Liver-type Fatty Acid-binding Protein Research Articles

Serum Copeptin and Zinc-α2-glycoprotein Levels Are Novel Biomarkers of Tolvaptan Treatment in Decompensated Cirrhotic Patients with Ascites.

Objective The efficacy of tolvaptan, an orally active vasopressin V2-receptor antagonist, has recently been reported in patients with massive ascites unresponsive to conventional diuretics. However, the effect of tolvaptan varies among patients. Recently, the prognostic role of the tolvaptan response in cases of decompensated liver cirrhosis (LC) has been attracting increasing attention. Using serum copeptin (vasopressin precursor), zinc-α2-glycoprotein (ZAG), cystatin C (renal biomarker), neutrophil gelatinase-associated lipocalin (NGAL) and liver-type fatty acid-binding protein (L-FABP), we explored which factors portend a good response to tolvaptan in LC patients with ascites. Methods We enrolled 113 LC patients and divided them into the tolvaptan treatment group and non-treatment group. Tolvaptan (3.75 or 7.5 mg/day) was administrated to 38 LC patients with ascites, and a follow-up assessment was performed after a 7-day tolvaptan treatment regimen. Results We determined the predictive ability for kidney and/or liver damage of serum copeptin, ZAG, cystatin C, NGAL and L-FABP levels in all patients. After 7-day tolvaptan treatment, 19 patients had lost more than 1.5 kg of body weight (Responders), while 19 showed no marked change in their body weight (Non-responders). Basal blood urea nitrogen (BUN) (p=0.0014), serum copeptin (p=0.0265) and serum ZAG levels (p=0.0142) were significantly higher in the Non-responders than in the Responders. BUN (odds ratio 7.43, p=0.0306), copeptin (odds ratio 9.12, p=0.0136) and ZAG (odds ratio 7.43, p=0.0306) were determined to be predictive factors of drug responsiveness using a multivariate logistic regression analysis. Conclusion Serum BUN, copeptin and ZAG levels predict the patient response to tolvaptan, even when measured prior to treatment.

Microchip Immunoassays for Monitoring Renal Function: Rapid, Low-Cost, and Highly Sensitive Quantification of Urinary Biomarkers of Diabetic Nephropathy.

This study developed low-cost and highly sensitive immunoassay devices possessing the ability to rapidly analyze urine samples. Further, they can quantitatively detect three biomarkers indicating renal injury: monocyte chemotactic protein 1 (MCP-1), angiotensinogen (AGT), and liver-type fatty acid binding protein (L-FABP). The devices were used to successfully estimate the concentrations of the three biomarkers in urine samples within 2 min; the results were consistent with those obtained via conventional enzyme-linked immunosorbent assay (ELISA), which requires several hours. In addition, the estimated detection limits for the three biomarkers were comparable to those of commercially available ELISA kits. Thus, the proposed and fabricated devices facilitate high-precision and frequent monitoring of renal function.

Predicting acute kidney injury and future cardiac events using urinary liver-type fatty acid-binding protein in patients with acute myocardial infarction

Abstract Background Urinary liver-type fatty acid-binding protein (L-FABP) has been known as a candidate biomarker for early detection of acute kidney injury (AKI). It has also been suggested to have an effective predictive value for cardiovascular mortality in patients. Therefore, this study aimed to examine the ability of urinary L-FABP in predicting AKI and future cardiovascular events in patients with acute myocardial infarction (AMI). Methods We evaluated consecutive 258 patients with AMI. Urinary L-FABP was measured at admission and a 2-year follow-up was performed. AKI was defined as an increase of >0.3 mg/dl in serum creatinine level within 2 days after emergency percutaneous coronary intervention. The composite endpoint was cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Results AKI was detected in 20 patients (7.8%). Patients with AKI had significantly higher urinary L-FABP levels (68.0 μg/gCr vs 3.1 μg/gCr, p<0.001) compared to those with non-AKI. Receiver operating characteristic analysis showed urinary L-FABP levels exhibited 85.7% sensitivity and 96.0% specificity, at a cutoff value of 29.7 μg/gCr. We used propensity score analyses to balance measurable confounders between patients with and without AKI, including age, left ventricular ejection fraction, an inflammation marker, renal function, and albuminuria. In logistic regression adjustment with the propensity score, urinary L-FABP level of >29.7 μg/gCr was an independent predictor of AKI (p=0.001). Furthermore, high urinary L-FABP (>29.7 μg/gCr) on admission correlated with an increased risk of the composite endpoints during 2-year follow-up in the Kaplan–Meier analysis (p<0.001). Conclusions Urinary L-FABP level may be a useful biomarker for predicting not only the onset of AKI but also adverse cardiovascular events in patients with AMI. Funding Acknowledgement Type of funding sources: None.

Home-based aerobic exercise and resistance training for severe chronic kidney disease: a randomized controlled trial.

BackgroundThe potential effects of aerobic and resistance training in patients with severe chronic kidney disease (CKD) are not fully elucidated. This study investigated the effects of a home‐based exercise programme on physical functioning and health‐related quality of life (HRQOL) in patients with Stage 4 CKD, equivalent to estimated glomerular filtration rate of 15–30 mL/min/1.73 m2.MethodsForty‐six patients with Stage 4 CKD (median age, 73 years; 33 men) were randomly assigned to exercise (n = 23) and control (n = 23) groups. Exercise group patients performed aerobic exercise at 40–60% peak heart rate thrice weekly and resistance training at 70% of one‐repetition maximum twice weekly at home for 6 months. Control patients received no specific intervention. Primary outcomes were distance in incremental shuttle walking test and HRQOL assessed using the Kidney Disease Quality of Life—Short Form questionnaire. Secondary outcomes included kidney function assessed with combined urea and creatinine clearance, urinary biomarkers, and anthropometric and biochemical parameters associated with CKD.ResultsImprovement in incremental shuttle walking test was significantly greater in the exercise group compared with controls (39.4 ± 54.6 vs. −21.3 ± 46.1; P < 0.001). Among Kidney Disease Quality of Life domains, significant mean differences were observed between the exercise group and the control group in work status, quality of social interaction, and kidney disease component summary outcomes (12.76 ± 5.76, P = 0.03; 5.97 ± 2.59, P = 0.03; and 4.81 ± 1.71, P = 0.007, respectively). There were greater reductions in natural log (ln)‐transformed urinary excretion of liver‐type fatty acid‐binding protein, ln serum C‐reactive protein, and acylcarnitine to free carnitine ratio in the exercise group compared with controls, with significant between‐group differences of −0.579 ± 0.217 (P = 0.008), −1.13 ± 0.35 (P = 0.003), and −0. 058 ± 0.024 (P = 0.01), respectively.ConclusionsOur 6 month home‐based exercise programme improved aerobic capacity and HRQOL in patients with Stage 4 CKD, with possible beneficial effects on kidney function and CKD‐related parameters.

Accuracy of Liver-Type Fatty Acid-Binding Protein in Predicting Acute Kidney Injury: AMeta-Analysis.

Liver-type fatty acid-binding protein (L-FABP) is a promising biomarker for the early prediction of acute kidney injury (AKI). However, the clinical utility of L-FABP in different populations or settings remains unclear. We present a meta-analysis of studies evaluating the performance of L-FABP in AKI prediction. We performed a literature search in MEDLINE, EMBASE, and Cochrane library, using search terms "acute kidney injury" and "L-FABP." Studies investigating the performance characteristics of L-FABP for the early diagnosis of AKI were included. Data about patient characteristics, diagnostic criteria of AKI, quantitative data required for construction of a 2 × 2 table (number of participants, sensitivity, specificity, and case number), study settings, and outcomes were extracted. The bivariable model was applied to calculate the estimated sensitivity and specificity of L-FABP. A summary ROC curve was created by plotting the true-positive rate against the false-positive rate at various cutoff values from different studies. We found 27 studies reporting measurement of urine (n = 25 studies) or plasma (n = 2 studies) L-FABP. Overall, the estimated sensitivity was 0.74 (95% CI: 0.69-0.80) and specificity was 0.78 (95% CI: 0.71-0.83). L-FABP demonstrated a stable area under the ROC of 0.82 (95% CI: 0.79-0.85) in variable clinical settings including intensive care unit, surgery, and contrast-induced AKI. In subgroup analysis excluding pediatric and post radiocontrast exposure cohorts, L-FABP had comparative diagnostic performance with neutrophil gelatinase associated lipocalin (NGAL). Despite broad prevalence, L-FABP is a clinically useful marker with moderate accuracy in variable clinical settings as demonstrated in our subgroup analysis. Except for pediatric patients and those post-radiocontrast exposure, L-FABP has comparable discriminative capability as NGAL.

Hexafluoropropylene oxide dimer acid (HFPO-DA) induced developmental cardiotoxicity and hepatotoxicity in hatchling chickens: Roles of peroxisome proliferator activated receptor alpha

Hexafluoropropylene oxide dimer acid (HFPO-DA) is a perfluorooctanoic acid (PFOA) substitute. In the current study, potential developmental cardiotoxicity and hepatotoxicity following HFPO-DA exposure in chicken embryo has been investigated, focusing on the roles of peroxisome proliferator activated receptor alpha (PPARα), the major molecular target in PFOA-induced toxicities. HFPO-DA was exposed to fertile chicken eggs via air cell injection, morphology and function of the target organs (heart and liver) in hatchlings were investigated with histopathology and electrocardiography, and the serum levels of HFPO-DA had been measured with quadrupole-time of flight liquid chromatograph-mass spectrometer (Q-TOF LC/MS). Additionally, lentivirus-mediated in ovo PPARα silencing was used to assess the roles of PPARα in HFPO-DA induced developmental toxicities. The results indicated that developmental exposure to HFPO-DA induced developmental cardiotoxicity, including thinned right ventricular wall and elevated heart rates, similar to those observed with PFOA exposure, as well as developmental hepatotoxicity in the form of steatosis. Silencing of PPARα alleviated such effects, suggesting participation of PPARα in HFPO-DA induced developmental toxicities in chicken embryo. Moreover, enhanced expression of PPARα downstream genes, cluster of differentiation 36 (CD36) and enoyl-CoA hydratase and 3-hydroxyacyl CoA dehydrogenase (EHHADH), were observed in HFPO-DA exposed animal heart tissues, which can be abolished by PPARα silencing. On the other hand, liver-type fatty acid binding protein (L-FABP) and CD36 expression were effectively enhanced in exposed liver tissues, but not EHHADH, suggesting differential mechanism of toxicity in heart and liver tissues. In summary, developmental exposure to HFPO-DA induced developmental cardiotoxicity and hepatotoxicity in hatchling chickens similar to PFOA, and PPARα still participates in such toxicities, with some differential downstream gene regulations in different organs. Further investigation on HFPO-DA-induced developmental toxicities is guaranteed.

Clinical Utility of Urinary Biomarkers for Prediction of Acute Kidney Injury and Chronic Renal Dysfunction After Open Abdominal Aortic Aneurysm Repair.

PurposeWe examined the clinical utility of perioperative monitoring of urinary liver-type fatty acid binding protein (L-FABP), neutrophil gelatinase-associated lipocalin (NGAL), and albumin, for prediction of acute kidney injury (AKI) and prediction of chronic renal dysfunction in patients undergoing open surgical repair (OSR) of an abdominal aortic aneurysm.Patients and MethodsUrine and serum samples were obtained perioperatively from 64 such patients (n=64). Patients in whom OSR-related AKI (defined by the Kidney Disease Improving Global Outcomes criteria) occurred were identified. Renal function was evaluated 3 years after OSR in patients with OSR-related AKI.ResultsThe urinary biomarkers examined increased to maximum levels by 2 hours after aortic cross-clamping (AXC), regardless of whether AKI occurred. Notably, the serum creatinine (Cr) levels increased significantly immediately after OSR in patients with AKI (n=19) (vs that in patients without AKI). In patients with AKI, the increased serum Cr elevation rate, the urinary L-FABP levels 2 hours after AXC and immediately after OSR, and a reduction in eGFR documented 3 years after OSR were significantly greater in patients who underwent suprarenal AXC (n=11) than in those who underwent infrarenal AXC (n=8). Furthermore, urinary L-FABP levels 2 hours after AXC correlated significantly with the reductions in eGFR 3 years after OSR in patients with AKI.ConclusionUrinary L-FABP, NGAL and albumin concentrations 2 hours after AXC may be useful for early detection of OSR-related AKI. Furthermore, the increase in urinary L-FABP 2 hours after AXC may be predictive of chronic renal dysfunction in patients with OSR-related AKI.

Renal hemodynamics across the adult lifespan: Relevance of flow pulsatility to chronic kidney disease.

Elevated renal flow pulsatility may contribute to the pathogenesis of chronic kidney disease (CKD). The purpose of this study was to investigate the associations among age, renal flow pulsatility, and CKD biomarkers in non-CKD adults and CKD patients. Non-CKD adults (n=415) and CKD patients (n=136) aged between 22 and 83years underwent the renal blood flow measurement using duplex ultrasonography. Pulsatility index (PI) and resistive index (RI) were calculated to assess renal flow pulsatility. The CKD biomarkers such as urinary liver-type fatty acid-binding protein (L-FABP) and serum fibroblast growth factor 23 (FGF23) were measured from each participant. Aortic hemodynamic parameters were measured by applanation tonometry. In non-CKD adults, advancing age was associated with elevations of renal PI and RI which slowly increased during middle-aged (PI: β=0.14, RI: β=0.17) and accelerated in older adults (PI: β=0.34, RI: β=0.33). In CKD patients, age-related increases in renal PI and RI were observed only in the middle age group (PI: β=0.23, RI: β=0.26). Multivariate analysis demonstrated that renal PI and RI were independently associated with CKD biomarkers, including urinary L-FABP and serum FGF23, and aortic pulse pressure. Advancing age is associated with a progressive elevation of renal flow pulsatility which manifests during middle age and accelerates in later life. Moreover, elevated renal flow pulsatility is associated with the presence of CKD in each age group and also with biomarker levels that reflect CKD progression.

Biomarkers for the early prediction of contrast-induced nephropathy after percutaneous coronary intervention in adults: A systematic review and meta-analysis.

Contrast-induced nephropathy (CIN) is a complication of patients undergoing percutaneous coronary intervention (PCI). Promising biomarkers for the early prediction of CIN can significantly improve outcomes of these patients. We searched PubMed, EMBASE, Web of Science, and Cochrane Library for studies. Trials reporting an area under the curve (AUC) for the utility of novel biomarkers in the early prediction of CIN in adults after PCI were included. In total, 42 studies comprising 11,984 adult patients undergoing PCI met the criteria. Four urinary biomarkers and four blood biomarkers were included. For urine biomarkers, the pooled AUCs for neutrophil gelatinase-associated lipocalin (NGAL), interleukin-18 (IL-18), liver-type fatty acid-binding protein (L-FABP), and kidney injury molecule-1 (KIM-1) were 0.91 (95% CI 0.89-0.94), 0.79 (0.75-0.82), 0.78 (0.74-0.82), and 0.79 (0.76-0.83), respectively. The blood biomarkers NGAL, cystatin C, brain natriuretic peptide (BNP), and C-reactive protein (CRP) had pooled AUCs of 0.93 (0.91-0.95), 0.92 (0.89-0.94), 0.78 (0.74-0.81), and 0.75 (0.71-0.79), respectively. Subgroup analysis showed that blood NGAL in early CIN predictive time (<6 h) was more effective in predicting CIN. The efficiency of cystatin C in predicting CIN was reduced, whereas that of L-FABP was increased among chronic kidney disease (CKD) patients.

Tardigrade Secretory-Abundant Heat-Soluble Protein Has a Flexible β-Barrel Structure in Solution and Keeps This Structure in Dehydration.

Secretory-abundant heat-soluble (SAHS) proteins are unique heat-soluble proteins of Tardigrada and are believed to play an essential role in anhydrobiosis, a latent state of life induced by desiccation. To investigate the dynamic properties, molecular dynamics (MD) simulations of a SAHS protein, RvSAHS1, were performed in solution and under dehydrating conditions. For comparison purposes, MD simulations of a human liver-type fatty-acid binding protein (LFABP) were performed in solution. Furthermore, high-speed atomic force microscopy observations were conducted to ascertain the results of the MD simulations. Three properties of RvSAHS1 were found as follows. (1) The entrance region of RvSAHS1 is more flexible and can be more extensive in solutions compared with that of a human LFABP because there is no salt bridge between the βD and βE strands. (2) The intrinsically disordered domain in the N-terminal region significantly fluctuates and can form an amphiphilic α-helix. (3) The size of the entrance region gets smaller along with dehydration, keeping the β-barrel structure. Overall, the obtained results provide atomic-level dynamics of SAHS proteins.

A New Clinical Utility for Tubular Markers to Identify Kidney Responders to Saxagliptin Treatment in Adults With Diabetic Nephropathy

ObjectivesIn recent clinical studies, saxagliptin exhibited nephroprotective potential by lowering albuminuria. In this study, we aimed to determine whether these kidney effects of saxagliptin were mediated by changes in markers of kidney tubular damage, including urinary neutrophil gelatinase-associated protein (uNGAL) and liver-type fatty acid–binding protein (uL-FABP). MethodsOur study included 80 patients with type 2 diabetes, hypertension and mild to moderate diabetic kidney disease (DKD) with prevalent albuminuria. Patients were either randomly assigned to saxagliptin as add-on therapy or remained unchanged on their stable antidiabetic therapy as a control arm. ResultsSaxagliptin significantly reduced uNGAL with a median change of −25.4% (interquartile range [IQR], −35.6% to −12.2%) compared with the control group (median change, −0.91%; IQR, −12% to 11.88%; p<0.001) after 3 months. Similarly, patients given saxagliptin had a highly significant reduction in uL-FABP (median change, −24.4%; IQR, −30.5% to −15.1%) compared with controls (median change, −3.8%; IQR −10% to 12.5%; p<0.001). Median estimated glomerular filtration rate (eGFR) values after 3 months in the saxagliptin arm were significantly higher (76.5 mL/min per 1.73 m2; IQR, 70 to 92.75 mL/min per 1.73 m2) in the low-risk uNGAL group compared with controls (59.8 mL/min per 1.73 m2; IQR, 51 to 76.2 mL/min per 1.73 m2; p=0.002). Also, higher—although not significantly—posttreatment eGFR levels were observed in patients with low risk of uL-FABP (73 mL/min per 1.73 m2; IQR, 58 to 91.3 mL/min per 1.73 m2) compared with controls (57.3 mL/min per 1.73 m2; IQR, 49.5 to 72.6 mL/min per 1.73 m2; p=0.06). No significant increase was observed in high-risk patients for either marker when compared with controls. ConclusionsThe albuminuria-lowering effect of saxagliptin may be due to inhibition of kidney tubular damage. Use of tubular markers may be a promising approach to identifying kidney responders to gliptins.

URINARY LIVER TYPE FATTY ACID BINDING PROTIEN AND PLASMA CYSTATIN C PREDICT ACUTE KIDNEY INJURY OUTCOMES IN CRITICALLY ILL PATIENTS

Acute kidney injury (AKI) is a devastating problem that is commonly associated with worse clinical outcomes in critically ill patients. AKI is an independent risk factor for chronic kidney disease, prolonged hospital stay and increased mortalities. several novel biomarkers have been validated for the early diagnosis of AKI. Some of them recently proved to be more effective than those usually used. Liver-type fatty acid-binding protein (L-FABP), a 14kDa protein in the cytoplasm of human renal proximal tubules and bind free fatty acids in response to renal injury. several studies showed that L-FABP is a promising biomarker of several kidney disease. Cystatin C (Cys-C), a low molecular weight protein produced by all nucleated cells of the body, is filtered through glomeruli, and reabsorbed completely through the proximal renal tubules. Also, plasma cystatin C is independent of several factors such as muscle mass, age and gender. Cys-C is investigated to be a good functional biomarker for diagnosis of AKI.

Chronic Exercise Protects against the Progression of Renal Cyst Growth and Dysfunction in Rats with Polycystic Kidney Disease.

ABSTRACTIntroductionPolycystic kidney disease (PKD) is a genetic disorder characterized by the progressive enlargement of renal epithelial cysts and renal dysfunction. Previous studies have reported the beneficial effects of chronic exercise on chronic kidney disease. However, the effects of chronic exercise have not been fully examined in PKD patients or models. The effects of chronic exercise on the progression of PKD were investigated in a polycystic kidney (PCK) rat model.MethodsSix-week-old male PCK rats were divided into a sedentary group and an exercise group. The exercise group underwent forced treadmill exercise for 12 wk (28 m·min−1, 60 min·d−1, 5 d·wk−1). After 12 wk, renal function and histology were examined, and signaling cascades of PKD progression, including arginine vasopressin (AVP), were investigated.ResultsChronic exercise reduced the excretion of urinary protein, liver-type fatty acid–binding protein, plasma creatinine, urea nitrogen, and increased plasma irisin and urinary AVP excretion. Chronic exercise also slowed renal cyst growth, glomerular damage, and interstitial fibrosis and led to reduced Ki-67 expression. Chronic exercise had no effect on cAMP content but decreased the renal expression of B-Raf and reduced the phosphorylation of extracellular signal-regulated kinase (ERK), mammalian target of rapamycin (mTOR), and S6.ConclusionChronic exercise slows renal cyst growth and damage in PCK rats, despite increasing AVP, with the downregulation of the cAMP/B-Raf/ERK and mTOR/S6 pathways in the kidney of PCK rats.

Combined evaluation of plasma B-type natriuretic peptide and urinary liver-type fatty acid-binding protein/creatinine ratio is related to worsening renal function in patients undergoing elective percutaneous coronary intervention.

There are few reports on the significance for the combined evaluation of blood humoral factors and urinary biomarkers in terms of worsening renal function (WRF) after coronary angiography (CAG)/percutaneous coronary arterial intervention (PCI). Urinary liver type-fatty acid-binding protein (L-FABP), neutrophil gelatinase associated lipocalin (NGAL), and adrenomedullin (AM) were measured less than 24h before and 3h, 6h, 1day, and 2days after CAG/PCI. WRF was defined as a > 20% decrease in the estimated GFR. WRF occurred in seven of 100 patients and the increase in L-FABP/creatinine (Cr) at 1day after CAG/PCI was significantly higher in the WRF group than in the non-WRF group. Plasma B-type natriuretic peptide (BNP) before CAG/PCI and L-FABP/Cr at 1day after CAG/PCI were independent predictors for WRF. The areas under the receiver-operating characteristic curves were as follows: 0.760 for BNP before CAG/PCI, 0.731 for L-FABP/Cr at 1day after CAG/PCI, and 0.892 for BNP and L-FABP/Cr. Urinary AM levels after PCI/CAG were negatively correlated only to serum potassium levels. Gene expressions of AM and AM-receptor were detectable in renal tubule epithelial cells. AM increased intracellular second messenger levels in a dose-dependent manner. Our results suggest that combined evaluation of plasma BNP and urinary L-FABP/Cr is useful as a predictor of renal dysfunction in CAG/PCI patients.

COVID-19-induced acute renal tubular injury associated with elevation of serum inflammatory cytokine.

BackgroundSevere acute respiratory syndrome Coronavirus 2 has rapidly spread worldwide, with acute kidney injury (AKI) as one of the manifestations with unknown causal mechanisms. We aimed to investigate tubular injury by assessing tubular markers and their association with the severity of Coronavirus disease 2019 (COVID-19).MethodsWe examined the associations between laboratory markers and urinary levels of N-acetyl-β-d-glucosaminidase (uNAG), β2-microglobulin (u β2MG), α1-microglobulin (u α1MG), and liver-type fatty acid binding protein (L-FABP). We studied 18 COVID-19 patients without previous chronic kidney disease and analyzed the relationship between the urinary biomarkers and inflammatory markers in patients with severe (n = 7) or non-severe (n = 11) COVID-19, defined by requirements of supplemental oxygen.ResultsFourteen patients (78%) showed abnormal urinalysis findings and two (11%) developed AKI. Patients with severe COVID-19 had significantly higher levels of proteinuria, uNAG, uβ2MG, uα 1MG, and L-FABP than those with non-severe disease. Serum levels of interleukin-6 (IL-6) were significantly higher on admission in all severe COVID-19 cases and correlated with the levels of L-FABP, uβ2MG, uα1MG, uNAG, and proteinuria. Moreover, the changes in serum IL-6 (ΔIL-6) levels from baseline to 7 days after admission significantly correlated with ΔL-FABP and Δuβ2MG.ConclusionsLevels of tubular injury markers, especially L-FABP and uβ2MG, were significantly associated with IL-6 levels even in patients with no evident AKI. This suggests that L-FABP and uβ2MG could be useful as early detective biomarkers for COVID-19 associated renal injury.

Acute Kidney Injury in Chemotherapy for Children with Pediatric Malignancy

Background: Acute kidney injury (AKI) is one of severe complications during the anti-cancer chemotherapy. The study by Lahoti et al. revealed that 36% of adult patients with acute myelogenous leukemia or high-risk myelodysplastic syndrome developed AKI on chemotherapy, and the 8-weeks mortality rates were about 15% of AKI patients in contrast to 3% of non-AKI patients. Therefore, it is very important to diagnose of AKI early and accurately.Purpose: The purpose of this study is to identify the predictive biomarker of AKI in children with pediatric cancer.Materials and Methods: In the present study, 16 children with cancer were enrolled. To evaluate AKI, we used RIFLE criteria modified by AKI Network group. The severity of AKI based on RIFLE criteria divided into 5 categories (Risk, Injury, Failure, Loss and End-stage). We measured five urinary biomarkers (total protein (TP), albumin (Alb), N-Acetyl-glucosaminidase (NAG), β2-microglobulin (BMG), and liver-type fatty acid-binding protein (L-FABP)) related AKI because these five biomarkers could measure commercially.Results: We obtained the Laboratory data of 16 children received total 58 courses of chemotherapy. In 31 (53.4%) of 58 courses, AKI developed. To reveal a predictive biomarker, we investigated as follows in total 31 times developed AKI; 1) the frequency that each biomarker increased, and 2) the day when each biomarker increased based on the day when AKI developed based on RIFLE criteria. In total, TP, Alb, NAG, BMG, and L-FABP increased 17 (55%), 16 (52%), 18 (58%), 20 (65%), and 24 (77%) in AKI of total 31 times, respectively. Also, the median day when TP, Alb, NAG, BMG, and L-FABP increased was 9.0 (range: 0-29), 8.5 (range: 0-29), 9.5 (range: 0-42), 6.0 (range: 0-35), and 13.0 (range: 0-42) days before the day when AKI developed, respectively. L-FABP was found to be a predictive marker of AKI showing the best area under the ROC curve value (AUC) during chemotherapy (AUC = 0.753, sensitivity = 77.4%, specificity = 63.3%).Conclusion: These results showed that L-FABP is a possible predict biomarker of AKI in chemotherapy for children with pediatric cancer. DisclosuresNo relevant conflicts of interest to declare.

Plasma heparin cofactor II activity is inversely associated with albuminuria and its annual deterioration in patients with diabetes.

Aims/IntroductionThrombin exerts various pathophysiological functions by activating protease‐activated receptors (PARs). Recent data have shown that PARs influence the development of glomerular diseases including diabetic kidney disease (DKD) by regulating inflammation. Heparin cofactor II (HCII) specifically inactivates thrombin; thus, we hypothesized that low plasma HCII activity correlates with DKD development, as represented by albuminuria.Materials and MethodsPlasma HCII activity and spot urine biomarkers, including albumin and liver‐type fatty acid‐binding protein (L‐FABP), were determined as the urine albumin‐to‐creatinine ratio (uACR) and the urine L‐FABP‐to‐creatinine ratio (uL‐FABPCR) in 310 Japanese patients with diabetes mellitus (176 males and 134 females). The relationships between plasma HCII activities and those DKD urine biomarkers were statistically evaluated. In addition, the relationship between plasma HCII activities and annual uACR changes was statistically evaluated for 201/310 patients (115 males and 86 females).ResultsThe mean plasma HCII activity of all participants was 93.8 ± 17.7%. Multivariate‐regression analysis including confounding factors showed that plasma HCII activity independently contributed to the suppression of the uACR and log‐transformed uACR values (P = 0.036 and P = 0.006, respectively) but not uL‐FABPCR (P = 0.541). In addition, plasma HCII activity significantly and inversely correlated with annual uACR and log‐transformed uACR increments after adjusting for confounding factors (P = 0.001 and P = 0.014, respectively).ConclusionsThe plasma HCII activity was inversely and specifically associated with glomerular injury in patients with diabetes. The results suggest that HCII can serve as a novel predictive factor for early‐stage DKD development, as represented by albuminuria.

Assessment of Cardiopulmonary Bypass Duration Improves Novel Biomarker Detection for Predicting Postoperative Acute Kidney Injury after Cardiovascular Surgery.

Urinary liver-type fatty acid binding protein (L-FABP) is a novel biomarker with promising performance in detecting kidney injury. Previous studies reported that L-FABP showed moderate discrimination in patients that underwent cardiac surgery, and other studies revealed that longer duration of cardiopulmonary bypass (CPB) was associated with a higher risk of postoperative acute kidney injury (AKI). This study aims to examine assessing CPB duration first, then examining L-FABP can improve the discriminatory ability of L-FABP in postoperative AKI. A total of 144 patients who received cardiovascular surgery were enrolled. Urinary L-FABP levels were examined at 4 to 6 and 16 to 18 h postoperatively. In the whole study population, the AUROC of urinary L-FABP in predicting postoperative AKI within 7 days was 0.720 at 16 to 18 h postoperatively. By assessing patients according to CPB duration, the urinary L-FABP at 16 to 18 h showed more favorable discriminating ability with AUROC of 0.742. Urinary L-FABP exhibited good performance in discriminating the onset of AKI within 7 days after cardiovascular surgery. Assessing postoperative risk of AKI through CPB duration first and then using urinary L-FABP examination can provide more accurate and satisfactory performance in predicting postoperative AKI.

Significance of urinary liver-type fatty acid-binding protein in patients with normal renal function after undergoing intestinal urinary diversion: a preliminary study.

Liver-type fatty acid-binding protein (L-FABP) in urine is one of the early diagnostic biomarkers for acute and chronic kidney injuries. Although this protein is also identified in the intestine, there is no verified reference value for patients with intestinal urinary diversion (UD). The aim of the present study was to measure L-FABP values in such patients and compare them with the results for patients without UD. Spot urine specimens were collected from 41 patients with UD and 50 subjects without UD with estimated glomerular filtration rates of over 60ml/min/1.73m2, and the L-FABP values were measured. The normal upper cutoff value in healthy subjects without UD is considered to be 7.24μg/g Cr. First, the median values of the two groups were compared. Next, the subjects with negative proteinuria and without comorbidities associated with renal function were further selected and the median values of the groups were compared. The mean age was significantly higher in the UD group. The types of UD were ileal conduit (38 patients) and ileal neobladder (three patients). The median L-FABP value in the UD group was significantly higher than that in the non-diversion group (89.1μg/g Cr vs. 2.0μg/g Cr, p < 0.0001). After adjustment for their backgrounds, the median value remained higher in the UD group. L-FABP values in subjects with UD are higher than in those without UD. By this result, to develop a reference value in patients with intestinal UD population, further studies are required.

Changing trends in lipid profile and biomarkers of renal function and bone metabolism before and after switching from tenofovir disoproxil fumarate to tenofovir alafenamide: a prospective observational study

BackgroundAntiretrovirals, including tenofovir, can suppress human immunodeficiency virus (HIV) infection but cannot completely eradicate it. Patients with HIV infection are administered antiretroviral drugs over a long term; thus, managing consequent adverse drug reactions, such as renal dysfunction and bone mineral loss, is important. Currently, highly sensitive biomarkers that can detect adverse drug reactions early have not been well studied.MethodsThis single-center, prospective, observational study explored changes in the biomarkers of renal function, bone metabolism, and lipid profile before and after switching from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF) in patients with HIV infection.ResultsAll 31 enrolled patients had been treated with antiretrovirals for more than 5 years. The rate of proteinuria decreased significantly after starting TAF-containing antiretroviral regimen. The urinary liver-type fatty acid binding protein (L-FABP)/creatinine ratio was significantly decreased at 3 and 6 months after switching to TAF compared with that before switching to TAF (− 0.5 μg/g Cr at 3 months, and − 0.8 μg/g Cr at 6 months; p < 005 for both at 3 and 6 months). The urinary N-terminal telopeptide (NTx)/creatinine ratio decreased over the study period, and the ratios were significantly different between 3 and 6 months (− 11 nmol/mmol Cr at 3 months, − 15.2 nmol/mmol Cr at 6 months; p = 0.0069 at 3 months, p < 0.0001 at 6 months). Low density lipoprotein-cholesterol level significantly increased at 3 (+ 26 mg/dL) and 6 months (+ 13 mg/dL) compared with that at the baseline (p < 0.0001).ConclusionsSwitching from TDF to TAF decreased the levels of renal and bone biomarkers, such as urinary L-FABP and NTx, but increased low density lipoprotein-cholesterol levels. Future studies should evaluate if these biomarkers, such as urinary L-FABP and NTx, truly detect serious adverse drug reactions early.