The occurrence of acute kidney injury (AKI) in critically ill patients is often associated with increased morbidity and mortality rates. Despite extensive research, a consensus is yet to be arrived, especially regarding the optimal timing and indications for initiation of kidney replacement therapy (KRT) for critically ill patients. There is no clear guidance available on the timing of weaning from KRT. More recently, various biomarkers have produced promising prognostic prediction in such patients, regarding the need for KRT and its termination. Most of these biomarkers are indicative of kidney damage and stress, rather than recovery. However, large-scale validation studies are required to guide the cutoff values of these biomarkers among different patient cohorts so as to identify the optimum timing for KRT. This article reviews the kidney biomarkers in detail and summarizes the individual roles of biomarkers in the decision-making process for initiation and termination of the KRT among critically ill AKI patients and the supportive literature.

• Biomarker
• Neutrophil gelatinase-associated lipocalin
• Kidney replacement therapy
• Proenkephalin 119–159
• Acute kidney injury
• Cystatin C

• Diabetes mellitus
• Diabetic nephropathy
• Microalbuminuria
• Urinary biomarker

• Humans
• Diabetic Nephropathies/urine
• Diabetic Nephropathies/diagnosis
• Biomarkers/urine
• Oxidative Stress
• MicroRNAs/urine

• Biomarkers
• Cardiorenal
• Heart failure
• Kidney disease
• Kidney function

• Acquired Fanconi syndrome
• Dog
• Urinary L-FABP

Liver-type fatty acid-binding protein (L-FABP) is a biomarker for the early detection of renal diseases in humans. L-FABP is a cytotoxic oxidation product secreted from the proximal tubules under ischemic and oxidative stress conditions. First, L-FABP gene expression in the kidney and liver was evaluated. Next, the urinary L-FABP concentrations in dogs with or without renal diseases were measured using a novel enzyme-linked immunosorbent assay kit. Urinary L-FABP was normalized relative to urinary creatinine (uCre) concentrations (µg/g uCre). Finally, the relationships between urinary L-FABP and renal biomarkers used in canine medicine or serum alanine transaminase (ALT) as an indicator of liver damage were examined. Serum and urine samples from 94 client-owned dogs including 23 dogs with renal diseases and 71 dogs without renal diseases were used for analysis. Relative L-FABP gene expression was confirmed both in the liver and kidney. Dogs with renal diseases had a significantly higher urinary L-FABP than those without, and its predictive cutoff value was 26 µg/g uCre. Urinary L-FABP was significantly correlated with serum creatinine (r=0.4674, P<0.01), urea nitrogen (r=0.4907, P<0.01), urine specific gravity (r=−0.5100, P<0.01), and urine protein/creatinine ratio (r=0.7216, P<0.01), but not with serum ALT. Hence, dogs with a high urinary L-FABP value were more likely to have renal diseases.

• dog
• renal disease
• urinary liver-type fatty acid-binding protein

Liver-type fatty acid-binding protein (L-FABP) is a predictive marker for the early detection of acute kidney injury; however, less is known about how useful it is for predicting residual renal function (RRF) decline in patients on peritoneal dialysis (PD).

The study subjects were 35 patients on PD who underwent multiple peritoneal equilibration tests (PETs) between October 2011 and October 2019. Urinary L-FABP levels were analyzed with enzyme-linked immunosorbent assay. The relationship between baseline clinical data, including urinary L-FABP levels and the subsequent annual rate of renal Kt/V decline, was investigated.

The median follow-up duration was 11 months and the rate of renal Kt/V decline was 0.29/y. Compared with outcomes in the group with renal Kt/V preservation, renal Kt/V decline was associated with both high daily levels of urinary protein excretion (0.60 g/d [range, 0.50–0.87] vs. 0.36 g/d [range, 0.19–0.48]; P=0.01) and high daily levels of urinary L-FABP excretion (111.2 mg/d [range, 76.1–188.6] vs. 61.5 mg/d [range, 35.7–96.0]; P=0.002). Multiple logistic regression analysis showed that only high daily levels of urinary L-FABP excretion were independently associated with renal Kt/V decline (odds ratio 1.03, 95% confidence interval 1.00–1.05; P=0.001). Furthermore, higher daily levels of urinary L-FABP excretion were significantly correlated with the higher annual rate of renal Kt/V decline (r=0.71, P<0.001).

We demonstrated that daily levels of urinary L-FABP are associated with RRF decline in patients on PD. The results of the present study indicate that assessment of urinary L-FABP levels may help predict RRF decline in patients on PD.

• Acute kidney injury
• C-reactive protein
• Prognosis
• Recurrence
• Tolvaptan

Acute kidney injury (AKI) is a life-threatening illness that continues to have an in-hospital mortality rate of patients with AKI ranges from 20% to 50% or greater, depending on underlying conditions. However, it has only marginally declined over the past 25 years. Previous authoritative publications have been pointed out that the lack of useful biomarkers for AKI has limited progress in improving the outcomes of this disorder. The purpose of this paper is to review the recent biomarkers involved in the early detection of AKI and main reasons for the failure to identify new AKI biomarkers. So far, several new AKI biomarkers have been discovered and validated to improve early diagnosis, degree of severity, pathophysiology, differential diagnosis, prediction for major kidney adverse events (MAKE, risk groups for progressive renal failure, need for renal replacement therapy [RRT], or death). These biomarkers can be classified into functional, damage and pre-injury phase biomarkers. However, the clinical use of the studied biomarkers in AKI prediction remains unclear because large prospective multicenter trials have failed to demonstrate troponin-like diagnostic performance. Reasons for the failure to identify AKI biomarkers are the heterogeneity of AKI itself, biomarker limitations and long roads to the validation of candidates for new AKI biomarkers. In an effort to overcome these barriers to identifying new AKI biomarkers, kidney biopsy specimens should be obtained and assessed in human AKI populations. Research in this field should be carried out in a pan-social approach rather than conducted by just a few medical institutions.

• AKI
• biomarkers
• journey
• pre-injury phase
• tissue-driven

• IGFBP7
• IL-18
• KIM-1
• NGAL
• TIMP-2

• Acute kidney injury
• L-FABP
• NGAL
• Pediatric cardiac surgery
• Urinary biomarkers

Liver‐type fatty acid‐binding protein (L‐FABP) is a biomarker for early detection of renal disease in humans. Liver‐type fatty acid‐binding protein is cytotoxic oxidation products secreted from proximal tubules under ischemia and oxidative stress.

To examine renal expression and quantify urinary excretion of L‐FABP in catswith renal disease.

One hundred and thirty‐four client‐owned cats including 34 cats with serum creatinine (sCre) values >1.6 mg/dL and 10 other cats that died in clinics.

Tissue expressions of L‐FABP were examined by reverse transcription polymerase chain reaction and Western blotting. Urinary L‐FABP (uL‐FABP) and serum L‐FABP (sL‐FABP) levels were determined by enzyme‐linked immunosorbent assay. Anti‐liver‐type fatty acid‐binding protein antibody immunostained renal sections.

Feline kidneys express L‐FABP. Strong L‐FABP signals were observed in the lumens of proximal tubular cells in 5 cats with high uL‐FABP excretion, but not in 5 cats with low uL‐FABP excretion. In 9 normal cats, uL‐FABP index was <1.2 μg/g urinary creatinine (uCre). High uL‐FABP indexes (>10.0 μg/g uCre) were detected in 7 of 100 cats with low sCre (<1.6 mg/dL) and 18 of 44 cats with high sCre (>1.6 mg/dL). There was a weak correlation between L‐FABP index and sCre, serum symmetric dimethylarginine (SDMA), or blood urea nitrogen (BUN), and these correlation coefficients were increased by analyzing only data of cats with sCre >1.6 mg/dL. There was a weak correlation between u L‐FABP index and sL‐FABP in all tested cats, but not in cats with high sCre.

This study demonstrates correlations between L‐FABP and current renal biomarkers for chronic kidney disease in cats, such as sCre and SDMA. Liver‐type fatty acid‐binding protein may be a potential biomarker to predict early pathophysiological events in feline kidneys.

• acute kidney injury
• biomarker
• chronic kidney disease
• kidney

Kidney transplantation is the treatment of choice for patients with advanced chronic kidney disease (CKD) and end stage renal disease (ESRD). However, acute rejection (AR) is a common complication in kidney transplantation and is associated with reduced graft survival. Current diagnosis of AR relies mainly on clinical monitoring including serum creatinine, proteinuria, and confirmation by histopathologic assessment in the biopsy specimen of graft kidney. Although an early protocol biopsy is indispensable for depicting the severity of pathologic lesions in subclinical acute rejection (subAR), it is not acceptable in some cases and cannot be performed because of its invasive nature. Therefore, we examined the detection of noninvasive biomarkers that are closely related to the pathology of subAR in protocol biopsies three months after kidney transplantation. In this study, the urinary level of microtubule-associated protein 1 light chain 3 (LC3), monocyte chemotactic protein-1 (MCP-1), liver-type fatty acid-binding protein (L-FABP), neutrophil gelatinase-associated lipocalin (NGAL), and human epididymis secretory protein 4 (HE4) were measured three months after kidney transplantation. Urine samples of 80 patients undergoing kidney transplantation between August 2014 to September 2016, were prospectively collected after three months. SubAR was observed in 11 patients (13.8%) in protocol biopsy. The urinary levels of LC3, MCP-1, NGAL, and HE4 were significantly higher in patients with subAR than in those without, while those of L-FABP did not differ between the two groups. Multivariate regression models, receiver-operating characteristics (ROC), and areas under ROC curves (AUC) were used to identify predicted values of subAR. Urinary HE4 levels were able to better identify subAR (AUC = 0.808) than the other four urinary biomarkers. In conclusion, urinary HE4 is increased in kidney transplant recipients of subAR three months after kidney transplantation, suggesting that HE4 has the potential to be used as a novel clinical biomarker for predicting subAR.

• HE4
• WFDC2
• acute kidney injury
• urinary biomarker
• whey-acidic four-disulfide core domain protein 2

• Acute Disease
• Aged
• Biomarkers/urine
• Female
• Graft Rejection/diagnosis
• Graft Rejection/immunology
• Graft Rejection/urine
• Humans
• Kidney Transplantation/adverse effects
• Male
• Middle Aged
• Severity of Illness Index
• WAP Four-Disulfide Core Domain Protein 2/metabolism

The importance of true worsening renal failure (WRF), which is associated with a poor prognosis, had been suggested in patients with acute heart failure (AHF). The aim of the present study was to establish the biomarker strategy for the prediction of true WRF in AHF.

Two hundred eighty‐one patients with AHF were analysed. Their biomarkers were measured within 30 min of admission. Patients were assigned to the non‐WRF (n = 168), pseudo‐WRF (n = 56), or true‐WRF (n = 57) groups using the criteria of both acute kidney injury on admission and increasing serum creatinine value during the first 7 days. A Kaplan–Meier curve showed that the survival and heart failure event rate of the true‐WRF group within 1000 days was significantly lower than that of the non‐WRF and pseudo‐WRF groups (P ≤ 0.001). The multivariate Cox regression model also indicated that true WRF was an independent predictor of 1000 day mortality and heart failure events [hazard ratio: 4.315, 95% confidence interval (CI): 2.466–7.550, P ≤ 0.001, and hazard ratio: 2.834, 95% CI: 1.893–4.243, P ≤ 0.001, respectively]. The serum heart‐type fatty acid‐binding protein (s‐HFABP) levels were significantly higher in the true‐WRF group than in the non‐WRF and pseudo‐WRF groups (P ≤ 0.001). The multivariate logistic regression model indicated that the predictive biomarker for the true‐WRF group was the s‐HFABP level (odds ratio: 5.472, 95% CI: 2.729–10.972, P ≤ 0.001). The sensitivity and specificity for indicating the presence of true WRF were 73.7% and 76.8% (area under the curve = 0.831) for s‐HFABP in whole patients, respectively, and 94.7% and 72.7% (area under the curve = 0.904) in non‐chronic kidney disease (CKD) patients, respectively.

Cardiac biomarkers, especially the s‐HFABP, might predict the development of true WRF in AHF patients. Furthermore, the predictive value was higher in AHF patients without CKD than in those with CKD.

• Acute kidney injury
• Heart-type fatty acid-binding protein
• Liver fatty acid-binding protein
• Mortality
• Neutrophil gelatinase-associated lipocalin

• Animals
• Caprylates/pharmacokinetics
• Caprylates/toxicity
• Environmental Pollutants/pharmacokinetics
• Fluorocarbons/pharmacokinetics
• Fluorocarbons/toxicity
• Male
• Models, Biological
• Permeability
• Rats
• Tissue Distribution

• Acute decompensated heart failure
• Acute kidney injury
• Liver fatty acid-binding protein
• Mortality
• Neutrophil gelatinase-associated lipocalin
• Worsening renal function

Acute kidney injury (AKI) is characterized by an acute decline in renal function and is associated to increased mortality rate, hospitalization time, and total health-related costs. The severity of this ‘fearsome’ clinical complication might depend on, or even be worsened by, the late detection of AKI, when the diagnosis is based on the elevation of serum creatinine (SCr). For these reasons, in recent years a great number of new tools, biomarkers and predictive models have been proposed to clinicians in order to improve diagnosis and prevent the development of AKI. The purpose of this narrative paper is to review the current state of the art in prediction and early detection of AKI and outline future challenges.

• Acute kidney injury
• Biomarkers
• Genetics
• New OMICs
• Prediction

• Acute Kidney Injury/blood
• Acute Kidney Injury/complications
• Acute Kidney Injury/diagnosis
• Acute Kidney Injury/genetics
• Biomarkers/blood
• Cystatin C/blood
• Early Diagnosis
• Fatty Acid-Binding Proteins/blood
• Genetic Predisposition to Disease
• Genomics
• Hepatitis A Virus Cellular Receptor 1/blood
• Humans
• Insulin-Like Growth Factor Binding Proteins/blood
• Interleukin-18/blood
• Kidney Function Tests
• Lipocalin-2/blood
• Models, Biological
• Ouabain/blood
• Renal Insufficiency, Chronic/blood
• Renal Insufficiency, Chronic/etiology
• Risk Factors
• Severity of Illness Index
• Tissue Inhibitor of Metalloproteinase-2/blood

• Aerobic fitness
• Muscular strength
• Peritubular capillary blood flow

• Children
• Liver fatty acid-binding protein (L-FABP)
• Renal parenchymal scarring
• Vesicoureteral reflux

• Fatty acid binding protein (FABP1)
• Liver
• Triglyceride

• Animals
• Body Mass Index
• Brain/metabolism
• Cerebral Infarction/etiology
• Cerebral Infarction/genetics
• Dyslipidemias/genetics
• Dyslipidemias/metabolism
• Endocannabinoids/metabolism
• Fatty Acid-Binding Proteins/chemistry
• Fatty Acid-Binding Proteins/genetics
• Humans
• Liver/metabolism
• Mice
• Non-alcoholic Fatty Liver Disease/genetics
• PPAR alpha/metabolism
• Polymorphism, Single Nucleotide
• Protein Structure, Secondary
• Rats
• Species Specificity

• R25 OD016574 NIH HHS
• R01 DA035923 NIDA NIH HHS
• T35 OD010991 NIH HHS
• R21 DA032232 NIDA NIH HHS
• R01 DA035949 NIDA NIH HHS

SET domain-containing 2 (SETD2) is responsible for the trimethylation of histone H3 lysine36 (H3K36me3) and is one of the genes most frequently mutated in clear cell renal cell carcinoma (ccRCC). It is located at 3p21, one copy of which is lost in the majority of ccRCC tumors, suggesting that SETD2 might function as a tumor suppressor gene. However, the manner in which loss of SETD2 contributes to ccRCC development has not been studied in renal primary tubular epithelial cells (PTECs). Therefore, we studied the consequences of SETD2 knockdown through lentiviral shRNA in human PTECs. Consistent with its known function, SETD2 knockdown (SETD-KD) led to loss of H3K36me3 in PTECs. In contrast to SETD2 wild-type PTECs, which have a limited proliferation capacity; the SETD2-KD PTECs continued to proliferate. The expression profiles of SETD2-KD PTECs showed a large overlap with the expression profile of early-passage, proliferating PTECs, whereas nonproliferating PTECs showed a significantly different expression profile. Gene set enrichment analysis revealed a significant enrichment of E2F targets in SETD2-KD and proliferating PTECs as compared with nonproliferating PTECs and in proliferating PTEC compared with SETD2-KD. The SETD2-KD PTECs maintained low expression of CDKN2A and high expression of E2F1, whereas their levels changed with continuing passages in untreated PTECs. In contrast to the nonproliferating PTECs, SETD2-KD PTECs showed no β-galactosidase staining, confirming the protection against senescence. Our results indicate that SETD2 inactivation enables PTECs to bypass the senescence barrier, facilitating a malignant transformation toward ccRCC.

• AKI to CKD transition
• Acute kidney injury
• chronic kidney disease
• renal damage

• fatty liver
• ginger
• hesperidin
• hypercholesterolemia
• ogi

This cross-sectional study was to evaluate the levels of urinary liver-type fatty acid binding protein (u-LFABP pg/mg urine creatinine ratio) at different stages of diabetic nephropathy and to see its correlation with other clinical parameters in South Indian patients with type 2 diabetes mellitus (T2DM). A total of 65 (M: F; 42:23) T2DM subjects were divided into three groups, and were compared with 13 (M: F; 3:10) nondiabetic controls. The study groups were as follows: normoalbuminuric (n = 22), microalbuminuric (n = 22) and macroalbuminuric (n = 21). Estimated glomerular filtration rate (eGFR) was calculated using Cockcroft and Gault formula. u-LFABP levels in spot urine samples were measured with a solid phase enzyme linked immunosorbent assay. This study showed that u-LFABP levels were undetectable in healthy controls and was very low in the normoalbuminuric subjects. Elevated levels of u-LFABP are evident from the microalbuminuric stage indicating tubular damage. The levels of u-LFABP increased gradually with declining renal function. Geometric mean (95% confidence interval) for normoalbuminuria was 0.65 (0.47–0.97), microalbuminuria was 0.99 (0.55–1.97) and macroalbuminuria was 5.16 (1.8–14.5), (P = 0.005). In conclusion, u-LFABP levels were elevated in patients with reduced eGFR and showed a positive correlation with systolic blood pressure and protein to creatinine ratio in the total study subjects.

• Diabetic nephropathy
• type 2 diabetes
• urinary liver-type fatty acid binding protein
• urinary marker

• Acute kidney injury
• Biomarkers
• Mortality
• Renal replacement therapy

• Cholesterol uptake
• Hepatocyte
• Human FABP1
• Lipoprotein

Fatty acid-binding protein 4 (FABP4/A-FABP/aP2) is expressed in not only adipocytes and macrophages but also peritubular capillaries in the normal kidney. We recently demonstrated that ectopic expression of FABP4, but not FABP1 known as liver FABP (L-FABP), in the glomerulus is associated with progression of proteinuria and renal dysfunction. However, urinary excretion of FABP4 has not been investigated.

Subjects who participated in the Tanno-Sobetsu Study, a study with a population-based cohort design, in 2011 (n = 392, male/female: 166/226) were enrolled. Urinary FABP4 (U-FABP4) and urinary albumin-to-creatinine ratio (UACR) were measured. Change in estimated glomerular filtration rate (eGFR) was followed up one year later.

In 93 (23.7%) of the 392 subjects, U-FABP4 level was below the sensitivity of the assay. Subjects with undetectable U-FABP4 were younger and had lower UACR and higher eGFR levels than subjects with measurable U-FABP4. U-FABP4 level was positively correlated with age, systolic blood pressure and levels of serum FABP4 (S-FABP4), triglycerides, hemoglobin A1c (HbA1c), urinary FABP1 (U-FABP1) and UACR (r = 0.360, p<0.001). Age, S-FABP4, U-FABP1 and UACR were independent predictors of U-FABP4. On the other hand, systolic blood pressure, HbA1c and U-FABP4 were independently correlated with UACR. Reduction in eGFR after one year was significantly larger in a group with the highest tertile of baseline U-FABP4 than a group with the lowest tertile.

Urinary FABP4 level is independently correlated with level of albuminuria and possibly predicts yearly decline of eGFR. U-FABP4 would be a novel biomarker of glomerular damage.

• Aged
• Aged, 80 and over
• Albuminuria/physiopathology
• Biomarkers/urine
• Cohort Studies
• Fatty Acid-Binding Proteins/urine
• Female
• Glomerular Filtration Rate
• Humans
• Kidney Diseases/diagnosis
• Kidney Diseases/physiopathology
• Kidney Glomerulus/physiopathology
• Male
• Renal Elimination

• Bofutsushosan
• Boiogito
• Keishibukuryogan
• fatty liver
• hypercholesterolemia

• Dip-test
• Enzyme-linked immunosorbent assay
• Point of care testing
• Urinary liver-type fatty acid-binding protein

• Biomarker
• I-FABP
• IL-8
• Interleukin-8
• Intestinal fatty acid binding protein
• L-FABP
• Liver fatty acid binding protein
• NEC
• Necrotizing enterocolitis

• acute renal failure
• pathophysiology of renal disease and progression
• renin-angiotensin system

• l-fabp
• fibrate
• liver
• human

• Amino Acid Substitution
• Animals
• Binding Sites
• Cells, Cultured
• Fatty Acid Transport Proteins/agonists
• Fatty Acid Transport Proteins/genetics
• Fatty Acid Transport Proteins/metabolism
• Fatty Acid-Binding Proteins/agonists
• Fatty Acid-Binding Proteins/chemistry
• Fatty Acid-Binding Proteins/genetics
• Fatty Acid-Binding Proteins/metabolism
• Fenofibrate/analogs & derivatives
• Fenofibrate/metabolism
• Fenofibrate/pharmacology
• Fibric Acids/metabolism
• Fibric Acids/pharmacology
• Gene Expression Regulation/drug effects
• Hot Temperature
• Humans
• Hypolipidemic Agents/metabolism
• Hypolipidemic Agents/pharmacology
• Ligands
• Liver/cytology
• Liver/metabolism
• Mice
• PPAR alpha/agonists
• PPAR alpha/genetics
• PPAR alpha/metabolism
• Phytanic Acid/metabolism
• Phytanic Acid/pharmacology
• Polymorphism, Single Nucleotide
• Protein Stability
• Protein Structure, Secondary
• Rats
• Recombinant Proteins/chemistry
• Recombinant Proteins/metabolism

• R56 DK070965 NIDDK NIH HHS
• DK70965 NIDDK NIH HHS
• P30 DK020572 NIDDK NIH HHS
• R01 DK041402 NIDDK NIH HHS
• DK41402 NIDDK NIH HHS
• R01 DK070965 NIDDK NIH HHS

• Adult
• Albuminuria/urine
• Diabetes Mellitus, Type 1/pathology
• Diabetes Mellitus, Type 1/urine
• Diabetic Nephropathies/pathology
• Diabetic Nephropathies/urine
• Fatty Acid-Binding Proteins/urine
• Female
• Humans
• Male
• Middle Aged

Women with polycystic ovary syndrome (PCOS) have higher risk for cardiovascular disease (CVD). Heart type fatty acid binding protein (HFABP) has been found to be predictive for myocardial ischemia.Wet ested whether HFABP is the predictor for CVD in PCOS patients, who have an increased risk of cardiovascular disease.

This was a prospective, cross sectional controlled study conducted in a training and research hospital.The study population consisted of 46 reproductive-age PCOS women and 28 control subjects. We evaluated anthropometric and metabolic parameters, carotid intima media thickness and HFABP levels in both PCOS patients and control group.

Mean fasting insulin, homeostasis model assessment insulin resistance index (HOMA-IR), triglyceride, total cholesterol, low density lipoprotein cholesterol, free testosterone, total testosterone, carotid intima media thickness (CIMT) levels were significantly higher in PCOS patients. Although HFABP levels were higher in PCOS patients, the difference did not reach statistically significant in early age groups. After adjustment for age and body mass index, HFABP level was positive correlated with hsCRP, free testosterone levels, CIMT and HOMA-IR.

Heart type free fatty acid binding protein appeared to have an important role in metabolic response and subsequent development of atherosclerosis in insulin resistant, hyperandrogenemic PCOS patients.