Value of urine IL-8, NGAL and KIM-1 for the early diagnosis of acute kidney injury in patients with ureteroscopic lithotripsy related urosepsis / 中华创伤杂志(英文版)

PURPOSE@#To investigate the clinical value of urine interleukin-18 (IL-8), neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) for the early diagnosis of acute kidney injury (AKI) in patients with ureteroscopic lithotripsy (URL) related urosepsis.@*METHODS@#A retrospective study was carried out in 157 patients with urosepsis after URL. The patients were divided into AKI group and non-AKI group according to the Kidigo guideline and urine IL-8, NGAL and KIM-1 levels were detected by enzyme-linked immunosorbent assay at 0, 4, 12, 24 and 48 h after the surgery. Receiver operating characteristic curve (ROC) was used to evaluate the diagnostic value of these three biomarkers for postoperative AKI.@*RESULTS@#The level of urine IL-8, NGAL and KIM-1 in AKI group was significantly higher than that in non-AKI group at 4, 12, 24 and 48 h (p < 0.01). The ROC analysis showed the combined detection of urine IL-8, NGAL and KIM-1 at 12 h had a larger area under curve (AUC) than a single marker (0.997, 95% CI: 0.991-0.998), and the sensitivity and specificity were 98.2% and 96.7%, respectively. Pearson correlation analysis showed that the levels of urine NGAL at 4, 12, 24 and 48 h in AKI patients were positively correlated with the levels of urine KIM-1 and IL-18 (p < 0.01).@*CONCLUSION@#AKI could be quickly recognized by the elevated level of urine IL-8, NGAL and KIM-1 in patients with URL-related urosepsis. Combined detection of the three urine biomarkers at 12 h after surgery had a better diagnostic performance, which may be an important reference for the early diagnosis of AKI.

Early diagnosis of acute kidney injury in aged patients undergoing percutaneous coronary intervention / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

In aged patients, acute kidney injury (AKI) is a common clinical complication after percutaneous coronary intervention (PCI), highlighting the need for timely and certain diagnosis of this disease. A single centre, nested case-control study was conducted, which assessed the usefulness of urinary liver-type fatty acid-binding protein (uL-FABP), neutrophil gelatinase-associated lipocalin (uNGAL), and kidney injury molecule-1 (uKIM-1) for early detection of AKI. One hundred and thirty-two patients at or over 60 years old undergoing PCI were included. Serum creatinine (SCr) was measured before PCI, 24 and 48 h after PCI; uL-FABP, uNGAL, and uKIM-1 were measured before PCI, 6, 24, and 48 h after PCI. We identified 16 AKI patients and selected 32 control patients matched by admission time (<1 week), age (±5 years), and gender. In the receiver operating characteristic (ROC) curve analysis, the areas under the curve (AUCs) for the relative measurements of uL-FABP, uNGAL, and uKIM-1 were 0.809, 0.867, and 0.512 at 6 h after PCI, and 0.888, 0.840, and 0.676 at 24 h after PCI, respectively. AUC for the combination of uL-FABP and uNGAL was 0.899 at 6 h after PCI, and 0.917 at 24 h after PCI. Thus, measurement of uL-FABP and uNGAL levels at 6 and 24 h after PCI may be useful in detecting AKI in aged patients. Measurement of uKIM-1 levels provides inferior predictive power for early diagnosis of AKI.

Early term effect of ureterorenoscopy (URS) on the Kidney: research measuring NGAL, KIM-1, FABP and CYS C levels in urine

ABSTRACT Aim: URS is a very commonly used procedure for treatment of ureter stones. Increased hydrostatic pressure in the collecting system linked to fluids used during the procedure may cause harmful effects on the kidney. The aim of this study is to determine whether the URS procedure has a negative effect on the kidney by investigating NGAL, KIM-1, FABP and Cys C levels in urine. Material and Methods: This study included 30 patients undergoing ureterorenoscopy (URS) for ureter stones. Urine samples were collected 5 times; before the URS procedure (control) and at 1, 3, 5 and 12 hours following the procedure. NGAL, KIM-1, FBAP and Cys C levels were measured in urine and compared with the control values. Results: The NGAL levels in urine before the procedure and at 1, 3, 5 and 12 hours after the procedure were 34.59±35.34; 62.72±142.32; 47.15±104.48; 45.23±163.16 and 44.99±60.79ng/mL, respectively (p=0.001). Similarly, the urinary KIM-1, FABP and Cys C levels were found to increase compared to control values; however this increase did not reach statistical significance (p >0.05). Conclusions: After the URS procedure, there were important changes in NGAL, FABP, KIM-1 and Cys C levels. These changes reached statistical significance for NGAL, but did not reach significance for the other parameters. In conclusion, the URS procedure significantly affects the kidney; however, this effect disappears over time.

Performance of urinary kidney injury molecule-1, neutrophil gelatinase-associated lipocalin, and N-acetyl-beta-D-glucosaminidase to predict chronic kidney disease progression and adverse outcomes

Urinary biomarkers can predict the progression of chronic kidney disease (CKD). In this study, kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), and N-acetyl-β-D-glucosaminidase (NAG) were correlated with the stages of CKD, and the association of these biomarkers with CKD progression and adverse outcomes was determined. A total of 250 patients, including 111 on hemodialysis, were studied. Urinary KIM-1, NGAL, and NAG were measured at baseline. Patients not on dialysis at baseline who progressed to a worse CKD stage were compared with those who did not progress. The association of each biomarker and selected covariates with progression to more advanced stages of CKD, end-stage kidney disease, or death was evaluated by Poisson regression. NGAL was moderately correlated (rs=0.467, P<0.001) with the five stages of CKD; KIM-1 and NAG were also correlated, but weakly. Sixty-four patients (46%) progressed to a more advanced stage of CKD. Compared to non-progressors, those patients exhibited a trend to higher levels of KIM-1 (P=0.064) and NGAL (P=0.065). In patients not on dialysis at baseline, NGAL was independently associated with progression of CKD, ESKD, or death (RR=1.022 for 300 ng/mL intervals; CI=1.007-1.037, P=0.004). In patients on dialysis, for each 300-ng/mL increase in urinary NGAL, there was a 1.3% increase in the risk of death (P=0.039). In conclusion, urinary NGAL was associated with adverse renal outcomes and increased risk of death in this cohort. If baseline urinary KIM-1 and NGAL predict progression to worse stages of CKD is something yet to be explored.

Diagnostic values of urinary netrin-1 and kidney injury molecule-1 for acute kidney injury induced by neonatal asphyxia / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To investigate the values of urinary netrin-1 and kidney injury molecule-1 (KIM-1) in the early diagnosis of acute kidney injury (AKI) induced by neonatal asphyxia.</p><p><b>METHODS</b>A total of 80 full-term neonates with asphyxia were enrolled (mild asphyxia: 34 neonates; severe asphyxia: 46 neonates). Forty normal full-term neonates were selected as the control group. Urinary samples were collected from the neonates in the three groups within 12 hours and 13-48 hours after birth. ELISA was applied to measure urinary levels of netrin-1 and KIM-1. Peripheral venous blood samples were also collected to measure serum creatinine (Scr) level.</p><p><b>RESULTS</b>Compared with the control group, the asphyxia group had significantly higher urinary levels of netrin-1 and KIM-1 within 48 hours after birth and a significantly higher Scr level within 13-48 hours after birth (P<0.05). The neonates in the AKI group had significantly higher urinary levels of netrin-1 and KIM-1 and Scr level within 48 hours after birth than those in the non-AKI group (P<0.05). The areas under the receiver operating characteristic curve for urinary netrin-1 and KIM-1 levels within 12 hours after birth to predict AKI after asphyxia were 0.878 (95% CI: 0.775-0.981; P<0.01) and 0.899 (95% CI: 0.829-0.969; P<0.01), respectively. Any two indicators of urinary netrin-1 level, urinary KIM-1 level, and Scr level within 12 hours after neonatal asphyxia had a positive correlation (P<0.05).</p><p><b>CONCLUSIONS</b>Urinary netrin-1 and KIM-1 levels increase significantly when neonates with asphyxia develop AKI. Urinary netrin-1 and KIM-1 can be used as indicators for the early diagnosis of AKI after asphyxia.</p>

Value of acute renal injury associated biomarkers for patients in intensive care unit / 中南大学学报(医学版)

OBJECTIVE@#To evaluate the early predictive and diagnostic significance of the acute kidney injury (AKI) associated biomarkers for patients in the intensive care unit (ICU).
@*METHODS@#From January to June, 2014, relevant clinical data of participants were collected upon admission to the intensive care unit (ICU) in Affiliated Hospital of Zunyi Medical College. Levels of serum cystatin C (sCys C), neutrophil gelatinase-associated lipocalin (sNGAL), urinary neutrophil gelatinase-associated lipocalin (uNGAL), urinary kidney injury molecule-1 (uKIM-1), interleukin-18 (uIL-18), and N-acetyl-beta-D-glucosaminidase (uNAG) were detected by enzyme linked immune sorbent assay (ELISA), and compared between AKI and non-AKI patients. Diagnostic significance of these biomarkers was evaluated by a receiver operating characteristic (ROC) curve and the area under the ROC curve.
@*RESULTS@#A total of 176 patients were enrolled in this study. Among them, 71 patients were diagnosed as AKI, in which 57 patients hospitalized with AKI and 14 developed AKI after 24 h hospitalization. The renal replacement therapy ratio was increased with the progress of clinical stage for AKI. AKI mortality rate was 18.8% (46.5% of the total number of deaths). The levels of sCys C, sNGAL, uNGAL, and uIL-18 in AKI patients were increased compared with those in the non-AKI patients (P<0.05). With the progress of AKI, sCys C, and uNGAL levels were also elevated. In 14 patients who suffered from AKI 24 h after hospitalization, the average levels of sCys C, uNGAL, uIL-18, and uKIM-1 were significantly increased (P<0.05). Sensitivity and specificity of the uNGAL, sCys C, and uIL-18 in AKI diagnosis were 97.2%, 76.1%, 54.9% and 93.3 %, 96.2%, 78.1%, respectively. The areas under the ROC curve of uNGAL, sCys C, and uIL-18 were 0.99, 0.90, and 0.69, respectively.
@*CONCLUSION@#uNGAL, sCys C and uIL-18 can be used to predict and diagnose AKI, and to evaluate the AKI clinical stage.

Effect of percutaneous nephrostolithotomy combined with flexible ureteroscopy on renal function in elderly patients with renal calculi / 中南大学学报(医学版)

OBJECTIVE@#To detect the levels of neutrophil gelatinase-associated lipocalin (NGAL), cystatin C (Cys-C ) in blood and the level of kidney injury molecule 1 (KIM-1) in urine in elderly patients with renal calculi at diff erent times, and to explore the eff ect of percutaneous nephrostolithotomy (PCNL) combined with flexible ureteroscopy (FU) on early postoperative renal function.@*METHODS@#A total of 46 patients with renal calculi were selected, and their blood or urine specimens were collected respectively at preoperative and postoperative 2, 12, 24, 48, and 72 h. The concentrations of NGAL, Cys-C, KIM-1 were detected.@*RESULTS@#The levels of NGAL and Cys-C began to increase respectively at postoperative 2 and 12 h, and reached peak at postoperative 12 to 24 h. There was significant difference in the levels of NGAL and Cys-C between the postoperative 12 and 2 h or between postoperative 48 and 24 h (all P<0.05). The levels of NGAL and Cys-C began to decline and eventually returned to preoperative levels respectively at postoperative 48 and postoperative 72 h. The KIM-1 began to increase at postoperative 2 h and peaked at postoperative 24 h, which was significant difference between the postoperative 24 and 12 h or postoperative 48 and 24 h (both P<0.05). The level of KIM-1 began to decline and eventually returned to preoperative levels at postoperative 48 h.@*CONCLUSION@#After the combined treatment of percutaneous nephrostolithotomy with flexible ureteroscopy, the concentrations of NGAL, Cys-C and KIM-1 are significantly increased, suggesting injuries on renal function. The time of renal tubular injury and recovery is earlier than that of renal glomerulus.

TIM-1 acts a dual-attachment receptor for Ebolavirus by interacting directly with viral GP and the PS on the viral envelope

Ebolavirus can cause hemorrhagic fever in humans with a mortality rate of 50%-90%. Currently, no approved vaccines and antiviral therapies are available. Human TIM1 is considered as an attachment factor for EBOV, enhancing viral infection through interaction with PS located on the viral envelope. However, reasons underlying the preferable usage of hTIM-1, but not other PS binding receptors by filovirus, remain unknown. We firstly demonstrated a direct interaction between hTIM-1 and EBOV GP in vitro and determined the crystal structures of the Ig V domains of hTIM-1 and hTIM-4. The binding region in hTIM-1 to EBOV GP was mapped by chimeras and mutation assays, which were designed based on structural analysis. Pseudovirion infection assays performed using hTIM-1 and its homologs as well as point mutants verified the location of the GP binding site and the importance of EBOV GP-hTIM-1 interaction in EBOV cellular entry.

Predict value of monitoring changes of urinary neutrophil gelatinase-associated lipocalin and kidney injury molecule-1 after coronary angiography and percutaneous coronary intervention on early diagnosis of contrast-induced nephropathy / 中华心血管病杂志

<p><b>OBJECTIVE</b>To explore the predict value of monitoring changes of urinary neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1(KIM-1) after coronary angiography (CAG) and percutaneous coronary intervention (PCI) on the early diagnosis of contrast-induced nephropathy(CIN).</p><p><b>METHODS</b>One hundred and sixty patients underwent CAG and PCI were enrolled in this prospective study. There were 14 patients with CIN and non-CIN patients were selected with the proportion of 2: 1 (n = 28).Serum creatinine (SCr) was measured before and at 24, 48 and 72 h after the procedure. Urinary NGAL and KIM-1 were measured before and at 4 and 24 h after the procedure. The relationship between NGAL, KIM-1 and CIN were analyzed. Receiver operating characteristic (ROC) curve and area under the ROC curve (AUC) were used to analyze the diagnostic sensitivity and specificity of CIN by urinary NGAL and KIM-1.</p><p><b>RESULTS</b>(1) The values of urinary NGAL was significantly higher in the CIN group than in non-CIN group at 4 h after CAG or PCI (P < 0.01); the value of urinary NGAL was significantly increased from the baseline to 4 h after the procedure in the CIN group (P < 0.01). (2) Uurinary KIM-1 levels of CIN group was significantly higher than in non-CIN group at 24 h after the CAG or PCI (P < 0.01) ; the urinary KIM-1 levels was significantly increased from baseline to 24 h after the procedure in the CIN group (P < 0.01). (3) Pearson correlation analysis showed that there was a positive correlation between urinary NGAL and SCr (r = 0.814, P < 0.01) and urinary KIM-1(r = 0.758, P < 0.01) in the CIN group. (4) ROC curve analysis showed that the AUC for urinary NGAL was 0.897. When the cut-off value of NGAL was set at 11.950 µg/L, the sensitivity and specificity for the diagnosis of CIN were 92.9% and 71.4%, respectively. The AUC for urinary KIM-1 was 0.839. With the cut-off value of urinary KIM-1 set as 4.595 µg/L, the diagnostic sensitivity and specificity for CIN were 85.7% and 71.4%, respectively.</p><p><b>CONCLUSIONS</b>Urinary NGAL serves as a good biomarker for early diagnosis of CIN suggesting acute kidney injury at 4 h post CAG and PCI. Urinary KIM-1 can reflect the change of renal function after contrast injection earlier than SCr and may also be a good biomarker for early diagnosis of CIN.</p>

An evaluation of genotoxicity and cytotoxicity of melamine in combination with cyanuric acid at three mass ratios / 生物医学与环境科学（英文）

Melamine in combination with cyanuric acid has been considered to be more toxic than either melamine or cyanuric acid alone. The objective of this study was designed to evaluate the combined genotoxicity and cytotoxicity of melamine (M) and cyanuric acid (C) at three mass ratios (1:1, 1:2, 2:1). MC (1:1), MC (1:2), and MC (2:1) were evaluated for their potential genotoxic risk, at gene level by Ames test, and at chromosomal level by micronucleus test. In order to evaluate cytotoxicity in HEK-293 cells, the MTT assay was included. Western blot was also employed to investigate the renal injury molecule-1 (Kim-1) expression in HEK-293 cells exposed to MC. Neither genotoxicity at gene level nor at chromosomal level was observed for MC (1:1), MC (1:2), and MC (2:1). Based on MTT assay, three ratios of MC at 82.5 and 165 µg/mL slightly inhibited viability of HEK-293 cells (P<0.05). MC (1:1) at 41.25 and 82.50 µg/mL could elevate the Kim-1 expression in HEK-293 cells.

Expression of TIM-1 and TIM-3 in spleen mononuclear cells and their role in Th1 polarization in primary immune thrombocytopenia patients / 中华血液学杂志

<p><b>OBJECTIVE</b>To explore the expression and clinical significance of T cell immunoglobulin mucin (TIM)-1, TIM-3 and T cell-specific transcription factors T-bet and GATA-3 in spleen mononuclear cells in patients with primary immune thrombocytopenia (ITP).</p><p><b>METHODS</b>The spleen samples were obtained from 17 active ITP patients and 10 controls with spleen traumatic rupture. By using real-time quantitative polymerase chain reaction, the mRNA expressions of TIM-3, TIM1, T-bet and GATA-3 were studied in all subjects.</p><p><b>RESULTS</b>TIM-3 mRNA levels of active ITP patients were significantly decreased to (29 ± 16)% of that of control, TIM-1 mRNA levels of active ITP patients increased to (3.20 ± 2.18) folds of that of control, but the difference was not significant. The ratio of TIM-1/ TIM-3 was elevated in active ITP patients. T-bet mRNA levels were up-regulated in ITP patients by (2.82 ± 1.57) folds (P<0.05) and the expression of GATA3 was decreased by 14% folds (P<0.05) compared to controls. The ratio of T-bet/GATA3 were significantly elevated in ITP patients.</p><p><b>CONCLUSION</b>The imbalance between TIM-3 and TIM-1 expression might play an important role in pathogenesis of ITP.</p>

Expression and clinical significance of kidney injury molecule-1 in renal epithelial neoplasms / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the expression and clinical significance of kidney injury molecule-1 (KIM-1) in primary and metastatic renal epithelial neoplasms.</p><p><b>METHODS</b>A total of 136 cases of kidney neoplasms were retrospectively reviewed including 63 primary clear cell renal cell carcinomas (RCCs), 22 papillary RCCs, 13 chromophobe RCCs, 7 oncocytomas, 7 RCCs associated with Xp11.2 translocation/TFE3 gene fusions and 24 metastatic clear cell RCCs. Immunostaining for KIM-1 and kidney-specific-protein (Ksp)-cadherin were performed and the relationship to tumor stage and grade in clear cell RCCs was investigated.</p><p><b>RESULTS</b>Expression of KIM-1 was detected in 77.8% (49/63) of clear cell RCCs, 90.9% (20/22) of papillary RCCs, 1/13 of chromophobe RCCs, 7/7 of RCCs associated with Xp11.2 translocation/TFE3 gene fusions and 87.5%(21/24) of the metastatic RCCs, but not detected in 7 cases of oncocytomas. A diffuse expression of KIM-1 was more frequently observed in Furhman nuclear grade III/IV clear cell RCCs (P = 0.010). Ksp-cadherin expression was mainly observed in chromophobe RCCs and oncocytomas.</p><p><b>CONCLUSIONS</b>KIM-1 is a specific biomarker for injuried kidney proximal tubules and the corresponding neoplasms, and has a high specificity and sensitivity for primary or metastatic clear cell RCCs, papillary RCCs and RCCs associated with Xp11.2 translocation/TFE3 gene fusions. Combination of KIM-1 and Ksp-cadherin immunostaining can lead to a more precise histological classification of primary kidney epithelial neoplasms and improve the diagnostic accuracy of metastatic RCCs.</p>