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The accumulation of uremic toxins, such as asymmetric dimethylarginine (ADMA), has emerged as one of the major cardiovascular disease-related risk factors in patients with end-stage renal disease (ESRD). Based on the low molecular weight of ADMA, hemodialysis (HD) should theoretically effectively remove ADMA. In this study, we investigated the clearance behavior of ADMA during high-flux HD. Eight HD patients without residual renal function were included. Blood samples were collected at 0, 30, 60, 120 and 240 min after dialysis started, as well as 1 h and 48 h after dialysis. ADMA level was detected by HPLC-MS/MS. Herein, the ADMA level in blood cells and the ADMA protein binding rate were measured. Accordingly, the dialyzer extraction ratio was also determined. The reduction ratio (RR) of ADMA (corrected for hemoconcentration) was significantly lower, at only 37.21 ± 6.44%, than that of urea and creatinine (p <.05). Interestingly, its clearance from plasma was precipitous early in dialysis and became slowly from 60 to 240 min. Additionally, a greater inlet erythrocyte than plasma concentration was found for ADMA. The dialyzer extraction ratio was comparable between ADMA and creatinine or urea (83 ± 5% for ADMA vs. 84 ± 3% and 88 ± 2% for creatinine and urea, respectively; both p>.05). Urea and creatinine had a slight rebound ratio of less than 10% at 1 h after the completion of HD. In contrast, considerable rebound of approximately 30% was detected in ADMA. This study suggests that ADMA may present a multicompartmental distribution that cannot be representatively reflected by the urea kinetics model. [ABSTRACT FROM AUTHOR]

Background: Acute kidney injury (AKI) is a common post-cardiac surgery complication. It leads to increased morbidity and mortality. The aim of our study is to identify the prevalence and risk factors of AKI and to demonstrate if early postoperative serum cystatin C (sCyC) could accurately predict the development of AKI. Methods: We prospectively studied 628 patients undergoing elective cardiac surgery. Pre-morbid and operative variables known to be or potentially associated with AKI or other adverse outcomes were examined. AKI was defined according to Kidney Disease Improving Global Outcomes (KDIGO) creatinine criteria. Blood samples for biomarker measurement were collected at baseline, within 10 h of surgical completion and daily for three days. Logistic regression was used to assess predictive factors for AKI including 10 h sCyC. Model discrimination was assessed using receiver operator characteristic (ROC) curves. Results: AKI occurred in 178 (28.3%) patients, Stage 1 in 17.5%, Stage 2 in 8.6% and Stage 3 in 2.2%. Mortality rose progressively with increased AKI stage (non-AKI 0.2%, Stage 1 1.8%, Stage 2 11.1% and Stage 3 35.7%). Age > 75 years, baseline estimated glomerular filtration rate (eGFR), proteinuria, diabetes mellitus, hypertension, hyperuricaemia, NYHA classification >2, recent myocardial infarction were associated with AKI in univariate analysis. A multivariate logistic model with clinical factors (age, eGFR, hypertension, NYHA classification >2, combined surgery and operation time) demonstrated moderate discrimination for AKI (area under ROC curve [AUC] 0.75). The 10 h postoperative sCyC levels strongly associated with AKI. After multivariable adjustment, the highest quartile of sCyC was associated with 13.1 – higher odds of AKI, compared with the lowest quartile. Elevated 10 h sCyC levels associated with longer hospital stay, longer intensive care unit stay and duration of mechanical ventilation. The addition of 10 h sCyC improved model discrimination for AKI (AUC 0.81). Conclusions: AKI following cardiac surgery was identified using KDIGO criteria in around one fourth of the patients. These patients had significantly increased morbidity and mortality. When added to prediction model, 10 h sCyC may enhance the identification of patients at higher risk of AKI, providing a readily available prognostic marker. [ABSTRACT FROM AUTHOR]

Background: Acute kidney injury (AKI) is common following cardiac surgery and is associated with poor outcomes. However, the detection of those preoperative patients who will develop AKI is still difficult. In this study, we compared serum cystatin C combined with dipstick proteinuria as early markers to predict AKI available before surgery. Methods: We prospectively followed 616 patients undergoing cardiac surgery and identified 179 that developed AKI, defined as an increase in serum creatinine (SCr) of ≥ 0.3 mg/dL or ≥ 50% increase in creatinine level. Preoperative values for cystatin C were categorized into quartiles. We defined proteinuria, measured with a dipstick, as mild (trace to 1+) or heavy (2 + to 4+). Univariate as well as multivariate regression was performed. Cystatin C combined with dipstick proteinuria before surgery was assessed for its' predictive value of AKI using receiver operating characteristic (ROC) curves. Results: The final cohort consisted of 616 patients aged 60.7 ± 13.2 years, and baseline SCr was 75.8 ± 26.4 μmol/L, estimated glomerular filtration rate (eGFR) 96.3 ± 29.0 mL/min/1.73 m2 and cystatin C 1.05 ± 0.33 mg/L. Patients in higher cystatin C quartiles were older ( p < 0.001), more often to have heavy proteinuria ( p = 0.021), hyperuricemia ( p < 0.001), heart failure ( p < 0.001) and recent myocardial infarction ( p = 0.002). Those with heavy proteinuria were more often to have diabetes mellitus ( p = 0.010), hyperuricemia ( p = 0.043), worse cardiac function ( p < 0.05), higher creatinine levels ( p < 0.001) and lower eGFR levels ( p < 0.001). In a multiple logistic regression model, preoperative heavy proteinuria [OR: 3.14, 95% confidence interval (CI): 1.26-7.77] and preoperative cystatin C quartiles (Q2:OR: 1.60, 95% CI: 0.72-3.60; Q3:OR: 1.87, 95% CI: 0.85-4.14; Q4:OR: 3.10, 95% CI: 1.37-7.02) each associated with an increased odds of AKI, independent of advanced age (OR: 1.04, 95% CI: 1.01-1.06), hypertension (OR: 1.88, 95% CI: 1.13-3.12) and combined surgery (OR: 3.47, 95% CI: 1.35-8.89). The risk for adverse outcomes such as postoperative AKI, persistent AKI, severe AKI, dialysis and mortality were highest in patients with highest quartile of cystatin C ( p < 0.05, respectively) and heavy proteinuria ( p < 0.05, respectively). The area under the ROC curve for preoperative cystatin C combined with proteinuria to detect AKI, persistent AKI and severe AKI were 0.695 ( p < 0.001; 95% CI = 0.637-0.754), 0.753 ( p < 0.001; 95% CI = 0.693-0.812) and 0.718 ( p < 0.001; 95% CI = 0.642-0.795), respectively. Conclusion: These data suggest that preoperative serum cystatin C combined with dipstick proteinuria may improve prediction of AKI among patients undergoing cardiac surgery. [ABSTRACT FROM AUTHOR]

Background/Aim: The early detection of acute kidney injury (AKI) may be become possible by several promising early biomarkers which may facilitate the early detection, differentiation and prognosis prediction of AKI. In this study, we investigated the value of urinary liver-type fatty acid-binding protein (L-FABP), neutrophil gelatinase-associated lipocalin (NGAL) and their combination in predicting the occurrence and the severity of AKI following cardiac surgery. Methods: We prospectively followed 109 patients undergoing open heart surgery and identified 26 that developed AKI, defined as an increase in serum creatinine of ≥0.3 mg/dl or ≥150% of baseline creatinine. Serum creatinine (SCr), urinary L-FABP, and NGAL corrected by urine creatinine were tested pre-operation, at 0 hour and 2 hours post-operation. Each marker was assessed at each time point between patients with and without AKI. Receiver operating characteristic (ROC) curves and area under curves (AUC) were used to evaluate the diagnostic accuracy of urinary L-FABP, NGAL and their combination for predicting AKI. Results: Patients were aged 63.0 ± 11.3 years, 66.1% were male and baseline SCr was 70.5 ± 19.1 umol/L. Of 109 patients, 26(23.9%) developed AKI (AKIN stage I, II and III were 46.2%, 34.6% and 19.2% separately). The levels of urinary L-FABP and NGAL were significantly higher in AKI patients than non-AKI patients at 0 hour and 2 hours postoperative. AUCs for L-FABP was 0.844 (sensitivity (ST) 0.846, specificity (SP) 0.819, cut-off (CO) 2226.50 μg/g Ucr) at 0 hours and 0.832 at 2 hours (ST 0.808, SP 0.747, CO 673.09 μg/g Ucr) while 0.866 for NGAL at 0 hours (ST 0.769, SP 0.819, CO 131.12 μg/g Ucr) and 0.871 at 2 hours (ST 0.808, SP 0.831, CO 33.73 μg/g Ucr) to predict AKI occurrence. Using a combination of L-FABP and NGAL analyzed at the same timepoint as above, we were able to obtain an AUC of 0.911-0.927, p < 0.001. Similar AUCs of 0.81-0.87 were found to predict AKI stage II-III. Conclusions: Urinary L-FABP and NGAL increased at an early stage after cardiac surgery. The combination of the two biomarkers enhanced the accuracy of the early detection of postoperative AKI after cardiac surgery before a rise in SCr. [ABSTRACT FROM AUTHOR]

Objective: We examined the value of two potential novel urinary biomarkers, neutrophil gelatinase-associated lipocalin (NGAL) and L-type fatty acid binding protein (L-FABP), in diagnosing acute kidney injury (AKI) in liver transplant recipients. Methods: NGAL and L-FABP in urinary sample from Twenty-five patients before surgery and at 2, 4, 6, 12, 24, 48, 72 and 120 h after the anhepatic phase were tested. Standard statistics were used along with receiver-operating characteristic (ROC) analysis to evaluate the diagnostic value of selected markers. Results: Urinary NGAL was only slightly elevated at 2 h in the non-AKI group while rose and stayed high from 2-6 h in the AKI group. However, urinary L-FABP rose transiently in both groups 2-120 h following surgery. The level of urinary NGAL presented differences at 2-6 h ( p < 0.05) and urinary L-FABP at 4 h ( p < 0.05) between AKI and non-AKI groups. ROC analysis showed that area under the curves (AUCs) of NGAL were 0.766, 0.773, and 0.773 at 2, 4 and 6 h respectively while 0.760 of L-FABP at 4 h. Conclusion: Urinary NGAL rather than L-FABP appeared to be a sensitive and specific marker of AKI in liver transplant recipients. [ABSTRACT FROM AUTHOR]