Liver-type Fatty Acid-binding Protein Research Articles

Prognostic Value of Urinary Liver-Type Fatty Acid-Binding Protein (uL-FABP) for Major Adverse Kidney Outcomes Among Critically Ill Adult Septic Patients

Prognostic Value of Urinary Liver-Type Fatty Acid-Binding Protein (uL-FABP) for Major Adverse Kidney Outcomes Among Critically Ill Adult Septic Patients

Association between liver-type fatty acid-binding protein and hyperuricemia before and after laparoscopic sleeve gastrectomy.

BackgroundLiver-type fatty acid-binding protein (FABP1) contributes to metabolic disorders. However, the relationship between FABP1 and hyperuricemia remains unknown. We aimed to evaluate the correlation between serum FABP1 and hyperuricemia in patients with obesity before and after laparoscopic sleeve gastrectomy (LSG).MethodsWe enrolled 105 patients (47 men and 58 women) with obesity who underwent LSG. They were divided into two groups: normal levels of uric acid (UA) (NUA, n = 44) and high levels of UA (HUA, n = 61) with matching sexes. FABP1 levels and other biochemical parameters were measured at baseline and 3, 6, and 12 months after LSG.ResultsSerum FABP1 levels were significantly higher in the HUA group than in the NUA group (34.76 ± 22.69 ng/mL vs. 25.21 ± 21.68 ng/mL, P=0.024). FABP1 was positively correlated with UA (r=0.390, P=0.002) in the HUA group. The correlation still existed after adjusting for confounding factors. Preoperative FABP1 levels were risk factors for hyperuricemia at baseline. UA and FABP1 levels decreased at 3, 6, and 12 months postoperatively. FABP1 showed a more significant decrease in the HUA group than in the NUA group at 12 months (27.06 ± 10.98 ng/mL vs. 9.54 ± 6.52 ng/mL, P=0.003). Additionally, the change in FABP1 levels positively correlated with changes in UA levels in the HUA group 12 months postoperatively (r=0.512, P=0.011).ConclusionsFABP1 was positively associated with UA and may be a risk factor for hyperuricemia in obesity. FABP1 levels were higher but decreased more after LSG in obese patients with hyperuricemia than in those without hyperuricemia.

Lipid metabolism disorders of hybrid grouper (♀Epinephelus fuscointestinestatus × ♂E. lanceolatu) induced by high-lipid diet

This study investigated the effect of lipid levels on growth, body composition, lipid metabolism enzymes activity and related genes expression in hybrid grouper (♀Epinephelus fuscointestinestatus× ♂E. lanceolatu). Three diets with different lipid levels of 6% (low-lipid feed, LF), 11% (medium-lipid feed, MF) and 16% (high-lipid feed, HF) were designed and each diet was fed to triplicate groups of 30 fish each (6.73 ± 0.00g) for eight weeks. The results revealed the following. 1) The maximum weight gain rate (WGR), specific growth rate (SGR), protein efficiency ratio (PER) and the lowest feed conversion ratio (FCR) values were found in the HF group. There was no significant difference in the survival rate (SR) among the groups (P> 0.05). 2) Condition factor (CF), hepatosomatic index (HSI) and visceralsomatic index (VSI) increased with increasing dietary lipid. 3) Crude lipid content in the whole-body and muscle increased significantly as the dietary lipid level increased (P< 0.05). 4) Principal component analysis of fatty acids showed that sum n-3 polyunsaturated fatty acids (∑n-3PUFA)/sum n-6 polyunsaturated fatty acids (∑n-6PUFA) was significantly higher in the HF group than in the other two groups (P< 0.05). 5) Biochemical serum indexes showed higher triglycerides (TG), total cholesterol (TC), alkaline phosphatase (AKP) and low-density lipoprotein-cholesterol (LDL-C) levels but lower high-density lipoprotein-cholesterol (HDL-C) level in the HF group. 6) Liver lipid metabolism enzymes activity and biochemical indicators showed that fish fed the MF diet had higher lipoprotein lipase (LPL), hepatic lipase (HL) and triglyceride lipase (ATGL) activity but lower fatty acid synthase (FAS) activity and very-low density lipoprotein-cholesterol (VLDL-C) level. 7) The relative expression levels of lipoprotein lipase (lpl), adipocyte-type fatty acid-binding protein (a-fabp), liver-type fatty acid-binding protein (l-fabp), heart-type fatty acid-binding protein (h-fabp) and hormone-sensitive lipase (hsl) genes in the fish liver were higher in the MF group with increasing dietary lipid (P< 0.05), while the fatty acid synthase (fas) gene was expressed at lower relative level (P< 0.05). 8) Histological oil-red sections of the liver showed that fish in the HF group had larger and more hepatic lipid droplets than those fed the other diets. It was concluded that fish fed the HF diet had better growth performance but this diet was not conducive to the progress of lipid metabolism, resulting in lipid accumulation and affecting the quality of the fish. This study provides useful information for the formulation of environmentally friendly and cost-effective diets for hybrid grouper.

Utility of urinary liver-type fatty acid-binding protein as a prognostic marker in adult congenital heart patients hospitalized for acute heart failure.

Progression to acute kidney injury (AKI) under treatment in adult congenital heart disease (ACHD) patients with heart failure is associated with poor prognosis, early detection and interventions are necessary. We aimed to explore the utility of urinary liver-type fatty acid binding protein (L-FABP) in ACHD patients hospitalized for acute decompensated heart failure (ADHF). We prospectively evaluated hemodynamic, biochemical data, and urinary biomarkers including urinary L-FABP in ACHD patients hospitalized in our institution from June 2019 to March 2022. The primary outcomes were the development of AKI and death. AKI was defined as serum creatinine level increased by 0.3mg/dl or more within 5days after hospitalization. A total of 104 ADHF patients aged 31 (36-51) years were enrolled. 26 cases (25% of ADHF patients) developed AKI during hospitalization and 4 died after hospital discharge. Serum creatinine (sCr), serum total bilirubin, brain natriuretic peptide (BNP), and urinary L-FABP in AKI patients were significantly higher than in non-AKI patients, whereas systemic oxygen saturation of the peripheral artery (SpO2) and estimated glomerular filtration ratio in AKI patients were lower than non-AKI patients. There was no difference in the intravenous diuretic dose on admission and during hospitalization between the two groups. In the receiver operating characteristic (ROC) analysis, the maximum area under the curve (AUC) of urinary biomarkers in AKI patients was urinary L-FABP (AUC = 0.769, p < 0.001) with a cutoff value of 4.86µg/gCr. Urinary L-FABP level on admission was associated with a predictor for AKI development during hospitalization after adjusting for sCr, BNP and SpO2. Urinary L-FABP was a useful predictor for the development of AKI in ACHD patients hospitalized for ADHF. Monitoring of urinary L-FABP allows us to detect a high-risk patient earlier than the conventional biomarkers.

Serum and urine profiling by high-throughput TMT-based proteomics for the investigation of renal dysfunction in canine babesiosis

Canine babesiosis is a tick-borne disease caused by Babesia canis, with acute kidney injury as one of the common complications. In the study 8 healthy control dogs and 22 dogs with naturally occurring babesiosis were enrolled, with the aim to analyse differences in serum and urinary proteomes between healthy dogs and dogs with different degree of renal dysfunction in babesiosis using a label-based high-throughput quantitative proteomic approach. In serum, 58 proteins were found differentially abundant between healthy controls and groups of dogs with different degrees of renal dysfunction in babesiosis, while in urine there were 259 differentially abundant proteins. In addition, altered biological pathways were detected in the diseased dogs using bioinformatics tools and validation of several candidate biomarkers was performed. SignificanceThe main aim of this comprehensive study was to perform analyses of serum and urinary proteomes of dogs with renal dysfunction in babesiosis compared to healthy dogs using, for the first time, a high-throughput proteomic method and functional enrichment analyses. Serum and urine samples of the same dogs were investigated in order to gain a more complete picture of pathologic changes taking place in renal dysfunction in babesiosis. We highlighted two putative biomarkers validated herein which could be of importance for early diagnosis of renal dysfunction in canine babesiosis, as they are easily accessible from urine and their concentration rises before the appearance of azotaemia: urinary neutrophil gelatinase-associated lipocalin (NGAL) and urinary liver-type fatty acid-binding protein (L-FABP).

Performance of urinary liver-type fatty acid-binding protein in diabetic nephropathy: A meta-analysis

AimsDiabetic nephropathy (DN) is one of the main causes of chronic kidney disease (CKD), which increases the risk of cardiovascular diseases and progresses to end-stage renal failure. Thus, early diagnostic markers for diabetic patients are urgently needed to improve the prognosis of DN and predict DN progression.Materials and methodsPubMed, MEDLINE, EMBASE, and Scopus were searched for publications until February 24, 2021. Review Manager 5.4 software was used for meta-analysis. We performed the heterogeneity test using the I2 statistic: P < 0.1 and I2> 50% meant statistical significance.ResultsWe included 13 studies. The urinary liver-type fatty acid-binding protein (uL-FABP) concentrations in the normal albuminuria group were significantly higher than those in the normal control group without diabetes mellitus (DM) [P = 0.009, SMD 1.72, 95% CI (0.44, 2.99)]. Urinary F-LABP levels were elevated in the macroalbuminuria group compared with those in the microalbuminuria group with DM [P = 0.002, SMD 2.82, 95% CI (1.03, 4.61)]. Urinary L-FABP levels were also significantly increased in the progression and CKD groups compared with non-progression and CKD subjects with DM [P = 0.02, P < 0.00001, respectively]. Furthermore, uL-FABP concentrations were positively correlated with the albumin-to-creatinine ratio and systolic blood pressure in patients with DM [Summary Fisher’s Z = 0.58 P < 0.00001; Summary Fisher’s Z = 0.24 P < 0.0001, respectively] and negatively correlated with estimated glomerular filtration rate in patients with DM [Summary Fisher’s Z = −0.36, P < 0.0001].ConclusionUrinary L-FABP may be a potential marker for the detection of all stages of DN and for the prediction of the progression and severity of DN in patients with type 1 and 2 DM.

Effects of dietary phosphorus concentration and phosphate salt form on renal tubule function in unilateral nephrectomized rats.

Background: Excessive consumption of phosphorus (P) impairs renal tubule function; however, the effects of different dietary phosphate salts on chronic kidney disease (CKD) are unclear. Aim: To examine the effects of potassium dihydrogen phosphate (KH2PO4) and potassium tripolyphosphate (K5P3O10) and P concentration on renal function in a rat model of early CKD. Methods: Male sham-operated Sprague-Dawley rats were fed a diet containing KH2PO4 with a normal P level. Kidney injury was induced by unilateral nephrectomy (UNx), and the rats were divided into four groups fed dietary KH2PO4 or K5P3O10 with a normal (UNx-NKH, UNx-NKP) or high (UNx-HKH, UNx-HKP) P concentration, respectively, for 21 days. Results: UNx-NKH rats showed significantly lower creatinine clearance (CCr) and higher albumin (ALB) compared with those of sham rats, confirming UNx-induced kidney injury. The urinary levels of liver-type fatty acid-binding protein (L-FABP) and ALB were significantly higher in UNx-HKP rats than in UNx-HKH rats. However, other markers of renal tubule function, such as CCr, serum creatinine (CRE), calcium (Ca), and hormones, only differed among groups according to the P concentration and not the dietary phosphate salt form. Histological examination showed higher incidence and severity of tubulointerstitial lesions, tubule regeneration, tubule dilation, and calcification in the high-phosphorus than in the normal-phosphorus UNx groups. These changes were more severe in the UNx-HKP group compared with the UNx-HKH group. Conclusion: This study highlights the importance of controlling dietary P intake in terms of both concentration and source to prevent the progression of CKD.

The Correlations of Plasma Liver-Type Fatty Acid-Binding Protein with Amyloid-β and Tau Levels in Patients with Alzheimer's Disease.

The dysregulation of lipid metabolism plays an important role in the pathogenesis of Alzheimer's disease (AD). Liver-type fatty acid-binding protein (L-FABP, also known as FABP1) is critical for fatty acid transport and may be involved in AD. To investigate whether the FABP1 level is altered in patients with AD, and its associations with levels of amyloid-β (Aβ) and tau in the plasma and cerebrospinal fluid (CSF). A cross-sectional study was conducted in a Chinese cohort consisting of 39 cognitively normal controls and 47 patients with AD. The levels of FABP1 in plasma, and Aβ and tau in CSF, were measured by enzyme-linked immunosorbent assay (ELISA). A single-molecule array (SIMOA) was used to detect plasma Aβ levels. The level of plasma FABP1 was significantly elevated in the AD group (p = 0.0109). Further analysis showed a positive correlation of FABP1 with CSF total tau (t-tau) and phosphorylated tau (p-tau) levels. Besides, plasma FABP1/Aβ42 (AUC = 0.6794, p = 0.0071) and FABP1/t-tau (AUC = 0.7168, p = 0.0011) showed fair diagnostic efficacy for AD. When combined with other common AD biomarkers including plasma Aβ42, Aβ40, and t-tau, both FABP1/Aβ42 and FABP1/t-tau showed better diagnostic efficacy than using these biomarkers alone. Among all AUC analyses, the combination of plasma FABP1/t-tau and Aβ42 had the highest diagnostic value (AUC = 0.8075, p < 0.0001). These findings indicate that FABP1 may play a role in AD pathogenesis and be worthy of further investigation in the future.

407-P: Skin Autofluorescence Is Associated with Tubular Injury Represented by Urinary Excretion of Liver-Type Fatty Acid–Binding Protein in People with Diabetes

Background: Advanced glycation end product (AGE) accumulation is thought to be an independent predictor for cardiovascular disease in people with diabetes and renal failure. Since it has remained unclear whether AGE has a clinical impact on diabetic kidney disease (DKD) , the aim of this study was to determine the association between AGE accumulation, measured as skin autofluorescence (AF) , and the progression of DKD. Methods: Skin AF was measured by AGE reader® 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 300 Japanese people with diabetes (173 males and 127 females, mean age, 67.8 ± 10.7 years) . The relationships between skin AF and those urine biomarkers of DKD were statistically evaluated. Results: Simple regression analysis showed that skin AF was associated with uACR (p&amp;lt;0.05) , log-transformed uACR (p&amp;lt;0.01) and uL-FABPCR (p&amp;lt;0.001) . On the other hand, multivariate regression analysis including clinical confounding factors showed that skin AF independently contributed to the increment of uL-FABPCR (P &amp;lt;0.05) but not to that of uACR (P=0.399) or log-transformed uACR (P=0.315) . Conclusion: Skin AF was associated with urinary L-FABP but not with albuminuria in people with diabetes. The results suggest that skin AF can serve as a novel predictive factor for the development of diabetic tubular injury. Disclosure H.Yamagami: None. T.Yuasa: None. S.Yoshida: None. A.Kuroda: None. M.Matsuhisa: Research Support; Nissui , Sysmex Corp., Speaker's Bureau; Astellas Pharma Inc., Eli Lilly and Company, Merck Sharp &amp; Dohme Corp., Mitsubishi Tanabe Pharma Corporation, Novo Nordisk, Sanofi, Sumitomo Dainippon Pharma Co., Ltd., Takeda Pharmaceutical Company Limited. I.Endo: None. K.Aihara: None. M.Abe: None. S.Yasui: None. M.Hosoki: None. T.Hori: None. T.Hara: None. Y.Mitsui: None. K.Kurahashi: None. S.Nakamura: None. T.Otoda: None.

Xanthine oxidoreductase activity in marathon runners: potential implications for marathon-induced acute kidney injury.

Excess activation of circulating xanthine oxidoreductase (XOR) may contribute to the pathogenesis of widespread remote organ injury, including kidney injury. The purpose of this study was to determine the acute impact of marathon running on plasma XOR activity and to examine whether plasma XOR activity is associated with marathon-induced elevations in biomarkers of acute kidney injury (AKI). Twenty-three young men (aged 20-25 yr) who participated in the 38th Tsukuba Marathon were included. Blood and urine samples were collected before, immediately, 2 h (only blood sample), and 24 h after a full marathon run. Plasma XOR activity was evaluated using a highly sensitive assay utilizing a combination of [13C2,15N2] xanthine and liquid chromatography-triple quadrupole mass spectrometry. The levels of several AKI biomarkers, such as serum creatinine and urinary liver-type fatty acid-binding protein (L-FABP) were measured in each participant. Marathon running caused a transient elevation in plasma XOR activity and levels of purine degradation products (hypoxanthine, xanthine, and uric acid) as well as serum creatinine, urinary albumin, and urinary L-FABP levels. Immediately after the marathon, individual relative changes in plasma XOR activity were independently correlated with corresponding changes in serum creatinine and urinary L-FABP levels. In addition, the magnitude of marathon-induced elevation in plasma XOR activity and levels of purine degradation products were higher in individuals who developed AKI. These findings collectively suggest that marathon running substantially influences the purine metabolism pathway including XOR activity. Moreover, activated circulating XOR can be partly associated with elevated biomarkers of AKI after marathon running.NEW & NOTEWORTHY This study is the first to show marathon running transiently increases plasma XOR activity and levels of purine degradation products (hypoxanthine, xanthine, and uric acid), and further to demonstrate that activated plasma XOR may contribute to marathon-induced elevations in biomarkers of AKI. These findings significantly extend our prior knowledge of the purine metabolic pathway and several AKI biomarkers under strenuous exercise conditions.

Usefulness of urinary biomarkers to estimate the interstitial fibrosis surface in diabetic nephropathy with normal kidney function.

Kidney biopsies of patients with diabetic nephropathy (DN) and normal kidney function may exhibit interstitial fibrosis (IF) without reduction of glomerular filtration rate (GFR) because of hyperfiltration. The aim of our study was to analyse the performance of a set of biomarkers of tubular injury to estimate the extent of IF in patients with DN and normal kidney function. This cross-sectional study included 118 adults with DN diagnosed by kidney biopsy and GFR≥90mL/min/1.73 m2 and a control group of healthy subjects. We measured the urinary excretion of monocyte chemoattractant protein-1 (MCP-1) neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), liver-type fatty acid-binding protein (L-FABP), β2-microglobulin and dickkopf-3 protein (DKK-3) at the time of kidney biopsy. GFR was measured by chromium-51 labeled ethylenediamine tetraacetic acid (Cr-EDTA) (measured GFR). IF was quantified using a quantitative morphometric procedure. Predictive multivariate models were developed to estimate the IF surface. Patients with DN showed significantly higher levels of DKK-3, MCP-1 and L-FABP and significantly lower levels of epidermal growth factor (EGF) than healthy controls. There were no significant between-group differences in the levels of β2-microglobulin, KIM-1 or NGAL. IF was negatively associated with EGF and positively with age, proteinuria, MCP-1, DKK-3 and L-FABP, but not with β2-microglobulin, KIM-1, NGAL or GFR. The best model to predict IF surface accounted for 59% of its variability and included age, proteinuria, EGF, DKK-3 and MCP-1. Our study provides a model to estimate the IF in DN that can be useful to assess the progression of IF in patients with normal kidney function.

Usefulness of urinary tubule injury markers for predicting progression of renal dysfunction in patients with type 2 diabetes and albuminuria: The Fukuoka Diabetes Registry

AimsWe prospectively investigated the association of urinary tubule injury markers with estimated glomerular filtration rate (eGFR) decline in Japanese patients with type 2 diabetes. MethodsUrinary kidney injury molecule 1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), liver-type fatty-acid-binding protein (L-FABP), and urinary albumin-to creatinine ratio (UACR) were measured in 2,685 participants with type 2 diabetes. Renal outcomes were ≥ 30% decline in eGFR from the baseline and annual eGFR decline for 5 years. ResultsIn normoalbuminuric participants, no tubular markers were associated with ≥ 30% decline in eGFR or annual eGFR changes. In those with UACR ≥ 30 mg/gCr, hazard ratios for ≥ 30% eGFR decline were 1.37 (95% confident interval (CI) 1.07–1.75) for urinary KIM-1 (>1.5 µg/gCr), 1.46 (95% CI 1.13–1.66) for urinary NGAL (>16.4 µg/gCr), and 1.26 (95% CI 0.94–1.66) for urinary L-FABP (>12.5 µg/gCr), 2.61 (95% CI 1.64–4.17) for the combination of 3 tubular markers above the cutoff after multivariable adjustments including UACR and eGFR. ConclusionsThe current study demonstrated that urinary tubule injury markers and their combination were significant predictors for the future eGFR decline in those with type 2 diabetes and albuminuria independently of UACR and eGFR. Urinary tubular markers may be useful to identify high-risk patients with albuminuria.

Urine sediment findings were milder in patients with COVID-19-associated renal injuries than in those with non-COVID-19-associated renal injuries

BackgroundAcute renal injury is an important complication of coronavirus disease 2019 (COVID-19). Both COVID-19-specific mechanisms, such as damage to the renal parenchyma by direct infection, and non-specific mechanisms, such as the pre-renal injury factors, have been proposed to be involved in COVID-19-associated renal injuries. In this study, we aimed to elucidate the characteristics of COVID-19-associated renal injuries, focusing mainly on urine sediment findings. MethodsWe compared the urine sediment findings and their associations with renal functions or urinary clinical parameters between subjects with COVID-19 and subjects without COVID-19 with acute renal injuries. ResultsWe found that the number of urine sediment particles and the levels of N-acetyl-β-D-glucosaminidase, α1-microglobulin, liver type fatty acid-binding protein, and neutrophil gelatinase-associated lipocalin were associated with the severity of COVID-19. In addition, we observed that the number of granular casts, epithelial casts, waxy casts, and urinary chemical marker levels were lower in the subjects with COVID-19 than subjects without COVID-19 with acute renal injuries when the subjects were classified according to their renal function. ConclusionsThese results suggest that pre-renal injury factors might be largely involved in the pathogenesis of COVID-19-associated renal injuries compared with non-COVID-19-associated renal injuries arising from surgery or sepsis.

Metformin use in patients hospitalized with COVID-19: lower inflammation, oxidative stress, and thrombotic risk markers and better clinical outcomes.

Diabetes mellitus (DM) is associated with a greater risk of COVID-19 and an increased mortality when the disease is contracted. Metformin use in patients with DM is associated with less COVID-19-related mortality, but the underlying mechanism behind this association remains unclear. Our aim was to explore the effects of metformin on markers of inflammation, oxidative stress, and hypercoagulability, and on clinical outcomes. Patients with DM on metformin (n = 34) and metformin naïve (n = 41), and patients without DM (n = 73) were enrolled within 48 h of hospital admission for COVID-19. Patients on metformin compared to naïve patients had a lower white blood cell count (p = 0.02), d-dimer (p = 0.04), urinary 11-dehydro thromboxane B2 (p = 0.01) and urinary liver-type fatty acid binding protein (p = 0.03) levels and had lower sequential organ failure assessment score (p = 0.002), and intubation rate (p = 0.03), fewer hospitalized days (p = 0.13), lower in-hospital mortality (p = 0.12) and lower mortality plus nonfatal thrombotic event occurrences (p = 0.10). Patients on metformin had similar clinical outcomes compared to patients without DM. In a multiple regression analysis, metformin use was associated with less days in hospital and lower intubation rate. In conclusion, metformin treatment in COVID-19 patients with DM was associated with lower markers of inflammation, renal ischemia, and thrombosis, and fewer hospitalized days and intubation requirement. Further focused studies are required to support these findings.

Collagen Remodeling and Fatty Acid Regulation Biomarkers in Understanding the Molecular Pathogenesis of Atrial Fibrillation.

Atrial Fibrillation (AF) is the most common cardiac arrythmia in the world. Structural remodeling and fatty acid metabolism dysregulation are believed to play a role in the development of AF. This study explored different biomarkers in the blood of AF patients and a control population to determine if there was a significant difference between the two groups. Plasma samples were collected from 73 patients with confirmed diagnosis of AF from Loyola University Clinic. Control group represented commercially available plasma (n = 50). Sandwich ELISA kits were used to quantify the collagen remodeling proteins and liver type fatty acid binding protein (L-FABP) in the AF population and the control population. Non-esterified fatty acids (NEFAs) were measured using an enzymatic colorimetric kit from Wako Diagnostics. Statistical analyses were performed using GraphPad Prism. All the collagen remodeling biomarkers were significantly higher in AF patients compared to the control group. The fatty acid dysregulation biomarkers were elevated in the AF patients. Spearman correlation analyses yielded significant correlations between L-FABP and TIMP-1 (r = 0.47, P < 0.001), NEFA and TIMP-2 (r = 0.41, P = 0.002), NEFA and ICTP (r = 0.41, P =0 .002), and NEFA and PIIINP (r = 0.61, P < 0.0001). The elevation of collagen remodeling biomarkers suggests an upregulation of these biomarkers and their potential role in AF, which may contribute to atrial fibrosis. L-FABP and NEFAs were elevated in AF patients. The correlations between the collagen remodeling and fatty acid dysregulation biomarkers may be due to their involvement in structural remodeling of the atria.

Clinical Utility of a Biomarker to Detect Contrast-Induced Acute Kidney Injury during Percutaneous Cardiovascular Procedures

Introduction: Contrast-induced acute kidney injury (CI-AKI) is a major clinical complication of percutaneous cardiovascular procedures requiring iodinated contrast. Despite its relative frequency, practicing physicians are unlikely to identify or treat this condition. Methods: In a 2-round clinical trial of simulated patients, we examined the clinical utility of a urine-based assay that measures liver-type fatty acid-binding protein (L-FABP), a novel marker of CI-AKI. We sought to determine if interventional cardiologists’ ability to diagnose and treat potential CI-AKI improved using the biomarker assay for 3 different patient types: pre-procedure, peri-procedure, and post-procedure patients. Results: 154 participating cardiologists were randomly divided into either control or intervention. At baseline, we found no difference in the demographics or how they identified and treated potential complications of AKI, with both groups providing less than half the necessary care to their patients (46.4% for control vs. 47.6% for intervention, p = 0.250). The introduction of L-FABP into patient care resulted in a statistically significant improvement of 4.6% (p = 0.001). Compared to controls, physicians receiving L-FABP results were 2.9 times more likely to correctly identify their patients’ risk for AKI (95% CI 2.1–4.0) and were more than twice as likely to treat for AKI by providing volume expansion and withholding nephrotoxic medications. We found the greatest clinical utility in the pre-procedure and peri-procedure settings but limited value in the post-procedure setting. Conclusion: This study suggests L-FABP as a clinical marker for assessing the risk of potential CI-AKI, has clinical utility, and can lead to more accurate diagnosis and treatment.

Urinary liver-type fatty acid-binding protein as a prognostic marker in patients with acute heart failure.

AimsUrinary liver‐type fatty acid‐binding protein (L‐FABP) is expressed in proximal tubular epithelial cells and excreted into the urine during tubular injury. We hypothesized that high urinary L‐FABP is associated with poor prognosis in patients with acute heart failure (AHF).Methods and resultsWe analysed 623 patients (74 ± 13 years old; 60.0% male patients) with AHF. Urinary L‐FABP levels were measured at the time of admission and adjusted for the urinary creatinine concentration. The primary endpoint was all‐cause mortality. The median value and interquartile range of urinary L‐FABP levels were 6.66 and 3.37–21.1 μg/gCr, respectively. Urinary L‐FABP levels were significantly correlated with both beta‐2 microglobulin and cystatin C levels; the correlation with the former was higher than that with the latter. During the follow‐up of 631 (interquartile range: 387–875) days, 142 deaths occurred. A high tertile of urinary L‐FABP level was associated with high mortality; this association was retained after adjusting for other covariates (second tertile hazard ratio 1.40, P = 0.152 vs. first tertile; third tertile hazard ratio 1.94, P = 0.005 vs. first tertile).ConclusionsUrinary L‐FABP is more closely associated with tubular dysfunction than with glomerular dysfunction. Tubular dysfunction, which was evaluated based on urinary L‐FABP levels, in patients with AHF is associated with all‐cause mortality and is independent of pre‐existing risk factors. L‐FABP should be considered for use in the prognosis of AHF.

Role of Novel Kidney Biomarkers in Patients With Cirrhosis and After Liver Transplantation.

Acute kidney injury (AKI) and chronic kidney disease (CKD) are important drivers of morbidity and mortality in patients with cirrhosis before and after liver transplantation (LT). In this review, we examine the role of novel kidney biomarkers for early recognition of kidney injury. Studies are limited by lack of reference standards, heterogeneous definitions of outcomes and biomarker cutoffs, and inconsistent diagnostic performance. Overall, a change in biomarker is more relevant than an absolute cutoff. Cystatin C and urinary neutrophil gelatinase-associated lipocalin (uNGAL) are the most studied candidate biomarkers and identify AKI or progression of AKI earlier than serum creatinine (sCr). Kidney injury molecule 1 and liver-type fatty acid-binding protein (L-FABP) also show potential. NGAL and interleukin 18 may play a role in differentiating acute tubular necrosis from other forms of AKI. Combining novel biomarkers with the Model for End-Stage Liver Disease score may assist prognosis. Persistent elevations in select markers (eg, NGAL) can portend irreversible injury. Several pretransplantation markers (including sCr) predict posttransplantation kidney dysfunction. Pretransplantation assessment of clinical factors (eg, age, diabetes) and novel markers (osteopontin and tissue inhibitor of metalloproteinases 1 [TIMP-1]) may predict renal kidney recovery after LT. Intraoperative changes in biomarkers predict early post-LT AKI. Prediction of CKD remains difficult, although a combination of biomarkers (eg, beta-2 microglobulin, CD40) is promising. Novel biomarkers have yet to replace sCr in guideline-based evaluation and management of kidney dysfunction in patients with cirrhosis. We propose a theoretical framework for practical incorporation of these biomarkers that considers patient characteristics (risk for irreversible injury), markers of functional and structural change, and assessment of the AKI-CKD continuum to identify patients at the highest risk for progressive kidney disease before and after LT.

Neutrophil gelatinase-associated lipocalin does not originate from the kidney during reperfusion in clinical renal transplantation

BackgroundAcute Kidney Injury (AKI) is a common clinical complication. Plasma/serum neutrophil gelatinase-associated lipocalin (NGAL) has been proposed as a rapid marker of AKI. However, NGAL is not kidney-specific. It exists in three isoforms (monomeric, homo-dimeric and hetero-dimeric). Only the monomeric isoform is produced by renal tubular cells and plasma NGAL levels are confounded by the release of all NGAL isoforms from neutrophils. Our aim was to investigate whether NGAL is released into blood from injured renal tubules.MethodsKidney transplantation (n = 28) served as a clinical model of renal ischaemic injury. We used ELISA to measure NGAL concentrations at 2 minutes after kidney graft reperfusion in simultaneously taken samples of renal arterial and renal venous blood. Trans-renal gradients (venous–arterial) of NGAL were calculated. We performed Western blotting to distinguish between renal and non-renal NGAL isoforms. Liver-type fatty acid binding protein (LFABP) and heart-type fatty acid binding protein (HFABP) served as positive controls of proximal and distal tubular damage.ResultsSignificant renal release of LFABP [trans-renal gradient 8.4 (1.7–30.0) ng/ml, p = 0.005] and HFABP [trans-renal gradient 3.7 (1.1–5.0) ng/ml, p = 0.003] at 2 minutes after renal graft reperfusion indicated proximal and distal tubular damage. NGAL concentrations were comparable in renal venous and renal arterial blood. Thus, there was no trans-renal gradient of NGAL. Western blotting revealed that the renal NGAL isoform represented only 6% of the total NGAL in renal venous blood.ConclusionsIschaemic proximal and distal tubular damage occurs in kidney transplantation without concomitant NGAL washout from the kidney graft into blood. Plasma/serum NGAL levels are confounded by the release of NGAL from neutrophils. Present results do not support the interpretation that increase in plasma NGAL is caused by release from the renal tubules.

Abstract 12228: Metformin Use in Patients Hospitalized With COVID-19: Lower Inflammation, Oxidative Stress, and Thrombotic Risk Markers and Better Clinical Outcomes

Introduction: Diabetes mellitus (DM) is associated with a greater risk of COVID-19 and an increased mortality when the disease is contracted. Metformin use in patients with DM is associated with less COVID-19-related mortality, but the underlying mechanism behind this association remains unclear. Hypothesis: We hypothesize that inhibitory effect of metformin on markers of inflammation, oxidative stress, and hypercoagulability is associate with better clinical outcomes. Methods: Patients with DM on metformin (n=34) and metformin naïve (n=41), and patients without DM (n=73) were enrolled within 48 hours of hospital admission and were diagnosed with COVID-19 by reverse transcription-polymerase chain reaction assay. Laboratory assessments were conducted within 48 hours of hospital admission. The chi-squared test was used to determine whether there was a significant difference in frequencies between disease groups; p&lt; 0.05 was considered a significant difference between groups. Results: DM patients on metformin compared to naïve patients had a lower white blood cell count (p=0.02), d-dimer (p=0.04), urinary 11-dehydro thromboxane B 2 (p=0.01) and urinary liver-type fatty acid binding protein (p=0.03) levels and had lower sequential organ failure assessment score (p=0.0002), intubation rate (p=0.03), and a trend for fewer hospitalized days (p=0.13), lower in-hospital mortality (p= 0.12) and lower mortality plus nonfatal thrombotic event occurrences (p=0.10). Patients on metformin had similar clinical outcomes compared to patients without DM. Conclusion: In conclusion, metformin treatment in COVID-19 patients with DM was associated with lower markers of inflammation, renal ischemia, and thrombosis; and fewer hospitalized days and intubation requirement. Further focused studies are required to support these findings.