Single-cell sequencing reveals peritoneal environment and insights into fibrosis in CAPD patients.

Long-term peritoneal dialysis (PD) is associated with the development of peritoneal fibrosis (PF). Understanding the changes of immune environments and peritoneal mesothelial cells (PMCs) may lead to the discovery of mechanisms of PF. Therefore, we used single-cell RNA sequencing to interrogate cell composition and transcriptome characteristics in dialysate of continuous ambulatory PD (CAPD) patients at different stages. Results showed that six major cell populations were identified in overnight effluent dialysate. Two subsets of macrophages (Macro-c2-SSP1 and Macro-c5-FCN1&SSP1) and PMCs (HSPA1A + PMCs and RPL34 + PMCs) had the property of promoting fibrosis. Long-term patients had higher markers of cytotoxic CD8+T cells. Moreover, the expression levels of fibrosis-related genes were significantly increased and PMCs interacted closely with immune cells in the long-term group (p < 0.05). These data reveal new phenotypes and functional characteristics of immune cells and PMCs in dialysate of CAPD patients with different stages, which provide potential mechanisms and therapeutic strategies for PF.

Impact of pulmonary hypertension on arteriovenous fistula failure of hemodialysis patients: A 10 years follow-up cohort study.

BACKGROUND: Pulmonary hypertension (PH) is common in patients with end-stage renal disease (ESRD). Arteriovenous fistulas (AVF) creation may involve in the pathogenesis of PH. The aim of this study was to explore the impact of PH after AVF creation on the AVF failure rate in maintenance hemodialysis (MHD) patients. METHODS: From January 1, 2009, to January 1, 2019, we retrospectively collected data of 578 MHD patients in Guangdong Provincial People's Hospital Blood Purification Center, China. Patients were followed-up until AVF failure or death or May 25, 2020. According to the systolic pulmonary artery pressure (SPAP) within 1 year after the establishment of AVF, the MHD patients were divided into three groups: SPAP ⩽ 35 mmHg, 35 < SPAP < 45 mmHg, SPAP ⩾ 45 mmHg. The primary outcome was AVF failure defined as AVF cannot complete hemodialysis. The secondary outcomes were all-cause mortality. RESULTS: A total of 578 patients were analyzed. The average age was 60.66 ± 15.34 years (58.1% men). Of these, 26.1% of patients were reported PH. The SPAP exhibited a left-skewed nonparametric distribution and the overall SPAP after the creation of AVF was 39.00 (29.00-52.00) mmHg. The median follow-up was 5.8 (5.5-6.3) years. Overall, 12.8% (74/578) patients were reported AVF failure events. There was no significant difference in AVF failure rate among three groups (p = 0.070). A total of 111 (19.2%) died during the follow-up period. Compared with the SPAP ⩽35 mmHg group, only the all-cause death rate significantly increased in MHD patients with PH (p < 0.001). CONCLUSIONS: The secondary pulmonary hypertension after AVF creation did not increase the risk of AVF failure in MHD patients, but significantly increased the risk of mortality for this portion of the patients. Future larger sample sizes, multi-center, and prospective trials are needed to make sure which type of access will benefit on their survival for MHD patients with SPAP ⩾35 mmHg.

The value of the ACEF II score in Chinese patients with elective and non-elective cardiac surgery.

OBJECTIVE: To evaluate the value of the ACEF II score in predicting postoperative hospital death and acute kidney injury requiring dialysis (AKI-D) in Chinese patients. METHODS: This retrospective study included adult patients who underwent cardiopulmonary bypass open heart surgery between January 2010 and December 2015 at Guangdong Provincial People's Hospital. ACEF II was evaluated to predict in-hospital death and AKI-D using the Hosmer-Lemeshow goodness of fit test for calibration and area under the receiver operating characteristic (ROC) curve for discrimination in non-elective and elective cardiac surgery. RESULTS: A total of 9748 patients were included. Among them, 1080 underwent non-elective surgery, and 8615 underwent elective surgery. Mortality was 1.8% (177/9748). In elective surgery, the area under the ROC (AUC) of the ACEF II score was 0.704 (95% CI: 0.648-0.759), similar to the ACEF score of 0.709 (95% CI: 0.654-0.763). In non-elective surgery, the AUC of the ACEF II score was 0.725 (95% CI: 0.663-0.787), higher than the ACEF score (AUC = 0.625, 95% CI: 0.553-0.697). The incidence of AKI-D was 3.5% (345/9748). The AUC of the ACEF II score was 0.718 (95% CI: 0.687-0.749), higher than the ACEF score (AUC = 0.626, 95% CI: 0.594-0.658). CONCLUSION: ACEF and ACEF II have poor discrimination ability in predicting AKI-D in non-elective surgery. The ACEF II and ACEF scores have the same ability to predict in-hospital death in elective cardiac surgery, and the ACEF II score is better in non-elective surgery. The ACEF II score can be used to assess the risk of AKI-D in elective surgery in Chinese adults.

Derivation and validation of a model to predict acute kidney injury following cardiac surgery in patients with normal renal function.

BACKGROUND: The study aimed to construct a clinical model based on preoperative data for predicting acute kidney injury (AKI) following cardiac surgery in patients with normal renal function. METHODS: A total of 22,348 consecutive patients with normal renal function undergoing cardiac surgery were enrolled. Among them, 15,701 were randomly selected for the training group and the remaining for the validation group. To develop a model visualized as a nomogram for predicting AKI, logistic regression was performed with variables selected using least absolute shrinkage and selection operator regression. The discrimination, calibration, and clinical value of the model were evaluated. RESULTS: The incidence of AKI was 25.2% in the training group. The new model consisted of nine preoperative variables, including age, male gender, left ventricular ejection fraction, hypertension, hemoglobin, uric acid, hypomagnesemia, and oral renin-angiotensin system inhibitor and non-steroidal anti-inflammatory drug within 1 week before surgery. The model had a good performance in the validation group. The discrimination was good with an area under the receiver operating characteristic curve of 0.740 (95% confidence interval, 0.726-0.753). The calibration plot indicated excellent agreement between the model prediction and actual observations. Decision curve analysis also showed that the model was clinically useful. CONCLUSIONS: The new model was constructed based on nine easily available preoperative clinical data characteristics for predicting AKI following cardiac surgery in patients with normal kidney function, which may help treatment decision-making, and rational utilization of medical resources.

Thromboxane A2 is involved in the development of hypertension in chronic kidney disease rats.

Hypertension is one of the most common complications of chronic kidney disease (CKD). Some research has indicated that changes in large artery function especially caused by thromboxane A2 (TXA2) may be a novel factor acting to induce hypertension in CKD. We studied the 5/6 nephrectomy rat model and measured serum levels of creatinine (Cr), calcium (Ca), phosphorus (P), TXA2-stable metabolites (thromboxane B2, TXB2), and caudal artery pressure after nephrectomy. The tension variations in thoracic aortas were measured after stimulating by vasoconstrictor/vasodilator using the cumulative concentration administration method and then tested the expression of TXA2 receptors in the thoracic aortas through western blots. The CKD rats developed uremia, electrolyte imbalances，and hypertension. They also exhibited a significant increase in TXB2 concentration. The aortic rings of CKD rats showed an increased contraction response to U46619 (a TXA2 analogue) and the expression of TXA2 receptors also enhanced. In the meanwhile, the diastolic function decreased in the CKD group. Our results demonstrate that the impairment of artery contractile function caused by the increase of TXA2 receptors on the wall of aortic rings may be involved in hypertension in CKD rats.

The effect of amiloride in decreasing albuminuria in patients with diabetic kidney diseases: a prospective, crossover, open-label study.

BACKGROUND: Diabetic kidney diseases (DKD) were the leading cause of End-stage renal diseases worldwide. Albuminuria was a target for treatment in DKD and decreasing albuminuria was particularly important for improving its prognosis. However, there is still a lack of specific treatment for DKD. METHODS: We conducted a prospective, crossover, open-label study to investigate the effect of amiloride in patients with DKD. Safety and efficacy were assessed by monitoring urine protein creatinine ratio(uPCR), urinary albumin creatinine ratio (uACR), blood pressure, weight, serum sodium, serum potassium, cholesterol, triglyceride, uric acid, serum soluble urokinase-type plasminogen activator receptor (suPAR) and urinary suPAR. Ten subjects were enrolled in the trial. RESULTS: In this prospective, crossover, open-label design, amiloride could induce a significant decrease of uACR in DKD. The decrease of serum and urinary suPAR in the amiloride/hydrochlorothiazide (HCTZ) group was also significant compared with those patients using HCTZ as the control group. Correlation analysis showed that the levels of urinary suPAR were positively associated with uPCR and uACR. No significant difference in blood pressure, weight, serum sodium, serum potassium, cholesterol, triglyceride, uric acid was seen between the amiloride/HCTZ group and the control group. CONCLUSION: In summary, among patients with DKD, amiloride could decrease albuminuria without severe side effects, which was accompanied by the significant decline of urinary suPAR.

Prospective model for predicting renal recovery in cardiac surgery patients with acute kidney injury requiring renal replacement therapy.

AIM: To develop a model for predicting renal recovery in cardiac surgery patients with acute kidney injury (AKI) requiring renal replacement therapy (RRT). METHODS: Data from a prospective randomized controlled trial, conducted in a tertiary hospital to compare the survival effect of two dosages of hemofiltration for continuous RRT in cardiac surgery patients between 20 March 2012 and 9 August 2015, were used to develop the model. The outcome was renal recovery defined as alive and dialysis-free 90 days after RRT initiation. Multivariate logistic regression with a stepwise backward selection of variables based on Akaike Information Criterion was applied to develop the model, which was internally validated using bootstrapping. Model discrimination, calibration and clinical value were assessed using the concordance index (C-Index), calibration plots and decision curve analysis, respectively. RESULTS: Totally, 211 patients with AKI requiring RRT (66.8% male) with median age of 57 years were included. The incidence of renal recovery was 33.2% (n = 70). The model included six variables: body mass index stratification, baseline estimated glomerular filtration rate, hypertension, sepsis, mean arterial pressure and mechanical ventilation. The C-Index for this model was 0.807 (95% CI, 0.744-0.870). After correction by the bootstrap, the C-Index was 0.780 (95% CI, 0.720-0.845). The calibration plots indicated good consistency between actual observations and model prediction of renal recovery. Decision curve analysis demonstrated the model was clinical usefulness. CONCLUSION: We developed and validated a model to predict the chance of renal recovery in cardiac surgery patients with AKI requiring RRT.

Effect of forkhead box O1 in renal tubular epithelial cells on endotoxin-induced acute kidney injury.

Mitochondrial damage in renal tubular epithelial cells (RTECs) is a hallmark of endotoxin-induced acute kidney injury (AKI). Forkhead box O1 (FOXO1) is responsible for regulating mitochondrial function and is involved in several kidney diseases. Here, we investigated the effect of FOXO1 on endotoxin-induced AKI and the related mechanism. In vivo, FOXO1 downregulation in mouse RTECs and mitochondrial damage were found in endotoxin-induced AKI. Overexpression of FOXO1 by kidney focal adeno-associated virus (AAV) delivery improved renal function and reduced mitochondrial damage. Peroxisome proliferator-activated receptor-γ coactivator 1-α (PGC1-α), a master regulator of mitochondrial biogenesis and function, was reduced in endotoxin-induced AKI, but the reduction was reversed by FOXO1 overexpression. In vitro, exposure to LPS led to a decline in HK-2 cell viability, mitochondrial fragmentation, and mitochondrial superoxide accumulation, as well as downregulation of FOXO1, PGC1-α, and mitochondrial complex I/V. Moreover, overexpression of FOXO1 in HK-2 cells increased HK-2 cell viability and PGC1-α expression, and it alleviated the mitochondrial injury and superoxide accumulation induced by LPS. Meanwhile, inhibition of FOXO1 in HK-2 cells by siRNA treatment decreased PGC1-α expression and HK-2 cell viability. Chromatin immunoprecipitation assays and PCR analysis confirmed that FOXO1 bound to the PGC1-α promoter in HK-2 cells. In conclusion, downregulation of FOXO1 in RTECs mediated endotoxin-induced AKI and mitochondrial damage. Overexpression of FOXO1 could improve renal injury and mitochondrial dysfunction, and this effect occurred at least in part as a result of PGC1-α signaling. FOXO1 might be a potential target for the prevention and treatment of endotoxin-induced AKI.

The impact of coexisting diabetes mellitus on clinical outcomes in patients with idiopathic membranous nephropathy: a retrospective observational study.

BACKGROUND: Idiopathic membranous nephropathy (IMN) is frequently coexisted with diabetes mellitus (DM). Few researches investigate clinical outcomes in IMN patients coexisting diabetes mellitus (DM), including remission rates, renal survival and complications. Concurrent DM also pose therapeutic challenges to IMN patients due to the influence of glucocorticoids and immunosuppressant on metabolic disorders. We performed this study to investigate the impact of DM on clinical outcomes in IMN and the influence of therapeutic regime on metabolic parameters in diabetic IMN patients. METHODS: Two hundred and six adult hospitalized patients diagnosed with biopsy-proven IMN were retrospectively studied, including 42 patients coexisted with DM. Clinical outcomes including remission rates, renal outcome and complications were compared between groups. Impact of cyclophosphamide and ciclosporin on metabolism and complications were analyzed in IMN patients coexisting DM. RESULTS: IMN patients coexisted with DM were presented with advanced age, lower level of eGFR and hemoglobin. Patients coexisted with DM experienced worse renal function deterioration and higher incidence of infection. COX regression analysis showed that DM was an independent risk factor for renal function deterioration in IMN patients. There was no significant difference in remission rates and incidence of venous thromboembolism between two groups. Further exploration on the impact of therapeutic regimens on complications and metabolism showed that cyclophosphamide and ciclosporin had no significant difference in incidence of complications including infection and venous thromboembolism, and posed comparable influences on blood glucose, uric acid and blood lipids in IMN patients coexisted with DM. CONCLUSION: Coexisting DM was an independent risk factor for renal function deterioration in IMN patients but did not influence the remission of proteinuria. Glucocorticoids in combination with cyclophosphamide or ciclosporine had similar impact on complications and metabolic index including blood glucose, uric acid and blood lipids in IMN patients coexisted with DM.

Metabolic syndrome and concomitant diabetes mellitus are associated with higher risk of cardiovascular comorbidity in patients with primary glomerular diseases: A retrospective observational study.

BACKGROUND: Metabolic syndrome (MS) and diabetes mellitus (DM) are risk factors for cardiovascular diseases in general population. However, there was a paucity of studies investigating their impact in primary glomerular diseases (PGD). HYPOTHESIS: MS and concomitant DM are associated with higher risk of cardiovascular comorbidity in PGD. METHODS: In a retrospective observational design, we analyzed 3622 hospitalized adult PGD patients and compared the prevalence of cardiovascular comorbidity in non-MS, MS with and without DM. Risk factors for cardiovascular comorbidity were identified using univariate and multivariate logistic regression. RESULTS: Among 3622 PGD patients, 308 (8.5%) cases accompanied with MS, including 180 (5.0%) patients with DM and 128 (3.5%) without DM. One hundred and sixty four (4.5%) cases coexisted with cardiovascular comorbidity. Patients with MS and concomitant DM exhibited a higher prevalence of cardiovascular comorbidity than those without MS stratified by estimated glomerular filtration rate and pathological types. Logistic regression showed that MS and concomitant DM (OR: 2.496, 95% CI: 1.600-3.894, P < .001), older age (OR: 1.060, 95% CI: 1.047-1.074, P < .001), male (OR: 1.536, 95% CI: 1.072-2.200, P = .019), higher level of serum ti (OR: 1.002, 95% CI: 1.001-1.003, P < .001), hyperuricemia (OR: 1.901, 95% CI: 1.327-2.725, P < .001), idiopathic membranous nephropathy (OR: 2.874, 95% CI: 1.244-6.640, P < .001) and focal segmental glomerulosclerosis (OR: 2.906, 95% CI: 1.147-7.358, P < .001) were independently associated with a higher risk for cardiovascular comorbidity. CONCLUSIONS: In PGD patients, MS and concomitant DM are associated with an increased risk for cardiovascular comorbidity. More evidence for the causal link between MS/DM and cardiovascular outcomes is needed to be clarified.

Clinical value of renal phospholipase A2 receptor deposit in the prognosis evaluation and treatment options of idiopathic membranous nephropathy: A retrospective cohort study.

AIM: Phospholipase A2 receptor (PLA2R) is a target antigen for idiopathic membranous nephropathy (IMN). However, the association between renal PLA2R antigen and disease prognosis had not been fully investigated. In addition, there was a paucity of studies investigating the difference of therapeutic effects between cyclophosphamide and cyclosporine A in PLA2R-associated IMN. METHODS: This retrospective cohort study recruited 300 eligible patients diagnosed with biopsy-proven IMN between September 2015 and July 2018 in Guangdong Provincial People's Hospital. The remission of proteinuria was compared between PLA2R-associated and non-PLA2R-associated IMN. The difference of therapeutic effects between cyclophosphamide and cyclosporine A were also investigated in PLA2R-associated IMN. RESULTS: The positive rate of renal PLA2R antigen in recruited IMN patients was 82.3%. Non-PLA2R-associated IMN patients had a higher probability to achieve remission than PLA2R-associated IMN patients (Log-rank test, P = .013). Multivariate COX analysis showed that renal PLA2R antigen was an independent risk factor for not achieving remission in IMN patients (Hazard Ratio: 1.619; 95% confidence interval: 1.133 to 2.313; P = .008). In PLA2R-associated IMN, patients receiving cyclophosphamide had a higher probability to achieve remission compared with those receiving cyclosporine A (Log-rank test, P = .018) while there was no difference in renal survival. Multivariate COX regression analysis showed that compared with cyclosporine A, patients receiving cyclophosphamide had a higher probability to achieve remission. CONCLUSION: Phospholipase A2 receptor -associated IMN patients had a lower probability to achieve remission compared with non-PLA2R-associated IMN. Compared with cyclosporine A, cyclophosphamide exerted better therapeutic effects in remission of proteinuria and may be the preferred immunosuppressant for PLA2R-associated IMN. SUMMARY AT A GLANCE This article highlighted the prognostic value of intra-renal phospholipase A2 receptor deposition in idiopathic membranous nephropathy (IMN). Renal phospholipase A2 receptor (PLA2R)-associated IMN patients had a lower probability to achieve remission compared with non-PLA2R-associated IMN.

Modified regional citrate anticoagulation is optimal for hemodialysis in patients at high risk of bleeding: a prospective randomized study of three anticoagulation strategies.

BACKGROUND: Recommended regular saline flushing presents clinical ineffectiveness for hemodialysis (HD) patients at high risk of bleeding with heparin contraindication. Regional citrate anticoagulation (RCA) has previously been used with a Ca2+ containing dialysate with prefiltered citrate in one arm (RCA-one). However, anticoagulation is not always achievable and up to 40% results in serious clotting in the venous expansion chamber. In this study, we have transferred one-quarter of the TSC from the prefiltered to the post filter based on RCA-one, which we have called RCA-two. The objective of this study was to compare the efficacy and safety of RCA-two with either saline flushing or RCA-one in HD patients with a high bleeding risk. METHOD: In this investigator-initiated, multicenter, controlled, prospective, randomized clinical trial, 52 HD patients (77 sessions) were randomized to the RCA-2 and RCA-one group in part one of the trial, and 45 patients (64 sessions) were randomized to the RCA-2 and saline group in part two of the trial. Serious clotting events, adverse events and blood analyses were recorded. RESULTS: Serious clotting events in the RCA-two group were significantly lower compared with the RCA-one and saline group (7.89% vs. 30.77%, P = 0.011; 3.03% vs. 54.84%, P < 0.001, respectively). The median circuit survival time was 240 min (IQR 240 to 240) in the RCA-two group, was significantly longer than 230 min (IQR 155 to 240, P < 0.001) in the RCA-one group and 210 min (IQR 135 to 240, P = 0.003) in the saline group. The majority of the AEs were hypotension, hypoglycemia and chest tightness, most of which were mild in intensity. Eight patients (20.51%) in the RCA-one group, 4 patients (12.90%) in the saline group and 10 patients (26.31%) in the RCA-two group, P > 0.05. CONCLUSIONS: Our data demonstrated that the modified anticoagulation protocol was more effective and feasible during hemodialysis therapy for patients at high risk of bleeding. TRIAL REGISTRATION: GDREC, GDREC2017250H. Registered February 2, 2018; retrospectively registered.

Prevalence of Concomitant Coronary Artery Disease and Its Impact on Acute Kidney Injury for Chinese Adult Patients Undergoing Valvular Heart Surgery.

INTRODUCTION: Significant coronary artery disease (CAD) in patients undergoing valvular heart surgery (VHS) is an indication for combined valvular heart surgery and coronary artery bypass grafting. However, the impact of nonsignificant CAD on postoperative outcomes is not well understood. This study illustrated the epidemiological characteristics of CAD in China and investigated the impact of CAD on postoperative acute kidney injury (AKI), intensive care unit (ICU) stay, and postoperative mortality. METHODS: This study comprised an epidemiological survey followed by a case-control investigation. The epidemiological characteristics of CAD were studied in 4,172 consecutive patients who underwent coronary angiography before planned VHS at a core cardiovascular center. Then, 3,618 patients were selected for the subsequent case-control study to further analyze the associations between CAD and postoperative advanced AKI (grade 2 or 3 by KDIGO criteria), longer ICU stay (highest quartile), and increased mortality by logistic regression. RESULTS: Of the participants, 5.1 and 9.3% had moderate and significant CAD, respectively. The incidence of CAD increased after 60 years of age. Although CAD was not related to longer postoperative ICU stay in a multivariate logistic model, moderate CAD (OR 1.539 [95% CI 1.078-2.199]) and significant CAD (OR 1.798 [95% CI 1.094-2.955]) remained independent risk factors for postoperative advanced AKI after adjusting for multiple traditional risk factors. Significant CAD, but not nonsignificant CAD, was associated with postoperative mortality. CONCLUSIONS: Concomitant CAD is common in Chinese patients who undergo VHS. Moderate and significant CAD might have detrimental effects on postoperative advanced AKI.

Caspase-11 Mediates Pyroptosis of Tubular Epithelial Cells and Septic Acute Kidney Injury.

BACKGROUND/AIMS: Acute kidney injury (AKI) is a serious complication of sepsis and has a high morbidity and mortality rate. Caspase-11 induces pyroptosis, a form of programmed cell death that plays a critical role in endotoxic shock, but its role in tubular epithelial cell death and whether it contributes to sepsis-associated AKI remains unknown. METHODS: The caspase-11-/- mouse received an intraperitoneal injection of lipopolysaccharide (LPS, 40 mg/kg body weight). Caspase-11-/- renal tubular epithelial cells (RTECs) form C57BL caspase-11-/- mice were treated with LPS in vitro. The IL-1ß ELISA kit and Scr assay kit were used to measure the level of interleukin-1ß and serum creatinine. Annexin V-FITC assay and TUNEL staining assay were used to detect the cell death in different groups in vitro and in vivo. Western blot was performed to analyze the protein expression of caspase-11 and Gsdmdc1. RESULTS: LPS-induced sepsis results in lytic death of RTECs, accompanied by increased expression of the pyroptosis-related proteins caspase-11 and Gsdmd. However, the increase in pyroptosis-related protein expression induced by LPS was attenuated with caspase-11 knockout, both in vitro and in vivo. Furthermore, when challenged with lethal doses of systemic LPS, pathologic abnormalities in renal structure, increased serum and kidney interleukin-1ß, increased serum creatinine, and animal death were observed in wild-type mice but prevented in caspase-11-/- mice. CONCLUSIONS: Caspase-11-induced pyroptosis of RTECs is a key event during septic AKI, and targeting of caspase-11 in RTECs may serve as a novel therapeutic target in septic AKI.

Soluble Urokinase Plasminogen Activator Receptor is Associated with Coronary Artery Calcification and Cardiovascular Disease in Patients Undergoing Hemodialysis.

BACKGROUND/AIMS: Cardiovascular disease (CVD) is an important cause of morbidity and mortality in hemodialysis patients. Vascular calcification is thought to play an important role in causing CVD. Soluble urokinase plasminogen activator receptor (suPAR) is a biomarker strongly predictive of cardiovascular outcomes in the pathogenesis of diabetic patients with renal disease treated with hemodialysis. We investigated the relationship between suPAR and coronary artery calcification (CAC) in patients undergoing maintenance hemodialysis. METHODS: A total of 99 adult hemodialysis patients were enrolled in this study. Plasma samples were analyzed for suPAR with an enzyme-linked immunosorbent assay and the CAC score was determined with multidetector computed tomography. The occurrence of cardiovascular events and all-cause mortality during follow-up were recorded from January 1, 2010 to June 1, 2016. RESULTS: In 99 patients treated with maintenance hemodialysis, 91 (91.9%) had varying degrees of CAC, and suPAR correlated positively with the CAC score in a Spearman analysis. In a mean follow-up period of 33 months, 36 patients (36.4%) experienced at least one cardiovascular event. When the quartiles of suPAR concentrations were used as the cutoff points for a subgroup analysis, the incidence of CVD and all-cause mortality was much higher in the higher quartiles of suPAR. In a univariate Cox regression analysis, high suPAR was a risk factor for CVD and all-cause mortality. CONCLUSION: suPAR is associated with the CAC score and is a risk factor for new-onset CVD in patients undergoing hemodialysis.

Attitudes and practices of Chinese physicians regarding chronic kidney disease and acute kidney injury management: a questionnaire-based cross-sectional survey in secondary and tertiary hospitals.

OBJECTIVE: This questionnaire-based cross-sectional survey reported the attitudes and practices of Chinese doctors regarding chronic kidney disease (CKD) and acute kidney injury (AKI) management. METHODS: An online questionnaire consisting of general information, awareness of CKD and AKI, education status, renal laboratory items, and clinical practices between February 20, 2017 and August 15, 2017. RESULTS: Among the 1289 respondents from secondary and tertiary hospitals in 30 provinces, 718 (55.7%) were nephrologists, 94.3% had the ability to evaluate glomerular filtration rates, and 98.8% could evaluate urinary protein excretion, indicating that Chinese doctors met the minimum requirements to manage CKD. However, nearly half of all respondents reported that easy methods for spot urine creatinine-adjusted urinary protein assessments were unavailable. Awareness of the CKD risk stratification system and AKI definition was inadequate, and only 54.2% of respondents reported that they had received nutritional education for renal diseases. Although most of the respondents were nephrologists at university hospitals, 66.4% and 76.3% of respondents reported nephrology referrals and nephrology consultations, respectively, after AKI, suggesting an insufficient role for nephrologists. Finally, management models differed significantly, indicating that universal guidelines for CKD and AKI management are required across China. CONCLUSIONS: Several considerable challenges remain regarding CKD and AKI management in China, including inadequate knowledge and training systems, an absence of clinical protocols, and insufficient multidisciplinary cooperation.

Value of electronic alerts for acute kidney injury in high-risk wards: a pilot randomized controlled trial.

PURPOSE: To investigate the application value of "electronic alerts" ("e-alerts") for acute kidney injury (AKI) among high-risk wards of hospitals. METHODS: A prospective, randomized, controlled study was conducted. We developed an e-alert system for AKI and ran the system in intensive care units and divisions focusing on cardiovascular disease. The e-alert system diagnosed AKI automatically based on serum creatinine levels. Patients were assigned randomly to an e-alert group (467 patients) or non-e-alert group (408 patients). Only the e-alert group could receive pop-up messages. RESULTS: The sensitivity, specificity, Youden Index and accuracy of the AKI e-alert system were 99.8, 97.7, 97.5 and 98.1%, respectively. The prevalence of the diagnosis for AKI and expanded-AKI (AKI or multiple-organ failure) in the e-alert group was higher than that in the non-e-alert group (AKI 7.9 and 2.7%, P = 0.001; expanded-AKI 16.3 and 6.1%, P < 0.001). The prevalence of nephrology consultation in the e-alert group was higher than that in the non-e-alert group (9.0 and 3.7%, P = 0.001). There was no significant difference in the prevalence dialysis, rehabilitation of renal function or death in the two groups. CONCLUSION: The e-alert system described here was a reliable tool to make an accurate diagnosis of AKI.

Necrostatin-1 attenuates sepsis-associated acute kidney injury by promoting autophagosome elimination in renal tubular epithelial cells.

The aim of the present study was to investigate the protective effect of necrostatin­1 (Nec­1) in sepsis­associated acute kidney injury (SA­AKI). An SA­AKI mouse model was established through an intraperitoneal injection of lipopolysaccharide (LPS), and Nec­1 was administered to the mice prior to the establishment of SA­AKI. Renal function and histological changes were evaluated, and the expression levels of microtubule­associated protein light chain 3­II (LC3­II) and p62, as markers of autophagic flux, were detected. Autophagosomes and autolysosomes in renal tubular epithelial cells were also identified using electron microscopy. Pretreatment with Nec­1 could attenuate the LPS­induced increases in the concentrations of blood urea nitrogen (LPS+Nec­1 vs. LPS group, 14.15±4.14 mmol/l vs. 32.54±5.46 mmol/l, respectively; P<0.001) and serum creatinine (11.50±1.67 µmol/l vs. 30.08±4.18 µmol/l, respectively; P<0.001). However, there were no significant differences in the rate of renal tubular epithelial cell necrosis between the groups. In the renal tissues of SA­AKI mice, protein analysis showed that the LC3­II and p62 proteins were increased, while a reverse transcription­quantitative Reverse transcription­polymerase chain reaction analysis detected no increase in LC3­II or p62 mRNA. Additionally, a high number of autophagosomes, but not of autolysosomes, were observed by electron microscopy. When mice were pretreated with Nec­1, the levels of LC3­II and p62 decreased, and a large number of autolysosomes were observed by electron microscopy in the Nec­1 pretreatment group. These results indicated that Nec­1 improved autophagosome elimination, a process that is impaired by LPS, in renal tubular epithelial cells. This potentially enabled Nec­1 to prevent SA­AKI. Furthermore, the findings suggested that the protective effect of Nec­1 may not have involved the inhibition of necroptosis, but may have occurred through the promotion of autophagosome elimination in renal tubular epithelial cells.

Red blood cell distribution width as a marker of cerebral infarction in hemodialysis patients.

BACKGROUND: Red blood cell distribution width (RDW) is a cardiovascular biomarker. We evaluated the association between RDW and cerebral stroke risk in hemodialysis patients. METHODS: A cohort of 442 adult patients on hemodialysis was studied. Strokes were defined according to ICD-10 diagnosis codes. Routine complete blood counts, evaluated every 3-6 months, were used for RDW values. RESULTS: Among 442 hemodialysis patients, during the 50-month follow-up, there were 62 cases (14.0%) of cerebral stroke: 41 (9.3%) with cerebral infarction and 21 (4.8%) with cerebral hemorrhage. Compared with nonstroke patients, a significantly higher RDW was measured in patients with cerebral stroke and cerebral infarction. However, no significant difference was seen in RDW between patients with cerebral hemorrhage and nonstroke patients. After adjustment by age, hypertension, albumin, Charlson Comorbidity Score, and C-reactive protein in different multivariable Cox regression models, patients with the highest mean RDW quartile had a 2.55-fold (hazard ratio = 3.55; 95% confidence interval: 1.33-9.51) higher risk of developing cerebral infarction relative to those with the lowest mean RDW quartile. RDW was not an independent risk factor for cerebral hemorrhage. CONCLUSIONS: Increased RDW is an independent risk factor of cerebral infarction in hemodialysis patients.

NADPH oxidase inhibitor, diphenyleneiodonium prevents necroptosis in HK-2 cells.

The aim of the present study was to investigate the protective effect of the NADPH oxidase inhibitor, diphenyleneiodonium (DPI) against necroptosis in renal tubular epithelial cells. A necroptosis model of HK-2 cells was established using tumor necrosis factor-α, benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone and antimycin A (collectively termed TZA), as in our previous research. The necroptosis inhibitor, necrostatin-1 (Nec-1) or the NADPH oxidase inhibitor, DPI were administered to the necroptosis model. Production of reactive oxygen species (ROS) was detected by dichlorodihydrofluorescein diacetate in the different groups, and the manner of cell death was identified by flow cytometry. Western blot analysis was used to determine the levels of phosphorylation of receptor-interacting protein kinase 3 (RIP-3) and mixed lineage kinase domain-like (MLKL), which are essential to necroptosis. The results revealed that TZA increased the percentages of propidium iodide-positive HK-2 cells from 1.22±0.69 to 8.98±0.73% (P<0.001), and augmented the phosphorylation of RIP-3 and MLKL. ROS levels were increased in the TZA group compared with the control group (27.74±1.60×104 vs. 18.51±1.10×104, respectively; P<0.001), and could be inhibited by Nec-1 (TZA + Nec-1 group, 22.90±2.22×104 vs. TZA group, 27.74±1.60×104; P=0.01). DPI decreased ROS production (TZA + DPI group, 22.13±1.86×104 vs. TZA group, 27.74±1.60×104; P<0.001) and also reduced the proportions of necrosis in the necroptosis model (TZA + DPI group, 4.40±1.51% vs. TZA group, 8.98±0.73%; P<0.001). Phosphorylated RIP-3 and MLKL were also decreased by DPI treatment. The results indicate that ROS production increases in HK-2 cells undergoing necroptosis, and that the NADPH oxidase inhibitor, DPI may protect HK-2 cells from necroptosis via inhibition of ROS production.