Liver-type Fatty Acid-binding Protein Research Articles

Urinary liver-type fatty acid binding protein predicts renal angina in patients undergoing cardiac angiography: comparison with intrarenal arterial duplex

Background Patients undergoing cardiac angiography may suffer from acute kidney injury (AKI) due to the effect of the contrast medium. Different biomarkers described the clinical condition and had led to concepts like subclinical AKI or renal angina (RA). Objective Detection of the usefulness of the biomarker urinary liver-type fatty acid binding protein (L-FABP) which increases along with renal tubular hypoxia, in early prediction of RA in patients subjected to coronary angiography (CA). Patients and methods Forty patients (54.10±9.13 years, 34 males) routinely scheduled for CA were included. The risk for AKI was evaluated, and the renal function was assessed using RIFLE (risk, injury, failure, loss, and end stage kidney) criteria. L-FABP was detected on admission and 4 h after CA. The intrarenal duplex was performed on admission and after CA, and resistivity index (RI) and pulsatility index were estimated. Results Compared to serum creatinine before CA, its values increased significantly but within the normal range 4 h after CA (0.86±0.23 vs 1.08±0.52 mg/dl, P Conclusion This study highlighted the importance of L-FABP and RI in early prediction of RA 4 h after contrast media injection and earlier than either serum creatinine or its clearance rate. Although L-FABP is more specific, but RI showed more sensitivity to RA.

Urinary Level of Liver-Type Fatty Acid Binding Protein Reflects the Degree of Tubulointerstitial Damage in Polycystic Kidney Disease

Background/Aims: Polycystic kidney disease (PKD) is a common, progressive, and heritable type of kidney disease. Although certain imaging modalities are useful for the diagnosis and staging of PKD, they cannot adequately monitor the severity of interstitial inflammation and fibrosis. Therefore, the present study evaluated the urinary level of liver-type fatty acid binding protein (L-FABP) as a marker of interstitial inflammation and fibrosis in PKD. Methods: Male PCK/CrljCrl-Pkhd1pck/Crl (PCK) rats (n = 34) were used as an animal model of the PKD. Age-and sex-matched Sprague–Dawley rats (SD) (n = 34) were used as controls. Urine samples were obtained from the rats at 8, 12, 16, 20, and 24 weeks of age, and the sera and kidney tissues were obtained at 8, 16, 20, and 24 weeks of age. Results: All PCK rats developed cysts, and the degrees of tubular epithelial cell proliferation and interstitial inflammation increased linearly with age in these model rats relative to the controls. Interstitial fibrosis tended to increase in the PCK rats from 8 to 20 weeks of age, and revealed a peak level at 20 weeks. The urinary L-FABP levels increased linearly with age in the PCK rats, and the levels at 12, 16, 20, and 24 weeks were significantly higher than those in the controls. The urinary levels of L-FABP in the PCK rats correlated significantly with the severity of tubulointerstitial damage; specifically, we observed a significant correlation of the urinary levels at 16 weeks of age with the total kidney volume at 20 weeks. In contrast, both PCK and SD rats exhibited similar serum levels of L-FABP. Conclusion: Urinary L-FABP reflects the progression of tubulointerstitial damage, and therefore, may be a useful marker for monitoring the progression of PKD.

Prospective randomized study to evaluate urinary liver-type fatty acid binding protein in early detection of diabetic nephropathy in type 2 diabetic patients

Prospective randomized study to evaluate urinary liver-type fatty acid binding protein in early detection of diabetic nephropathy in type 2 diabetic patients

Chronic kidney disease in children: Using novel biomarkers as predictors of disease

Chronic kidney disease (CKD) in children contributes to the global health burden. The focus on using novel biomarkers to predict the onset and progression of the disease has increased tremendously over the past decade. Discovery of these biomarkers offers prospects for the early anticipation of the late stages of CKD, slowing down disease progression, and achieving better disease outcomes. The aim of this article is to classify and highlight the utility of these novel biomarkers in predicting disease-onset and progression. Biomarkers of CKD are broadly classified into biomarkers of kidney function and biomarkers of kidney damage. Glomerular filtration rate (GFR) remains the most important marker of kidney function, but it cannot be easily measured in most clinical and research settings. Its estimating equations, therefore, depend on filtration biomarkers such as serum creatinine and serum cystatin C. For instance, the CKD-epidemiology collaboration equation has been suggested as the preferred prediction equation for the staging and classification of estimated GFR (eGFR) in CKD. Although albuminuria is the traditional biomarker of kidney damage, it precedes any decline in eGFR and may be absent in tubulointerstitial disease. Thus, more sensitive and specific novel biomarkers of kidney damage are emerging which hold prospects for earlier prediction of CKD in children. They have been classified as tubular and miscellaneous biomarkers. Tubular biomarkers are represented by markers such as kidney injury molecule-1, neutrophil gelatinase-associated lipocalin, N-acetyl-ß-D glucosaminidase, liver-type fatty-acid binding protein, cystatin C and a-1-microglobulin. Miscellaneous biomarkers include monocyte chemoattractant protein-1, interleukin-18, and retinol binding protein 4. Despite their advantages over albuminuria, they still require validation before they can be applied in clinical practice.

雌性SDT fattyラットを用いた、血清中肝臓型脂肪酸結合蛋白（L-FABP）量の非アルコール性脂肪性肝炎(NASH)バイオマーカーとしての有用性に関する研究

雌性SDT fattyラットを用いた、血清中肝臓型脂肪酸結合蛋白（L-FABP）量の非アルコール性脂肪性肝炎(NASH)バイオマーカーとしての有用性に関する研究

Predictive value of novel biomarkers for acute kidney injury in critically ill patients at Assiut University Hospitals

Introduction Acute kidney injury (AKI) is a clinical problem in critically ill patients, which is associated with adverse outcomes. There is a persistent need to find reliable biomarkers for the early diagnosis and prediction of AKI. Many genes are upregulated in the damaged kidneys, with the subsequent protein products appearing in the urine. Urinary liver-type fatty acid-binding protein (uL-FABP) and urinary kidney injury molecule-1 (uKIM-1) are among the promising upregulated biomarkers. Aim To assess the ability of uL-FABP in comparison with kidney injury molecule-1 for early prediction of AKI in adult critically ill patients. Patients and methods A cohort study was conducted enrolling 100 critically ill patients admitted to medical critical care units (CCUs) who had risk factors for developing AKI. Acute Physiology and Chronic Health Evaluation II score was calculated on admission. Serum creatinine was measured on admission and thereafter daily till the seventh day of CCU stay. Urine samples for uL-FABP and uKIM-1 assay were collected at the time of CCU admission, on day 3, and on day 5. Results Among critically ill patients, 60% had AKI diagnosed mostly on the second (53.3%) and third (40%) day of CCU admission. There was a significant difference in Acute Physiology and Chronic Health Evaluation II score (P Conclusion UKIM-1 was a sensitive and specific biomarker (superior to uL-FABP) for the prediction of AKI in critically ill patients.

Urinary C-megalin for screening of renal scarring in children after febrile urinary tract infection.

BackgroundFebrile urinary tract infection (fUTI) in children may cause renal scarring. This study aimed to investigate the usefulness of urinary biomarkers for diagnosing renal scarring after fUTI.MethodsThirty-seven children (median age: 1.36 years, range: 0.52-12.17 years, 25 boys) with a history of fUTI, who underwent renal scintigraphy for 4 months or longer after the last episode of fUTI, were analyzed. A spot urine sample was obtained on the day of renal scintigraphy to measure levels of total protein, N-acetyl-β-D-glucosaminidase (NAG), β2-microglobulin (BMG), neutrophil gelatinase-associated lipocalin (NGAL), liver-type fatty acid binding protein (L-FABP), and C-megalin (full-length megalin). Results were corrected for urinary creatinine (Cr) and compared between the group with renal scarring (n=23) and that without scarring (n=14). Urinary levels of C-megalin were also measured in healthy control subjects.ResultsNo significant differences in total protein, NGAL, L-FABP, NAG, and BMG levels were found between the groups. However, C-megalin levels were significantly higher in the renal scarring group than in the non-renal scarring group and healthy controls (P<0.001). A cutoff value of 6.5 pmol/nmol of urinary C-megalin/Cr yielded 73.9% of specificity and 92.9% of sensitivity.ConclusionUrinary C-megalin is useful for diagnosing renal scarring caused by fUTI.

Cyclic and intermittent very low‐protein diet can have beneficial effects against advanced diabetic nephropathy in Wistar fatty (fa/fa) rats, an animal model of type 2 diabetes and obesity

A low-protein diet (LPD), particularly, very low-protein diet (VLPD) is expected for reno-protection in advanced chronic kidney disease, including diabetic nephropathy. We previously also demonstrated that a VLPD clearly improved advanced diabetic nephropathy in a type 2 diabetes and obesity rat. However, clinically, an everyday long-term VLPD contributes to poor adherence, which may be related to controvertial results of an LPD on the suppression for diabetic nephropathy, and has nutritional issues, such as sarcopenia or protein-energy wasting. The aim of this study is to elucidate the reno-protective effect of a cyclic and intermittent VLPD, not an everyday VLPD, against the advanced experimental diabetic nephropathy. Diabetic male Wistar fatty (fa/fa) rats (WFRs) were treated with a standard diet (STD; 23.84% protein) or a cyclic and intermittent VLPD (5.77% protein) consisting of an STD for 3 days and a VLPD for 4 days a week for 20 weeks beginning at 24 weeks of age. A cyclic and intermittent VLPD significantly improved renal hypertrophy, and significantly decreased urinary albumin and liver-type fatty acid binding protein (L-FABP) excretion without changes in body weight or exacerbation of HbA1c levels in diabetic rats. Additionally, diabetes-induced renal injuries including fibrosis, tubular cell damage and inflammation were significantly ameliorated by a cyclic and intermittent VLPD in diabetic rats. Thus, based on our experimental data, a cyclic and intermittent VLPD may be a dietary regimen that is easy to continue and has less risk of malnutrition, compared to an everyday long-term VLPD, against advanced diabetic nephropathy.

Biomarkers for Early Detection of Acute Kidney Injury.

Acute kidney injury (AKI) is common in hospitalized patients and is associated with increased morbidity, mortality, and cost. Currently, AKI is diagnosed after symptoms manifest; available diagnostic tests (e.g., serum creatinine, urine microscopy, urine output) have limited ability to identify subclinical AKI. Because of the lack of treatment strategies, AKI typically is managed with supportive measures. However, strategies exist that may prevent renal insults in critically ill patients; therefore, early recognition of AKI is crucial for minimizing damage propagation. Experimental and clinical studies have identified biomarkers that may facilitate earlier recognition of AKI or even identify patients at risk of AKI. Such biomarkers might aid in earlier implementation of preventive strategies to slow disease progression and potentially improve outcomes. This review describes some of the most promising novel biomarkers of AKI, including neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule 1 (KIM-1), interleukin 18 (lL-18), liver-type fatty-acid-binding protein (L-FABP), insulin-like-growth-factor-binding protein 7 (IGFBP7), and tissue inhibitor of metalloproteinase 2 (TIMP-2). We discuss biomarker test characteristics, their strengths and weaknesses, and future directions of their clinical implementation.

Role of bardoxolone methyl, a nuclear factor erythroid 2-related factor 2 activator, in aldosterone- and salt-induced renal injury

The aim of this study was to investigate the renoprotective effect of bardoxolone methyl (BM), a nuclear factor erythroid 2-related factor 2 (Nrf2) activator with an antioxidant effect, in a salt-sensitive hypertension model induced by aldosterone (Ald) and salt. Tubulointerstitial damage with urinary liver-type fatty acid-binding protein (L-FABP) was evaluated using human L-FABP chromosomal transgenic (L-FABP+/−) male mice. The mice in the Ald group (n=7) received systemic Ald infusions via an osmotic minipump and were given 1% NaCl water for 35 days. Those in the Ald-BM group (n=8) were administered BM intraperitoneally in addition to an injection of Ald and salt. The dose of BM was gradually increased every 7 days up to 10 mg kg−1 per day, which was maintained for 14 days. The administration of BM significantly increased renal expression of the Nrf2 target antioxidant gene. Tubulointerstitial damage was significantly ameliorated in the Ald-BM group compared to the Ald group. The increase in reactive oxygen species (ROS) and upregulation of angiotensinogen expression in the kidneys of the Ald group was significantly prevented in the Ald-BM group. The upregulation of human L-FABP expression induced in the kidneys and increase in urinary L-FABP in the Ald group were significantly suppressed by BM administration. In conclusion, BM ameliorated tubulointerstitial damage in the Ald- and salt-induced hypertension model through suppression of both ROS production and intrarenal renin–angiotensin system activation. Urinary L-FABP may be a useful marker reflecting the therapeutic efficacy of BM.

O38-4 - Changes of urinary Liver-type Fatty Acid Binding during Therapeutic Course of Acute Decompensated Heart Failure

Introduction: Urinary Liver-type Fatty Acid Binding Protein (uL-FABP) is known as a marker reflecting renal tubular impairment in worsening renal function (WRF). However, its clinical significance has not been elucidated in patients with acute decompensated heart failure (ADHF), especially changes of uL-FABP is little known. Methods and Results: This prospective, observational study included 208 patients (mean age: 77 year, 51% male) presenting with ADHF. uL-FABP and other biomarkers were measured at admission and before discharge. WRF was defined as a rise in serum creatinine >0.3 mg/dl within seven days from admission. Median uL-FABP/Cr levels significantly decreased from 7.8 to 2.9 µg/gCr (P < .0001). These changes of uL-FABP were correlated with changes of aspartate aminotransferase (r = 0.27, P < .0001) and alanine aminotransferase (r = 0.24, P < .0001), although they were not correlated with changes of brain natriuretic peptide and estimated glomerular filtration rate. uL-FABP/Cr levels at admission were associated with WRF in the univariate logistic regression analysis (P = .03), but changes of uL-FABP/Cr were not associated. Conclusion: In patients with ADHF, uL-FABP decreased significantly during treatment. The decrease was correlated with changes of liver enzyme, though it was not associated with WRF.

Renoprotective effect of the xanthine oxidoreductase inhibitor Topiroxostat under decreased angiotensin II type 1a receptor expression

The aim of this study was to confirm the renoprotective effect of xanthine oxidoreductase (XOR) inhibitor, topiroxostat, compared with another XOR inhibitor, febuxostat, under decreased angiotensin II type 1a (AT1a) receptor expression in the model of renal injury caused by adenine. To evaluate the degree of tubular damage using urinary liver-type fatty acid-binding protein (L-FABP) under decreased AT1a expression, we used AT1a receptor knockdown hetero and human L-FABP chromosomal transgenic (Tg) mice (AT1a+/-L-FABP+/-). Male AT1a+/-L-FABP+/- mice were divided into two groups: the adenine diet group (n = 40) was given a diet containing only 0.2% w/w adenine, and the normal diet group (n = 5) was given a normal diet. When renal dysfunction was confirmed in the adenine diet group 4 weeks after starting the diet, the adenine diet group was further divided into five groups. The adenine diet group (n = 8) was continuously given only the adenine diet. Each group receiving high-dose (3mg/kg) or low-dose (1mg/kg) topiroxostat (Topiroxostat-H group, n = 8, Topiroxostat-L group, n = 8) or febuxostat (Febuxostat-H group, n = 8, Febuxostat-L group, n = 8) was given the adenine diet including the drug for another 4 weeks. The levels of renal XOR, renal dysfunction, urinary L-FABP, tubulointerstitial damage, hypoxia, and oxidative stress were decreased or attenuated after treatment with topiroxostat or febuxostat compared with the adenine diet group. Furthermore, antioxidant capacity was maintained owing to these treatments.In conclusion, topiroxostat and febuxostat attenuated renal damage under decreased AT1a expression in the adenine-induced renal injury model.

Urinary liver-type fatty acid-binding protein is associated with subendocardial viability ratio in middle- and older-aged adults

ABSTRACTBackground: To identify one of the physiological underlying mechanisms of the predictive effects of urinary liver-type fatty acid-binding protein (L-FABP) for the onset of cardiovascular disease (CVD), we investigated the relationship between urinary L-FABP levels and subendocardial viability ratio (SEVR), a marker of myocardial perfusion, in middle- and older-aged adults.Methods: This was a cross-sectional study of 249 middle- and older-aged adults (aged 46–83 years). We measured urinary L-FABP levels and central hemodynamic parameters, including SEVR, calculated by pulse wave analysis using an applanation tonometry.Results: In the participants stratified in accordance with the tertiles of urinary L-FABP levels, SEVR decreased in a stepwise fashion with increasing tertiles (p < 0.001). Furthermore, this association remains significant after the consideration of various confounders. On the contrary, urinary albumin levels were not independently related with SEVR.Conclusion: Our results demonstrated that urinary L-FABP levels were independently associated with the SEVR of the middle- and older-aged adults. This result suggests that the increase in urinary L-FABP levels even within the normal range might be related to the decrease in myocardial perfusion (SEVR).

Effect of Hydroxyethyl Starch Priming on the Systemic Inflammatory Response and Lung Edema after Cardiopulmonary Bypass in a Rat Model.

Cardiopulmonary bypass (CPB) preserves patients' lives during open heart surgery by providing sufficient oxygen delivery and blood supply to vital organs. However, previous studies have suggested that the interaction of hemodilution and vascular hyperpermeability induces tissue edema and an inflammatory response during CPB. In this study, we hypothesized the suppression of the systemic inflammatory response and tissue edema during CPB by a plasma substitute (hydroxyethyl starch [HES]). Rats (450-500 g) were divided into a SHAM group (n = 5), a Ringer's acetate CPB group (n = 7), and an HES CPB group (n = 7). In the Ringer's acetate group, the CPB circuit was primed with Ringer's acetate solution, and in the HES CPB group, it was primed with HES formulation (6% HES 130/0.4). Blood samples were collected before (baseline) and 30, 60, 90 and 120 min after initiation of CPB. Plasma cytokine levels of tumor necrosis factor-α, interleukin (IL)-6, and IL-10, and biochemical markers (lactate dehydrogenase, aspartate aminotransferase, alanine aminotransferase, blood urea nitrogen, creatinine, liver-type fatty acid-binding protein, and colloid osmotic pressure [COP]) were measured before and 30, 60, 90, and 120 min after the initiation of CPB. In the Ringer's acetate CPB group, the inflammatory cytokines and biochemical markers increased significantly during CPB compared with the SHAM group, but such increases were significantly suppressed in the HES CPB group. In addition, during CPB, it was possible to preserve normal plasma COP in the HES CPB group. The data suggest that 6% HES 130/0.4 is effective for suppressing the inflammatory response during CPB.

Performance of Serum Creatinine and Kidney Injury Biomarkers for Diagnosing Histologic Acute Tubular Injury

The diagnosis of acute kidney injury (AKI), which is currently defined as an increase in serum creatinine (Scr) concentration, provides little information on the condition's actual cause. To improve phenotyping of AKI, many urinary biomarkers of tubular injury are being investigated. Because AKI cases are not frequently biopsied, the diagnostic accuracy of concentrations of Scr and urinary biomarkers for histologic acute tubular injury is unknown. Cross-sectional analysis from multicenter prospective cohort. Hospitalized deceased kidney donors on whom kidney biopsies were performed at the time of organ procurement for histologic evaluation. (1) AKI diagnosed by change in Scr concentration during donor hospitalization and (2) concentrations of urinary biomarkers (neutrophil gelatinase-associated lipocalin [NGAL], liver-type fatty acid-binding protein [L-FABP], interleukin 18 [IL-18], and kidney injury molecule 1 [KIM-1]) measured at organ procurement. Histologic acute tubular injury. Of 581 donors, 98 (17%) had mild acute tubular injury and 57 (10%) had severe acute tubular injury. Overall, Scr-based AKI had poor diagnostic performance for identifying histologic acute tubular injury and 49% of donors with severe acute tubular injury did not have AKI. The area under the receiver operating characteristic curve (AUROC) of change in Scr concentration for diagnosing severe acute tubular injury was 0.58 (95% CI, 0.49-0.67) and for any acute tubular injury was 0.52 (95% CI, 0.45-0.58). Compared with Scr concentration, NGAL concentration demonstrated higher AUROC for diagnosing both severe acute tubular injury (0.67; 95% CI, 0.60-0.74; P=0.03) and any acute tubular injury (0.60; 95% CI, 0.55-0.66; P=0.005). In donors who did not have Scr-based AKI, NGAL concentrations were higher with increasing severities of acute tubular injury (subclinical AKI). However, compared with Scr concentration, AUROCs for acute tubular injury diagnosis were not significantly higher for urinary L-FABP, IL-18, or KIM-1. The spectrum of AKI cause in deceased donors may be different from that of a general hospitalized population. Concentrations of Scr and kidney injury biomarkers (L-FABP, IL-18, and KIM-1) lack accuracy for diagnosing acute tubular injury in hospitalized deceased donors. Although urinary NGAL concentration had slightly higher discrimination for acute tubular injury than did Scr concentration, its overall AUROC was still modest.

Urinary biomarkers of cell cycle arrest are delayed predictors of acute kidney injury after pediatric cardiopulmonary bypass.

Several novel biomarkers that predict acute kidney injury (AKI) have recently been proposed. We have evaluated the sequential patterns of biomarker elevation after pediatric cardiopulmonary bypass (CPB) and determined their diagnostic accuracy. We measured the ability of neutrophil gelatinase-associated lipocalin (NGAL), interleukin-18 (IL-18), liver type fatty-acid binding protein (L-FABP), kidney injury molecule-1 (KIM-1), tissue inhibitor of metalloproteinase-2 (TIMP-2), and insulin-like growth factor binding protein 7 (IGFBP7), to predict AKI (≥50% increase in serum creatinine from baseline). Areas under the receiver-operator characteristic curves (AUCs) were calculated for each biomarker and for various biomarker combinations at multiple time points after CPB. Of 150 patients examined, AKI had developed in 50 patients by 24h after CPB, with an elevated NGAL concentration first noted at 2h post-CPB, increases in IL-18, L-FABP, and the product of TIMP-2 and IGFBP7 first noted at 6h, and an elevated KIM-1 level noted at 12h. At each time point, urine NGAL remained the marker with the highest predictive ability (AUC > 0.9). The addition of any other biomarker did not increase the predictive accuracy of NGAL alone at 2 and 6h. At 12h, when compared to NGAL alone, the combination of NGAL, IL-18, and TIMP2 improved the AUC for AKI prediction (from 0.938 to 0.973). While urine NGAL remains a superior stand-alone test at the 2 and 6h time points after pediatric CPB, a panel of carefully selected biomarkers may prove optimal at later time points.

Clinical Relevance and Predictive Value of Damage Biomarkers of Drug-Induced Kidney Injury.

Nephrotoxin exposure accounts for up to one-fourth of acute kidney injury episodes in hospitalized patients, and the associated consequences are as severe as acute kidney injury due to other etiologies. As the use of nephrotoxic agents represents one of the few modifiable risk factors for acute kidney injury, clinicians must be able to identify patients at high risk for drug-induced kidney injury rapidly. Recently, significant advancements have been made in the field of biomarker utilization for the prediction and detection of acute kidney injury. Such biomarkers may have a role both for detection of drug-induced kidney disease and implementation of preventative and therapeutic strategies designed to mitigate injury. In this article, basic principles of renal biomarker use in practice are summarized, and the existing evidence for six markers specifically used to detect drug-induced kidney injury are outlined, including liver-type fatty acid binding protein, neutrophil gelatinase-associated lipocalin, tissue inhibitor of metalloproteinase-2 times insulin-like growth factor-binding protein 7 ([TIMP-2]·[IGFBP7]), kidney injury molecule-1 and N-acetyl-β-D-glucosaminidase. The results of the literature search for these six kidney damage biomarkers identified 29 unique articles with none detected for liver-type fatty acid binding protein and [TIMP-2]·[IGFBP7]. For three biomarkers, kidney injury molecule-1, neutrophil gelatinase-associated lipocalin and N-acetyl-β-D-glucosaminidase, the majority of the studies suggest utility in clinical practice. While many questions need to be answered to clearly articulate the use of biomarkers to predict drug-induced kidney disease, current data are promising.

Anagliptin ameliorates albuminuria and urinary liver-type fatty acid-binding protein excretion in patients with type 2 diabetes with nephropathy in a glucose-lowering-independent manner

ObjectiveThe objective of this study is to elucidate the effect of anagliptin on glucose/lipid metabolism and renoprotection in patients with type 2 diabetic nephropathy.MethodsTwenty-five patients with type 2 diabetic nephropathy...

Urinary liver-type fatty acid binding protein is an independent predictor of stroke and mortality in individuals with type 1 diabetes.

In type 1 diabetes, cardiovascular disease (CVD) and diabetic nephropathy progress in parallel, thereby potentiating the risk of premature death during their development. Since urinary liver-type fatty acid binding protein (L-FABP) predicts the progression of diabetic nephropathy, the aim of this study was to investigate whether urinary L-FABP also predicts cardiovascular outcomes and mortality. We tested our hypothesis in a Finnish cohort of 2329 individuals with type 1 diabetes and a median follow-up of 14.1years. The L-FABP to creatinine ratio was determined from baseline urine samples. The predictive value of urinary L-FABP was evaluated using Cox regression models, while its added predictive benefit for cardiovascular outcomes and mortality was evaluated using a panel of statistical indexes. Urinary L-FABP predicted incident stroke independently of traditional risk factors (HR 1.33 [95% CI 1.20, 1.49]) and after further adjustment for eGFR (HR 1.28 [95% CI 1.14, 1.44]) or AER (HR 1.24 [95% CI 1.06, 1.44]). In addition, it predicted mortality independently of traditional risk factors (HR 1.34 [95% CI 1.24, 1.45]), and after adjustment for eGFR (HR 1.29 [95% CI 1.18, 1.39]) or AER (HR 1.22 [95% CI 1.09, 1.36]). Urinary L-FABP was as good a predictor as eGFR or AER, and improved the AUC for both outcomes on top of traditional risk factors, with no reclassification benefit (integrated discrimination improvement/net reclassification improvement) for stroke or mortality when AER or eGFR were added to traditional risk factors. However, urinary L-FABP was not a predictor of other cardiovascular endpoints (coronary artery disease, peripheral vascular disease and overall CVD events) when adjusted for the AER. Urinary L-FABP is an independent predictor of stroke and mortality in individuals with type 1 diabetes.

Kidney injury in infants and children with iron-deficiency anemia before and after iron treatment

ABSTRACTBackground: Our study aimed to investigate the effects of iron-deficiency anemia (IDA) on renal tubular functions before and after iron treatment for infants and children with IDA. We measured urinary levels of two kidney injury markers: neutrophil gelatinase-associated lipocalin (NGAL) and liver-type fatty acid-binding protein (L-FABP).Material and methods: Thirty-six infants and children with IDA and 20 matched healthy controls were included. We assessed different laboratory parameters, estimated glomerular filtration rate, urinary levels of NGAL, and L-FABP. Urinary kidney injury markers were measured in IDA patients before and after 3 months of oral iron therapy.Results: IDA patients had significantly higher urinary NGAL and L-FABP levels compared to their healthy controls. After 3 months of oral iron treatment, there was a significant improvement (decrease) in urinary NGAL and L-FABP in infants and children with IDA. Urinary markers returned to normal levels (healthy control levels) in children with IDA, but not for infants with IDA compared to their healthy controls.Conclusion: Subclinical kidney injury was found in infants and children with IDA. This injury was completely reversible in older children with IDA and partially reversible in infants with IDA after iron therapy. Higher urinary levels of kidney injury molecules in IDA infants after iron treatment are suggestive of more sensitivity of these infants to oxidative stress caused by iron therapy or may be due to the immaturity of the kidney and more damage caused by IDA which may require more time to recover.