Urinary L-FABP as an Early Biomarker for Pediatric Acute Kidney Injury Following Cardiac Surgery with Cardiopulmonary Bypass: A Systematic Review and Meta-Analysis.

Acute kidney injury (AKI) following surgery with cardiopulmonary bypass (CPB-AKI) is common in pediatrics. Urinary liver-type fatty acid binding protein (uL-FABP) increases in some kidney diseases and may indicate CPB-AKI earlier than current methods. The aim of this systematic review with meta-analysis was to evaluate the potential role of uL-FABP in the early diagnosis and prediction of CPB-AKI. Databases Pubmed/MEDLINE, Scopus, and Web of Science were searched on 12 November 2023, using the MeSH terms "Children", "CPB", "L-FABP", and "Acute Kidney Injury". Included papers were revised. AUC values from similar studies were pooled by meta-analysis, performed using random- and fixed-effect models, with p < 0.05. Of 508 studies assessed, nine were included, comprising 1658 children, of whom 561 (33.8%) developed CPB-AKI. Significantly higher uL-FABP levels in AKI versus non-AKI patients first manifested at baseline to 6 h post-CPB. At 6 h, uL-FABP correlated with CPB duration (r = 0.498, p = 0.036), postoperative serum creatinine (r = 0.567, p < 0.010), and length of hospital stay (r = 0.722, p < 0.0001). Importantly, uL-FABP at baseline (AUC = 0.77, 95% CI: 0.64-0.89, n = 365), 2 h (AUC = 0.71, 95% CI: 0.52-0.90, n = 509), and 6 h (AUC = 0.76, 95% CI: 0.72-0.80, n = 509) diagnosed CPB-AKI earlier. Hence, higher uL-FABP levels associate with worse clinical parameters and may diagnose and predict CPB-AKI earlier.

Comparison of Urinary Liver Fatty Acid Binding Protein Level and Pathologic Biopsy Findings 1 Year After Kidney Transplantation.

BACKGROUND: For the early detection of abnormal findings considering for therapeutic intervention, we regularly undertake protocol renal allograft biopsy at 1 year after kidney transplantation (KT). We examined whether urinary liver fatty acid binding protein (L-FABP) level predicts some pathologic findings of renal allograft. METHODS: We retrospectively enrolled recipients with stable graft function who routinely were biopsied renal allograft specimens 1 year after KT between January 2015 and May 2021 in our center. We assessed the association urinary L-FABP level with pathologic findings of renal allograft biopsies. RESULTS: We enrolled 56 recipients in this study. Their median age at KT was 49.5 and their median serum creatinine at 1 year after KT was 1.22 mg/dL. In 9 of 56 patients, abnormal high value of urinary L-FABP were observed. All of them had abnormal findings pathologically in the renal allografts (border line change 3, medullary ray injury [MRI] with calcineurin inhibitor toxicity [CNI-T] 1, MRI without CNI-T 1, CNI-T with IgA deposition 1, and BK virus nephropathy 3). On the other hand, 30 of 47 patients with normal value of urinary LFABP had no pathologically abnormal findings. Both specificity and positive predictive value of urinary L-FABP for pathologic findings were 100.0༅. CONCLUSIONS: Our results suggest that patients with renal transplant with elevated urinary L-FABP levels might benefit from renal allograft biopsy. Comparison of urinary liver fatty acid binding protein level and pathologic biopsy findings 1 year after KT.

Elevation of Urinary Liver-Type Fatty Acid-Binding Protein Is a Harbinger of Poor Patient Prognosis after Allogeneic Stem Cell Transplantation.

Several recent studies have demonstrated that urinary levels of liver-type fatty acid-binding protein (L-FABP) can be used to stratify the prognosis of cardiac disease, cardiac intensive care unit admission, cirrhosis, and coronavirus disease 2019. Our initial prospective study revealed that urinary L-FABP (uL-FABP) was associated with a high probability of acute kidney injury after stem cell transplantation (SCT); however, the relevance of elevated uL-FABP to the prognosis of patients undergoing SCT remains to be determined. We aimed to investigate whether uL-FABP levels can be used to stratify patient prognosis after SCT. To achieve this aim, we conducted a new long-term follow-up study using data from patients enrolled in our preceding prospective cohort study. Patients were classified into high and low uL-FABP groups based on levels measured at baseline (ie, before initiating the conditioning regimen), using an uL-FABP cutoff of 8.4 µg/gCr, which was determined based on data from healthy adults. uL-FABP levels were also measured on days 0, 7, and 14 after SCT. Cox proportional hazard regression was used to examine the effects of each factor on survival outcomes, and Fine-Gray regression was used in the presence of competing risks. Multivariate analysis incorporating confounders was then performed for factors with P < .1 in univariate analysis. In total, 20 of 84 patients (23.8%), 57 of 84 patients (67.9%), 34 of 49 patients (69.4%), and 34 of 46 patients (73.9%) were classified into the high uL-FABP group at baseline and on days 0, 7, and 14, respectively. The 5-year overall survival (OS) rate was 23.9% in the high uL-FABP group and 68.9% in the low uL-FABP group. The multivariate analysis identified a high uL-FABP level at baseline as a significant prognostic factor for poor OS (hazard ratio [HR], 3.54; P = .002). The 5-year cumulative incidence rate for nonrelapse mortality (NRM) was 50.0% in the high uL-FABP group and 19.9% in the low uL-FABP group. In the multivariate analysis, high uL-FABP at baseline was a significant prognostic factor for NRM (HR, 3.37; P = .01). uL-FABP levels did not significantly stratify the cumulative incidence of relapse (HR, 2.13; P = .11). uL-FABP levels on days 0, 7, and 14 were not significant predictors of survival. High uL-FABP level before initiation of conditioning significantly influences OS and NRM following SCT, whereas a high uL-FABP level at any point after the conditioning regimen does not. Our results show that measuring uL-FABP level at baseline may be a simple way to predict survival in patients undergoing SCT.

Early biomarkers for kidney injury in heat-related illness patients: a prospective observational study at Japanese Self-Defense Force Fuji Hospital.

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-ß-D-glucosaminidase (NAG) and ß2-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.

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

BACKGROUND: Kidney biopsies of patients with diabetic nephropathy (DN) and normal kidney function may exhibit interstitial fibrosis (IF) without reduction of glomerular filtration rate (GFR) because of hyperfiltration. The aim of our study was to analyse the performance of a set of biomarkers of tubular injury to estimate the extent of IF in patients with DN and normal kidney function. METHODS: This cross-sectional study included 118 adults with DN diagnosed by kidney biopsy and GFR ≥90 mL/min/1.73 m2 and a control group of healthy subjects. We measured the urinary excretion of monocyte chemoattractant protein-1 (MCP-1) neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), liver-type fatty acid-binding protein (L-FABP), ß2-microglobulin and dickkopf-3 protein (DKK-3) at the time of kidney biopsy. GFR was measured by chromium-51 labeled ethylenediamine tetraacetic acid (Cr-EDTA) (measured GFR). IF was quantified using a quantitative morphometric procedure. Predictive multivariate models were developed to estimate the IF surface. RESULTS: Patients with DN showed significantly higher levels of DKK-3, MCP-1 and L-FABP and significantly lower levels of epidermal growth factor (EGF) than healthy controls. There were no significant between-group differences in the levels of ß2-microglobulin, KIM-1 or NGAL. IF was negatively associated with EGF and positively with age, proteinuria, MCP-1, DKK-3 and L-FABP, but not with ß2-microglobulin, KIM-1, NGAL or GFR. The best model to predict IF surface accounted for 59% of its variability and included age, proteinuria, EGF, DKK-3 and MCP-1. CONCLUSIONS: Our study provides a model to estimate the IF in DN that can be useful to assess the progression of IF in patients with normal kidney function.

Urinary L-type fatty acid-binding protein is a predictor of cisplatin-induced acute kidney injury.

BACKGROUND: Although cisplatin-based chemotherapy is a standard treatment for urothelial carcinoma, it often causes acute kidney injury (AKI). AKI and dysfunction are observed in 25-35% of cisplatin-based chemotherapy patients, who may require treatment down-titration or withdrawal. In this study, we evaluated whether urinary L-FABP is a marker for early diagnosis of cisplatin-caused AKI. METHODS: We included 42 adult patients who underwent cisplatin-based chemotherapy for bladder cancer or upper tract urothelial carcinoma from January 2018 to March 2019. Urinary L-FABP and serum creatinine were measured at 2 and 6 h, and 1, 2, 3, 7 and 28 days after taking cisplatin. RESULTS: In the first week after receiving cisplatin, 10 patients (23.8%) were diagnosed with AKI (AKI+ group). Pre-treatment (baseline) measurements did not significantly differ between the AKI+ and AKI- groups. However, urinary L-FABP concentrations rapidly increased in the AKI+ group and were significantly greater than in the AKI- group at Hour 2, Hour 6, Day 1 and Day 2. Serum creatinine also significantly differed between the AKI+ group and the AKI- group on Days 3 and 7. ROC analysis was performed to evaluate the superiority of urinary L-FABP magnification which had the highest at the hour 6. The urinary L-FABP magnification and levels of aria under curve was 0.977. Based on ROC analysis, the best cut-off value of urinary L-FABP magnification was 10.28 times urinary L-FABP levels at the hour 0 (base line urinary L-FABP). CONCLUSIONS: Acute renal function deterioration was predicted by increased urinary L-FABP excretion within 6 h after receiving CIS-CT and, in those with AKI, the increase in urinary L-FABP excretion preceded the rise in sCr by over 2 days. In contrast, no appreciable changes in urinary L-FABP levels were observed in patients with stable renal function throughout the whole observation period. So early increase in urinary L-FABP may identify patients at risk of cisplatin-induced AKI, who might benefit from treatment to prevent nephrotoxicity. TRIAL REGISTRATION: This study was retrospectively registered.

Urinary Biomarkers Can Predict Weaning From Acute Dialysis Therapy in Critically Ill Patients.

CONTEXT.­: Critically ill patients with acute kidney injury (AKI) requiring renal replacement therapy (RRT) have a poor prognosis. Several urinary AKI biomarkers have been proposed to predict renal recovery, but with limited discriminatory ability. OBJECTIVE.­: To validate the predictive performances of novel biomarkers to identify which critical patients with AKI may successfully wean from RRT. DESIGN.­: We prospectively recorded and analyzed clinical variables at several time points: (1) before starting RRT, (2) at the time of weaning off RRT, and (3) 24 hours after stopping RRT. A total of 140 critically ill patients who received RRT at a multicenter referral hospital from August 2016 to January 2019 were enrolled. The outcomes of interest were the ability to wean from RRT and 90-day mortality. RESULTS.­: The 90-day mortality rate was 13.6% (19 of 140), and 47.9% (67 of 140) of the patients were successfully weaned from RRT. Cluster analysis showed that the following biomarkers were correlated with estimated glomerular filtration rate at the time of weaning off RRT: urinary neutrophil gelatinase-associated lipocalin, kidney injury molecule 1, hemojuvelin, C-C motif chemokine ligand 14, interleukin 18, and liver-type fatty acid-binding protein (L-FABP). Among these, urinary L-FABP/creatinine (uL-FABP/Cr) at the time of weaning off RRT showed the best predictive performance for mortality (area under the receiver operating characteristic curve = 0.79). Taking mortality as a competing risk, Cox proportional hazards analysis indicated that a low uL-FABP/Cr (log) level was an independent prognostic factor for weaning from RRT (subdistribution hazard ratio, 0.35; P = .01). CONCLUSIONS.­: uL-FABP/Cr at the time of weaning off RRT could predict weaning from RRT and 90-day mortality.

Urinary liver-type fatty acid-binding protein in two dogs with acquired Fanconi syndrome: A case report.

Background: Fanconi syndrome (FS) is defined as multiple defects of the proximal tubules and is diagnosed by clinical symptoms. However, in dogs with FS, the damage in the proximal tubules that is responsible for the clinical symptoms has not been evaluated. Among FS cases, tubular damage in acquired FS is reversible following the elimination of a causative factor. Liver-type fatty acid-binding protein (L-FABP) is a biomarker of tubular damage in various animals including dogs. Urinary L-FABP measurement may be useful for the diagnosis and follow-up evaluation in canine FS. Case Description: At the first visit, two Toy Poodles that had no remarkable findings on physical examination presented with glycosuria without hyperglycemia, hypokalemia, hyperchloremia, increased levels of plasma alkaline phosphatase, and metabolic acidosis. Considering all the factors involved, the dogs were clinically diagnosed with acquired FS. The owner reported that they routinely fed the dog with chicken jerky, a recently considered cause of acquired FS. Following the withdrawal of the jerky, abnormalities including glycosuria improved in both dogs. Moreover, urinary L-FABP levels, which were high at diagnosis, presented a decreasing trend during the follow-up. However, in one dog, the elevated urinary L-FABP level did not return to normal. Conclusion: Although the clinical symptoms of acquired FS in dogs could be improved by the elimination of a causative factor, the severity of tubular damage described by urinary L-FABP may not be necessarily linked to the degree of functional deterioration. Therefore, the evaluation of proximal tubular damage by L-FABP may be of clinical value during the follow-up of acquired FS in canines.

Urinary concentrations of neonicotinoid insecticides were related to renal tubular dysfunction and neuropsychological complaints in Dry-zone of Sri Lanka.

Neonicotinoids are systemic insecticides used since the 1990's , that possess renal tubular toxicity. We conducted a field-based descriptive study in the North Central Dry-zone of Sri Lanka, where chronic kidney disease (CKD) of unknown etiology has been increasing since the 1990's. To elucidate the relationship between renal tubular dysfunctions and urinary neonicotinoids concentrations, we collected spot urine samples from15 CKD patients, 15 family members, and 62 neighbors in 2015, analyzed two renal tubular biomarkers, Cystatin-C and L-FABP, quantified seven neonicotinoids and a metabolite N-desmethyl-acetamiprid by LC-MS/MS; and we investigated their symptoms using a questionnaire. Cystatin-C and L-FABP had a positive correlation (p < 0.001). N-Desmethyl-acetamiprid was detected in 92.4% of the urine samples, followed by dinotefuran (17.4%), thiamethoxam (17.4%), clothianidin (9.8%), thiacloprid and imidacloprid. Dinotefuran and thiacloprid have never been registered in Sri Lanka. In High Cystatin-C group (> 70 µg/gCre, n = 7), higher urinary concentration of dinotefuran (p = 0.009), and in Zero Cystatin-C group (< LOQ, n = 7), higher N-desmethyl-acetamiprid (p = 0.013), dinotefuran (p = 0.049), and thiacloprid (p = 0.035), and more complaints of chest pains, stomachache, skin eruption and diarrhea (p < 0.05) were found than in Normal Cystatin-C group (n = 78). Urinary neonicotinoids may be one of the potential risk factors for renal tubular dysfunction in this area.

COVID-19-induced acute renal tubular injury associated with elevation of serum inflammatory cytokine.

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-ß-D-glucosaminidase (uNAG), ß2-microglobulin (u ß2MG), 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, uß2MG, 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, uß2MG, 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 Δuß2MG. CONCLUSIONS: Levels of tubular injury markers, especially L-FABP and uß2MG, were significantly associated with IL-6 levels even in patients with no evident AKI. This suggests that L-FABP and uß2MG could be useful as early detective biomarkers for COVID-19 associated renal injury.

Significance of urinary liver-type fatty acid-binding protein in patients with normal renal function after undergoing intestinal urinary diversion: a preliminary study.

BACKGROUND: Liver-type fatty acid-binding protein (L-FABP) in urine is one of the early diagnostic biomarkers for acute and chronic kidney injuries. Although this protein is also identified in the intestine, there is no verified reference value for patients with intestinal urinary diversion (UD). The aim of the present study was to measure L-FABP values in such patients and compare them with the results for patients without UD. METHODS: Spot urine specimens were collected from 41 patients with UD and 50 subjects without UD with estimated glomerular filtration rates of over 60 ml/min/1.73 m2, and the L-FABP values were measured. The normal upper cutoff value in healthy subjects without UD is considered to be 7.24 µg/g Cr. First, the median values of the two groups were compared. Next, the subjects with negative proteinuria and without comorbidities associated with renal function were further selected and the median values of the groups were compared. RESULTS: The mean age was significantly higher in the UD group. The types of UD were ileal conduit (38 patients) and ileal neobladder (three patients). The median L-FABP value in the UD group was significantly higher than that in the non-diversion group (89.1 µg/g Cr vs. 2.0 µg/g Cr, p < 0.0001). After adjustment for their backgrounds, the median value remained higher in the UD group. CONCLUSIONS: L-FABP values in subjects with UD are higher than in those without UD. By this result, to develop a reference value in patients with intestinal UD population, further studies are required.

Urinary Markers and Chronic Effect of Physical Exercise.

Chronic kidney disease (CKD) is a type of kidney disease in which there is gradual loss of kidney function over a period of months to years. The clinical protocol of CKD forecasts that markers such as serum creatinine, the estimate of the glomerular filtration rate value, microalbuminuria, cystatin c are evaluated as routine markers. In recent years, new studies have identified new markers to diagnose and assess the level of kidney damage.The prevalence of CKD increases in subjects suffering from cardiovascular and metabolic diseases. The highest risk of cardiovascular risk in the CKD patient compared to the general population is related to risk factors such as hypertension, obesity, and specific renal disease factors such as albuminuria.Physical exercise, especially aerobic, has been seen through the analysis of urinary markers, able to mitigate the adverse effect of sedentary, hypertension and interstitial damage in patients with CKD and decrease the urinary levels liver-type fatty acid binding protein (L-FABP) and lower urinary albumin excretion.

Significance of urinary fatty acid-binding protein 4 level as a possible biomarker for the identification of minimal change disease in patents with nephrotic-range proteinuria.

BACKGROUND: Fatty acid-binding protein 4 (FABP4), but not FABP1 (liver-type FABP), is ectopically induced in injured glomerular endothelial cells, and urinary FABP4 (U-FABP4) level is associated with proteinuria and renal dysfunction in a general population. METHODS: The clinical significance of U-FABP4 was investigated in 81 patients (male/female: 43/38, age: 57 ± 17 years) who underwent kidney biopsy. RESULTS: U-FABP4 was negatively correlated with estimated glomerular filtration rate (eGFR) (r = - 0.56, P < 0.01) and was positively correlated with age, blood pressure, triglycerides, proteinuria (r = 0.58, P < 0.01), plasma FABP4 and urinary FABP1 (U-FABP1) (r = 0.52, P < 0.01). Multivariable regression analysis showed that eGFR, proteinuria and U-FABP1 were independent predictors of U-FABP4. The level of U-FABP4, but not that of proteinuria, eGFR or U-FABP1, in minimal change nephrotic syndrome (MCNS) was significantly lower than the level in membranous nephropathy (MN) and that in diabetic nephropathy. Receiver operating characteristic curve analysis indicated that U-FABP4 level ≤ 0.78 µg/gCr predicted MCNS in patients who had nephrotic-range proteinuria with a high level of accuracy. When divided by the median value of U-FABP4 at baseline in 33 of the 81 patients who could be followed up, the yearly change (post-pre) in eGFR in the low U-FABP4 group was significantly greater than that in the high U-FABP4 group (median: 11.0 vs. -5.0 mL/min/1.73m2/year). CONCLUSIONS: U-FABP4 level is independently associated with proteinuria and renal dysfunction in patients with glomerular kidney disease. A low U-FABP4 level may predict MCNS in patients with nephrotic syndrome and would be a useful biomarker for differential diagnosis of MCNS and MN, which are common causes of nephrotic syndrome.

Analysis of the association between kidney injury biomarkers concentration and nephritis in immunoglobulin A vasculitis: A pediatric cohort study.

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.

The need for disruptive innovation in acute kidney injury.

Acute kidney injury (AKI) is a threatening medical condition associated with poor outcomes at different settings. The development of standardized diagnostic criteria and new biomarkers addressed significant clinical impacts of AKI and the need for an early AKI detection, respectively. There have been some breakthroughs in understanding the pathogenesis of AKI through basic research; however, treatments against AKI aside from renal replacement therapy (RRT) have not shown adequate successful results. Biomarkers that could identify good responders to certain treatment are expected to facilitate translation of basic research findings. Most patients with severe AKI treated with RRT died due to multiple-organ failure, not renal dysfunction. Hence, it is essential to identify other organ dysfunctions induced by AKI as organ crosstalk. Also, a multidisciplinary approach of critical care nephrology is needed to evaluate a complex organ crosstalk in AKI. For disruptive innovation for AKI, we further explore these new aspects of AKI, which previously were considered outside the scope of nephrology.

Biomarkers of Contrast-Induced Nephropathy:: Which Ones are Clinically Important?

Contrast-induced acute kidney injury (CI-AKI) is a common complication after intravascular injection of iodinated contrast media, and it is associated with a prolonged in-hospital stay and unfavorable outcome. CI-AKI occurs in 5% to 20% among hospitalized patients. Its diagnosis relies on the increase in serum creatinine levels, which is a late biomarker of kidney injury. Novel and early serum and urinary biomarkers have been identified to detect kidney damage before the expected serum creatinine increase.

Longitudinal kidney injury biomarker trajectories in children with obstructive uropathy.

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.

Urinary I-FABP, L-FABP, TFF-3, and SAA Can Diagnose and Predict the Disease Course in Necrotizing Enterocolitis at the Early Stage of Disease.

Necrotizing enterocolitis (NEC) is a severe gastrointestinal disease affecting mainly preterm newborns. It is characterized by unexpected onset and rapid progression with specific diagnostic signs as pneumatosis intestinalis or gas in the portal vein appearing later in the course of the disease. Therefore, we analyzed diagnostic and prognostic potential of the markers of early NEC pathogenesis, such as excessive inflammatory response (serum amyloid A (SAA)) and gut epithelium damage (intestinal and liver fatty acid-binding protein (I-FABP and L-FABP, respectively) and trefoil factor-3 (TFF-3)). We used ELISA to analyze these biomarkers in the urine of patients with suspected NEC, either spontaneous or surgery-related, or in infants without gut surgery (controls). Next, we compared their levels with the type of the disease (NEC or sepsis) and its severity. Already at the time of NEC suspicion, infants who developed NEC had significantly higher levels of all tested biomarkers than controls and higher levels of I-FABP and L-FABP than those who will later develop sepsis. Infants who will develop surgery-related NEC had higher levels of I-FABP and L-FABP than those who will develop sepsis already during the first 6 hours after the abdominal surgery. I-FABP was able to discriminate between infants who will develop NEC or sepsis and the SAA was able to discriminate between medical and surgical NEC. Moreover, the combination of TFF-3 with I-FABP and SAA could predict pneumatosis intestinalis, and the combination of I-FABP, L-FABP, and SAA could predict gas in the portal vein or long-term hospitalization and low SAA predicts early full enteral feeding. Thus, these biomarkers may be useful not only in the early, noninvasive diagnostics but also in the subsequent NEC management.

Clinical and subclinical acute kidney injury in multidrug-resistant septic patients treated with colistimethate sodium: Incidence and clinical outcomes.

AIM: Colistimethate sodium (CMS) has been postulated as the principal cause of high incidence of clinical acute kidney injury (AKI) in multidrug-resistance (MDR) septic patients with normal baseline serum creatinine (sCr) who were treated with CMS. This prospective observational study was conducted to examine the incidence and clinical outcomes of clinical and subclinical AKI in MDR septic patients receiving CMS. METHODS: Forty-two MDR septic patients with normal sCr who required CMS were included. Clinical AKI was diagnosed by increased sCr levels according to the KDIGO2012 criteria while subclinical AKI was identified by elevated levels of urinary neutrophil gelatinase-associated lipocalin (uNGAL > 150 ng/mL) or urinary liver-type fatty-acid-binding protein (uL-FABP > 10.5 ng/mL). RESULTS: Clinical AKI was noted in 47.6% of patients on day 5 and 38.1% on day 7 after initiating CMS. By using uL-FABP, subclinical AKI was observed in 45.2% and 54.8% on day 5 and 7, respectively. At baseline prior to CMS treatment, subclinical AKI was already present in 90%. The baseline uL-FABP was superior to the baseline uNGAL in early prediction of clinical AKI on day 5. The subclinical AKI patients had comparable worse outcomes as clinical AKI patients. CONCLUSION: The incidence of subclinical AKI in MDR septic patients before CMS treatment was extremely high. The baseline uL-FABP provided the best predictive capacity of clinical AKI. The causes of clinical AKI might include the persistence of sepsis process, subclinical AKI and CMS nephrotoxicity. Proper management of subclinical AKI patients before CMS initiation should be concerned to prevent further renal damage and improve patient and renal outcomes.

Novel Urinary Biomarkers for Acute Kidney Injury and Prediction of Clinical Outcomes After Pediatric Cardiac Surgery.

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.