RESUMEN

OBJECTIVES: To investigate the incidence and risk factors for acute kidney injury (AKI) in children with primary nephrotic syndrome (PNS), as well as the role of neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) in the early identification of AKI in these children. METHODS: A prospective collection of clinical data from children hospitalized with PNS at the Children's Hospital of the Capital Institute of Pediatrics from January 2021 to October 2022 was conducted. The children were divided into two groups based on the presence of AKI: the AKI group (47 cases) and the non-AKI group (169 cases). The risk factors for AKI in children with PNS were identified by multivariate logistic regression analysis. Urinary KIM-1 and NGAL levels were compared between the AKI and non-AKI groups, as well as among the different stages of AKI. RESULTS: The incidence of AKI in children with PNS was 21.8%. Multivariate logistic regression analysis revealed that steroid-resistant nephrotic syndrome, gastrointestinal infections, and heavy proteinuria were independent risk factors for AKI in these children with PNS (P<0.05). Urinary KIM-1 and NGAL levels were higher in the AKI group compared to the non-AKI group (P<0.05), and the urinary NGAL and KIM-1 levels in the AKI stage 2 and stage 3 subgroups were higher than those in the AKI stage 1 subgroup (P<0.017). CONCLUSIONS: KIM-1 and NGAL can serve as biomarkers for the early diagnosis of AKI in children with PNS. Identifying high-risk populations for AKI in children with PNS and strengthening the monitoring of related risk factors is of significant importance.

Asunto(s)

Lesión Renal Aguda , Receptor Celular 1 del Virus de la Hepatitis A , Lipocalina 2 , Síndrome Nefrótico , Humanos , Síndrome Nefrótico/complicaciones , Síndrome Nefrótico/orina , Masculino , Femenino , Lesión Renal Aguda/etiología , Lesión Renal Aguda/orina , Lesión Renal Aguda/diagnóstico , Preescolar , Niño , Lipocalina 2/orina , Receptor Celular 1 del Virus de la Hepatitis A/análisis , Factores de Riesgo , Estudios Prospectivos , Lactante , Modelos Logísticos , Diagnóstico Precoz

RESUMEN

Aim: To evaluate the urinary biomarkers related to sepsis in preterm newborns (NBs) and to investigate the predictive capacity of these biomarkers for a longer hospital stay.Methods: Serum and urine were collected from 27 healthy NBs, 24 NBs with neonatal infection without sepsis and 11 NBs with sepsis for the measurement of sindecan-1, lipocalin associated with urinary neutrophil gelatinase (uNGAL), urinary cystatin-C (uCysC) and urinary kidney injury molecule-1.Results: Levels of uNGAL and urinary cystatin-C were elevated in NBs with sepsis and neonatal infection, and uNGAL was significant predictor of hospital stay longer than 30 days (odds ratio: 1.052; 95% CI: 1.012-1.093; p = 0.01).Conclusion: uNGAL was associated with sepsis in preterm NBs and was useful to predict extended hospital stay.

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Asunto(s)

Biomarcadores , Cistatina C , Recien Nacido Prematuro , Tiempo de Internación , Lipocalina 2 , Sepsis , Humanos , Recién Nacido , Cistatina C/sangre , Cistatina C/orina , Lipocalina 2/orina , Lipocalina 2/sangre , Biomarcadores/orina , Biomarcadores/sangre , Sepsis/orina , Sepsis/diagnóstico , Sepsis/sangre , Masculino , Femenino , Recien Nacido Prematuro/orina , Proteínas de Fase Aguda/orina , Proteínas Proto-Oncogénicas/orina , Proteínas Proto-Oncogénicas/sangre

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Nephrotoxicity, including electrolytic disorders and acute kidney injury (AKI), limits the clinical dosage and utility of platinated antineoplastics such as cisplatin. Cisplatin nephrotoxicity embodies a tubulopathy involving the medullary S2 and S3 segments of the proximal and the distal tubules. Higher dosage extends damage over the cortical S1 segment and intensifies overall injury. However, the standard diagnosis based on plasma creatinine as well as novel injury biomarkers lacks enough pathophysiological specificity. Further granularity in the detection of renal injury would help understand the implications of individual damage patterns needed for personalized patient handling. In this article, we studied the association of urinary ganglioside GM2 activator protein (GM2AP) with the patterns of tubular damage produced by 5 and 10 mg/kg cisplatin in rats. Our results show that GM2AP appears in the urine only following damage to the cortical segment of the proximal tubule. The information provided by GM2AP is not redundant with but distinct and complementary to that provided by urinary neutrophil gelatinase-associated lipocalin (NGAL). Similarly, treatment with 150 mg/kg/day gentamicin damages the renal cortex and increases GM2AP urinary excretion; whereas renal ischemia, which does not affect the cortex, has no effect on GM2AP. Because of the key role of the cortical proximal tubule in renal function, we contend GM2AP as a potential diagnostic biomarker to stratify AKI patients according to the underlying damage and follow their evolution and prognosis. Prospectively, urinary GM2AP may help grade the severity of platinated antineoplastic nephrotoxicity by forming part of a non-invasive liquid biopsy.

Asunto(s)

Lesión Renal Aguda , Antineoplásicos , Biomarcadores , Cisplatino , Proteína Activadora de G (M2) , Corteza Renal , Cisplatino/toxicidad , Animales , Masculino , Ratas , Biomarcadores/orina , Antineoplásicos/toxicidad , Corteza Renal/efectos de los fármacos , Corteza Renal/patología , Corteza Renal/metabolismo , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/patología , Lesión Renal Aguda/orina , Gentamicinas/toxicidad , Ratas Sprague-Dawley , Lipocalina 2/orina , Índice de Severidad de la Enfermedad

RESUMEN

Vancomycin, a first-line drug for treating methicillin-resistant Staphylococcus aureus infections, is associated with acute kidney injury (AKI). This study involved an evaluation of biomarkers for AKI detection and their comparison with traditional serum creatinine (SCr). We prospectively enrolled patients scheduled to receive intravenous vancomycin for methicillin-resistant S aureus infection. Blood samples for pharmacokinetic assessment and SCr and cystatin C (CysC) measurements were collected at baseline and on days 3, 7, and 10 from the initiation of vancomycin administration (day 1). Urinary biomarkers, including kidney injury molecule 1 (KIM-1), neutrophil gelatinase-associated lipocalin, and clusterin, were collected from days 1 to 7 and adjusted for urinary creatinine levels. The estimated glomerular filtration rate (eGFR) was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation. Of the 42 patients, 6 experienced vancomycin-induced AKI. On day 7, the change from baseline eGFR using CysC (ΔeGFRCysC) showed a stronger correlation with vancomycin area under the curve (r = -0.634, P < .001) than that using SCr (ΔeGFRSCr; r = -0.437, P = .020). ΔeGFRSCr showed no significant correlation with vancomycin pharmacokinetic in patients with body mass index ≥23. The median (interquartile range) level of KIM-1 (µg/mg) was significantly higher in the AKI group (0.006 [0.005-0.008]) than in the non-AKI group (0.004 [0.001-0.005]) (P = .039, Mann-Whitney U test), with area under the receiver operating characteristic curve (95% confidence interval) of 0.788 (0.587-0.990). Serum CysC, particularly in overweight individuals or those with obesity, along with urinary KIM-1 are important predictors of vancomycin-induced AKI. These results may aid in selecting better biomarkers than traditional SCr for detecting vancomycin-induced AKI.

Asunto(s)

Lesión Renal Aguda , Antibacterianos , Biomarcadores , Creatinina , Cistatina C , Receptor Celular 1 del Virus de la Hepatitis A , Vancomicina , Humanos , Vancomicina/efectos adversos , Vancomicina/farmacocinética , Vancomicina/administración & dosificación , Vancomicina/sangre , Biomarcadores/orina , Biomarcadores/sangre , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/orina , Lesión Renal Aguda/sangre , Masculino , Femenino , Estudios Prospectivos , Persona de Mediana Edad , Antibacterianos/efectos adversos , Antibacterianos/farmacocinética , Antibacterianos/administración & dosificación , Anciano , Receptor Celular 1 del Virus de la Hepatitis A/análisis , Cistatina C/sangre , Cistatina C/orina , Creatinina/sangre , Creatinina/orina , Tasa de Filtración Glomerular , Lipocalina 2/orina , Lipocalina 2/sangre , Infecciones Estafilocócicas/tratamiento farmacológico , Staphylococcus aureus Resistente a Meticilina , Clusterina/orina , Clusterina/sangre

RESUMEN

OBJECTIVES: To study the urinary neutrophil gelatinase-associated lipocalin (NGAL) and beta-2-microglobulin (ß2M) levels as markers of tubular damage in children with type 1 diabetes (T1DM). METHODS: Forty T1DM children and 40 age-matched controls were enrolled. Subjects with coexisting kidney disorder, intake of oral glucose lowering drugs and syndromic diabetes mellitus were excluded. Fasting plasma glucose, glycated hemoglobin (HbA1c), kidney function, urinary albumin-creatinine ratio (UACR), NGAL and ß2M were measured and compared in cases and controls. RESULTS: The median (IQR) age of cases and controls was 10.6 (8, 14.2) and 10.7 (8.4, 13.7) years, respectively. Cases had disease duration of 4 (3, 6.8) years and HbA1c 10.9 (9, 13.1) %. Microalbuminuria was seen in 14 (35 %). Median (IQR) levels of UACR were higher in cases than controls [19.38 (10.27, 35.26) and 6.49 (3.10, 11.65) µg/mg; p<0.001], similarly NGAL/creatinine [352.21 (191.49, 572.45) and 190.54 (125.91, 322.83) ng/mg; p=0.006], unlike ß2M/creatinine [1.7 (0.43, 6.02) and 2.12 (1.05, 4.47) µg/mg; p=0.637]. Children with higher HbA1c (≥10 %) had higher urinary ACR and tubular biomarkers than HbA1c<10 % (p>0.05). Urinary ACR showed positive correlation with NGAL/creatinine (r=0.38, p=0.019) and ß2M/creatinine (r=0.42, p=0.009). CONCLUSIONS: Urinary biomarkers NGAL and ß2M were elevated in the presence of normal urinary microalbumin levels suggestive of early tubular damage in T1DM.

Asunto(s)

Biomarcadores , Diabetes Mellitus Tipo 1 , Lipocalina 2 , Microglobulina beta-2 , Humanos , Diabetes Mellitus Tipo 1/orina , Diabetes Mellitus Tipo 1/complicaciones , Microglobulina beta-2/orina , Niño , Biomarcadores/orina , Masculino , Femenino , Adolescente , Lipocalina 2/orina , Estudios de Casos y Controles , Albuminuria/orina , Albuminuria/etiología , Pronóstico , Hemoglobina Glucada/análisis , Nefropatías Diabéticas/orina , Nefropatías Diabéticas/etiología , Estudios de Seguimiento , Creatinina/orina

RESUMEN

OBJECTIVE: To investigate the distribution of nine (9) urine biomarkers in people living with type 2 diabetes mellitus (T2DM), with or without microvascular complications. METHODS: In total, 407 people with T2DM were enrolled from 2021 to 2022. According to diabetic retinopathy (DR) and urinary albumin-creatinine ratio (UACR), the 407 people were divided into four (4) groups, DR(-)UACR(-), DR(+)UACR(-), DR(-)UACR(+), and DR( + )UACR(+). In addition, 112 healthy volunteers were enrolled during the same period. The nine (9) urine markers included α1-microglobulin (u-α1MG), immunoglobulin G (u-IgG), neutrophil gelatinase-associated lipid carrier protein (u-NGAL), cystatin C (u-CysC), retinol-binding protein (u-RBP), ß2-microglobulin (u-ß2MG), N-acetyl-ß-D-glucosaminidase (u-NAG), transferrin (u-Trf), and collagen type IV (u-Col). For each marker, the respective level of 97.5 percentile in healthy volunteers was taken as an upper reference limit. RESULTS: Among the 407 people, 248 individuals (61%) were DR(-)UACR(-), 100 (25%) were DR(-)UACR(+), 37 (9%) were DR(+)UACR(-), and 22 (5%) were DR(+)UACR(+). The u-NAG/Cr biomarker level showed a significant difference between healthy participants and people with T2DM. In the DR(-)UACR(-)group, u-Trf/Cr showed the highest positive rate (21.37%), followed by u-IgG/Cr (14.52%); u-NAG/Cr (10.48%); u-ß2MG/Cr (4.44%); u-CysC/Cr (4.03%); u-NGAL/Cr (4.03%); u-RBP/Cr (2.82%); u-α1MG/Cr (2.42%); 17.34% of people with T2DM showed multiple biomarkers positive (≥2 biomarkers). The positive rates of one biomarker (21.33%) and two biomarkers (18.67%) in people who have less than five (5) years of T2DM were almost close to those of the DR(-)UACR(-) group (21.37%, and 12.10%, respectively). CONCLUSION: Renal tubule biomarkers may be used as an indicator in the early detection and monitoring of renal injury in diabetes mellitus. The u-NAG biomarker should be measured for the people with T2DM of the first-time diagnosis.

Asunto(s)

Albuminuria , Biomarcadores , Diabetes Mellitus Tipo 2 , Retinopatía Diabética , Humanos , Diabetes Mellitus Tipo 2/orina , Diabetes Mellitus Tipo 2/complicaciones , Biomarcadores/orina , Masculino , Femenino , Persona de Mediana Edad , Retinopatía Diabética/orina , Albuminuria/orina , Anciano , Creatinina/orina , alfa-Globulinas/orina , Microglobulina beta-2/orina , Cistatina C/orina , Cistatina C/sangre , Proteínas de Unión al Retinol/orina , Nefropatías Diabéticas/orina , Adulto , Angiopatías Diabéticas/orina , Lipocalina 2/orina

RESUMEN

Canine leishmaniosis (CanL), caused by Leishmania sp., presents a wide array of symptoms; renal dysfunction is frequently observed in these dogs and is associated with a poor prognosis and increased mortality. The traditional biomarkers namely urea and creatinine can detect renal damage but only in advanced stages of the disease. However, it has been shown that the symmetric dimethylarginine assay (SDMA) or the protein/creatinine ratio (UPC) and are early biomarkers of renal dysfunction. Their elevation occurs earlier than that of creatinine, but other novel biomarkers such as neutrophil gelatinase-associated lipocalin (NGAL) are currently under investigation. Our objective was to determine whether the urine NGAL-creatinine ratio (uNGAL/c) can provide very early diagnosis of kidney disease in CanL. In total, 68 dogs were included in the study: 15 healthy dogs and 53 dogs with CanL who were classified according to International Renal Interest Society (IRIS) classification: IRIS 1 (N= 34), IRIS 2 (N= 9) and IRIS 3/4 (N= 10). IRIS 1 was subdivided according to proteinuria in IRIS 1NP (13 dogs with UPC < 0.2), IRIS 1BL (8 dogs with UPC = 0.2-0.5) and IRIS 1 P (13 dogs with UPC > 0.5). Blood samples were collected for complete hematological and biochemistry analysis including plasma NGAL. Urinalysis included specific gravity, UPC, CysC and NGAL expressed as a ratio with creatinine. The mean concentrations of pCysC and SDMA in CanL, show a statistically significant increase from IRIS 1NP, not being statistically significant for pCysC in the IRIS 1BL group. The UPC show a statistically significant increase from IRIS 1NP. In all groups with CanL for uCysC/c and uNGAL/c was observed a statistically significant increase. The uNGAL/c in the group proteinuric animals, presents a positive correlation with all renal biomarkers studied. In the group of non-proteinuric animals, the uNGAL/c presents a positive correlation with SDMA and UPC. The uNGAL/c can be considered a reliable indicator of renal disease in dogs diagnosed with CanL who are non-azotemic and non-proteinuric.

Asunto(s)

Biomarcadores , Creatinina , Enfermedades de los Perros , Enfermedades Renales , Leishmaniasis , Lipocalina 2 , Animales , Perros , Enfermedades de los Perros/diagnóstico , Enfermedades de los Perros/orina , Enfermedades de los Perros/parasitología , Biomarcadores/orina , Biomarcadores/sangre , Leishmaniasis/veterinaria , Leishmaniasis/orina , Leishmaniasis/diagnóstico , Lipocalina 2/orina , Enfermedades Renales/veterinaria , Enfermedades Renales/diagnóstico , Enfermedades Renales/orina , Enfermedades Renales/parasitología , Masculino , Creatinina/sangre , Creatinina/orina , Femenino

RESUMEN

Development of efficient portable sensors for accurately detecting biomarkers is crucial for early disease diagnosis, yet remains a significant challenge. To address this need, we introduce the enhanced luminescence lateral-flow assay, which leverages highly luminescent upconverting nanoparticles (UCNPs) alongside a portable reader and a smartphone app. The sensor's efficiency and versatility were shown for kidney health monitoring as a proof of concept. We engineered Er3+- and Tm3+-doped UCNPs coated with multiple layers, including an undoped inert matrix shell, a mesoporous silica shell, and an outer layer of gold (UCNP@mSiO2@Au). These coatings synergistically enhance emission by over 40-fold and facilitate biomolecule conjugation, rendering UCNP@mSiO2@Au easy to use and suitable for a broad range of bioapplications. Employing these optimized nanoparticles in lateral-flow assays, we successfully detected two acute kidney injury-related biomarkers─kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL)─in urine samples. Using our sensor platform, KIM-1 and NGAL can be accurately detected and quantified within the range of 0.1 to 20 ng/mL, boasting impressively low limits of detection at 0.28 and 0.23 ng/mL, respectively. Validating our approach, we analyzed clinical urine samples, achieving biomarker concentrations that closely correlated with results obtained via ELISA. Importantly, our system enables biomarker quantification in less than 15 min, underscoring the performance of our novel UCNP-based approach and its potential as reliable, rapid, and user-friendly diagnostics.

Asunto(s)

Biomarcadores , Oro , Receptor Celular 1 del Virus de la Hepatitis A , Lipocalina 2 , Nanopartículas , Humanos , Biomarcadores/orina , Lipocalina 2/orina , Receptor Celular 1 del Virus de la Hepatitis A/análisis , Oro/química , Nanopartículas/química , Erbio/química , Lesión Renal Aguda/orina , Lesión Renal Aguda/diagnóstico , Dióxido de Silicio/química , Tulio/química , Mediciones Luminiscentes/métodos , Luminiscencia , Técnicas Biosensibles/métodos , Técnicas Biosensibles/instrumentación , Límite de Detección

RESUMEN

INTRODUCTION: Acute kidney injury (AKI) defined by a substantial decrease in kidney function within hours to days and is often irreversible with higher risk to chronic kidney disease (CKD) transition. AREAS COVERED: The authors discuss the diagnostic and predictive utilities of serum and urinary biomarkers on AKI and on the risk of AKI-to-CKD progression. The authors focus on the relevant literature covering evidence of circulating and urinary biomarkers' capability to predict the transition of AKI to CKD. EXPERT OPINION: Based on the different modalities of serum and urinary biomarkers, multiple biomarker panel seems to be potentially useful to distinguish between various types of AKI, to detect the severity and the risk of AKI progression, to predict the clinical outcome and evaluate response to the therapy. Serum/urinary neutrophil gelatinase-associated lipocalin (NGAL), serum/urinary uromodulin, serum extracellular high mobility group box-1 (HMGB-1), serum cystatin C and urinary liver-type fatty acid-binding protein (L-FABP) were the most effective in the prediction of AKI-to-CKD transition regardless of etiology and the presence of critical state in patients. The current clinical evidence on the risk assessments of AKI progression is mainly based on the utility of combination of functional, injury and stress biomarkers, mainly NGAL, L-FABP, HMGB-1 and cystatin C.

Asunto(s)

Lesión Renal Aguda , Biomarcadores , Progresión de la Enfermedad , Insuficiencia Renal Crónica , Humanos , Biomarcadores/orina , Biomarcadores/sangre , Lesión Renal Aguda/orina , Lesión Renal Aguda/diagnóstico , Lesión Renal Aguda/sangre , Lesión Renal Aguda/etiología , Insuficiencia Renal Crónica/orina , Insuficiencia Renal Crónica/sangre , Insuficiencia Renal Crónica/diagnóstico , Lipocalina 2/orina , Lipocalina 2/sangre , Pronóstico , Proteínas de Unión a Ácidos Grasos/orina , Proteínas de Unión a Ácidos Grasos/sangre

RESUMEN

BACKGROUND AND AIMS: Cholemic nephropathy is a cause of acute kidney injury occurring in patients with jaundice. The aim of this study was to evaluate early renal function impairment in patients with mild acute hyperbilirubinemia in the absence of alterations of the common parameters used in clinical practice (serum creatinine or urea) and with normal renal morphology. We studied urinary biomarkers of tubular damage urinary neutrophil gelatinase-associated lipocalin (u-NGAL), urinary beta-2-microglobulin (u-B2M), urinary osteopontin (u-OPN), urinary trefoil factor 3 (u-TFF3) and urinary Cystatin C (u-Cys). METHODS: This is a case-control study investigating the following urinary biomarkers of tubular damage: u-NGAL, u-B2M, u-OPN, u-TFF3 and u-Cys, in patients with mild acute hyperbilirubinemia. Seventy-four patients were included in this study: 36 patients with jaundice and 38 patients without jaundice. RESULTS: Subjects with jaundice (total bilirubin 12.4 ± 7.3 mg/dL) showed higher u-NGAL, u-B2M, u-OPN, u-TFF3 and u-Cys compared with controls. After logistic regression analyses, including the following independent variables: age, estimated Glomerular Filtration Rate (eGFR), haemoglobin, diabetes, hypertension and jaundice, we observed a higher risk of elevated u-NGAL values (OR = 3.8, 95% CI 1.07-13.5, p = .03) and u-B2M (OR = 9.4, 95% CI 2.3-38.9, p = .0018) in jaundiced subjects. Moreover, urinary biomarkers had a direct correlation with serum cholestasis indexes. CONCLUSIONS: This study demonstrated increased urinary biomarkers of tubular damage (u-NGAL, u-B2M, u-OPN, u-TFF3, and u-Cys) in patients with mild hyperbilirubinemia in comparison with a control group. These findings suggest early renal tubular damage in the absence of alterations of the normal parameters used in clinical practice (eGFR, serum urea and renal morphology).

Asunto(s)

Lesión Renal Aguda , Biomarcadores , Lipocalina 2 , Humanos , Biomarcadores/orina , Biomarcadores/sangre , Estudios de Casos y Controles , Masculino , Femenino , Persona de Mediana Edad , Lesión Renal Aguda/orina , Lesión Renal Aguda/etiología , Lesión Renal Aguda/sangre , Lesión Renal Aguda/diagnóstico , Lipocalina 2/orina , Lipocalina 2/sangre , Anciano , Cistatina C/sangre , Cistatina C/orina , Hiperbilirrubinemia/complicaciones , Hiperbilirrubinemia/sangre , Hiperbilirrubinemia/orina , Microglobulina beta-2/orina , Microglobulina beta-2/sangre , Túbulos Renales/patología , Osteopontina/orina , Osteopontina/sangre , Lipocalinas/orina , Lipocalinas/sangre , Proteínas Proto-Oncogénicas/orina , Proteínas Proto-Oncogénicas/sangre , Modelos Logísticos , Adulto , Proteínas de Fase Aguda/orina , Bilirrubina/sangre , Bilirrubina/orina

RESUMEN

A growing body of research is categorizing sex differences in both sickle cell anemia (SCA) and acute kidney injury (AKI); however, most of this work is being conducted in high-resource settings. Here, we evaluated risk factors and clinical parameters associated with AKI and AKI severity, stratified by sex, in a cohort of children hospitalized with SCA and vaso-occlusive pain crisis (VOC). The purpose of this study was to explore sex disparities in a high-risk, vulnerable population. This study was a secondary analysis of data collected from a cohort of Ugandan children between 2 and 18 yr of age prospectively enrolled. A total of 185 children were enrolled in the primary study; 41.6% were female and 58.4% were male, with a median age of 8.9 yr. Incident or worsening AKI (P = 0.026) occurred more frequently in female compared with male children, despite no differences in AKI on admission. Female children also had altered markers of renal function including higher creatinine levels at admission (P = 0.03), higher peak creatinine (P = 0.006), and higher urine neutrophil gelatinase-associated lipocalin (NGAL) at admission (P = 0.003) compared with male children. Female children had elevated total (P = 0.045) and conjugated bilirubin at admission (P = 0.02) compared with male children and higher rates of hematuria at admission (P = 0.004). Here, we report sex differences in AKI in children with SCA and VOC, including increased incidence and worsening of AKI in female pediatric patients, in association with an increase in biological indicators of poor renal function including creatinine, estimated glomerular filtration rate, and NGAL.NEW & NOTEWORTHY In this study, we report an increased risk of developing acute kidney injury (AKI) during hospitalization, worsening AKI, and death among females with sickle cell anemia (SCA) hospitalized with an acute pain crisis compared with males. The sex differences in AKI were not explained by socioeconomic differences, severity of pain, or disease severity among females compared with males. Together, these data suggest that female children with SCA may be at increased risk of AKI.

Asunto(s)

Lesión Renal Aguda , Anemia de Células Falciformes , Humanos , Anemia de Células Falciformes/complicaciones , Anemia de Células Falciformes/epidemiología , Femenino , Masculino , Lesión Renal Aguda/epidemiología , Lesión Renal Aguda/orina , Lesión Renal Aguda/diagnóstico , Niño , Uganda/epidemiología , Preescolar , Adolescente , Factores Sexuales , Factores de Riesgo , Incidencia , Biomarcadores/sangre , Biomarcadores/orina , Hospitalización , Estudios Prospectivos , Índice de Severidad de la Enfermedad , Lipocalina 2/orina , Riñón/fisiopatología

RESUMEN

INTRODUCTION: Tachycardia caused by sympathetic overactivity impairs myocardial function and raises septic patients' mortality. This study examined whether tachycardia is associated with acute kidney injury (AKI) period-prevalence among critically ill patients with and without sepsis. METHODS: In 328 patients (119 sepsis and 209 non-sepsis) admitted to our intensive care unit (ICU), we assessed heart rate at ICU admission, plasma neutrophil gelatinase-associated lipocalin (NGAL) and N-terminal pro-B-type natriuretic peptide, and urinary L-type fatty acid-binding protein and N-acetyl-ß-d-glucosaminidase (NAG) at 0 and 48 h after admission. Tachycardia was defined as a heart rate above 100 beats/min. RESULTS: Tachycardia was independently correlated with AKI prevalence during the first week after ICU admission in the septic patients, but not in the non-septic patients. A dose-dependent increase in AKI period-prevalence was observed across ascending heart rate ranges. Furthermore, we discovered a dose-dependent increase in renal biomarker-positive patients regarding plasma NGAL and urinary NAG over increasing heart rate ranges 48 h after admission. CONCLUSION: The findings revealed an independent relationship between tachycardia and AKI prevalence during the first week of ICU in septic patients. Heart rate was found to have a dose-dependent effect on AKI prevalence and renal insult monitored by biomarkers.

Asunto(s)

Lesión Renal Aguda , Enfermedad Crítica , Sepsis , Taquicardia , Humanos , Lesión Renal Aguda/etiología , Lesión Renal Aguda/sangre , Sepsis/complicaciones , Taquicardia/etiología , Taquicardia/complicaciones , Masculino , Femenino , Persona de Mediana Edad , Estudios Prospectivos , Anciano , Biomarcadores/sangre , Biomarcadores/orina , Unidades de Cuidados Intensivos , Lipocalina 2/sangre , Lipocalina 2/orina , Frecuencia Cardíaca , Proteínas de Fase Aguda/orina , Prevalencia , Péptido Natriurético Encefálico/sangre , Fragmentos de Péptidos/sangre , Acetilglucosaminidasa/orina

RESUMEN

BACKGROUND: Prediction and/or early identification of acute kidney injury (AKI) and individuals at greater risk remains of great interest in clinical medicine. Acute kidney injury continues to be a common complication among hospitalized patients, with an incidence ranging from 6 to 58%, depending on the setting. Aim of this study was to determine the performance of Insulin-like growth factor binding protein-7 (IGFBP7), tissue metallopeptidase inhibitor 2 (TIMP2), and urinary neutrophil gelatinase-associated lipocalin (uNGAL) in early detection of AKI among non-critically ill patients. METHODS: In this prospective observational study at Mayo Clinic Hospitals in Rochester, Minnesota, USA, non-critically ill patients admitted from the emergency department between October 31st, 2016 and May 1st, 2018, who had an acute kidney injury (AKI) probability of 5% or higher were included. Biomarkers were measured in residual urine samples collected in the emergency department. The primary outcome was biomarker performance in predicting AKI development within the first 72 h. RESULTS: Among 368 included patients, the mean age was 79 ± 12 years, and 160 (43%) were male. Acute kidney injury occurred in 62 (17%) patients; 11.5% stage 1, 2.5% stage 2, and 3% stage 3. Twelve patients (3%) died during hospitalization and 102 (28%) within nine months after admission. The median uNGAL and IGFBP7-TIMP2 were 57 [20-236 ng/ml], and 0.3 [0.1-0.8], respectively. The C-statistic of uNGAL and IGFBP7-TIMP2 of > 0.3 and > 2.0 for AKI prediction were 0.56, 0.54, and 0.53, respectively. In a model where one point is assigned to each marker of AKI (elevated serum creatinine, IGFBP7-TIMP2 > 0.3, and uNGAL), a higher score correlated with higher nine-month mortality [OR of 1.32 per point (95% CI 1.02-1.71)]. CONCLUSION: Among non-critically ill hospitalized patients, the performance of uNGAL and IGFBP7-TIMP2 for AKI prediction within 72 h of admission was modest. This suggests a limited role for these biomarkers in AKI risk stratification among non-critically ill patients. Key learning points What was known Acute kidney injury (AKI) is a common complication among hospitalized patients. It is associated with increased morbidity and mortality. Various clinical prediction models and biomarkers have been developed to identify patients in special populations (such as ICU and cardiac surgery) who are at risk of AKI and diagnose AKI early. This study adds The performance of the biomarkers uNGAL, TIMP-2, and IGFBP-7 in predicting AKI within 72 h of admission in non-critically ill patients was modest. However, these biomarkers were found to have a prognostic value for predicting 9-month mortality. One potential application of these biomarkers is identifying patients at higher AKI risk before exposing them to nephrotoxic agents. Potential impact This study provides evidence regarding the real-world performance of current FDA-approved biomarkers (uNGAL, TIMP-2, and IGFBP-7) for predicting acute kidney injury (AKI) within 72 h of hospital admission among noncritically ill patients. While the performance of these biomarkers for predicting short-term AKI was modest, they may have a prognostic value for predicting 9-month mortality.

Asunto(s)

Lesión Renal Aguda , Biomarcadores , Diagnóstico Precoz , Proteínas de Unión a Factor de Crecimiento Similar a la Insulina , Lipocalina 2 , Inhibidor Tisular de Metaloproteinasa-2 , Humanos , Lesión Renal Aguda/diagnóstico , Lesión Renal Aguda/orina , Masculino , Biomarcadores/orina , Biomarcadores/sangre , Femenino , Proteínas de Unión a Factor de Crecimiento Similar a la Insulina/orina , Inhibidor Tisular de Metaloproteinasa-2/orina , Anciano , Estudios Prospectivos , Anciano de 80 o más Años , Lipocalina 2/orina , Valor Predictivo de las Pruebas , Persona de Mediana Edad , Factores de Tiempo

RESUMEN

Introduction: Diabetic kidney disease (DKD) is one of the major microvascular complications of type 1 diabetes mellitus (T1DM). Some studies suggest that changes of renal tubular components emerge before the glomerular lesions thus introducing the concept of diabetic tubulopathy with urinary neutrophil gelatinase-associated lipocalin (uNGAL) as a potential marker of DKD. This concept was not confirmed in all studies. Materials and methods: In 198 T1DM patients with median age 15 years and diabetes duration over one year, an albumin/creatinine ratio (ACR) was determined and uNGAL measured in spot urine sample. Urine samples for ACR and uNGAL were also collected in the control group of 100 healthy children of similar age. Results: There was no significant difference in uNGAL concentration or uNGAL/creatinine between T1DM children and healthy subjects (6.9 (2.8-20.1) ng/mL vs 7.9 (2.9-21.0) ng/mL, P = 0.969 and 6.8 (2.2-18.4) ng/mg vs 6.5 (1.9-13.4) ng/mg, P = 0.448, respectively) or between T1DM subjects with albuminuria A2 and albuminuria A1 (P = 0.573 and 0.595, respectively). Among T1DM patients 168 (85%) had normal uNGAL concentrations, while in 30 (15%) patients uNGAL was above the defined cut-off value of 30.9 ng/mL. There was no difference in BMI, HbA1c and diabetes duration between patients with elevated uNGAL compared to those with normal uNGAL. Conclusions: We found no significant difference in uNGAL concentration or uNGAL/creatinine between T1DM children and healthy subjects or between albuminuria A2 and albuminuria A1 T1DM subjects. Therefore, uNGAL should not be recommended as a single marker for detecting diabetic kidney disease in children and adolescents.

Asunto(s)

Diabetes Mellitus Tipo 1 , Nefropatías Diabéticas , Lipocalina 2 , Humanos , Diabetes Mellitus Tipo 1/orina , Diabetes Mellitus Tipo 1/complicaciones , Adolescente , Femenino , Masculino , Lipocalina 2/orina , Niño , Nefropatías Diabéticas/orina , Nefropatías Diabéticas/diagnóstico , Biomarcadores/orina , Creatinina/orina , Albuminuria/orina , Estudios de Casos y Controles

RESUMEN

BACKGROUND: Tubular biomarkers, which reflect tubular dysfunction or injury, are associated with incident chronic kidney disease and kidney function decline. Several tubular biomarkers have also been implicated in the progression of autosomal dominant polycystic kidney disease (ADPKD). We evaluated changes in multiple tubular biomarkers in four groups of patients with ADPKD who participated in one of two clinical trials (metformin therapy and diet-induced weight loss), based on evidence suggesting that such interventions could reduce tubule injury. METHODS: 66 participants (26 M/40 F) with ADPKD and an estimated glomerular filtration rate (eGFR) ≥ 30 ml/min/1.73m2 who participated in either a metformin clinical trial (n = 22 metformin; n = 23 placebo) or dietary weight loss study (n = 10 daily caloric restriction [DCR]; n = 11 intermittent fasting [IMF]) were included in assessments of urinary tubular biomarkers (kidney injury molecule-1 [KIM-1], fatty-acid binding protein [FABP], interleukin-18 [IL-18], monocyte chemoattractant protein-1 [MCP-1], neutrophil gelatinase-associated lipocalin [NGAL], clusterin, and human cartilage glycoprotein-40 [YKL-40]; normalized to urine creatinine), at baseline and 12 months. The association of baseline tubular biomarkers with both baseline and change in height-adjusted total kidney volume (HtTKV; percent change from baseline to 12 months) and estimated glomerular filtration rate (eGFR; absolute change at 12 months vs. baseline), with covariate adjustment, was also assessed using multiple linear regression. RESULTS: Mean ± s.d. age was 48 ± 8 years, eGFR was 71 ± 16 ml/min/1.73m2, and baseline BMI was 30.5 ± 5.9 kg/m2. None of the tubular biomarkers changed with any intervention as compared to placebo. Additionally, baseline tubular biomarkers were not associated with either baseline or change in eGFR or HtTKV over 12 months, after adjustments for demographics, group assignment, and clinical characteristics. CONCLUSIONS: Tubular biomarkers did not change with dietary-induced weight loss or metformin, nor did they associate with kidney disease progression, in this cohort of patients with ADPKD.

Asunto(s)

Biomarcadores , Restricción Calórica , Tasa de Filtración Glomerular , Túbulos Renales , Metformina , Riñón Poliquístico Autosómico Dominante , Humanos , Metformina/uso terapéutico , Riñón Poliquístico Autosómico Dominante/orina , Riñón Poliquístico Autosómico Dominante/tratamiento farmacológico , Riñón Poliquístico Autosómico Dominante/dietoterapia , Masculino , Femenino , Biomarcadores/orina , Persona de Mediana Edad , Túbulos Renales/patología , Túbulos Renales/efectos de los fármacos , Adulto , Lipocalina 2/orina , Quimiocina CCL2/orina , Proteínas de Unión a Ácidos Grasos/orina , Receptor Celular 1 del Virus de la Hepatitis A/metabolismo , Receptor Celular 1 del Virus de la Hepatitis A/análisis , Proteína 1 Similar a Quitinasa-3/orina , Hipoglucemiantes/uso terapéutico

RESUMEN

Early kidney injury may be detected by urinary markers, such as beta-2 microglobulin (B2M), tissue inhibitor of metalloproteinases-2 (TIMP-2), insulin-like growth factor-binding protein 7 (IGFBP7), kidney injury molecule-1 (KIM-1) and/or neutrophil gelatinase-associated lipocalin (NGAL). Of these biomarkers information on pathophysiology and reference ranges in both healthy and diseased populations are scarce. Differences in urinary levels of B2M, TIMP-2, IGFBP7, KIM-1 and NGAL were compared 24 h before and after nephrectomy in 38 living kidney donors from the REnal Protection Against Ischaemia-Reperfusion in transplantation study. Linear regression was used to assess the relation between baseline biomarker concentration and kidney function 1 year after nephrectomy. Median levels of urinary creatinine and creatinine standardized B2M, TIMP-2, IGFBP7, KIM-1, NGAL, and albumin 24 h before nephrectomy in donors were 9.4 mmol/L, 14 µg/mmol, 16 pmol/mmol, 99 pmol/mmol, 63 ng/mmol, 1390 ng/mmol and 0.7 mg/mmol, with median differences 24 h after nephrectomy of - 0.9, + 1906, - 7.1, - 38.3, - 6.9, + 2378 and + 1.2, respectively. The change of donor eGFR after 12 months per SD increment at baseline of B2M, TIMP-2, IGFBP7, KIM-1 and NGAL was: - 1.1, - 2.3, - 0.7, - 1.6 and - 2.8, respectively. Urinary TIMP-2 and IGFBP7 excretion halved after nephrectomy, similar to urinary creatinine, suggesting these markers predominantly reflect glomerular filtration. B2M and NGAL excretion increased significantly, similar to albumin, indicating decreased proximal tubular reabsorption following nephrectomy. KIM-1 did not change considerably after nephrectomy. Even though none of these biomarkers showed a strong relation with long-term donor eGFR, these results provide valuable insight into the pathophysiology of these urinary biomarkers.

Asunto(s)

Biomarcadores , Proteínas de Unión a Factor de Crecimiento Similar a la Insulina , Nefrectomía , Inhibidor Tisular de Metaloproteinasa-2 , Microglobulina beta-2 , Humanos , Nefrectomía/métodos , Nefrectomía/efectos adversos , Inhibidor Tisular de Metaloproteinasa-2/orina , Microglobulina beta-2/orina , Masculino , Femenino , Persona de Mediana Edad , Proteínas de Unión a Factor de Crecimiento Similar a la Insulina/orina , Adulto , Biomarcadores/orina , Trasplante de Riñón/efectos adversos , Donadores Vivos , Riñón/cirugía , Riñón/fisiopatología , Riñón/metabolismo , Receptor Celular 1 del Virus de la Hepatitis A/metabolismo , Receptor Celular 1 del Virus de la Hepatitis A/análisis , Creatinina/orina , Lipocalina 2/orina

RESUMEN

This study evaluates the diagnostic efficacy of urinary biomarkers, Neutrophil Gelatinase-Associated Lipocalin (uNGAL), and Kidney Injury Molecule-1 (uKIM-1), in identifying Acute Kidney Injury (AKI) in dogs affected with leptospirosis or babesiosis. Acute kidney injury was diagnosed based on the increase in serum creatinine levels above 0.3 mg/dL within 48 h and dogs were categorized according to AKI grades based on International Renal Interest Society guidelines. Traditional biomarkers (serum creatinine and blood urea nitrogen) and novel biomarkers like urinary NGAL and urinary KIM-1 levels were measured and compared to concentrations obtained in control dogs. Statistical analysis assessed significant differences (P < 0.01) across AKI grades, specifically noting elevated urinary NGAL and KIM-1 in IRIS grade I AKI (P < 0.001). The study highlights the diagnostic significance of urinary NGAL and KIM-1 as early indicators of renal damage, particularly valuable in non-azotemic AKI cases, offering promising markers for early AKI diagnosis in veterinary clinical settings. These biomarkers demonstrate clinical utility and underscore their potential for improving AKI management in veterinary medicine. Further validation studies involving larger cohorts and diverse etiologies of AKI are needed to confirm the diagnostic accuracy and clinical utility of urinary NGAL and KIM-1 in veterinary practice.

Asunto(s)

Lesión Renal Aguda , Babesiosis , Biomarcadores , Enfermedades de los Perros , Leptospirosis , Lipocalina 2 , Animales , Perros , Enfermedades de los Perros/orina , Enfermedades de los Perros/diagnóstico , Lesión Renal Aguda/veterinaria , Lesión Renal Aguda/orina , Lesión Renal Aguda/diagnóstico , Leptospirosis/veterinaria , Leptospirosis/orina , Leptospirosis/diagnóstico , Leptospirosis/complicaciones , Babesiosis/orina , Babesiosis/diagnóstico , Babesiosis/complicaciones , Biomarcadores/orina , Lipocalina 2/orina , Masculino , Femenino , Receptor Celular 1 del Virus de la Hepatitis A/metabolismo , Proteínas de Fase Aguda , Proteínas Proto-Oncogénicas , Lipocalinas

RESUMEN

BACKGROUND: Acute renal dysfunction and subsequent acute renal failure after cardiac surgery are associated with high mortality and morbidity. Early therapeutic or preventive intervention is hampered by the lack of an early biomarker for acute renal injury. Recent studies showed that urinary neutrophil gelatinase-associated lipocalin (NGAL or lipocalin 2) is upregulated early (within 1 to 3 h) after murine renal injury and in pediatric acute renal dysfunction after cardiac surgery. The authors hypothesized that postoperative urinary NGAL concentrations are increased in adult patients developing acute renal dysfunction after cardiac surgery compared with patients without acute renal dysfunction. METHODS: After institutional review board approval, 81 cardiac surgical patients were prospectively studied. Urine samples were collected immediately before incision and at various time intervals after surgery for NGAL analysis by quantitative immunoblotting. Acute renal dysfunction was defined as peak postoperative serum creatinine increase by 50% or greater compared with preoperative serum creatinine. RESULTS: Sixteen of 81 patients (20%) developed postoperative acute renal dysfunction, and the mean urinary NGAL concentrations in patients who developed acute renal dysfunction were significantly higher early after surgery (after 1 h, mean ± SD, 4,195 ± 6,520 vs. 1,068 ± 2,129 ng/ml; P < 0.01) compared with patients who did not develop acute renal dysfunction. Mean urinary NGAL concentrations continued to increase and remained significantly higher at 3 and 18 h after cardiac surgery in patients with acute renal dysfunction. In contrast, urinary NGAL in patients without acute renal dysfunction decreased rapidly after cardiac surgery. CONCLUSIONS: Patients developing postoperative acute renal dysfunction had significantly higher urinary NGAL concentrations early after cardiac surgery. Urinary NGAL may therefore be a useful early biomarker of acute renal dysfunction after cardiac surgery. These findings may facilitate the early detection of acute renal injury and potentially prevent progression to acute renal failure.

Asunto(s)

Lesión Renal Aguda , Proteínas de Fase Aguda , Biomarcadores , Procedimientos Quirúrgicos Cardíacos , Lipocalina 2 , Lipocalinas , Complicaciones Posoperatorias , Humanos , Lesión Renal Aguda/etiología , Lesión Renal Aguda/diagnóstico , Lesión Renal Aguda/fisiopatología , Lesión Renal Aguda/orina , Femenino , Lipocalina 2/orina , Lipocalina 2/sangre , Masculino , Estudios Prospectivos , Procedimientos Quirúrgicos Cardíacos/efectos adversos , Persona de Mediana Edad , Lipocalinas/orina , Anciano , Proteínas de Fase Aguda/orina , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/etiología , Biomarcadores/orina , Biomarcadores/sangre , Proteínas Proto-Oncogénicas/orina , Proteínas Proto-Oncogénicas/sangre , Adulto

RESUMEN

BACKGROUND: Chronic liver disease is a common and important clinical problem.Hepatorenal syndrome (HRS) is a life threatening complication. Serum creatinine (Cr) remains the only conventional indicator of renal function. However, the interpretation of serum Cr level can be confounded by malnutrition and reduced muscle mass often observed in patients with severe liver disease. Here, we present a cross-sectional study to explore the sensitivity and specificity of other markers as urinary KIM-1 and NGAL for cases of HRS. METHODS: Cross-sectional study was conducted on 88 patients who were admitted to Alexandria main university hospital. Enrolled patients were divided in two groups; group 1: patients with advanced liver cirrhosis (child B and C) who have normal kidney functions while group 2: patients who developed HRS. Stata© version 14.2 software package was used for analysis. RESULTS: Group 1 included 18 males and 26 females compared to 25 males and 19 females in group 2 (p = 0.135). Only the urinary KIM-1 showed a statistically significant difference between both groups in the multivariate logistic regression analysis adjusted for gender, serum bilirubin, serum albumin, INR, serum K, AST and ALT levels. CONCLUSION: In conclusion, our study aligns with prior research, as seen in the consistent findings regarding Urinary NGAL elevation in cirrhotic patients with AKI. Urinary KIM-1, independent of Urinary NGAL, may have a role in precisely distinguishing between advanced liver cirrhosis and HRS and merits further exploration.

Asunto(s)

Biomarcadores , Receptor Celular 1 del Virus de la Hepatitis A , Síndrome Hepatorrenal , Lipocalina 2 , Cirrosis Hepática , Humanos , Masculino , Femenino , Receptor Celular 1 del Virus de la Hepatitis A/análisis , Receptor Celular 1 del Virus de la Hepatitis A/metabolismo , Cirrosis Hepática/complicaciones , Cirrosis Hepática/orina , Estudios Transversales , Persona de Mediana Edad , Lipocalina 2/orina , Lipocalina 2/sangre , Biomarcadores/orina , Biomarcadores/sangre , Adulto , Síndrome Hepatorrenal/etiología , Síndrome Hepatorrenal/orina , Síndrome Hepatorrenal/diagnóstico , Modelos Logísticos , Anciano , Creatinina/sangre , Creatinina/orina , Sensibilidad y Especificidad

Asunto(s)

Biomarcadores , Paro Cardíaco , Lipocalina 2 , Valor Predictivo de las Pruebas , Humanos , Lipocalina 2/orina , Lipocalina 2/sangre , Paro Cardíaco/sangre , Biomarcadores/sangre , Pronóstico