Liver-type fatty acid-binding protein and neutrophil gelatinase-associated lipocalin in cats with chronic kidney disease and hyperthyroidism.
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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 (131 I) 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) 131 I 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.
SUBMITTER: Kongtasai T
PROVIDER: S-EPMC8162613 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundNeutrophil gelatinase-associated lipocalin (NGAL) is a biomarker for the early prediction of renal damage and the progression of chronic kidney disease (CKD) in humans and dogs.HypothesisNeutrophil gelatinase-associated lipocalin also may play a role in the progression of CKD in cats.AnimalsEighty CKD and 18 control cats.MethodsCats were categorized into different stages according to the International Renal Interest Society (IRIS) staging system. Urine and plasma samples were collected and tested for NGAL concentrations using an in-house sandwich ELISA system and urinary NGAL (uNGAL)-to-creatinine ratio (UNCR) was determined. Cats in which serum creatinine concentration increased by >0.5 mg/dL from baseline within 30 days were defined as exhibiting progression.ResultsThe urinary NGAL and UNCR of CKD cats were significantly higher than those of healthy cats (P < .05) and were highly correlated with serum creatinine concentration. The area under the receiver operating characteristic curve (AUROC) for uNGAL, when predicting the progression of CKD, was 0.71 and the best cutoff value was 2.06 ng/mL with a sensitivity of 76.9% and a specificity of 75%. The AUROC for UNCR when predicting the progression of CKD was 0.79 and the best cutoff value was 4.08 × 10-6 with a sensitivity of 76.9% and specificity of 79.2%. Cats with UNCR values higher than their cutoffs experienced significantly faster deterioration with a median of 19 days.ConclusionsBoth urinary NGAL and UNCR are useful markers for the prediction of CKD progression in cats.
| S-EPMC5259624 | biostudies-literature
Project description:BackgroundPlasma neutrophil gelatinase-associated lipocalin (pNGAL) has been investigated extensively in acute kidney injury. This study investigated its pathophysiological significance and utility as marker for graft failure and mortality in stable kidney transplant recipients (KTR).MethodsBaseline pNGAL was measured in 698 KTR (58% male, age 53 ± 13 years, estimated glomerular filtration rate 52.4 ± 20.4 mL/min/1.73 m2) at median 5.4 (interquartile range 1.8-12.0) years after transplantation, enrolled in the prospective TransplantLines Food and Nutrition Biobank and Cohort Study.ResultspNGAL concentrations were higher in males, younger patients, patients with a deceased-donor kidney and higher serum creatinine. Independent of these, pNGAL was positively associated with urinary protein excretion, systemic inflammation parameters and calcineurin inhibitor use. During median follow-up of 5.3 (4.5-6.0) years, death-censored graft failure rates were 3.9%, 7.3% and 25.0% across increasing tertiles of pNGAL (Plog-rank < 0.001). Cox-regression analyses showed no independent associations of pNGAL with mortality, but strong associations with graft failure (hazard ratio, per doubling 4.16; 95% confidence interval 3.03-5.71; P < 0.001), which remained independent of adjustment for confounders. These associations were present only in patients with pre-existent proteinuria and poor kidney function.ConclusionspNGAL is associated with parameters of kidney graft damage and with graft failure. The latter association is particularly present in KTR with pre-existent poor kidney function and proteinuria. Trial Registration: ClinicalTrials.gov NCT02811835.
| S-EPMC8824800 | biostudies-literature
Project description:Circulating levels of neutrophil gelatinase-associated lipocalin (NGAL) have been associated with acute kidney injury and the severity and progression of chronic kidney disease (CKD). This study investigated its potential utility as a biomarker for the risk of new-onset CKD in a population-based cohort study. Individuals without CKD at baseline (n = 4660) who participated in the Prevention of REnal and Vascular ENd-stage Disease (PREVEND) prospective population-based cohort study in the Netherlands were included. Baseline plasma NGAL concentrations were investigated for their associations with new-onset CKD, defined as a composite outcome of an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2, urinary albumin excretion (UAE) > 30 mg/24-h, or both. Mean (±SD) plasma NGAL concentrations were 104.0 (±34.7) μg/L and median eGFR was 96 [IQR: 85.3-105.8] mL/min/1.73 m2. After median follow-up of 8.3 [IQR: 7.8-8.9] years, 467 participants developed new-onset CKD. Plasma NGAL concentrations were significantly associated with an increased risk of new-onset CKD (hazard ratio [HR] per doubling 1.35 [95% CI: 1.11-1.63], p = 0.002), even after adjustment for potentially confounding factors (1.37 [1.09-1.73], p = 0.007) except baseline eGFR (1.09 [0.86-1.37], p = 0.490). In secondary analyses, plasma NGAL concentrations were significantly associated with new-onset CKD as defined by eGFR < 60 mL/min/1.73 m2 alone (adjusted HR per doubling 2.54 [1.69-3.80], p < 0.001), which was abrogated after adjustment for eGFR (1.05 [0.69-1.59], p = 0.828), also when UAE > 30 mg/24-h was set as individual outcome (1.05 [0.82-1.35], p = 0.705). Higher plasma NGAL concentrations are associated with an increased risk of developing CKD in the general population. This association is dependent on renal function, and mainly driven by new-onset CKD as defined by renal function decline.
| S-EPMC9953575 | biostudies-literature
Project description:BACKGROUND:Acute kidney injury (AKI) is a common complication in patients undergoing liver transplant (LT) and is associated with high morbidity and mortality. We aim to evaluate the pattern of urine and plasma neutrophil gelatinase-associated lipocalin (NGAL) elevation during the perioperative period of LT and to assess it as a prognostic marker for AKI progression, need for dialysis and mortality. METHODS:We assessed NGAL levels before induction of anesthesia, after portal reperfusion and at 6, 18, 24, and 48 h after surgery. Patients were monitored daily during the first week after LT. RESULTS:Of 100 enrolled patients undergoing liver transplant, 59 developed severe AKI based on the KDIGO serum creatinine (sCr) criterion; 34 were dialysed, and 21 died within 60 days after LT. Applying a cut-off value of 136 ng/ml, UNGAL values 6 h after surgery was a good predictor of AKI development within 7 days after surgery, having a positive predictive value (PPV) of 80% with an AUC of 0.76 (95% CI 0.67-0.86). PNGAL at 18 h after LT was also a good predictor of AKI in the first week, having a PPV of 81% and AUC of 0.74 (95% CI 0.60-0.88). Based on PNGAL and UNGAL cut-off criteria levels, time to AKI diagnosis was 28 and 23 h earlier than by sCr, respectively. The best times to assess the need for dialysis were 18 h after LT by PNGAL and 06 h after LT by UNGAL. CONCLUSION:In conclusion, the plasma and urine NGAL elevation pattern in the perioperative period of the liver transplant can predict AKI diagnosis earlier. UNGAL was an early independent predictor of AKI development and need for dialysis. Further studies are needed to assess whether the clinical use of biomarkers can improve patient outcomes. TRIAL REGISTRATION:Registered at Clinical Trials ( clinicaltrials.gov ) in March 24th, 2014 by title "Acute Kidney Injury Biomarkers: Diagnosis and Application in Pre-operative Period of Liver Transplantation (AKIB)" and identifier NCT02095431, retrospectively registered.
| S-EPMC6794911 | biostudies-literature
Project description:We evaluated urine NGAL as a marker of acute kidney injury in patients undergoing partial nephrectomy. We sought to identify the preoperative clinical features and surgical factors during partial nephrectomy that are associated with renal injury, as measured by increased urine NGAL vs controls.Using patients treated with radical nephrectomy or thoracic surgery as controls, we prospectively collected and analyzed urine and serum samples from patients treated with partial or radical nephrectomy, or thoracic surgery between April 2010 and April 2012. Urine was collected preoperatively and at multiple time points postoperatively. Differences in urine NGAL levels were analyzed among the 3 surgical groups using a generalized estimating equation model. The partial nephrectomy group was subdivided based on a preoperative estimated glomerular filtration rate of less than 60, or 60 ml/minute/1.73 m(2) or greater.Of 162 patients included in final analysis more than 65% had cardiovascular disease. The median estimated glomerular filtration rate was greater than 60 ml/minute/1.73 m(2) in the radical and partial nephrectomy, and thoracic surgery groups (61, 78 and 84.5 ml/minute/1.73 m(2), respectively). Preoperatively, a 10 unit increase in the estimated glomerular filtration rate was associated with a 4 unit decrease in urine NGAL in the partial nephrectomy group. Postoperatively, urine NGAL in the partial nephrectomy group was not higher than in controls and did not correlate with ischemia time. Patients with partial nephrectomy with a preoperative estimated glomerular filtration rate of less than 60 ml/minute/1.73 m(2) had higher urine NGAL postoperatively than those with a higher preoperative estimated rate.Urine NGAL does not appear to be a useful marker for detecting renal injury in healthy patients treated with partial nephrectomy. However, patients with poorer preoperative renal function have higher baseline urine levels and appear more susceptible to acute kidney injury, as detected by urine levels and Acute Kidney Injury Network criteria, than those with a normal estimated glomerular filtration rate.
| S-EPMC4167359 | biostudies-literature
Project description:Neutrophil gelatinase associated lipocalin (NGAL), was originally identified in neutrophil granules as a heterodimer complex with gelatinase B (matrix metalloproteinase 9, MMP9), but more recently has been found to be secreted by damaged epithelial cells. Ngal is a member of the lipocalin family and subsequently named as lipocalin 2 on the basis of structural similarity with other members of the lipocalin family and its potential association with hydrophobic retinol and cholesterol oleate more strongly than their hydrophilic counterparts. In 2002, a landmark paper suggested that Ngal is a bacteriostatic agent which blocks iron acquisition by interacting with a number of bacterial siderophores, especially enterobactin. Since then, more siderophore-carrying functions have been reported than the possibility of hydrophobic ligand transport. In this setting, Ngal was renamed Siderocalin. Functions of siderocalin include not only bacteriostatic activity but potentially as a mediator of cell growth and differentiation; some of these functions appear to be referable to the holo siderocalin:siderophore:iron complex and recent work suggests that metabolic products may act as mammalian siderophores bound by Ngal. While still speculative, it may be that the mammalian siderophores can establish the missing link between Ngal and a number of its functions in vivo. This review provides an overview of the discoveries of the different ligands of Ngal and consequently related functions. Hydrophobic ligands, bacterial siderophores as well as their modified structures (synthetic siderophores), and mammalian siderophores are summarized.
| S-EPMC5014392 | biostudies-literature
Project description:Chronic liver disease patients often have complications, such as hepatocellular carcinoma (HCC) and acute bacterial infection. Model for end-stage liver disease and Child-Pugh scores are useful prognostic factors for chronic liver diseases but not for all chronic conditions, such as HCC. Our investigative aim targeted the prognostic abilities of neutrophil gelatinase-associated lipocalin (NGAL) in rat and human chronic liver diseases. Blood NGAL levels were measured by enzyme-linked immunosorbent assay in rats with cirrhosis and 96 patients with chronic liver disease and HCC. We examined the correlation between blood NGAL levels and liver functions as well as survival. In our rat model, liver NGAL expression was assessed by immunostaining, real-time quantitative polymerase chain reaction, and immunoblot. In rats with cirrhosis, blood NGAL levels were continuously and significantly elevated in the deceased group and were significantly correlated with liver functions. Liver NGAL, toll-like receptor 4, and interleukin-6 levels were increased in the deceased group compared to the survival group. Blood NGAL levels were significantly correlated with liver NGAL levels, indicating blood NGAL was derived from the liver. In patients with chronic liver disease, blood NGAL levels were associated with liver function and renal function. Blood NGAL levels were significantly increased in patients with chronic liver disease with HCC compared to without HCC. For the survival group, 38 out of 96 patients were dead in the average follow-up period of 9.9 months. The patients with blood NGAL ?119?ng/mL had significantly longer rates of survival compared to patients with blood NGAL >119?ng/mL. Conclusion: Blood NGAL predicts the survival rate in rat and human chronic liver diseases. Our findings suggest blood NGAL may be prognostic of survival in chronic liver diseases complicated by HCC. (Hepatology Communications 2017;1:946-956).
| S-EPMC5721464 | biostudies-literature
Project description:BackgroundAcute kidney injury (AKI) due to Diabetic Ketoacidosis (DKA) is rather common. Novel biomarkers to diagnose AKI are being increasingly used in different settings. The use of urinary Neutrophil Gelatinase-Associated Lipocalin (uNGAL) in predicting persistent AKI in pediatric DKA cases is still not thoroughly investigated.MethodsThis was a secondary analysis of Saline versus Plasma-Lyte in Ketoacidosis (SPinK) trial data; 66 children (> 1 month-12 years) with DKA, defined by the International Society for Pediatric and Adolescent Diabetes (ISPAD), were analyzed. Children with cerebral edema, chronic kidney disease and those who received pre-referral fluids and/or insulin were excluded. uNGAL and urine NGAL-creatinine ratio (uNCR) at 0 and 24 h were measured in all. Persistent AKI was defined as a composite outcome of continuance of AKI defined by the Kidney Disease Improving Global Outcomes (KDIGO) stage 2 or 3 beyond 48 h from AKI onset, progression of AKI from either KDIGO stage 0 or 1 to a worse stage, need of renal replacement therapy or death.Main outcomesThirty-five (53%) children had AKI at admission; 32 (91.4%) resolved within 48 h. uNGAL was significantly higher in the AKI group at admission [79.8 ± 27.2 vs 54.6 ± 22.0, p = 0.0002] and at 24 h [61.4 ± 28.3 vs 20.2 ± 14.5, p = 0.0003]. Similar trend was observed with uNCR at admission [6.7 ± 3.7 vs 4.1 ± 2.6, p = 0.002] and at 24 h [6.3 ± 2.5 vs 1.2 ± 1.0, p = 0.01]. Furthermore, uNGAL at admission showed a moderate positive linear correlation with serum creatinine. Additionally, elevated uNGAL at 0 and 24 h correlated with corresponding KDIGO stages. Admission uNGAL >88 ng/ml and uNCR of >11.3 ng/mg had a sensitivity of 66% and 67%, specificity of 76% and 95%, and Area under the receiver operating characteristic curve (AUC) of 0.78 and 0.89 respectively for predicting persistent AKI at 48 h.ConclusionsMajority of AKI resolved with fluid therapy. While uNGAL and uNCR both correlated with serum creatinine and AKI stages, serial uNCR was a better predictor of persistent AKI than uNGAL alone. However, feasibility of routine uNGAL measurement to predict persistent AKI in DKA needs further elucidation.Trial registrationThis was a secondary analysis of the data of SPinK trial [CTRI/2018/05/014042 ( ctri.nic.in )].
| S-EPMC8559408 | biostudies-literature
Project description:Urine neutrophil gelatinase-associated lipocalin (uNGAL) has shown promise as a biomarker for the early detection of acute kidney injury (AKI) in fixed models of injury, but its ability to predict AKI and provide prognostic information in critically ill adults is unknown. We prospectively studied a heterogeneous population of 451 critically ill adults, 64 (14%) and 86 (19%) of whom developed AKI within 24 and 48 h of enrollment, respectively. Median uNGAL at enrollment was higher among patients who developed AKI within 48 h compared with those who did not (190 versus 57 ng/mg creatinine, P < 0.001). The areas under the receiver operating characteristic curves describing the relationship between uNGAL level and the occurrence of AKI within 24 and 48 h were 0.71 (95% Confidence Intervals [CI]: 0.63 to 0.78) and 0.64 (95% CI: 0.57 to 0.71), respectively. Urine neutrophil gelatinase-associated lipocalin remained independently associated with the development of AKI after adjustment for age, serum creatinine closest to enrollment, illness severity, sepsis, and intensive care unit (ICU) location, although it only marginally improved the predictive performance of the clinical model alone. A Cox proportional hazards model using time to first dialysis, adjusted for APACHE II score, suggested that uNGAL independently predicts severe AKI during hospitalization [HR 2.60, 95% CI:1.55 to 4.35]. In summary, although a single measurement of uNGAL exhibited moderate predictive utility for the development and severity of AKI in a heterogeneous ICU population, its additional contribution to conventional clinical risk predictors appears limited.
| S-EPMC2723988 | biostudies-literature
Project description:BackgroundNeutrophil gelatinase-associated lipocalin (NGAL), a promising renal biomarker, can exists as a monomer, a dimer and/or in a NGAL/matrix metalloproteinase-9 (MMP-9) complex form when associated with different urinary diseases in humans and dogs. In this study, the presence of the various different molecular forms of NGAL in cat urine (uNGAL) was examined and whether these forms are correlated with different urinary diseases was explored.ResultsOne hundred and fifty-nine urine samples from cats with various different diseases, including acute kidney injury (AKI, 22 cats), chronic kidney disease (CKD, 55 cats), pyuria (44 cats) and other non-renal and non-pyuria diseases (non-RP, 26 cats), as well as healthy animals (12 cats), were collected. The molecular forms of and concentrations of urinary NGAL in these cats were analyzed, and their uNGAL-to-creatinine ratio (UNCR) were determined. The cats with AKI had the highest UNCR (median: 2.92 × 10- 6), which was followed by pyuria (median: 1.43 × 10- 6) and CKD (median: 0.56 × 10- 6); all of the above were significantly higher than the healthy controls (median: 0.17 × 10- 6) (p < 0.05). Three different NGAL molecular forms as well as the MMP-9 monomer were able to be detected in the cat urine samples. Moreover, the cases where urine NGAL monomer were present also had significantly higher levels of BUN (median: 18.9 vs 9.6 mmol/L) and creatinine (327.1 vs 168 umol/L). The presence of dimeric NGAL was found to be associated with urinary tract infections. Most cats in the present study (126/159, 79.2%) and more than half of healthy cats (7/12, 58.3%) had detectable NGAL/MMP-9 complex present in their urine.ConclusionsThe monomeric and dimeric molecular forms of uNGAL suggest upper and lower urinary tract origins of disease, respectively, whereas the presence of the uNGAL/MMP-9 complex is able to be detected in most cats, including seemingly healthy ones.
| S-EPMC6712848 | biostudies-literature