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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.

• L-FABP is a novel biomarker for the early detection of abdominal injury and of hemorrhagic shock. • L-FABP is specific in the detection of an injury of the kidney and liver. • NGAL is a novel biomarker for the detection of abdominal injury and hemorrhagic shock. • NGAL failed to be specific in the detection of an injury of the liver and/or the kidney. Delayed diagnosis of abdominal injuries and hemorrhagic shock leads to secondary complications and high late mortality in severely traumatized patients. The liver fatty acid-binding protein (L-FABP) is expressed in intestine, liver and kidney; the neutrophil gelatinase-associated lipocalin (NGAL) in colon and kidney. We hypothesized that l -FABP is an early biomarker for abdominal injury and hemorrhagic shock and that l -FABP and NGAL are specific markers for detection of liver and/or kidney injuries. Traumatized patients with an age ≥18 years and an abdominal injury (AIS abd ≥2), independently from Injury Severity Score (ISS), were prospectively included from 04/2018 to 05/2021. 68 patients had an abdominal injury ("Abd") and 10 patients had an abdominal injury with hemorrhagic shock ("HS Abd"). 41 patients without abdominal injury and hemorrhagic shock but with an ISS ≥ 25 ("noAbd") were included as control group. Four abdominal subgroups with isolated organ injuries were defined. Plasma l -FABP and NGAL levels were measured at admission (ER) and up to two days post-trauma. All patient groups had a median ISS≥25. In ER, median l -FABP levels were significantly higher in "HS Abd" group (1209.2 ng/ml [IQR=575.2–1780.3]) compared to "noAbd" group (36.4 ng/ml [IQR=14.8–88.5]), and to "Abd" group (41.4 ng/ml [IQR=18.0–235.5]), p <0.001. In matched-pair-analysis l -FABP levels in the group "Abd" were significantly higher (108.3 ng/ml [IQR=31.4–540.9]) compared to "noAbd" (26.4 ng/ml [IQR=15.5–88.8]), p = 0.0016. l -FABP correlated significantly with clinical parameters of hemorrhagic shock; the optimal cut-off level of l -FABP for detection was 334.3 ng/ml (sensitivity: 90%, specificity: 78%). Median l -FABP-levels were significantly higher in patients with isolated liver or kidney injuries and correlated significantly with AST, ALT and creatinine value. Median NGAL levels in the ER were significantly higher in "HS Abd" group (115.9 ng/ml [IQR=90.6–163.8]) compared to "noAbd" group (58.5 ng/ml [IQR=41.0–89.6], p <0.001) and "Abd" group (70.5 ng/ml [IQR=53.3–115.5], p <0.05). The group "Abd" showed significant higher median NGAL levels compared to "noAbd", p = 0.019. NGAL levels correlated significantly with clinical parameters of hemorrhagic shock. : L-FABP and NGAL are novel biomarkers for detection of abdominal trauma and hemorrhagic shock. l -FABP may be a useful and promising parameter in diagnosis of liver and kidney injuries, NGAL failed to achieve the same. [ABSTRACT FROM AUTHOR]

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.

Background: Non-alcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease worldwide; thus, an early and accurate diagnosis will improve the prognosis therapeutic interventions. Aim: To assess the diagnostic value of liver fatty acid binding protein (L-FABP) for liver injury in non-alcoholic fatty liver disease (NAFLD). Patients and methods: This prospective case-control study was conducted at the Hepatology, Gastroenterology, and Infectious Diseases Clinics, Zagagzig University Hospitals, Egypt on 60 participants divided into three groups: 20 members of the NAFLD in group I had high liver enzymes, 20 members of the NAFLD in group II had normal liver enzymes and 20 members of the healthy control group in group III. L-FABP was measured in all subjects. Results: Regarding L-FABP levels, all of the examined groups showed a significant statistical difference; group I had higher levels than groups II and III, whereas group II had higher levels than group III. Conclusion: The diagnostic biomarker fatty acid-binding liver protein is very useful for NAFLD and a good diagnostic tool of fatty liver injury as its concentrations reflect the level invasion of fat into the liver tissue. [ABSTRACT FROM AUTHOR]

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.

• CKD is now recognized as a distinct risk factor for CVD. • This risk rises in tandem with the decline in kidney function and peaks at the end stage. • This review presents an update on markers, which facilitate the prediction of CKD progression. Chronic kidney disease (CKD) is defined by gradual deterioration of the renal parenchyma and decline of functioning nephrons. CKD is now recognized as a distinct risk factor for cardiovascular disease (CVD). This risk rises in tandem with the decline in kidney function and peaks at the end-stage. It is important to identify individuals with CKD who are at a higher risk of advancing to end-stage renal disease (ESRD) and the beginning of CVD. This will enhance the clinical benefits and so that evidence-based therapy may be started at the initial stages for those individuals. A promising biomarker must represent tissue damage, and be easy to detect using non-invasive methods. Current CKD progression indicators have difficulties in reaching this aim. Hence this review presents an update on markers studied in the last decade, which help in the prediction of CKD progression such as neutrophil gelatinase-associated lipocalin, kidney injury molecule-1, urinary liver-type fatty acid-binding protein, cystatin-C, asymmetric dimethylarginine, symmetric dimethylarginine, endotrophin, methylglyoxal, sclerostin, uric acid, and miRNA-196a. Additional research is needed to determine the predictive usefulness of these indicators in clinical samples for disease development. Their utility as surrogate markers need to be explored further for the early identification of CKD progression. [ABSTRACT FROM AUTHOR]

Background: The most important factor in the diagnosis of AKI is to accurately and early detect the damage that occurs in the kidney before the filtration capacity of the kidney decreases. Therefore, we discussed the use of NGAL and L-FABP in the early diagnosis of acute kidney injury, evaluation of clinical severity and prognosis as well as prediction of hemodialysis decision in this prospective study. Methods: We studied 82 participants which included 41 patients aged 18 years and older with the diagnosis of acute kidney injury. We compared the renal function tests collected at 0 and 6 hours with the plasma NGAL and LFABP levels measured using ELISA. Acute kidney injury was defined as serum creatinine increase of 0.3 mg/dL in the last 48 hours, or an increase more than 1.5 times, or an increase in the basal serum creatinine value in the last seven days, or less than 0.5/mL/kg of urine volume within six hours. We tested the power of these new biomarkers in the early diagnosis, and prediction of hemodialysis and survival of the patients with AKI using ROC analysis. Results: Fifteen (36.6%) of the patients were anuric and 26 (63.4%) were oliguric. Twenty-one (51.2%) patients were KDIGO Stage 3. Seventeen (41.5%) patients underwent hemodialysis. In the patient group, the mean NGAL level was 289.7 ± 117.4 ng/mL and the mean L-FABP level was 232.7 ± 72.8. Eleven (26.9%) of 41 patients died within the first 24 hours. In the dead patients, the mean plasma NGAL level was statistically significantly high (p = 0.005). The mean NGAL level was found to be statistically increased in correlation with the severity of acute kidney injury in patients (p < 0.05). To predict acute kidney injury, the ROC analysis showed that the area under the curve (AUC) was 0.819 (95% confidence interval (CI): 0.729 - 0.909) (p < 0.001) for plasma NGAL level, and the area under the curve (AUC) was 0.891 (95% confidence interval (CI): 0.822 - 0.959) for plasma L-FABP level (p < 0.001). Conclusions: Our study provides evidence that NGAL and L-FABP are effective biomarkers for early detection of AKI as well as predicting clinical severity and hemodialysis. [ABSTRACT FROM AUTHOR]

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

Isoniazid (INH)-induced liver injury is a great challenge for tuberculosis treatment. Existing biomarkers cannot accurately determine the occurrence of this injury in the early stage. Therefore, developing early specific sensitive biomarkers of INH-induced liver injury is urgent. A rat model of liver injury was established with gastric infusion of INH or INH plus rifampicin (RFP). We examined seven potential novel serum biomarkers, namely, glutamate dehydrogenase (GLDH), liver-fatty acid-binding protein (L-FABP), high-mobility group box-1 (HMGB1), macrophage colony-stimulating factor receptor (MCSF1R), osteopontin (OPN), total cytokeratin 18 (K18), and caspasecleaved cytokeratin-18 (ccK18), to evaluate their sensitivity and specificity on INHinduced liver injury. With the increase of drug dosage, combining with RFP and prolonging duration of administration, the liver injury was aggravated, showing as decreased weight of the rats, upgraded liver index and oxidative stress level, and histopathological changes of liver becoming marked. But the activity of serum aminotransferases decreased significantly. The area under the curve (AUC) of receiveroperating characteristic (ROC) curve of OPN, L-FABP, HMGB1, MCSF1R, and GLDH was 0.88, 0.87, 0.85, 0.71, and 0.70 (≥0.7), respectively, and 95% confidence interval of them did not include 0.5, with statistical significance, indicating their potential abilities to become biomarkers of INH-induced liver injury. In conclusion, we found traditional biomarkers ALT and AST were insufficient to discover the INH-induced liver injury accurately and OPN, L-FABP, and HMGB1 can be promising novel biomarkers. [ABSTRACT FROM AUTHOR]

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.

Decompensated cirrhosis (DC) is associated with high mortality, mainly owing to the development of acute-on-chronic liver failure (ACLF). Identifying the patients with DC who are at high risk of mortality and ACLF development is an unmet clinical need. Liver fatty acid-binding protein (L-FABP) is expressed in several organs and correlates with liver and systemic inflammation. Herein, we aimed to assess the prognostic value of L-FABP in patients with DC. A prospective series of 444 patients hospitalized for DC was divided into 2 cohorts: study cohort (305 patients) and validation cohort (139 patients). L-FABP was measured in urine and plasma samples collected at admission. Neutrophil gelatinase-associated lipocalin (NGAL) was also measured in urine samples for comparison. Urine but not plasma L-FABP correlated with 3-month survival on univariate analysis. On multivariate analysis, urine L-FABP and model for end-stage liver disease (MELD)-Na were the only independent predictors of prognosis. Urine L-FABP levels were higher in patients with ACLF than in those without and also predicted the development of ACLF, together with MELD-Na, during follow-up. In patients with ACLF, urine L-FABP correlated with liver, coagulation, and circulatory failure. Urine L-FABP levels were also increased in patients with acute kidney injury, particularly in those with acute tubular necrosis. The ability of urinary L-FABP to predict survival and ACLF development was confirmed in the validation cohort. Urine NGAL predicted outcome on univariate but not multivariate analysis. Urinary L-FABP levels are independently associated with the 3-month clinical course in patients with DC, in terms of mortality and ACLF development. Urinary L-FABP is a promising prognostic biomarker for patients with DC. Increased levels of liver fatty acid-binding protein (L-FABP), a protein related to lipid metabolism, have been associated with liver-related diseases. The present study analyzed urinary L-FABP levels in 2 independent groups of patients with decompensated cirrhosis and showed that higher urinary L-FABP levels correlated with increased mortality and risk of acute-on-chronic liver failure development. Therefore, urinary L-FABP levels could be useful as a new tool to predict complications in patients with decompensated cirrhosis. [Display omitted] • L-FABP is a mediator of lipid metabolism and has been associated with liver injury. • Urinary L-FABP and MELD-Na were associated with 90-day mortality in patients with decompensated cirrhosis. • Urinary L-FABP correlates with ACLF grade and liver, coagulation and circulatory failures. • Moreover, urinary L-FABP was related to the development of ACLF. [ABSTRACT FROM AUTHOR]

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

Objective: Although renal impairments are observed in patients with primary aldosteronism (PA), the association between plasma aldosterone concentration (PAC) and specific structural kidney damage remains unknown. Thus, we analysed the association between PAC, and markers of glomerular and tubular damage. Design: This was a retrospective cross‐sectional study of 96 PA patients, in which we analysed the association between PAC and markers of kidney damage, including urinary albumin‐creatinine ratio (ACR) for glomerular damage, and urinary liver fatty acid‐binding protein (L‐FABP), N‐acetyl‐β‐D‐glucosaminidase (NAG) and β2‐microglobulin (β2‐MG) for tubular damage. In addition, we evaluated the association between PAC and N‐terminal pro‐brain natriuretic peptide (NT‐proBNP) as a marker for body fluid volume. Results: Urinary ACR, L‐FABP, NAG, β2‐MG and NT‐proBNP significantly correlated with PAC. PAC (<415 pmol/L, 415‐550, 550‐740, 740 <)‐based quartile analysis revealed that both elevated markers of kidney damage and NT‐proBNP could be observed in PA patients with a PAC over 550 pmol/L. Logistic regression analysis showed that PAC was significantly associated with a risk of both microalbuminuria and lowered eGFR (<60 mL/min/1.73 m2), with its optimal cut‐offs for predicting each, 558 and 594 pmol/L, respectively. Conclusions: Increased PAC, especially over 550 pmol/L, is associated with excessive damage to the tubule and glomerulus. [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.

There is a pressing need to find reliable biomarkers for the early diagnosis of silica-induced nephropathy. Abundant genes are upregulated in damaged kidneys with subsequent protein products appearing in the urine. Liver-type fatty acid-binding protein (L-FABP) and kidney injury molecule-1 (KIM-1) are among the most promising. Our objective was to study the importance of L-FABP and KIM-1 genes and their urinary proteins in the early detection of silica-induced renal injury, as compared with other conventional biomarkers. A cross-sectional study was conducted among 90 pottery workers occupationally exposed to silica, as compared to 90 controls. A full history taking and complete clinical examination were performed. Levels of serum creatinine, liver enzymes, urinary silicon, KIM-1, and L-FABP gene expression and protein products were measured. Estimated glomerular filtration rate (eGFR) was calculated, and abdominal ultrasound was performed. The results showed that the silica-exposed group had a statistically significant increase in serum creatinine and urinary silica, as well as a significant decrease in eGFR. Additionally, a significant increase in KIM-1 and L-FABP gene expression, associated with a significant increase in their urinary protein, was found among the exposed group. A positive correlation between urinary silica level and L-FABP gene expression was also found. A receiver operating characteristic curve analysis for L-FABP and KIM-1 gene as predictors for silica-induced nephropathy showed that L-FABP gene and protein specificity were greater than the KIM-1 gene and protein. Taken together, these findings suggest that the L-FABP gene and its protein product may be used as early indicators for renal injury among silica exposed workers. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to assess the levels of selected markers in patients who underwent planned or emergency coronary angiography and to examine if they correlated with the occurrence of AKI. Methods: The study included 52 patients who underwent planned or emergency coronary angiography and received contrast agent. Serum levels of markers (NGAL, L-FABP, KIM-1, IL-18) were analyzed in all patients using ELISA tests, at baseline, after 24 and 72 h from angiography. Results: 9.62% of patients developed CI-AKI. No significant differences were observed between markers levels in patients who developed CI-AKI and those who did not. After 24 h, serum levels of IL-18 were higher in patients with CI-AKI, however, this difference was on the verge of significance. Increase in serum NGAL, KIM-1 and IL-18 was observed after 24 h. Serum levels of biomarkers were insignificantly higher in group with CI-AKI. Significant changes in levels in time (baseline vs. 24 h vs. 72 h) were observed only for NGAL [157.9 (92.4–221.0) vs. 201.8 (156.5–299.9) vs. 118.5 (73.4–198.7); p < 0.0001]. No significant correlations were observed between the decrease in eGFR or the increase in creatinine and biomarkers level. Conclusion: Obtained results do not allow for the indication of efficient AKI biomarkers. Their further validation in large studies of CI-AKI patients is required. [ABSTRACT FROM AUTHOR]

Background: Congenital obstructive uropathy (OU) is a leading cause of pediatric kidney failure, representing a unique mechanism of injury, in part from renal tubular stretch and ischemia. Tubular injury biomarkers have potential to improve OU-specific risk stratification. Methods: Patients with OU were identified in the Chronic Kidney Disease in Children (CKiD) study. "Cases" were defined as individuals receiving any kidney replacement therapy (KRT), while "controls" were age- and time-on-study matched and KRT free at last study visit. Urine and plasma neutrophil gelatinase-associated lipocalin (NGAL), interleukin 18 (IL-18), and liver-type fatty acid-binding protein (L-FABP) levels were measured at enrollment and annually and compared between cases and controls. Urine values were normalized to urine creatinine. Results: In total, 22 cases and 22 controls were identified, with median (interquartile range) ages of 10.5 (9.0–13.0) and 15.9 (13.9–16.9) years at baseline and outcome, respectively. At enrollment there were no differences noted between cases and controls for any urine (u) or plasma (p) biomarker measured. However, the mean pNGAL and uL-FABP/creatinine increased throughout the study period in cases (15.38 ng/ml per year and 0.20 ng/ml per mg/dl per year, respectively, p = 0.01 for both) but remained stable in controls. This remained constant after controlling for baseline glomerular filtration rate (GFR). Conclusions: In children with OU, pNGAL and uL-FABP levels increased over the 5 years preceding KRT; independent of baseline GFR. Future studies are necessary to identify optimal cutoff values and to determine if these markers outperform current clinical predictors. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to investigate the clinical course, selected biochemical parameters and concentrations of renal injury biomarkers such as neutrophil gelatinase‐associated lipocalin (NGAL), kidney injury molecule‐1 (KIM‐1) and liver‐fatty acid binding protein (L‐FABP) in patients with immunoglobulin A vasculitis (IgAV) to identify the markers associated with nephritis in the course of the disease (IgAVN). Methods: The study involved 29 children with IgAV and 34 healthy controls. Eleven (38%) patients had renal involvement (IgAV‐N) and 18 (62%) did not exhibit nephritis (IgAV‐noN). Initial laboratory tests, determining the concentrations of NGAL, KIM‐1 and L‐FABP in serum and urine, were conducted on children from the study group in an acute phase of IgAV as well as after an average of 6 months, during a follow‐up visit. The interconnection between renal involvement, anthropometric measurements, epidemiological data, laboratory parameters and levels of examined biomarkers have been thoroughly evaluated. Results: The serum and urine levels of NGAL, KIM‐1 and L‐FABP were significantly higher in children with an acute phase of IgAV as compared to the control group (P <.001) and markedly lower during follow‐up retesting in comparison with the values obtained at inclusion (P <.001). However, the concentration of none of the evaluated biomarkers correlated with nephrological indices. Among all examined parameters, only male subjects were associated with nephritis (P =.017). Conclusions: We have established no evident association between the concentrations of NGAL, KIM‐1 and L‐FABP and nephritis in the course of IgAV in children. Additionally, we confirmed a significant male predominance in patients with nephritis. [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. [ABSTRACT FROM AUTHOR]

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 serious complication of pediatric cardiac surgery, with high morbidity and mortality. We aimed to evaluate the perioperative risk factors for AKI, and the validity of novel diagnostic urinary biomarkers after pediatric cardiac surgery. We analyzed 103 consecutive pediatric patients (≤ 18 years old), who underwent cardiac surgery. AKI was defined by ≥ 50% increase in serum creatinine levels from baseline. Urinary liver-type fatty acid binding protein (L-FABP) and neutrophil gelatinase-associated lipocalin (NGAL) were measured postoperatively at the intensive care unit (ICU) admission, subsequently at 4, 12, and 24 h. Areas under the receiver-operating characteristic curves (AUC) were calculated at each assessment time. AKI had developed in 47 patients (45.6%) by the second postoperative day. Univentricular status, aortic cross-clamping time, and intraoperative fluid balance were independently associated with AKI (p = 0.02, 0.01 and 0.01, respectively). Urinary L-FABP and NGAL were significantly higher in the AKI group at each point (p < 0.05). The predictive abilities of both biomarkers (AUC = 0.78–0.90) at ICU admission and 4 h after were especially high. The patients with L-FABP greater than the cutoff value at ICU admission and 4 h after ICU admission had significantly longer intubation and hospitalization periods (p < 0.05). Those with elevated NGAL levels at admission, and 4 h and 24 h after ICU admission, had significantly longer intubation, ICU stay, and hospitalization (p < 0.05). L-FABP and NGAL can be useful biomarkers for detecting early AKI after pediatric cardiac surgery and predicting adverse clinical outcomes. [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]

Exogenous and endogenous regulatory effects on lipid metabolism were studied by examining the fatty acid (FA) composition of food and the expression of the regulatory protein L-FABP in 43 individuals without diabetes (23 of them had increased blood glucose and cholesterol level and 20 formed a control group) and 76 patients with complicated diabetes mellitus (DM2). The main difference of lipid metabolism in patients with diabetes mellitus and non-diabetic patients was in the redistribution of FA content in erythrocyte membranes in the form of a 1.5-fold increase (P<0.05) in the content of saturated FA and decrease in unsaturated FA due to polyunsaturated FA (PUFA) and an increase the serum protein L-FABP 1.5 times (P>0.05). Eating food sources of various FAs according to the indicator of "rationality of food consumption", which was obtained from food questionnaires analysis, did not differ in groups of people without diabetes and with diabetes. In the non-diabetic group with elevated blood glucose and cholesterol level, we revealed a decreased body mass index, a slight increase in PUFA in erythrocyte membranes and serum level L-FABP was 1.2 times lower than in relatively healthy subjects (P>0.05) and 2 times less than in patients with DM2 (P<0.05). It can be assumed, that under certain conditions, in the presence of metabolic shifts, it is the reduction of L-FABP expression with increased PUFA in cells that prevents the development of obesity and diabetes. Thus, the absence of a direct relationship between exogenous influences in the form of FA-source food products and the development of diabetes, the relationship between the expression of intracellular regulatory protein L-FABP and the redistribution of FA content in erythrocyte membranes allow us to consider endogenous cellular mechanisms as the basis of a deep violation of lipid homeostasis. [ABSTRACT FROM AUTHOR]

Background: Because fatty acid binding proteins (FABPs) and peroxisome proliferator-activated receptor (PPAR) γ 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 PPARγ-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 PPARγ-gene mediated phenotypes. Among wild-type carriers, arachidonic acid concentration increased 1.4-fold in those with the early stage of DR (p < 0.05) compared to controls and decreased 7.5-fold in those with DR progression (p < 0.05). Among carriers of the 12Ala allele, arachidonic acid concentration decreased twofold in those with the early stage of DR (p < 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 (p < 0.05), and gradually decreased with DR progression. [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]