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Although hyperglycemia and hypertension are well-known risk factors for glomerular injury in individuals with type 2 diabetes (T2D), specific risk factors for tubular injury remain unclear. We aimed to clarify the differences between risk factors for glomerular injury and risk factors for tubular injury in individuals with T2D. We categorized 1243 subjects into four groups based on urinary biomarkers, including the albumin-to-creatinine ratio (uACR) and L-type fatty acid-binding protein-to-creatinine ratio (uL-ABPCR) as a normal (N) group (uACR < 30 mg/gCr and uL-FABPCR < 5 μg/gCr; n = 637), a glomerular specific injury (G) group (uACR ≥ 30 mg/gCr and uL-FABPCR < 5 μg/gCr; n = 248), a tubular specific injury (T) group (uACR < 30 mg/gCr and uL-FABPCR ≥ 5 μg/gCr; n = 90), and a dual injury (D) group (uACR ≥ 30 mg/gCr and uL-FABPCR ≥ 5 μg/gCr; n = 268). Logistic regression analysis referencing the N group revealed that BMI, current smoking, and hypertension were risk factors for the G group, creatinine (Cr) and Fibrosis-4 (FIB-4) index were risk factors for the T group, and BMI, hypertension, HbA1c, Cr, and duration of diabetes were risk factors for the D group. While hypertension was a distinct specific risk factor for glomerular injury, the FIB-4 index was a specific contributor to the prevalence of tubular injury. On the other hand, the logistic regression analysis revealed that the hepatic steatosis index (HSI) did not show any significant association with the G group, T group, or D group. Taken together, the development of liver fibrosis rather than liver steatosis is an inherent threat relating to tubular injury in individuals with T2D. [ABSTRACT FROM AUTHOR]

The article aims to find potential biomarker for the detection of tubular damage in pediatric neurogenic bladder (NB) by investigating urinary levels of liver-type fatty acid-binding protein (uL-FABP). This prospective analysis was conducted on two groups: 42 children with NB and 18 healthy children. The uL-FABP concentrations were measured using ELISA methods. The medical charts of the children were examined to determine age, sex, anthropometric measurements, activity assessment using Hoffer's scale, and renal function parameters. The results revealed that the uL-FABP/creatinine ratio was higher in the study group compared with the reference group, but the difference was not statistically significant (p = 0.52, p > 0.05). However, the uL-FABP/creatinine ratio exhibited a wider range in NB patients compared to the reference group. NB children with proteinuria and the history of high-grade vesicoureteral reflux (VUR) tended to have the highest uL-FABP concentrations. In conclusion, uL-FABP may be considered a potential tubular damage biomarker in children with NB. Proteinuria and the history of VUR may be the factors influencing the uL-FABP. [ABSTRACT FROM AUTHOR]

Although hyperglycemia and hypertension are well-known risk factors for glomerular injury in individuals with type 2 diabetes (T2D), specific risk factors for tubular injury remain unclear. We aimed to clarify the differences between risk factors for glomerular injury and risk factors for tubular injury in individuals with T2D. We categorized 1243 subjects into four groups based on urinary biomarkers, including the albumin-to-creatinine ratio (uACR) and L-type fatty acid-binding protein-to-creatinine ratio (uL-ABPCR) as a normal (N) group (uACR < 30 mg/gCr and uL-FABPCR < 5 μg/gCr; n = 637), a glomerular specific injury (G) group (uACR ≥ 30 mg/gCr and uL-FABPCR < 5 μg/gCr; n = 248), a tubular specific injury (T) group (uACR < 30 mg/gCr and uL-FABPCR ≥ 5 μg/gCr; n = 90), and a dual injury (D) group (uACR ≥ 30 mg/gCr and uL-FABPCR ≥ 5 μg/gCr; n = 268). Logistic regression analysis referencing the N group revealed that BMI, current smoking, and hypertension were risk factors for the G group, creatinine (Cr) and Fibrosis-4 (FIB-4) index were risk factors for the T group, and BMI, hypertension, HbA1c, Cr, and duration of diabetes were risk factors for the D group. While hypertension was a distinct specific risk factor for glomerular injury, the FIB-4 index was a specific contributor to the prevalence of tubular injury. On the other hand, the logistic regression analysis revealed that the hepatic steatosis index (HSI) did not show any significant association with the G group, T group, or D group. Taken together, the development of liver fibrosis rather than liver steatosis is an inherent threat relating to tubular injury in individuals with T2D.

It has previously been unclear whether the accumulation of advanced glycation end products, which can be measured using skin autofluorescence (SAF), has a significant role in diabetic kidney disease (DKD), including glomerular injury and tubular injury. This study was therefore carried out to determine whether SAF correlates with the progression of DKD in people with type 2 diabetes (T2D). In 350 Japanese people with T2D, SAF values were measured using an AGE Reader®, and both urine albumin-to-creatinine ratio (uACR), as a biomarker of glomerular injury, and urine liver-type fatty acid-binding protein (uLFABP)-to-creatinine ratio (uL-FABPCR), as a biomarker of tubular injury, were estimated as indices of the severity of DKD. Significant associations of SAF with uACR (p < 0.01), log-transformed uACR (p < 0.001), uL-FABPCR (p < 0.001), and log-transformed uL-FABPCR (p < 0.001) were found through a simple linear regression analysis. Although SAF was positively associated with increasing uL-FABPCR (p < 0.05) and increasing log-transformed uL-FABPCR (p < 0.05), SAF had no association with increasing uACR or log-transformed uACR after adjusting for clinical confounding factors. In addition, the annual change in SAF showed a significant positive correlation with annual change in uL-FABPCR regardless of confounding factors (p = 0.026). In conclusion, SAF is positively correlated with uL-FABP but not with uACR in people with T2D. Thus, there is a possibility that SAF can serve as a novel predictor for the development of diabetic tubular injury. [ABSTRACT FROM AUTHOR]

Per- and polyfluoroalkyl substances (PFASs) are persistent organic pollutants that have been detected in various environmental media and human serum, but their safety assessment remains challenging. PFASs may accumulate in liver tissues and cause hepatotoxicity by binding to liver fatty acid binding protein (L-FABP). Therefore, evaluating the binding affinity of PFASs to L-FABP is crucial in assessing the potential hepatotoxic effects. In this study, two binding sites of L-FABP were evaluated, results suggested that the outer site possessed high affinity to polyfluoroalkyl sulfates and the inner site preferred perfluoroalkyl sulfonamides, overall, the inner site of L-FABP was more sensitive to PFASs. The binding affinity data of PFASs to L-FABP were used as training set to develop a machine learning model-based quantitative structure-activity relationship (QSAR) for efficient prediction of potentially hazardous PFASs. Further Bayesian Kernel Machine Regression (BKMR) model disclosed flexibility as the determinant molecular property on PFASs-induced hepatotoxicity. It can influence affinity of PFASs to target protein through affecting binding conformations directly (individual effect) as well as integrating with other molecular properties (joint effect). Our present work provided more understanding on hepatotoxicity of PFASs, which could be significative in hepatotoxicity gradation, administration guidance, and safer alternatives development of PFASs.

Abstract Background Urinary liver‐type fatty acid‐binding protein (uL‐FABP) is a promising biomarker to detect early chronic kidney disease (CKD) in cats. Few healthy cats show increased uL‐FABP for unknown reasons. Objectives The objective of this study was to evaluate uL‐FABP in a large healthy elderly cat population comparing cats with and without International Renal Interest Society (IRIS) stage 1 CKD and with and without borderline proteinuria. Methods This was a cross‐sectional study. One hundred ninety‐six clinically healthy client‐owned cats of ≥7 years old were subdivided based on two criteria: (1) having either IRIS stage 1 CKD or no evidence of CKD and (2) having borderline proteinuria or no proteinuria. Urinary L‐FABP was measured using a validated commercially available feline L‐FABP ELISA. Results Overall, uL‐FABP was detectable in 6/196 (3%) healthy elderly cats. For the first subdivision, nine (5%) cats had IRIS stage 1 CKD, 184 cats had no evidence CKD and three cats were excluded. All cats with IRIS stage 1 CKD had uL‐FABP concentrations below the detection limit, whereas 6/184 (3%) cats without IRIS stage 1 CKD had detectable uL‐FABP concentrations (median 1.79 ng/ml, range 0.79–3.66 ng/ml). For the second subdivision, 47 (24%) cats had borderline proteinuria, 147 cats had no proteinuria and two cats were excluded. One of the borderline proteinuric cats had a detectable uL‐FABP concentration, whereas the other five cats with detectable uL‐FABP concentrations were non‐proteinuric. Conclusion With the current assay, the screening potential of uL‐FABP as an early biomarker for feline CKD is limited as uL‐FABP was rarely detected in clinically healthy elderly cats independently of the presence of either IRIS stage 1 CKD or borderline proteinuria.

Patients undergoing cardiac catheterization are at high risk of post-procedure acute kidney injury (AKI) and may experience persistent renal damage after an initial insult, a state known as acute kidney disease (AKD). However, the association between AKD and urinary renal biomarkers has not yet been evaluated in this population. We enrolled 94 patients who underwent elective cardiac catheterization to investigate patterns of urinary renal biomarkers and their associations with post-procedure AKD. Serial urinary renal biomarker levels were measured during pre-procedure, early post-procedure (12–24 h), and late post-procedure (7–10 days) periods. In our investigation, 42.55% of the enrolled patients developed AKD during the late post-procedure period. While the liver-type free-fatty-acid-binding protein level increased sharply during the early post-procedure period, it returned to baseline during the late post-procedure period. In contrast, interleukin-18 (IL-18) levels increased steadily during the post-procedure period. Early post-procedure ratios of IL-18 and gelsolin (GSN) were independently associated with subsequent AKD (odds ratio (95% confidence interval), 4.742 (1.523–14.759) for IL-18 ratio, p = 0.007; 1.812 (1.027–3.198) for GSN ratio, p = 0.040). In conclusion, post-procedure AKD is common and associated with early changes in urinary IL-18 and GSN in patients undergoing cardiac catheterization. [ABSTRACT FROM AUTHOR]

Background Since heatstroke-induced acute kidney injury (AKI) can progress to chronic kidney disease, it would be useful to detect heatstroke-induced AKI and severe heat-related illness in the early phase. We studied the epidemiology of heat-related illness among patients in the Japanese Ground Self-Defense Force and evaluated the relationship between heat-related illness severity and early urinary biomarkers for AKI. Methods We enrolled patients who were diagnosed with heat-related illness at the Self-Defense Force Fuji Hospital from 1 May to 30 September 2020. We compared the urinary kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), liver fatty acid–binding protein (L-FABP), N-acetyl-β-D-glucosaminidase (NAG) and β2-microglobulin levels according to the severity of heat-related illness as defined by positive scores for the Japanese Association of Acute Medicine Heatstroke Working Group (JAAM-HS-WG) criteria (0, mild; 1, moderate; ≥2, severe). Results Of the 44 patients, kidney injury, defined as serum creatinine (sCr) ≥1.2 mg/dL, was seen in 9 (20.5%) patients. Urinary NAG, NGAL and L-FABP levels were significantly higher in the ≥2 JAAM-HS-WG criteria group than in the 0 group. Furthermore, urinary L-FABP levels were positively correlated with sCr levels. In contrast, the urinary KIM-1 levels showed the best correlation with serum cystatin C (sCysC) among these biomarkers. Conclusions We conclude even mild to moderate heatstroke could lead to AKI. Urinary L-FABP is useful for detecting heatstroke-induced AKI and patients with severe heat-related illness requiring immediate treatment. Urinary KIM-1 may detect heatstroke-induced AKI in terms of sCysC, although it was not related to the severity of heat-related illness. [ABSTRACT FROM AUTHOR]

It has previously been unclear whether the accumulation of advanced glycation end products, which can be measured using skin autofluorescence (SAF), has a significant role in diabetic kidney disease (DKD), including glomerular injury and tubular injury. This study was therefore carried out to determine whether SAF correlates with the progression of DKD in people with type 2 diabetes (T2D). In 350 Japanese people with T2D, SAF values were measured using an AGE Reader®, and both urine albumin-to-creatinine ratio (uACR), as a biomarker of glomerular injury, and urine liver-type fatty acid-binding protein (uLFABP)-to-creatinine ratio (uL-FABPCR), as a biomarker of tubular injury, were estimated as indices of the severity of DKD. Significant associations of SAF with uACR (p < 0.01), log-transformed uACR (p < 0.001), uL-FABPCR (p < 0.001), and log-transformed uL-FABPCR (p < 0.001) were found through a simple linear regression analysis. Although SAF was positively associated with increasing uL-FABPCR (p < 0.05) and increasing log-transformed uL-FABPCR (p < 0.05), SAF had no association with increasing uACR or log-transformed uACR after adjusting for clinical confounding factors. In addition, the annual change in SAF showed a significant positive correlation with annual change in uL-FABPCR regardless of confounding factors (p = 0.026). In conclusion, SAF is positively correlated with uL-FABP but not with uACR in people with T2D. Thus, there is a possibility that SAF can serve as a novel predictor for the development of diabetic tubular injury.

The results of published studies of modern biomarkers used in the diagnosis of acute kidney injury (AKI) were summarized. The search was carried out in the PubMed/MEDLINE, Scopus, eLibrary databases. AKI occurs in 10–15% of all inpatients and 50% of intensive care patients, and affects economic aspects of treatment and rehabilitation. The literature review allowed to draw conclusions about the significant advantage of new AKI biomarkers (cystatin C, neutrophil gelatinase-associated lipocalin, β2-microglobulin, kidney injury molecule-1, fatty acid binding protein) over the conventional glomerular filtration rate, serum creatinine and urinary volume. Serum creatinine increases only in cases when 50–60% of nephrons are damaged, urinary volume has limitations such as the overdiagnosis of AKI in dehydrated patients, the inability to assess based on a single measurement, and the need for regular and frequent follow-up. Modern biomarkers make it possible to verify renal dysfunction in advance, at the subclinical level. This allows to make a correction in the therapy of the underlying disease and initiate nephroprotection to prevent the development of AKI and the further development of multiple organ failure, which may be more effective than the treatment of already developed AKI.

Background Targeted treatment with mineralocorticoid receptor antagonists (MRAs) or adrenalectomy in patients with primary aldosteronism (PA) causes a decline in estimated glomerular filtration rate; however, the associated simultaneous changes in biomarkers of kidney tubule health still remain unclear. Methods and Results We matched 104 patients with newly diagnosed unilateral PA who underwent adrenalectomy with 104 patients with unilateral PA who were treated with MRAs, 104 patients with bilateral PA treated with MRAs, and 104 patients with essential hypertension who served as controls. Functional biomarkers were measured before the targeted treatment and 1 year after treatment, including serum markers of kidney function (cystatin C, creatinine), urinary markers of proximal renal tubular damage (L‐FABP [liver‐type fatty‐acid binding protein], KIM‐1 [kidney injury molecule‐1]), serum markers of kidney tubular reserve and mineral metabolism (intact parathyroid hormone), and proteinuria. Compared with the patients with essential hypertension, the patients with PA had higher pretreatment serum intact parathyroid hormone and urinary creatinine‐corrected parameters, including L‐FABP, KIM‐1, and albumin. The patients with essential hypertension and with PA had similar cystatin C levels. After treatment with MRAs or adrenalectomy of unilateral PA and MRAs of bilateral PA, the patients with PA had increased serum cystatin C and decreased urinary L‐FABP/creatinine, KIM‐1/creatinine, creatinine‐based estimated glomerular filtration rate, intact parathyroid hormone, and proteinuria (all P

Background: Urinary liver‐type fatty acid‐binding protein (uL‐FABP) is a promising biomarker to detect early chronic kidney disease (CKD) in cats. Few healthy cats show increased uL‐FABP for unknown reasons. Objectives: The objective of this study was to evaluate uL‐FABP in a large healthy elderly cat population comparing cats with and without International Renal Interest Society (IRIS) stage 1 CKD and with and without borderline proteinuria. Methods: This was a cross‐sectional study. One hundred ninety‐six clinically healthy client‐owned cats of ≥7 years old were subdivided based on two criteria: (1) having either IRIS stage 1 CKD or no evidence of CKD and (2) having borderline proteinuria or no proteinuria. Urinary L‐FABP was measured using a validated commercially available feline L‐FABP ELISA. Results: Overall, uL‐FABP was detectable in 6/196 (3%) healthy elderly cats. For the first subdivision, nine (5%) cats had IRIS stage 1 CKD, 184 cats had no evidence CKD and three cats were excluded. All cats with IRIS stage 1 CKD had uL‐FABP concentrations below the detection limit, whereas 6/184 (3%) cats without IRIS stage 1 CKD had detectable uL‐FABP concentrations (median 1.79 ng/ml, range 0.79–3.66 ng/ml). For the second subdivision, 47 (24%) cats had borderline proteinuria, 147 cats had no proteinuria and two cats were excluded. One of the borderline proteinuric cats had a detectable uL‐FABP concentration, whereas the other five cats with detectable uL‐FABP concentrations were non‐proteinuric. Conclusion: With the current assay, the screening potential of uL‐FABP as an early biomarker for feline CKD is limited as uL‐FABP was rarely detected in clinically healthy elderly cats independently of the presence of either IRIS stage 1 CKD or borderline proteinuria. [ABSTRACT FROM AUTHOR]

Purpose of the study. The purpose of the study was to analyze parameters of molecular markers of structural and cellular renal damage in localized renal cell carcinoma (RCC) with determining the nature of the initial abnormalities in the kidney functional state before the treatment.Patients and methods. The study included 46 patients receiving elective surgical treatment for localized renal cancer in the Department of Oncourology, National Medical Research Centre for Oncology. The comparison group included the clinical and laboratory data of 13 healthy people comparable with the RCC patients in terms of age and gender. Cystatin C, IL‑18, KIM‑1, L-FABP, NGAL were determined in blood and urine in all patients.Results. Evaluation of the kidney functional state of RCC patients showed that the initial values of serum creatinine and the glomerular filtration rate were similar to the reference levels in healthy people, but statistically significant differences were found in the ratios of cystatin C concentrations in the blood and urine in all patients, compared with normal values. Determination of L-FABP indices in RCC patients showed that their levels were 2.5 times higher than normal values, and the urine concentration of IL‑18 was 1.7 times higher than normal values (p < 0.05). Blood and urine levels of NGAL and KIM‑1 did not differ significantly from the comparison group.Conclusions. The development of localized RCC is accompanied by the formation of tubulointerstitial dysfunction with impaired renal filtration capacity. All RCC patients showed elevated endogenous markers of structural and cellular renal damage – cystatin C, L-FABP, and IL‑18.

Drug-induced kidney injury (DIKI) accounts for 8 to 60% of episodes of acute kidney injury (AKI) among hospital patients. Early DIKI detection and timely adjustment of therapy will help reduce the kidney injury incidence and mortality. The aim of the study was to analyse scientific literature on the biomarkers used in DIKI diagnosis. The study revealed that the use of such kidney damage markers as serum creatinine, urinary output, urea nitrogen, sodium excretion, urinary sediment microscopy is limited because they do not give a full picture of the kidney injury degree and progression and do not allow for early AKI diagnosis. It was demonstrated that some of the most promising biomarkers are KIM-1, L-FABP, NAG, NGAL, cystatin C, clusterin, β2-microglobulin, МСР-1, IGFBP7, and TIMP-2. However, recommendations for determination of these biomarkers’ urine or blood concentrations for AKI diagnosis are somewhat preliminary, because there have been insufficient clinical and preclinical studies to establish validity of such tests. No precise algorithms based on determination of the biomarkers levels in urea and/or blood serum have been developed for AKI risk assessment, diagnosis, monitoring, and treatment. Thus, further research is necessary to investigate different AKI biomarkers and improve experimental models (both in vivo and in vitro), which will support assessment of potential nephrotoxic properties of existing and new medicinal products.

Introduction: Currently there are no biomarkers that are predictive of when patients with type-2 diabetes (T2D) will progress to more serious kidney disease i.e., diabetic nephropathy (DN). Biomarkers that could identify patients at risk of progression would allow earlier, more aggressive treatment intervention and management, reducing patient morbidity and mortality. Materials and Methods: Study participants (N=88; control n=26; T2D n=32; DN n=30) were recruited from the renal unit at Antrim Area Hospital, Antrim, UK; Whiteabbey Hospital Diabetic Clinic, Newtownabbey, UK; Ulster University (UU), Belfast, UK; and the University of the Third Age (U3A), Belfast, UK; between 2019 and 2020. Venous blood and urine were collected with a detailed clinical history for each study participant. Results: In total, 13/25 (52.0%) biomarkers measured in urine and 25/34 (73.5%) biomarkers measured in serum were identified as significantly different between control, T2D and DN participants. DN patients, were older, smoked more, had higher systolic blood pressure and higher serum creatinine levels and lower eGFR function. Serum biomarkers significantly inversely correlated with eGFR. Conclusion: This pilot-study identified several serum biomarkers that could be used to predict progression of T2D to more serious kidney disease: namely, midkine, sTNFR1 and 2, H-FABP and Cystatin C. Our results warrant confirmation in a longitudinal study using a larger patient cohort. [ABSTRACT FROM AUTHOR]

Abstract Background Liver‐type fatty acid‐binding protein (L‐FABP) and neutrophil gelatinase‐associated lipocalin (NGAL) are candidate biomarkers for the detection of early chronic kidney disease (CKD) in cats. Objective To evaluate urinary and serum L‐FABP and NGAL concentrations in CKD cats and in hyperthyroid cats before and after radioiodine (131I) treatment. Animals Nine CKD cats, 45 healthy cats and hyperthyroid cats at 3 time points including before (T0, n = 49), 1 month (T1, n = 49), and 11 to 29 months after (T2, n = 26) 131I treatment. Methods Cross‐sectional and longitudinal study. Serum L‐FABP (sL‐FABP), serum NGAL (sNGAL), urinary L‐FABP (uL‐FABP), and urinary NGAL (uNGAL) were compared between the 3 groups and between hyperthyroid cats before and after treatment. Data are reported as median (min‐max). Results CKD cats had significantly higher sL‐FABP (13.50 [3.40‐75.60] ng/ml) and uL‐FABP/Cr (4.90 [0.97‐2139.44] µg/g) than healthy cats (4.25 [1.34‐23.25] ng/ml; P = .01 and 0.46 [0.18‐9.13] µg/g; P < .001, respectively). Hyperthyroid cats at T0 had significantly higher uL‐FABP/Cr (0.94 [0.15‐896.00] µg/g) than healthy cats (P < .001), thereafter uL‐FABP/Cr significantly decreased at T2 (0.54 [0.10‐76.41] µg/g, P = .002). For the detection of CKD, uL‐FABP/Cr had 100% (95% confidence interval [CI], 66.4‐100.0) sensitivity and 93.2% (95% CI, 81.3‐98.6) specificity. There were no significant differences in sNGAL and uNGAL/Cr between the 3 groups. Conclusions and Clinical Importance L‐FABP, but not NGAL, is a potential biomarker for the detection of early CKD in cats. Utility of uL‐FABP to predict azotemia after treatment in hyperthyroid cats remains unknown.

IntroductionCurrently there are no biomarkers that are predictive of when patients with type-2 diabetes (T2D) will progress to more serious kidney disease i.e., diabetic nephropathy (DN). Biomarkers that could identify patients at risk of progression would allow earlier, more aggressive treatment intervention and management, reducing patient morbidity and mortality.Materials and MethodsStudy participants (N=88; control n=26; T2D n=32; DN n=30) were recruited from the renal unit at Antrim Area Hospital, Antrim, UK; Whiteabbey Hospital Diabetic Clinic, Newtownabbey, UK; Ulster University (UU), Belfast, UK; and the University of the Third Age (U3A), Belfast, UK; between 2019 and 2020. Venous blood and urine were collected with a detailed clinical history for each study participant.ResultsIn total, 13/25 (52.0%) biomarkers measured in urine and 25/34 (73.5%) biomarkers measured in serum were identified as significantly different between control, T2D and DN participants. DN patients, were older, smoked more, had higher systolic blood pressure and higher serum creatinine levels and lower eGFR function. Serum biomarkers significantly inversely correlated with eGFR.ConclusionThis pilot-study identified several serum biomarkers that could be used to predict progression of T2D to more serious kidney disease: namely, midkine, sTNFR1 and 2, H-FABP and Cystatin C. Our results warrant confirmation in a longitudinal study using a larger patient cohort.

Patients undergoing cardiac catheterization are at high risk of post-procedure acute kidney injury (AKI) and may experience persistent renal damage after an initial insult, a state known as acute kidney disease (AKD). However, the association between AKD and urinary renal biomarkers has not yet been evaluated in this population. We enrolled 94 patients who underwent elective cardiac catheterization to investigate patterns of urinary renal biomarkers and their associations with post-procedure AKD. Serial urinary renal biomarker levels were measured during pre-procedure, early post-procedure (12–24 h), and late post-procedure (7–10 days) periods. In our investigation, 42.55% of the enrolled patients developed AKD during the late post-procedure period. While the liver-type free-fatty-acid-binding protein level increased sharply during the early post-procedure period, it returned to baseline during the late post-procedure period. In contrast, interleukin-18 (IL-18) levels increased steadily during the post-procedure period. Early post-procedure ratios of IL-18 and gelsolin (GSN) were independently associated with subsequent AKD (odds ratio (95% confidence interval), 4.742 (1.523–14.759) for IL-18 ratio, p = 0.007; 1.812 (1.027–3.198) for GSN ratio, p = 0.040). In conclusion, post-procedure AKD is common and associated with early changes in urinary IL-18 and GSN in patients undergoing cardiac catheterization.

Background Predicting the prognosis of intensive care unit (ICU) patients is crucial because it may lead to patient stratification that would in turn help in appropriately distributing limited medical resources. This study, therefore, aimed to investigate the use of the urinary liver-type fatty acid-binding protein (L-FABP) semi-quantitative kit in rapidly predicting the prognosis of patients admitted to the ICU. Methods We conducted a single-center, prospective, observational study wherein 100 consecutive patients admitted to the ICU with an indwelling bladder catheter were enrolled between April and October 2020. Urine specimens were collected at the time of admission (T1) and after 6 h (T2), and urinary L-FABP levels were semi-quantitatively measured. Based on the results, an L-FABP variation was defined as the change in L-FABP (negative, weakly positive, or strongly positive) from T1 to T2. Patients were divided into three groups (L-FABP decreased group, unchanged group, or increased group), following which we compared their 14-day mortality. Results Finally, a total of 79 patients were included in the analysis. In multivariate analysis, urinary L-FABP variation [Odds ratio (OR) = 14.327, 95% confidence interval (CI) = 1.819–112.868, p = 0.01] and lactate (OR = 1.234, 95%CI = 1.060–1.437, p = 0.01) were significantly associated with 14-day mortality. Conclusion Urinary L-FABP variation at 6 h after admission was significantly associated with 14-day mortality.

Predicting the prognosis of intensive care unit (ICU) patients is crucial because it may lead to patient stratification that would in turn help in appropriately distributing limited medical resources. This study, therefore, aimed to investigate the use of the urinary liver-type fatty acid-binding protein (L-FABP) semi-quantitative kit in rapidly predicting the prognosis of patients admitted to the ICU. We conducted a single-center, prospective, observational study wherein 100 consecutive patients admitted to the ICU with an indwelling bladder catheter were enrolled between April and October 2020. Urine specimens were collected at the time of admission (T1) and after 6 h (T2), and urinary L-FABP levels were semi-quantitatively measured. Based on the results, an L-FABP variation was defined as the change in L-FABP (negative, weakly positive, or strongly positive) from T1 to T2. Patients were divided into three groups (L-FABP decreased group, unchanged group, or increased group), following which we compared their 14-day mortality. Finally, a total of 79 patients were included in the analysis. In multivariate analysis, urinary L-FABP variation [Odds ratio (OR) = 14.327, 95% confidence interval (CI) = 1.819–112.868, p = 0.01] and lactate (OR = 1.234, 95%CI = 1.060–1.437, p = 0.01) were significantly associated with 14-day mortality. Urinary L-FABP variation at 6 h after admission was significantly associated with 14-day mortality. [ABSTRACT FROM AUTHOR]

Background: It is important to study cellular circulation of L-FABP-associated fatty acids (FA) and their oxidation through the classical pathway with activation of the PPARγ gene and under conditions of impaired lipid metabolism. Purpose: To investigate the pathogenetic mechanisms of diabetic retinopathy (DR) progression in type 2 diabetes mellitus (T2DM) patients differing in the PPARγ genotype. Material and Methods: This study involved 101 T2DM patients (101 eyes) with different stages of diabetic retinopathy (DR) as assessed by the ETDRS scale and 40 non-diabetics (controls) who were comparable in age, gender and body mass index. The polymorphism was detected by real-time PCR on a Real-Time Gene Amp® PCR System 7500 (Applied Biosystems). ELISA was used to determine serum L-FABP levels with Human L-FABP ELISA kit (Hycult Biotech). Results: Our findings allowed for developing a concept of differences in pathogenetic mechanisms of DR progression between patients differing in the PPARγ genotype. Among carriers of the wild-type PPARγ genotype, DR as a complication of diabetes develops as a result of chronic inflammation and through PPARγ-dependent gene transcription, expression of the enzymes that oxidize arachidonic acid, and synthesis of the metabolites affecting the endothelium, platelets, the blood clotting system, etc. In diabetic PPARγ polymorphism carriers, PPARγ-dependent gene transcription is inhibited, and fatty acids are utilized in the cell via other L-FABP mechanisms, which results in activation of direct peroxisomal oxidation and increased oxidative stress-induced inflammation. A new insight into differences in pathogenetic mechanisms of DR progression between T2DM patients differing in the PPARγ genotype provides the basis for subsequent clinical development of advanced, customized management schemes for patients with different DR stages to prevent further retinal damage.

Kidney involvement is one of the extraarticular manifestations of ankylosing spondylitis (AS). Due to a number of disadvantages of traditional parameters for evaluating renal function, an active search is underway for new markers.Objective: to evaluate urinary excretion of liver-type and heart-type fatty acid-binding proteins (L-FABP and H-FABP) in patients with AS.Subjects and methods. Urine samples were examined in 50 patients (37 men and 13 women) at least 18 years of age with a reliable diagnosis of AS without secondary nephropathy (with the exception of AS-associated changes). The median age of the patients was 39 [34; 56] years; the duration of AS was 10 [7; 18] years. L-FABP and H-FABP levels were measured by enzyme-linked immunosorbent assay. The values obtained were given for urinary creatinine excretion. The results were compared with those of the gender- and age-matched control group.Results and discussion. L-FABP excretion in patients with AS without chronic kidney disease (CKD) was significantly higher than that in the control group: 0.05 [0.01; 0.09] and 0.03 [0; 0.06] ng/mmol of creatinine, respectively (p=0.04). Only 6 patients were found to have H-FABP excretion and its level did not exceed 601.5 ng/mmol of creatinine. In healthy volunteers, the excretion of H-FABP was below the detection range. The level of FABPs did not depend on age, glomerular filtration rate (GFR), or disease activity. The level of H-FABP correlated with albuminuria (rs=0.49; p

Background: Because fatty acid binding proteins (FABPs) and peroxisome proliferator-activated receptor (PPAR) ? physically interact, the ability of FABPs to modulate lipid signaling could be exploited for developing medications, improving therapeutic or prophylactic measures for the control of metabolic disorders, and for controlling the activity of their therapeutic targets such as PPARs. Purpose: To examine PPAR?-mediated differences in energy substrate among type 2 diabetes mellitus (T2DM) patients differing in the stage of diabetic retinopathy. Material and Methods: This study involved 101 T2DM patients (101 eyes) with different stages of diabetic retinopathy (DR) and 40 non-diabetics (controls) who were comparable in age, gender and body mass index. DR was graded using the ETDRS scale. The polymorphism was detected by real-time PCR on a Real-Time Gene Amp® PCR System 7500 (Applied Biosystems). ELISA was used to determine serum L-FABP levels with Human L-FABP ELISA kit (Hycult Biotech). Conclusion: We found a significant variation in fatty acid (FA) concentrations in red blood cell membranes in T2DM patients differing in PPAR?-gene mediated phenotypes. Among wild-type carriers, arachidonic acid concentration increased 1.4-fold in those with the early stage of DR (р < 0.05) compared to controls and decreased 7.5-fold in those with DR progression (р < 0.05). Among carriers of the 12Ala allele, arachidonic acid concentration decreased twofold in those with the early stage of DR (р < 0.05) compared to controls, and further gradually decreased with DR progression. There was a gradual and not significant increase in L-FABP concentration with DR progression in T2DM patients carrying the wild genotype. Among carriers of the 12Ala allele, concentration of the chaperone increased fourfold in those with the early stage of DR compared to controls (р < 0.05), and gradually decreased with DR progression.

Purpose: We 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 Methods: Urine 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. Results: The 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. Conclusion: Urinary 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. [ABSTRACT FROM AUTHOR]

Background: Liver‐type fatty acid‐binding protein (L‐FABP) and neutrophil gelatinase‐associated lipocalin (NGAL) are candidate biomarkers for the detection of early chronic kidney disease (CKD) in cats. Objective: To evaluate urinary and serum L‐FABP and NGAL concentrations in CKD cats and in hyperthyroid cats before and after radioiodine (131I) treatment. Animals Nine CKD cats, 45 healthy cats and hyperthyroid cats at 3 time points including before (T0, n = 49), 1 month (T1, n = 49), and 11 to 29 months after (T2, n = 26) 131I treatment. Methods: Cross‐sectional and longitudinal study. Serum L‐FABP (sL‐FABP), serum NGAL (sNGAL), urinary L‐FABP (uL‐FABP), and urinary NGAL (uNGAL) were compared between the 3 groups and between hyperthyroid cats before and after treatment. Data are reported as median (min‐max). Results: CKD cats had significantly higher sL‐FABP (13.50 [3.40‐75.60] ng/ml) and uL‐FABP/Cr (4.90 [0.97‐2139.44] µg/g) than healthy cats (4.25 [1.34‐23.25] ng/ml; P =.01 and 0.46 [0.18‐9.13] µg/g; P <.001, respectively). Hyperthyroid cats at T0 had significantly higher uL‐FABP/Cr (0.94 [0.15‐896.00] µg/g) than healthy cats (P <.001), thereafter uL‐FABP/Cr significantly decreased at T2 (0.54 [0.10‐76.41] µg/g, P =.002). For the detection of CKD, uL‐FABP/Cr had 100% (95% confidence interval [CI], 66.4‐100.0) sensitivity and 93.2% (95% CI, 81.3‐98.6) specificity. There were no significant differences in sNGAL and uNGAL/Cr between the 3 groups. Conclusions and Clinical Importance: L‐FABP, but not NGAL, is a potential biomarker for the detection of early CKD in cats. Utility of uL‐FABP to predict azotemia after treatment in hyperthyroid cats remains unknown. [ABSTRACT FROM AUTHOR]

The value of neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (Kim-1), and liver-type fatty acid binding protein (L-FABP) was assessed in early diagnosis of gentamicin-induced acute kidney injury (AKI) in dogs.

Abstract Background This study’s aim is to measure liver-type fatty acid-binding protein (L-FABP) levels in urine using a rapid semiquantitative assay kit in the emergency department and to investigate whether the onset of acute kidney injury (AKI) after hospitalization can be predicted. Methods This was a prospective observation study. Patients transferred to the emergency and critical care center were divided into two groups: urinary L-FABP negative and positive groups. The status and severity of AKI were evaluated for the respective patients based on the Kidney Disease: Improving Global Outcome (KDIGO) classification. We compared the proportion of AKI patients in the two groups. Results In the urine L-FABP-positive group, many patients had a significant onset of AKI (p

Abstract Background Tenofovir disoproxil fumarate (TDF) is known to reduce estimated glomerular filtration rate (eGFR). It is clinically important to identify patients at high risk for renal dysfunction as early as possible. Among the tubular markers, urinary β2 microglobulin (Uβ2MG) is a well-known biomarker of TDF-related tubulopathy. However, renal dysfunction has often been occurred in patients receiving TDF with low Uβ2MG levels. Recently, urinary liver-type fatty acid–binding protein (UL-FABP) was suggested to be predictor of the progression of renal dysfunction. Thus, we focused on UL-FABP in patients receiving TDF with low Uβ2MG levels. Methods A retrospective, observational, single-center study, between January 2013 and December 2016, was conducted. Two renal end points (> 25% decrement in eGFR and > 20 mL/min/1.73 m2 decrement relative to the baseline) were assessed. To estimate the effect of UL-FABP on time to the first event, log-rank test was performed. Results A total of 24 Japanese outpatients with human immunodeficiency virus receiving TDF were enrolled. The outcome each occurred in two patients during the follow-up period. UL-FABP levels ≥4.0 μg/g creatinine was significantly associated with > 25% decrement and > 20 mL/min/1.73 m2 decrement (p = 0.006 and 0.001, respectively). Conclusion Based on our preliminary analysis, UL-FABP levels ≥4.0 μg/g creatinine predict renal dysfunction in patients receiving TDF with low Uβ2MG levels.

Purpose: Liver ischemia-reperfusion (I/R) injury is an inescapable problem. Diacerein, a chondro-protective drug, has antioxidant and anti-inflammatory effects. Its effect on liver I/R injury has not yet been fully clarified. Therefore, the current study aimed to detect its hepatic protective effect with the explanation of possible underlying mechanisms. Methods: Adult male albino rats were assigned to 4 groups: sham group, diacerein pretreated sham group, I/R non-treated group, and I/R diacerein pretreated group. Serum liver enzymes, hepatic tissue oxidative stress parameters, inflammatory biomarkers mainly Toll-like receptors-4 (TLR4), and liver fatty acid binding protein (L-FABP) levels were determined. Histopathological examination of liver tissues and immunohistochemical studies of heat shock protein 70, nuclear factor-kappa B, and Cluster of Differentiation 68 were also done. Results: Diacerein pretreatment has the ability to restore the hepatic I/R damaging effect, proved by the reduction of serum liver enzymes, the decrease of the oxidative stress and hepatic inflammation via down-regulation of TLR4/ NFκ-B signaling pathway together with the restoration of L-FABP level and improvement of the histopathological and immunohistochemical study findings in the hepatic tissue. Conclusion: These results suggested the hepatoprotective effect of diacerein relies on its antioxidant and anti-inflammatory effects reducing TLR4/ NFκ-B signaling pathway.

Introduction: We assessed the urinary level of L-FABP in patients with APN and compared between patients with scar versus normal kidneys.Methods: We enrolled children aged 2 months to 12 years old with APN. The urine concentration of L-FABP and L-FABP/Cr were measured. Patients divided into three groups; patients with scarring APN as group 1, patients with non-scarring APN as group 2, and controls.Results: 79 children (aged 57.4 ± 40.5 months, (87.5%) female) enrolled in the study. Group 1 was composed of 19 (16 female) cases, group two 35 (32 female) cases, and group three 26 (2 female) healthy controls. There was no significant difference in absolute urinary level of L-FABP between APN groups and controls. Group 1 patients had a significantly higher concentration than group 2 (P < .05). The UL-FABP /Cr was significantly higher in group 1, than groups 2 and 3 [(0.28 ± 0.39 pg/mg, 0.08 ± 0.08 pg/mg, and 0.10 ± 0.09 pg/mg; respectively), (P < .05, P < .05)]. The difference between group 2 and 3 was not significant (P > .05). The sensitivity and specificity of UL-FABP32 /Cr ratio in prediction of scar was 50% to 72% and 44% to 56%, respectively.Conclusion: The urinary ratio of L-FABP to creatinine is not a useful tool for diagnosis of APN or VUR but could be helpful in prediction of long-term potency to renal parenchymal scar formation. [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI) is a common complication in critically ill patients in the intensive settings with increased risks of short- and long-term complications and mortality. AKI is also associated with an increased length of stay in intensive care units (ICU) and worse kidney function recovery at hospital discharge. The management of AKI is one of the major challenges for nephrologists and intensivists overall for its early diagnosis. The current KDIGO criteria used to define AKI include the serum creatinine and urinary output that are neither sensitive nor specific markers of kidney function, since they can be altered only after hours from the kidney injury. In order to allow an early AKI detection, in the last years, several studies focused on the identification of new biomarkers. Among all these markers, urinary insulin-like growth factor-binding protein (IGFBP-7) and tissue inhibitor of metalloproteinase (TIMP-2) have been proven as the best-performing and have been proposed as a predictive tool for the AKI detection in the critical settings in order to perform an early diagnosis. Patients undergoing major surgery, cardiac surgery, those with hemodynamic instability or those with sepsis are believed to be the top priority patient populations for the biomarker test. In this view, the urinary [TIMP-2] x [IGFBP-7] becomes an important tool for the early detection of patients at high risk for AKI and its integration with the local ICU experience has to provide a multidisciplinary management of AKI with the institution of a rapid response team in order to assess patients and customize AKI management. [ABSTRACT FROM AUTHOR]

Abstract Sepsis due to microbial invasion often causes multiple organ failure (MOF), including acute kidney injury (AKI), with high mortality rates in serious cases. Hence, there is an urgent need for diagnostic biomarkers that can be used to rapidly, accurately, and easily detect sepsis to identify the condition early and guide the selection of appropriate treatment. Liver-type fatty acid-binding protein (L-FABP), which localizes in renal proximal tubules, is excreted into the urine in response to oxidative stress-induced tubular injury. Because of this mechanism, L-FABP has been reported to be a useful urinary biomarker not only for renal disease but also for the severity of sepsis. Based on this concept, we developed a new L-FABP point-of-care (POC) assay kit that can be used to rapidly measure human L-FABP in the urine to further improve the usefulness of this biomarker in clinical settings. In this review, we describe the molecular mechanisms of L-FABP, its clinical usefulness, and the performance of the POC assay kit.

The liver-type fatty acid binding proteins (L-FABP) gene in golden pompano Trachinotus ovatus larvae was cloned in the present study. The full length of L-FABP cDNA from golden pompano was 604 bp, including a 5'-untranslated region (UTR) of 154 bp, a 3'-UTR of 69 bp and an open reading frame (ORF) of 281 bp. L-FABP encoding a polypeptide of 126 amino acids with a predicted molecular weight of 14.06 kDa and a theoretical isoelectric point of 8.73. The results of qRT-PCR showed that the highest tissue expression of L-FABP gene was observed in fish liver on 18 DPH. Along with the ontogeny of fish larvae, the expression of L-FABP gene was low at hatching, and quickly increased with the increase of fish age from 0 DPH to 4 DPH, and reached the highest level on 12 DPH. The highest expression of L-FABP gene was observed in fish cultured at 29°C on both 12 DPH and 18 DPH (P< 0.05). Nutrition enhancement significantly affected the expression of L-FABP gene, the highest expression was observed in the Algamac 3080 treatment, and lowest expression was observed in the Nannochloropsis treatment. This study provides useful information on the functional mechanism of L-FABP gene in the ontogenetic development of golden pompano. [ABSTRACT FROM AUTHOR]

Per- and polyfluoroalkyl substances (PFASs) are persistent organic pollutants that have been detected in various environmental media and human serum, but their safety assessment remains challenging. PFASs may accumulate in liver tissues and cause hepatotoxicity by binding to liver fatty acid binding protein (L-FABP). Therefore, evaluating the binding affinity of PFASs to L-FABP is crucial in assessing the potential hepatotoxic effects. In this study, two binding sites of L-FABP were evaluated, results suggested that the outer site possessed high affinity to polyfluoroalkyl sulfates and the inner site preferred perfluoroalkyl sulfonamides, overall, the inner site of L-FABP was more sensitive to PFASs. The binding affinity data of PFASs to L-FABP were used as training set to develop a machine learning model-based quantitative structure-activity relationship (QSAR) for efficient prediction of potentially hazardous PFASs. Further Bayesian Kernel Machine Regression (BKMR) model disclosed flexibility as the determinant molecular property on PFASs-induced hepatotoxicity. It can influence affinity of PFASs to target protein through affecting binding conformations directly (individual effect) as well as integrating with other molecular properties (joint effect). Our present work provided more understanding on hepatotoxicity of PFASs, which could be significative in hepatotoxicity gradation, administration guidance, and safer alternatives development of PFASs. [Display omitted] • The inner site of L-FABP is the prioritized binding site of PFASs. • Molecular flexibility is the determinant of PFASs-induced hepatotoxicity. • A machine learning model for efficiently predicting the potential hepatotoxicity of PFASs is developed. [ABSTRACT FROM AUTHOR]

Background/Aims: Plasma neutrophil gelatinase-associated lipocalin (NGAL), urinary liver-type fatty acid-binding protein (L-FABP) and urinary kidney injury molecule-1 (KIM-1) have emerged as promising biomarkers for both acute and chronic kidney injury that also provide prognostic value for cardiovascular morbidity and mortality. Our aim was to evaluate their relationships with arterial stiffness and inflammation in coronary artery disease (CAD) patients and in clinically healthy controls. Methods: We studied 52 patients with CAD (age 63.2 ± 9.2 years) and 41 healthy controls (age 60.1 ± 7.2 years). Urinary L-FABP and KIM-1 as well as serum NGAL, adiponectin and resistin levels were measured using the enzyme-linked immunosorbent assay method. The technique of applanation tonometry was used for non-invasive pulse wave analysis and pulse wave velocity assessments. Results: Urinary L-FABP and KIM-1 were independent determinants of cf-PWV for the CAD patients (R2=0.584, Pr=0.31, P=0.028) only for the patients, while NGAL correlated with WBC count (rho=0.29, P=0.038; r=0.35, P=0.029) and resistin (rho=0.60, PConclusion: Our findings suggest that urinary L-FABP and KIM-1 may be independently associated with aortic stiffness in individuals with CAD.

OBJECTIVES: The objective of the present study was to evaluate the protective effect of pre-conditioning treatment with laser light on hepatic injury in rats submitted to partial ischemia using mitochondrial function and liver fatty acid binding protein as markers. METHODS: Rats were divided into four groups (n=5): 1) Control, 2) Control + Laser, 3) Partial Ischemia and 4) Partial Ischemia + Laser. Ischemia was induced by clamping the hepatic pedicle of the left and middle lobes of the liver for 60 minutes. Laser light at 660 nm was applied to the liver immediately prior to the induction of ischemia at 22.5 J/cm2, with 30 seconds of illumination at five individual points. The animals were sacrificed after 30 minutes of reperfusion. Blood and liver tissues were collected for analysis of mitochondrial function, determination of malondialdehyde and analysis of fatty acid binding protein expression by Western blot. RESULTS: Mitochondrial function decreased in the Partial Ischemia group, especially during adenosine diphosphate-activated respiration (state 3), and the expression of fatty acid binding protein was also reduced. The application of laser light prevented bioenergetic changes and restored the expression of fatty acid binding protein. CONCLUSION: Prophylactic application of laser light to the livers of rats submitted to partial ischemia was found to have a protective effect in the liver, with normalization of both mitochondrial function and fatty acid binding protein tissue expression.

PURPOSE: To determine the expression of hepatic L-FABP and intestinal I-FABP in an experimental model of necrotizing enterocolitis (NEC) in neonatal rats.METHODS: Newborn Sprague-Dawley rats were divided into four groups: Control (C1) - exclusive breastfeeding at the first and sixth procedures (C6), NEC1 - fed formula milk and submitted to hypoxia and hypothermia at the first and sixth procedures (NEC6). The newborn pups were fed twice a day for three days, for a total of six procedures. Samples were collected for morphometric evaluation (body weight, liver weight, liver weight/body weight ratio, intestinal weight and intestinal/body weight ratio) and for immunohistochemical and Western blotting analysis. The values obtained were analyzed statistically, with the level of significance set at p

Fatty acid-binding proteins (FABPs) are members of lipid-binding proteins that participate in lipid uptake and intracellular transport. This study was designed to investigate the effects of the liver bile acid-binding protein (L-BABP) and the liver fatty acid binding protein (L-FABP) genes on chicken growth and body composition traits. Three SNPs (SNP1, SNP2 and SNP3) of the L-BABP and six SNPs (SNP7-SNP9, SNP11-SNP13) of the L-FABP were detected firstly by DNA sequencing. Seven SNPs (SNP6 and SNP15-SNP20) of the L-FABP were detected by DNA sequencing and were found in the chicken genomic databases at the same time. Sequenom MassARRAY was developed to genotype 966 birds from the Northeast Agricultural University F2 (NEAUF2) resource population and the Northeast Agricultural University broiler lines divergently selected for abdominal fat content (NEAUHLF) population. Linkage disequilibrium analysis showed that the L-BABP SNPs appeared to be strongly linked with each other and were located within a haplotype block in both populations. SNP7 and SNP8, SNP12 and SNP13, SNP19 and SNP20 of the L-FABP were in strong linkage disequilibrium, respectively. The L-BABP polymorphisms were significantly associated with body weight (BW) (P

Dietary lipid absorption is dependent on chylomicron production whose rate-limiting step across the intestinal absorptive cell is the exit of chylomicrons from the endoplasmic reticulum (ER) in its ER-to-Golgi transport vesicle, the prechylomicron transport vesicle (PCTV). This study addresses the composition of the budding complex for PCTV. Immunoprecipitation (IP) studies from rat intestinal ER solubilized in Triton X-100 suggested that vesicle-associated membrane protein 7 (VAMP7), apolipoprotein B48 (apoB48), liver fatty acid-binding protein (L-FABP), CD36, and the COPII proteins were associated on incubation of the ER with cytosol and ATP. This association was confirmed by chromatography of the solubilized ER over Sephacryl S400-HR in which these constituents cochromatographed with an apparent kDa of 630. No multiprotein complex was detected when the ER was chromatographed in the absence of PCTV budding activity (resting ER or PKCζ depletion of ER and cytosol). Treatment of the ER with anti-apoB48 or anti-VAMP7 antibodies or using gene disrupted L-FABP or CD36 mice all significantly inhibited PCTV generation. A smaller complex (no COPII proteins) was formed when only rL-FABP was used to bud PCTV. The data support the conclusion that the PCTV budding complex in intestinal ER is composed of VAMP7, apoB48, CD36, and L-FABP, plus the COPII proteins.

Background Targeted treatment with mineralocorticoid receptor antagonists (MRAs) or adrenalectomy in patients with primary aldosteronism (PA) causes a decline in estimated glomerular filtration rate; however, the associated simultaneous changes in biomarkers of kidney tubule health still remain unclear. Methods and Results We matched 104 patients with newly diagnosed unilateral PA who underwent adrenalectomy with 104 patients with unilateral PA who were treated with MRAs, 104 patients with bilateral PA treated with MRAs, and 104 patients with essential hypertension who served as controls. Functional biomarkers were measured before the targeted treatment and 1 year after treatment, including serum markers of kidney function (cystatin C, creatinine), urinary markers of proximal renal tubular damage (L-FABP [liver-type fatty-acid binding protein], KIM-1 [kidney injury molecule-1]), serum markers of kidney tubular reserve and mineral metabolism (intact parathyroid hormone), and proteinuria. Compared with the patients with essential hypertension, the patients with PA had higher pretreatment serum intact parathyroid hormone and urinary creatinine-corrected parameters, including L-FABP, KIM-1, and albumin. The patients with essential hypertension and with PA had similar cystatin C levels. After treatment with MRAs or adrenalectomy of unilateral PA and MRAs of bilateral PA, the patients with PA had increased serum cystatin C and decreased urinary L-FABP/creatinine, KIM-1/creatinine, creatinine-based estimated glomerular filtration rate, intact parathyroid hormone, and proteinuria (all P <0.05). In multivariable regression models, a higher urinary L-FABP/creatinine ratio and older age were significantly correlated with the occurrence of kidney failure (estimated glomerular filtration rate dip ≥30%) in the patients with PA after targeted treatment. Conclusions Compared with the matched patients with essential hypertension, the incident patients with PA at diagnosis had higher levels of several biomarkers, including markers of kidney damage, tubular reserve/mineral metabolism, and proteinuria. Functional kidney failure in the patients with PA after treatment could be predicted by a higher baseline urinary L-FABP/creatinine ratio and older age. After targeted treatments in the patients with bilateral or unilateral PA, these biomarkers of kidney tubule health were restored, but creatinine-based estimated glomerular filtration rate declined, which may therefore reflect hemodynamic changes rather than intrinsic damage to kidney tubular cells.

Since conjugated linoleic acid (CLA) has structural and physiological characteristics similar to peroxisome proliferators, it is hypothesized that CLA would upregulate peroxisome proliferator-activated receptor (PPAR) and liver fatty acid binding protein (LFABP) in the liver of broiler chicken. The aim of the present study was to determine fatty acid composition of liver in CLA-fed broiler chickens and the genes associated with hepatic lipid metabolism. A total of 180-day-old broiler chicks were randomly assigned to two diets containing 0 and 2.5% CLA and fed for 6 weeks. Fatty acid (FA) composition of liver and PPAR α and γ and L-FABP were analyzed. It has been demonstrated that CLA was found in the liver of CLA-feed chicken compared to control group. Hepatic PPAR α and γ mRNA levels were upregulated 1.2 and 3-fold in CLA-fed chickens compared to chickens fed diet without CLA respectively. A similar response of upregulation was observed for L-FABP mRNA expression. Our data highlights the role of PPARs as a core regulator in the regulation of lipid metabolism in chicken liver.

Objective:Hypoxia occurs following convulsions, and hypoxia is one of the most common causes of acute renal damage. The aim of this study was to investigate urinary levels of kidney injury molecules, including neutrophil gelatinase-associated lipocalin (NGAL), N-acetyl-β-D-glucosaminidase (NAG), and liver-type fatty acid-binding protein (L-FABP) in children with febrile seizures (FS) for the first time. Methods:The study included 28 children with FS and 34 age and gender matched healthy children. Serum biochemistry and blood gases were measured in the serum samples. Estimated glomerular filtration rate (eGFR) was calculated. NGAL, NAG, L-FABP, and creatinine (Cr) were measured in the urine samples. The ratios of kidney injury markers to urinary Cr were used for comparisons. Results:There were no significant differences in eGFR and serum chemistry values between the FS and the control group (p > 0.05). Hypoxia was detected in 67.9% of the FS patients. The FS group had significantly higher urinary kidney injury molecules to Cr ratios compared to the controls, including NGAL/Cr (17.9 ± 9.8; 6.7 ± 4.0, respectively;p < 0.001), NAG/Cr (0.55 ± 0.29; 0.21 ± 0.16,p < 0.001), and L-FABP/Cr (4.85 ± 2.93; 1.74 ± 1.16,p < 0.001). Conclusion:Increased urinary NGAL/Cr, NAG/Cr, and L-FABP/Cr values, in patients with FS compared to healthy controls, suggest a possible subclinical renal damage in these patients. [ABSTRACT FROM AUTHOR]

Nordihydroguaiaretic acid (NDGA), the main metabolite of Creosote Bush, has been shown to have profound effects on the core components of metabolic syndrome, including lowering of blood glucose, free fatty acids and triglyceride levels, attenuating elevated blood pressure in several rodent models of dyslipidemia, and improving body weight, insulin resistance, diabetes and hypertension. In the present study, a high-fructose diet fed rat model of hypertriglyceridemia, dyslipidemia, insulin resistance and hepatic steatosis was employed to investigate the global transcriptional changes in the lipid metabolizing pathways in three insulin sensitive tissues: liver, skeletal muscle and adipose tissue in response to chronic dietary administration of NDGA. Sprague-Dawley male rats (SD) were fed a chow (control) diet, high-fructose diet (HFrD) or HFrD supplemented with NDGA (2.5 g/kg diet) for eight weeks. Dietary administration of NDGA decreased plasma levels of TG, glucose, and insulin, and attenuated hepatic TG accumulation. DNA microarray expression profiling indicated that dietary administration of NDGA upregulated the expression of certain genes involved in fatty acid oxidation and their transcription regulator, PPARα, decreased the expression of a number of lipogenic genes and relevant transcription factors, and differentially impacted the genes of fatty acid transporters, acetyl CoA synthetases, elongases, fatty acid desaturases and lipid clearance proteins in liver, skeletal muscle and adipose tissues. These findings suggest that NDGA ameliorates hypertriglyceridemia and steatosis primarily by inhibiting lipogenesis and enhancing fatty acid catabolism in three major insulin responsive tissues by altering the expression of key enzyme genes and transcription factors involved in de novo lipogenesis and fatty acid oxidation. [ABSTRACT FROM AUTHOR]