gLASSO-logistic regression and BNs. RESULTS: The incidences of CSA-AKI and severe CSA-AKI were 37.5% and 11.1%. BNs model revealed that gender, left ventricular ejection fractions (LVEF), serum creatinine (SCr), serum uric acid (SUA), platelet, and aortic cross-clamp time (ACCT) were found as the parent nodes of CSA-AKI, while ultrafiltration volume and postoperative central venous pressure (CVP) were connected with CSA-AKI as children nodes. In the severe CSA-AKI model, age, proteinuria, and SUA were directly linked to severe AKI; the new nodes of NYHA grade and direct bilirubin created relationships with severe AKI through was related to LVEF, surgery types, and SCr level. The internal AUCs for predicting CSA-AKI and severe AKI were 0.755 and 0.845, which remained 0.736 and 0.816 in the external validation. Given the known variables, the risk for CSA-AKI can be inferred at individual levels based on the established BNs model and prior information. CONCLUSION: BNs model has a high accuracy, good interpretability, and strong generalizability in predicting CSA-AKI. It facilitates physicians to identify high-risk patients and implement protective strategies to improve the prognosis.

Efficacy of Early Goal-Directed Renal Replacement Therapy for the Treatment of Acute Kidney Injury After Heart Transplantation: A Single-Center 10-Year Experience.

OBJECTIVE: Acute kidney injury (AKI) after heart transplantation is a common and serious complication. The present study aimed to evaluate the efficacy of early goal-directed renal replacement therapy (GDRRT) for the treatment of AKI after heart transplantation. DESIGN: Retrospective, observational study. SETTING: Grade A tertiary hospital that performs more than 4,000 cardiac surgery procedures per year. PARTICIPANTS: Patients who underwent heart transplantation with postoperative AKI and received renal replacement therapy from January 2008 to June 2018. INTERVENTIONS: Patients were divided into a late GDRRT group (LGDRRT) (January 2008-September 2012) or an early GDRRT group (EGDRRT) (October 2012-June 2018). RESULTS: The LGDRRT group comprised 30 patients, and the EGDRRT group comprised 46 patients. Duration between surgery to renal replacement therapy (RRT) initiation in the EGDRRT group was significantly shorter than in the LGDRRT group (1 [1-3] d v 2 [2-3] d; p = 0.020). The in-hospital mortality in the EGDRRT group was significantly lower than that of the LGDRRT group (39.1% v 63.3%; p = 0.039). After multivariate adjustment for confounding factors, the hazard ratio for death in the LGDRRT group relative to the EGDRRT group was 2.028 (95% confidence interval 1.072-3.655; p = 0.048). Length of intensive care unit and hospital stays in the EGDRRT group was significantly shorter than that of the LGDRRT group (26 ± 18 d v 38 ± 20 d; p = 0.008 and 38 ± 33 d v 64 ± 45 d; p = 0.005, respectively). The complete renal recovery rate was much greater in the EGDRRT group than that of the LGDRRT group (50.0% v 20.0%; p < 0.001). Serum creatinine at discharge was significantly less in the EGDRRT group than that of the LGDRRT group (134.8 ± 97.3 µmol/L v 220.7 ± 113.6 µmol/L; p < 0.001). Cost of RRT in the EGDRRT group was significantly less than that of the LGDRRT group (0.54 ± 0.10 v. 0.63 ± 0.11 ten thousand USD; p < 0.001). CONCLUSIONS: For heart transplantation recipients with AKI, EGDRRT can reduce the in-hospital mortality and the length of intensive care unit and hospital stays, improve the complete renal recovery rate, and reduce the cost of RRT.

Postoperative diastolic perfusion pressure is associated with the development of acute kidney injury in patients after cardiac surgery: a retrospective analysis.

BACKGROUND: We aimed to investigate the relationship between the perioperative hemodynamic parameters and the occurrence of cardiac surgery-associated acute kidney injury. METHODS: A retrospective study was performed in patients who underwent cardiac surgery at a tertiary referral teaching hospital. Acute kidney injury was determined according to the KDIGO criteria. We investigated the association between the perioperative hemodynamic parameters and cardiac surgery-associated acute kidney injury to identify the independent hemodynamic predictors for acute kidney injury. Subgroup analysis was further performed in patients with chronic hypertension. RESULTS: Among 300 patients, 29.3% developed acute kidney injury during postoperative intensive care unit period. Multivariate logistic analysis showed the postoperative nadir diastolic perfusion pressure, but not mean arterial pressure, central venous pressure and mean perfusion pressure, was independently linked to the development of acute kidney injury after cardiac surgery (odds ratio 0.945, P = 0.045). Subgroup analyses in hypertensive subjects (n = 91) showed the postoperative nadir diastolic perfusion pressure and peak central venous pressure were both independently related to the development of acute kidney injury (nadir diastolic perfusion pressure, odds ratio 0.886, P = 0.033; peak central venous pressure, odds ratio 1.328, P = 0.010, respectively). CONCLUSIONS: Postoperative nadir diastolic perfusion pressure was independently associated with the development of cardiac surgery-associated acute kidney injury. Furthermore, central venous pressure should be considered as a potential hemodynamic target for hypertensive patients undergoing cardiac surgery.