The predictive role of neutrophil gelatinase-associated lipocalin in coronary artery disease.

The prognosis holds significant implications for the long-term quality of life among patients suffering from coronary artery disease. However, a pressing challenge lies in the absence of reliable biomarkers that can establish a definitive correlation between these biomarkers and the prognosis of coronary artery heart disease. This review paper delves into the critical role of neutrophil gelatinase-associated lipocalin (NGAL) in predicting outcomes in coronary artery disease. It examines the influence of NGAL on various clinical manifestations, including stable angina, ST-segment elevation myocardial infarction, non-ST-segment elevation myocardial infarction, and isolated coronary artery dilation. Furthermore, this review provides recommendations aimed at enhancing the rigor and impact of future research, thereby serving as a valuable reference for subsequent studies in this domain.

Neutrophil Gelatinase-Associated Lipocalin for the Differentiation of Mucinous Pancreatic Cystic Lesions.

Undetermined pancreatic cystic lesion (PCL) differentiation benefits from endoscopic ultrasound (EUS) based on morphology and cyst fluid analysis, but room for new biomarkers exists. Our aim was to assess the intracystic and serum diagnostic value of neutrophil gelatinase-associated lipocalin (Ngal) and interleukin 1 beta (IL-1ß) for differentiation of PCLs. This prospective study included patients from one tertiary hospital, evaluated between April 2018 and May 2020. EUS fine-needle aspiration or pancreatic pseudocysts drainage was the source of PCL intracystic liquid. The final diagnosis was based on surgery or EUS results (morphology, cytology, glucose, and CEA-carcinoembryogenic antigen). The intracystic samples were tested for Ngal, IL-1ß, glucose, and CEA, and serum for Ngal and IL-1ß. We evaluated 63 cysts, 33 pseudocysts, and 30 non-inflammatory cysts. The diagnostic sensitivity and specificity for mucinous PCL was 70.8% and 92.3% for intracystic Ngal (cut-off: 500-800 ng/dL), without correlation with serum Ngal, no matter the inclusion of infected pseudocysts. After exclusion of infected pseudocysts, the sensitivity and specificity for glucose were 87% and 75%, respectively, and for CEA, they were 87.1%, and 96.8%, respectively. Intracystic Ngal shows promise in differentiating mucinous PCLs, but researchers need to conduct further studies to confirm its effectiveness. Intracystic IL-1ß and serum Ngal made no diagnostic contribution.

Urine biomarkers individually and as a consensus model show high sensitivity and specificity for detecting UTIs.

BACKGROUND: Current diagnoses of urinary tract infection (UTI) by standard urine culture (SUC) has significant limitations in sensitivity, especially for fastidious organisms, and the ability to identify organisms in polymicrobial infections. The significant rate of both SUC "negative" or "mixed flora/contamination" results in UTI cases and the high prevalence of asymptomatic bacteriuria indicate the need for an accurate diagnostic test to help identify true UTI cases. This study aimed to determine if infection-associated urinary biomarkers can differentiate definitive UTI cases from non-UTI controls. METHODS: Midstream clean-catch voided urine samples were collected from asymptomatic volunteers and symptomatic subjects ≥ 60 years old diagnosed with a UTI in a urology specialty setting. Microbial identification and density were assessed using a multiplex PCR/pooled antibiotic susceptibility test (M-PCR/P-AST) and SUC. Three biomarkers [neutrophil gelatinase-associated lipocalin (NGAL), and Interleukins 8 and 1ß (IL-8, and IL-1ß)] were also measured via enzyme-linked immunosorbent assay (ELISA). Definitive UTI cases were defined as symptomatic subjects with a UTI diagnosis and positive microorganism detection by SUC and M-PCR, while definitive non-UTI cases were defined as asymptomatic volunteers. RESULTS: We observed a strong positive correlation (R2 > 0.90; p < 0.0001) between microbial density and the biomarkers NGAL, IL-8, and IL-1ß for symptomatic subjects. Biomarker consensus criteria of two or more positive biomarkers had sensitivity 84.0%, specificity 91.2%, positive predictive value 93.7%, negative predictive value 78.8%, accuracy 86.9%, positive likelihood ratio of 9.58, and negative likelihood ratio of 0.17 in differentiating definitive UTI from non-UTI cases, regardless of non-zero microbial density. NGAL, IL-8, and IL-1ß showed a significant elevation in symptomatic cases with positive microbe identification compared to asymptomatic cases with or without microbe identification. Biomarker consensus exhibited high accuracy in distinguishing UTI from non-UTI cases. CONCLUSION: We demonstrated that positive infection-associated urinary biomarkers NGAL, IL-8, and IL-1ß, in symptomatic subjects with positive SUC and/or M-PCR results was associated with definitive UTI cases. A consensus criterion with ≥ 2 of the biomarkers meeting the positivity thresholds showed a good balance of sensitivity (84.0%), specificity (91.2%), and accuracy (86.9%). Therefore, this biomarker consensus is an excellent supportive diagnostic tool for resolving the presence of active UTI, particularly if SUC and M-PCR results disagree.

The Urinary Concentrations of Neutrophil Gelatinase-Associated Lipocalin, Cystatin C and Osteopontin in the Healthy Term and Stable Preterm Neonates: A Pilot Study.

BACKGROUND: In neonates, the assessment of kidney function with serum creatinine is limited; therefore, more effective biomarkers are needed. AIM: The study aimed at analyzing the concentrations of renal biomarkers (osteopontin, cystatin C, and NGAL) in neonates. MATERIAL AND METHODS: The study included 80 term and 20 preterm neonates aged 28-33 weeks of gestation. Biomarkers were measured in urine. Term neonates' urine was collected on the 1st day of life. Preterm neonates' urine was collected on the 1st, 8th, 15th, 22nd day of life. Biomarkers' concentrations were normalized to urinary creatinine (cr.) and presented as urinary biomarker/cr. ratios. RESULTS: Median values of biomarker/creatine ratios in term and preterm neonates were the following: cystatin C/cr.: 7.26 and 439.49; osteopontin/cr.: 135.86 and 1633.37; NGAL/cr. in girls: 212.14 and 256.93; and NGAL/cr. in boys 27.123 and 65.29 ng/mg cr. In preterm neonates the cystatin C/cr. ratio was higher on the 1st than on the 8th day. The osteopontin/cr. ratio did not differ between the days. The NGAL/cr. ratio in girls was higher on the 8th than on the 22nd day, and in boys, the lowest was on the 22nd day. CONCLUSIONS: Prematurity in stable, Caucasian neonates might cause higher osteopontin and cystatin C excretion, but not NGAL. The excretion of NGAL and cystatin C, but not osteopontin, may change during first weeks of premature neonate's life.

Elevated UTI Biomarkers in Symptomatic Patients with Urine Microbial Densities of 10,000 CFU/mL Indicate a Lower Threshold for Diagnosing UTIs.

The literature lacks consensus on the minimum microbial density required for diagnosing urinary tract infections (UTIs). This study categorized the microbial densities of urine specimens from symptomatic UTI patients aged ≥ 60 years and correlated them with detected levels of the immune response biomarkers neutrophil gelatinase-associated lipocalin (NGAL), interleukin-8 (IL-8), and interleukin-1-beta (IL-1ß). The objective was to identify the microbial densities associated with significant elevation of these biomarkers in order to determine an optimal threshold for diagnosing symptomatic UTIs. Biobanked midstream voided urine samples were analyzed for microbial identification and quantification using standard urine culture (SUC) and multiplex-polymerase chain reaction (M-PCR) testing, while NGAL, IL-8, and IL-1ß levels were measured via enzyme-linked immunosorbent assay (ELISA). NGAL, IL-8, and IL-1ß levels were all significantly elevated at microbial densities ≥ 10,000 cells/mL when measured via M-PCR (p < 0.0069) or equivalent colony-forming units (CFUs)/mL via SUC (p < 0.0104) compared to samples with no detectable microbes. With both PCR and SUC, a consensus of two or more elevated biomarkers correlated well with microbial densities > 10,000 cells/mL or CFU/mL, respectively. The association between ≥10,000 cells and CFU per mL with elevated biomarkers in symptomatic patients suggests that this lower threshold may be more suitable than 100,000 CFU/mL for diagnosing UTIs.

Low level mancozeb exposure causes copper bioaccumulation in the renal cortex of rats leading to tubular injury.

Mancozeb is a widely-used, broad-spectrum contact dithiocarbamate fungicide. Dithiocarbamates are known to trans-chelate metals. This study was designed to evaluate the potential of Mancozeb to mobilize and bioaccumulate essential trace metals in various tissues. Long-Evans rats were orally gavaged with 0, 50, or 100 mg/kg/day of Mancozeb for 28 days. Mancozeb caused a significant increase in copper and manganese in the hippocampus and manganese in the liver. Exceedingly higher level of copper was detected in the renal cortex using ICP-OES in both dose groups. This was confirmed histologically in the tubular epithelial cells. In addition, copper-associated protein levels were also increased. Copper bioaccumulation in the renal cortex was accompanied by oxidative damage and tubular insult indicated by increased 4-HNE, KIM-1, and NGAL immunoreactivity. These findings demonstrate that low-dose Mancozeb exposure is a potential risk for kidney injury due to copper overload and warrants further in vivo and human population-based investigations.

Incidences of and risk factors for clinical and subclinical contrast-associated acute kidney injury in patients who underwent neuroendovascular surgery.

BACKGROUND: Contrast-associated acute kidney injury (CA-AKI) can develop after intravascular administration of iodinated contrast media. Neutrophil gelatinase-associated lipocalin (NGAL) is an early marker for AKI that helps to detect subclinical CA-AKI. We investigated the incidence of and risk factors for clinical and subclinical CA-AKI in patients who underwent neuroendovascular surgery. METHODS: We retrospectively investigated 228 patients who underwent neuroendovascular surgery in 2020. Changes in serum creatinine and urine output were used to detect clinical CA-AKI. Urine NGAL concentration was used to detect subclinical CA-AKI in 67 out of 228 patients. RESULTS: In 228 patients, serum creatinine, hemoglobin, hematocrit, total protein, and blood urea nitrogen (BUN) decreased significantly (p < 0.001) after surgery. However, serum creatinine decreased less significantly (p < 0.05) than hemoglobin, hematocrit, total protein, and BUN on postoperative Day 3. Two patients out of 228 developed clinical CA-AKI, and seven patients out of 67 with urine NGAL measurements developed subclinical CA-AKI. Multivariate regression analysis revealed that diabetes mellitus and carotid artery stenosis were significantly (p < 0.05) associated with the development of clinical and/or subclinical CA-AKI. CONCLUSION: There was a large difference between the incidences of clinical CA-AKI (0.88%) and subclinical CA-AKI (10.4%). The difference might have primarily resulted from the different sensitivities between serum creatinine and urine NGAL and possibly from underestimation of the incidence of clinical AKI due to a postoperative decrease in serum creatinine caused by hemodilution. In addition to diabetes mellitus, carotid artery stenosis could also be a risk factor for CA-AKI.

Urinary Biomarkers of Kidney Disease in Dogs and Cats.

A variety of urinary markers of the renal disease show promise for the identification of glomerular and tubular damage and monitoring treatment. Most of the markers are currently not widely available, and all could benefit from further study. This review summarizes recent studies on urinary biomarkers of renal disease in dogs and cats.

Maternal serum NGAL in the first trimester of pregnancy is a potential biomarker for the prediction of gestational diabetes mellitus.

Objective: Gestational diabetes mellitus (GDM) has adverse effects on the health of mothers and their offspring. Currently, no known biomarker has been proven to have sufficient validity for the prediction of GDM in the first trimester of pregnancy. The aim of this study was to investigate the potential relationship between serum neutrophil gelatinase-associated lipocalin (NGAL) levels in the first trimester of pregnancy and later GDM risk and to evaluate the performance of serum NGAL as a biomarker for the prediction of GDM. Methods: The study was conducted by recruiting participants at 8-13 weeks of gestation from The First Affiliated Hospital of Chengdu Medical College between January and June 2021; participants were followed up for oral glucose tolerance test (OGTT) screening at 24-28 gestational weeks. We examined the serum NGAL levels of all subjects in the first trimester who met the inclusion and exclusion criteria. Anthropometric, clinical, and laboratory parameters of the study subjects were obtained during the same study period. A logistic regression model was carried out to investigate the potential relationship between serum NGAL levels in the first trimester of pregnancy and later GDM risk. The receiver operating characteristic (ROC) curve and area under the curve (AUC) were used to assess the discrimination and calibration of serum NGAL as a biomarker for the prediction of GDM in the first trimester of pregnancy. Results: Serum NGAL levels in the first trimester of pregnancy were significantly higher in women who later developed GDM than in those who did not develop GDM. Serum NGAL levels in the first trimester of pregnancy were positively associated with an increased risk of GDM after adjustment for potential confounding factors. The risk prediction model for GDM constructed by using serum NGAL levels in the first trimester of pregnancy achieved excellent performance. Conclusions: Maternal serum NGAL in the first trimester of pregnancy is a potential biomarker for the prediction of GDM, which could help guide the clinical practice of antenatal care.

Apamer-based sensitive and label-free electrochemical detection of neutrophil gelatinase-associated lipocalin via recycling amplification cascades.

Sensitive and selective detection of neutrophil gelatinase-associated lipocalin (NGAL) is critical for the prediction and early diagnosis of acute renal injury. In this work, the establishment of an aptamer-based, highly sensitive and label-free method for detecting NGAL in diluted human serums via metal ion-dependent DNAzyme- and exonuclease III (Exo III)-triggered recycling signal amplification cascades is described. NGAL binds with the aptamer strands in the DNAzyme/aptamer duplexes and results in the liberation of the metal ion-dependent DNAzyme sequences to cleave the hairpin signal probes on the electrode to liberate the G-quadruplex and intermediate strands. The released intermediate strands further complement with the DNAzyme/aptamer duplexes to form favorable substrate for Exo III, which digests the duplexes to release the DNAzyme strands to initiate the cascaded recycling cycles for the yield of plenty of G-quadruplex strands. Hemin can associate with G-quadruplex strands to produce many G-quadruplex/hemin complexes and electrochemical reduction of hemin thus generates highly amplified current for detecting NGAL with the detection limit of 4.45 ng mL-1. Such biosensor also shows high selectivity and can be utilized for monitoring NGAL spiked in diluted serum, indicating its extension potential for detecting various protein biomarkers with different aptamers for disease diagnosis.

Role of urinary Neutrophil Gelatinase-Associated Lipocalin (NGAL), Monocyte Chemoattractant Protein-1(MCP-1), and Interleukin-6(IL-6) as biomarkers in pediatric patients with hydronephrosis.

OBJECTIVES: The decision to surgically intervene in a hydronephrotic kidney in children is based on many debatable guidelines, some requiring repeated ultrasounds or renal scans. Urinary proteins have the potential to reflect renal disorders and hence can be the alternatives to such scans. Here, we aim to assess the role of urinary Neutrophil Gelatinase-Associated Lipocalin, Monocyte Chemoattractant Protein-1, and Interleukin-6 (IL-6) in such patients. METHODS: Seventeen children had obstructive hydronephrosis requiring pyeloplasty (UPJO), while seven were kept on conservative management in view of non-obstructive dilation (NOD). Urine samples were measured for the three urinary proteins at the time of presentation and following pyeloplasty using commercially available ELISA kits. RESULTS: The levels of all three urinary proteins were significantly higher in patients with UPJO children compared to the NOD group. Cut-off values to differentiate obstructive from non-obstructive hydronephrosis were obtained. A significant fall in the post-operative value of urinary IL-6 was also observed. CONCLUSION: This study highlights the potentiality of urinary proteins as biomarkers in identifying children with hydronephrosis and picking out the ones with obstructive hydronephrosis who will require pyeloplasty. The drop in levels after pyeloplasty can be employed to evaluate the effectiveness of pyeloplasty when sent serially.

Detection of weak non-covalent cation-π interactions in NGAL by single-molecule force spectroscopy.

Cation-π interaction is an electrostatic interaction between a cation and an electron-rich arene. It plays an essential role in many biological systems as a vital driving force for protein folding, stability, and receptor-ligand interaction/recognition. To date, the discovery of most cation-π interactions in proteins relies on the statistical analyses of available three-dimensional (3D) protein structures and corresponding computational calculations. However, their experimental verification and quantification remain sparse at the molecular level, mainly due to the limited methods to dynamically measure such a weak non-covalent interaction in proteins. Here, we use atomic force microscopy-based single-molecule force spectroscopy (AFM-SMFS) to measure the stability of protein neutrophil gelatinase-associated lipocalin (also known as NGAL, siderocalin, lipocalin 2) that can bind iron through the cation-π interactions between its three cationic residues and the iron-binding tri-catechols. Based on a site-specific cysteine engineering and anchoring method, we first characterized the stability and unfolding pathways of apo-NGAL. Then, the same NGAL but bound with the iron-catechol complexes through the cation-π interactions as a holo-form was characterized. AFM measurements demonstrated stronger stabilities and kinetics of the holo-NGAL from two pulling sites, F122 and F133. Here, NGAL is stretched from the designed cysteine close to the cationic residues for a maximum unfolding effect. Thus, our work demonstrates high-precision detection of the weak cation-π interaction in NGAL. Electronic Supplementary Material: Supplementary material (additional SDS-PAGE, UV-vis, protein sequences, and more experimental methods) is available in the online version of this article at 10.1007/s12274-021-4065-9.

Placental Neutrophil Infiltration Associated with Tobacco Exposure but Not Development of Bronchopulmonary Dysplasia.

Objective: In utero inflammation is associated with bronchopulmonary dysplasia (BPD) in preterm infants. We hypothesized that maternal tobacco exposure (TE) might induce placental neutrophil infiltration, increasing the risk for BPD. Study design: We compared the composite outcome of BPD and death in a prospective pilot study of TE and no-TE mothers and their infants born <32 weeks. Placental neutrophil infiltration was approximated by neutrophil gelatinase-associated lipocalin (NGAL) ELISA, and total RNA expression was analyzed via NanoString© (Seattle, WA, USA). Result: Of 39 enrolled patients, 44% were classified as tobacco exposure. No significant difference was noted in the infant's composite outcome of BPD or death based on maternal tobacco exposure. NGAL was higher in placentas of TE vs. non-TE mothers (p < 0.05). Placental RNA analysis identified the upregulation of key inflammatory genes associated with maternal tobacco exposure. Conclusion: Tobacco exposure during pregnancy was associated with increased placental neutrophil markers and upregulated inflammatory gene expression. These findings were not associated with BPD.

Development of a europium nanoparticles lateral flow immunoassay for NGAL detection in urine and diagnosis of acute kidney injury.

BACKGROUND: AKI is related to severe adverse outcomes and mortality with Coronavirus Disease 2019 (COVID-19) patients, that early diagnosed and intervened is imperative. Neutrophil gelatinase-associated lipocalin (NGAL) is one of the most promising biomarkers for detection of acute kidney injury (AKI), but current detection methods are inadequacy, so more rapid, convenient and accuracy methods are needed to detect NGAL for early diagnosis of AKI. Herein, we established a rapid, reliable and accuracy lateral flow immunoassay (LFIA) based on europium nanoparticles (EU-NPS) for the detection of NGAL in human urine specimens. METHODS: A double-antibody sandwich immunofluorescent assay using europium doped nanoparticles was employed and the NGAL monoclonal antibodies (MAbs) conjugate as labels were generated by optimizing electric fusion parameters. Eighty-three urine samples were used to evaluate the clinical application efficiency of this method. RESULTS: The quantitative detection range of NGAL in AKI was 1-3000 ng/mL, and the detection sensitization was 0.36 ng/mL. The coefficient of variation (CV) of intra-assay and inter-assay were 2.57-4.98 % and 4.11-7.83 %, respectively. Meanwhile, the correlation coefficient between europium nanoparticles-based lateral fluorescence immunoassays (EU-NPS-LFIA) and ARCHITECT analyzer was significant (R2 = 0.9829, n = 83, p < 0.01). CONCLUSIONS: Thus, a faster and easier operation quantitative assay of NGAL for AKI has been established, which is very important and meaningful to diagnose the early AKI, suggesting that the assay can provide an early warning of final outcome of disease.

Comparison of plasma neutrophil gelatinase-associated lipocalin (NGAL) levels after robot-assisted laparoscopic and retropubic radical prostatectomy: an observational study.

BACKGROUND AND OBJECTIVES: Patients undergoing radical prostatectomy are at increased risk of Acute Kidney Injury (AKI) because of intraoperative bleeding, obstructive uropathy, and older age. Neutrophil Gelatinase-Associated Lipocalin (NGAL) may become important for diagnosis of postoperative AKI after urogenital oncosurgery. The objective of this study was to evaluate and compare the efficacy of NGAL as a predictor of AKI diagnosis in patients who underwent Retropubic Radical Prostatectomy (RRP) and Robot-Assisted Laparoscopic Prostatectomy (RALP) for prostate cancer. METHODS: We included 66 patients who underwent RRP (n = 32) or RALP (n = 34) in this prospective, comparative, nonrandomized study. Patients' demographic data, duration of surgery and anesthesia, amount of blood products, vasopressor therapy, intraoperative blood loss, fluid administration, length of hospital stay, creatinine, and plasma NGAL levels were recorded. RESULTS: Intraoperative blood loss, crystalloid fluid administration, and length of hospital stay were significantly shorter in RALP. There was no statistically significant difference between the groups in terms of intraoperative blood transfusion. Postoperative creatinine and plasma NGAL levels were increased in both groups. The 6-h NGAL levels were higher in RRP (p = 0.026). The incidence of AKI was 28.12% in RRP and 26.05% in RALP, respectively. The NGAL level at 6 hours was more sensitive in the early diagnosis of AKI in RALP. CONCLUSION: Although postoperative serum NGAL levels were increased in both RRP and RALP, the 6-h NGAL levels were higher in RRP. RALP was associated with fewer intraoperative blood loss and fluid administration, and shorter length of hospital stay.

Prognostic Significance of Urinary Biomarkers in Patients Hospitalized With COVID-19.

RATIONALE & OBJECTIVE: Acute kidney injury (AKI) is common in patients with coronavirus disease 2019 (COVID-19) and associated with poor outcomes. Urinary biomarkers have been associated with adverse kidney outcomes in other settings and may provide additional prognostic information in patients with COVID-19. We investigated the association between urinary biomarkers and adverse kidney outcomes among patients hospitalized with COVID-19. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: Patients hospitalized with COVID-19 (n=153) at 2 academic medical centers between April and June 2020. EXPOSURE: 19 urinary biomarkers of injury, inflammation, and repair. OUTCOME: Composite of KDIGO (Kidney Disease: Improving Global Outcomes) stage 3 AKI, requirement for dialysis, or death within 60 days of hospital admission. We also compared various kidney biomarker levels in the setting of COVID-19 versus other common AKI settings. ANALYTICAL APPROACH: Time-varying Cox proportional hazards regression to associate biomarker level with composite outcome. RESULTS: Out of 153 patients, 24 (15.7%) experienced the primary outcome. Twofold higher levels of neutrophil gelatinase-associated lipocalin (NGAL) (HR, 1.34 [95% CI, 1.14-1.57]), monocyte chemoattractant protein (MCP-1) (HR, 1.42 [95% CI, 1.09-1.84]), and kidney injury molecule 1 (KIM-1) (HR, 2.03 [95% CI, 1.38-2.99]) were associated with highest risk of sustaining primary composite outcome. Higher epidermal growth factor (EGF) levels were associated with a lower risk of the primary outcome (HR, 0.61 [95% CI, 0.47-0.79]). Individual biomarkers provided moderate discrimination and biomarker combinations improved discrimination for the primary outcome. The degree of kidney injury by biomarker level in COVID-19 was comparable to other settings of clinical AKI. There was evidence of subclinical AKI in COVID-19 patients based on elevated injury biomarker level in patients without clinical AKI defined by serum creatinine. LIMITATIONS: Small sample size with low number of composite outcome events. CONCLUSIONS: Urinary biomarkers are associated with adverse kidney outcomes in patients hospitalized with COVID-19 and may provide valuable information to monitor kidney disease progression and recovery.

Serum neutrophil gelatinase-associated lipocalin as a potential biomarker of diabetic kidney disease in patients with childhood-onset type 1 diabetes.

BACKGROUND/PURPOSE: Diabetic kidney disease (DKD) is a major complication in patients with type 1 diabetes (T1D). The aim of this study was to evaluate the role of serum neutrophil gelatinase-associated lipocalin (sNGAL) in the early detection of DKD in childhood-onset T1D patients. METHODS: A total of 116 patients (mean age, 22.3 ± 6.9 years) with estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73 m2 were enrolled in this prospective cross-sectional study. Persistent albuminuria (PA) was defined as a urine albumin-to-creatinine ratio ≥ 30 mg/g for at least two consecutive years; non-albuminuria (NA) was defined otherwise. The patients were divided into the adult (Ad) (≥18 years, n = 91) and pediatric (Ped) (<18 years, n = 25) groups and further into the Ad-PA (n = 8), Ad-NA (n = 83), Ped-PA (n = 2), and Ad-NA (n = 23) subgroups. In all groups, the sNGAL level was determined. RESULTS: The mean diabetes duration was 14.2 ± 6.1 years, and 8.6% patients had PA. There was no significant difference in sNGAL levels between the PA and NA groups; notably, in adults, the sNGAL level was significantly higher in the Ad-PA than Ad-NA subgroups (P = 0.039). The sNGAL level was negatively correlated with the eGFR in adults (rho -0.41, P < 0.001). Multiple linear regression models showed that higher sNGAL levels in the adult group were independent and significant determinants of a lower eGFR (P < 0.001). CONCLUSION: An elevated sNGAL was significantly correlated with a decreased eGFR even in the range of normal to mildly decreased renal function. Thus, it is a potential biomarker of early deterioration of DKD in childhood-onset T1D.

Predictive value of kidney injury markers for early DGF in kidney transplant recipients / 器官移植

Objective To evaluate the predictive values of serum neutrophil gelatinase-associated lipocalin (NGAL), urine NGAL, serum cystatin C (Cys-C) and serum creatinine (Scr) for early delayed graft function (DGF) in kidney transplant recipients. Methods Clinical data, blood and urine samples of 159 kidney transplant recipients were collected. All recipients were divided into the DGF group (n=42) and immediate graft function (IGF) group (n=117) according to the incidence of DGF. Clinical data of all recipients were analyzed. The changes of serum NGAL, urine NGAL, Cys-C and Scr levels were statistically compared between two groups. The predictive values of different markers for early DGF were assessed. Results Among 159 kidney transplant recipients, DGF occurred in 42 cases with an incidence rate of 26.4%. There were statistically significant differences in donor age, cold ischemia time of donor kidney and complement-dependent cytoxicity (CDC) between the two groups(all P < 0.05). Within postoperative 2 weeks, the serum NGAL levels in the DGF group were higher than those in the IGF group (all P < 0.05). The Cys-C, Scr and urine NGAL levels in the DGF group were higher compared with those in the IGF group within 3 weeks after kidney transplantation(all P < 0.001). Serum NGAL, urine NGAL, Cys-C and Scr levels had certain predictive values for early DGF in kidney transplant recipients. Cys-C yielded the highest predictive value with a cut-off value of 4.73 mg/L, sensitivity of 0.833, specificity of 0.812 and area under the curve (AUC) of 0.895. Conclusions Cys-C has higher predictive value for early DGF in kidney transplant recipients compared with serum NGAL, urine NGAL and Scr.

Normothermic machine perfusion of kidney and ischemia-free kidney transplantation / 器官移植

To increase the utilization rate of expanded criteria donor (ECD) kidney, the kidney preservation methods have been ever advancing in recent years. The application of normothermic machine perfusion (NMP) promotes the preservation, evaluation and repair of ex vivo donor kidneys and accelerates the innovation of surgical approaches of kidney transplantation. Ischemia-free kidney transplantation (IFKT), which initiated by Organ Transplantation Center of the First Affiliated Hospital of Sun Yat-sen University, keeps the blood flow and oxygen supply of the donor kidney with NMP machine during the entire process of acquisition, preservation and transplantation, thereby fundamentally avoiding ischemia-reperfusion injury (IRI) of the donor kidney and reducing the risk of delayed graft function (DGF) and acute rejection after surgery. In this article, recent progresses upon the kidney NMP, surgical procedures and short-term outcomes of IFKT were reviewed, aiming to provide reference for enhancing the utilization rate of ECD donor kidney and resolving the issue of organ shortage.