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1.
Pediatr Nephrol ; 30(12): 2207-13, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-26248472

RESUMEN

BACKGROUND: Acute kidney injury (AKI) is a significant complication in patients with cancer, and nephrotoxic drugs are among the most common causes of AKI. To date, there is no study evaluating the potential role of renal biomarkers in children receiving nephrotoxic chemotherapy. METHODS: A prospective study was conducted in children receiving methotrexate (MTX) or platinum-based treatment. Urinary kidney injury molecule-1 (KIM-1) was measured 24 h after the initiation of the chemotherapy infusion, and serum creatinine (sCr) was measured prior to drug infusion and at 24, 48, 72, and 96 h, 1 and 2 weeks, and 3 months post-initiation of treatment. RESULTS: A total of 64 children were evaluated, of whom 21 (32.8%) developed AKI. The majority had AKI stage 1 (n = 12, 57.1%) and only one developed AKI stage 3. Median values of urinary KIM-1 were higher in patients with AKI than in those without AKI [10.7, interquartile range (IQR) 1.6-17.9 vs. 4.3 (IQR 1.3-6.1) ng/mg creatinine; p < 0.01]. Urinary KIM-1 showed good discrimination for AKI in patients receiving nephrotoxic chemotherapy, with an area under the receiver operator characteristic curve for AKI up to 1 week later of 0.82 (95% confidence interval 0.66-0.95). Even when measured only 24 h after drug infusion, urinary KIM-1 still showed good discrimination to predict persistent renal impairment three months later. CONCLUSION: Urinary KIM-1 measured 24 h after the start of drug infusion has the potential to detect early AKI in pediatric patients treated with MTX or platinum-class drugs.


Asunto(s)
Lesión Renal Aguda/inducido químicamente , Antineoplásicos/efectos adversos , Glicoproteínas de Membrana/orina , Metotrexato/efectos adversos , Compuestos de Platino/efectos adversos , Lesión Renal Aguda/orina , Biomarcadores/orina , Niño , Preescolar , Estudios de Cohortes , Femenino , Receptor Celular 1 del Virus de la Hepatitis A , Humanos , Riñón/fisiopatología , Pruebas de Función Renal , Masculino , Estudios Prospectivos , Curva ROC , Receptores Virales
2.
Clin Chim Acta ; 438: 350-7, 2015 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-25195004

RESUMEN

PURPOSE OF THE REVIEW: Acute kidney injury (AKI) and chronic kidney disease (CKD) are conditions that substantially increase morbidity and mortality. Although novel biomarkers are being used in practice, the diagnosis of AKI and CKD is still made with surrogate markers of GFR, such as serum creatinine (SCr), urine output and creatinine based estimating equations. SCr is limited as a marker of kidney dysfunction in both settings and may be inaccurate in several situations, such as in patients with low muscle mass or with fluid overload. New biomarkers have the potential to identify earlier patients with AKI and CKD and in the future potentially intervene to modify outcomes. RECENT FINDINGS: In particular KIM-1 and NGAL are considered excellent biomarkers in urine and plasma for the early prediction of AKI; however cycle arrest biomarkers have emerged as novel markers for risk stratification of AKI. Urine TIMP-2 and IGFBP7 performed better than any other biomarkers reported to date for predicting the development of moderate or severe AKI. Biomarker combinations are required to increase diagnostic accuracy in an acute setting. NGAL, cystatin C, and FGF-23 are promising and accurate biomarkers for CKD detection. Equations combining cystatin C and SCr perform better than the equations using either cystatin C or SCr alone, especially in situations where CKD needs to be confirmed. Combining creatinine, cystatin C and urine albumin to creatinine ratio improves risk stratification for kidney disease progression and mortality. SUMMARY: Recent advances in molecular biology have resulted in promising biomarkers for AKI and CKD diagnoses; however more research is necessary to implement them successfully into clinical practice in order to facilitate early diagnosis, guide interventions and monitor disease progression. The following review describes the most important biomarkers studied in kidney disease and will discuss the use and the value of these biomarkers in different clinical settings.


Asunto(s)
Lesión Renal Aguda/diagnóstico , Riñón/metabolismo , Lipocalinas/sangre , Glicoproteínas de Membrana/sangre , Proteínas Proto-Oncogénicas/sangre , Receptores Virales/sangre , Insuficiencia Renal Crónica/diagnóstico , Lesión Renal Aguda/sangre , Lesión Renal Aguda/patología , Lesión Renal Aguda/orina , Proteínas de Fase Aguda/orina , Biomarcadores/sangre , Biomarcadores/orina , Creatinina/sangre , Cistatina C/sangre , Progresión de la Enfermedad , Diagnóstico Precoz , Factor-23 de Crecimiento de Fibroblastos , Factores de Crecimiento de Fibroblastos/orina , Tasa de Filtración Glomerular , Receptor Celular 1 del Virus de la Hepatitis A , Humanos , Proteínas de Unión a Factor de Crecimiento Similar a la Insulina/orina , Riñón/patología , Lipocalina 2 , Lipocalinas/orina , Glicoproteínas de Membrana/orina , Proteínas Proto-Oncogénicas/orina , Insuficiencia Renal Crónica/sangre , Insuficiencia Renal Crónica/patología , Insuficiencia Renal Crónica/orina , Inhibidor Tisular de Metaloproteinasa-2/orina
3.
Nephrology (Carlton) ; 19(6): 352-8, 2014 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-24666430

RESUMEN

AIM: To evaluate the performance of urinary neutrophil gelatinase-associated lipocalin (uNGAL), kidney injury molecule, interleukin-18 and heat shock protein 72 for differential diagnosis between causes of acute kidney injury in kidney transplant recipients, especially immunological rejection. PATIENTS AND METHODS: We measured these biomarkers in 67 kidney transplant recipients with acute kidney injury according to the RIFLE criteria. RESULTS: There were no statistical differences in biomarkers between kidney transplant recipients with immunological rejection (n = 20), pre-renal causes (n = 20) and other AKI causes (n = 27). Only the uNGAL level relative to urinary creatinine (uNGAL/uCr) for immunological rejection was different in comparison with others (P < 0.001); a cut-off of 59 µg/g of uNGAL/uCr had a sensitivity and specificity of 60% and 58% respectively (area under the curve in receiver-operating characteristic curve, 0.65). The other biomarkers were not useful in differentiating the causes of acute kidney injury. CONCLUSION: The biomarkers tested are not useful in identifying immunological rejection as cause of acute kidney injury in kidney transplant recipients.


Asunto(s)
Lesión Renal Aguda , Rechazo de Injerto , Trasplante de Riñón/efectos adversos , Túbulos Renales/metabolismo , Lesión Renal Aguda/diagnóstico , Lesión Renal Aguda/etiología , Lesión Renal Aguda/orina , Proteínas de Fase Aguda/orina , Adulto , Biomarcadores/orina , Diagnóstico Diferencial , Femenino , Rechazo de Injerto/diagnóstico , Rechazo de Injerto/etiología , Rechazo de Injerto/orina , Proteínas del Choque Térmico HSP72/orina , Receptor Celular 1 del Virus de la Hepatitis A , Humanos , Interleucina-18/orina , Lipocalina 2 , Lipocalinas/orina , Masculino , Glicoproteínas de Membrana/orina , Persona de Mediana Edad , Proteínas Proto-Oncogénicas/orina , Curva ROC , Receptores Virales , Sensibilidad y Especificidad , Adulto Joven
4.
Clin Chim Acta ; 421: 17-30, 2013 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-23485645

RESUMEN

Diabetic nephropathy (DN) is one of the major microvascular complications of diabetes and it is defined as a rise in the urinary albumin excretion (UAE) rate and abnormal renal function. Currently, changes in albuminuria are considered a hallmark of onset or progression of DN. However, some patients with diabetes have advanced renal pathological changes and progressive kidney function decline even if urinary albumin levels are in the normal range, indicating that albuminuria is not the perfect marker for the early detection of DN. The present article provides an overview of the literature reporting some relevant biomarkers that have been found to be associated with DN and that potentially may be used to predict the onset and/or monitor the progression of nephropathy. In particular, biomarkers of renal damage, inflammation, and oxidative stress may be useful tools for detection at an early stage or prediction of DN. Proteomic-based biomarker discovery represents a novel strategy to improve diagnosis, prognosis and treatment of DN; however, proteomics-based approaches are not yet available in most of the clinical chemistry laboratories. The use of a panel with a combination of biomarkers instead of urinary albumin alone seems to be an interesting approach for early detection of DN, including markers of glomerular damage (e.g., albumin), tubular damage (e.g., NAG and KIM-1), inflammation (e.g., TNF-α) and oxidative stress (e.g., 8-OHdG) because these mechanisms contribute to the development and outcomes of this disease.


Asunto(s)
Albuminuria/diagnóstico , Nefropatías Diabéticas/diagnóstico , Riñón/metabolismo , Proteómica , 8-Hidroxi-2'-Desoxicoguanosina , Acetilglucosaminidasa/orina , Albuminuria/patología , Albuminuria/orina , Biomarcadores/orina , Desoxiguanosina/análogos & derivados , Desoxiguanosina/orina , Nefropatías Diabéticas/patología , Nefropatías Diabéticas/orina , Progresión de la Enfermedad , Diagnóstico Precoz , Receptor Celular 1 del Virus de la Hepatitis A , Humanos , Inflamación , Riñón/patología , Glicoproteínas de Membrana/orina , Proteínas de Neoplasias/orina , Estrés Oxidativo , Pronóstico , Receptores Virales , Factor de Necrosis Tumoral alfa/orina
5.
PLoS One ; 8(3): e58480, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-23520515

RESUMEN

The diagnosis of Chagas disease in humans is generally limited to the detection of specific antibodies. Detection of T. cruzi antigens in urine has been reported previously, but is not used in the diagnosis. In this study, soluble T. cruzi antigens and DNA were detected in urine samples and were associated with kidney injury and systemic detection of the parasite. We used 72 guinea pigs infected with T. cruzi Y strain and 18 non-infected guinea pigs. Blood, kidney, heart and urine samples were collected during the acute phase and chronic phase. Urine samples were concentrated by ultrafiltration. Antigens were detected by Western Blot using a polyclonal antibody against trypomastigote excretory-secretory antigen (TESA). T. cruzi DNA was detected by PCR using primers 121/122 and TcZ1/TcZ2. Levels of T. cruzi DNA in blood, heart and kidney were determined by quantitative PCR. T. cruzi antigens (75 kDa, 80 kDa, 120 kDa, 150 kDa) were detected in the acute phase (67.5%) and the chronic phase (45%). Parasite DNA in urine was detected only in the acute phase (45%). Kidney injury was characterized by high levels of proteinuria, kidney injury molecule-1 (KIM-1) and urea, and some histopathological changes such as inflammation, necrosis, fibrosis and scarce parasites. The detection of antigens and DNA in urine was associated with the presence of parasite DNA in blood and heart and with high levels of parasite DNA in blood, but not with the presence of parasite in kidney or kidney injury. These results suggest that the detection of T. cruzi in urine could be improved to be a valuable method for the diagnosis of Chagas disease, particularly in congenital Chagas disease and in immunocompromised patients.


Asunto(s)
Enfermedad de Chagas/orina , ADN Protozoario/orina , Enfermedades Renales/orina , Trypanosoma cruzi , Animales , Antígenos de Protozoos , Enfermedad de Chagas/sangre , ADN Protozoario/sangre , Cobayas , Corazón/parasitología , Riñón/metabolismo , Riñón/parasitología , Enfermedades Renales/sangre , Enfermedades Renales/parasitología , Glicoproteínas de Membrana/sangre , Glicoproteínas de Membrana/orina , Reacción en Cadena de la Polimerasa/métodos
6.
Transplant Proc ; 44(8): 2297-9, 2012 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-23026578

RESUMEN

BACKGROUND: Kidney graft fibrosis is a major factor related to chronic loss of kidney function. At present, the finding of fibrosis depends on the analysis of tissue in the renal biopsy, which has important limitations. In this study, we evaluated the messenger mRNA transcription and gene expression of kidney injury molecule-1 (KIM-1) in kidney tissue and in urinary sediment cells of kidney transplant patients with graft dysfunction aiming at the development of techniques that may allow the noninvasive diagnosis of interstitral fibrosis/tubular atrophy (IF/TA). PATIENTS AND METHODS: RNA extracted from cells in tissue and urine of 77 renal transplant patients whose biopsies were classified according to the Banff scheme-2007. Four diagnostic groups were established: (1) acute tubular necrosis (n = 9); (2) acute rejection (n = 49); (3) acute calcineurin inhibitors nephrotoxicity (n = 10); and (4) interstitial fibrosis and tubular atrophy (IFTA, n = 29). Tissue and urine cell RNA was amplified and quantification were made by real-time polymerase chain reactron. Data from the quantification of gene expression are presented as median and 25th to 75th percentiles. RESULTS: Messenger RNA levels of the KIM-1 gene were higher in the biopsies (26.17; 3.38-294.53) and urinary sediment cells (0.09; 0-5.81) of the patients classified as having IF/TA as compared with all others groups. A significant correlation between gene expression in samples of urine and tissue cells was found (P < .01). CONCLUSION: These initial data suggests that KIM-1 gene mRNA quantification can be used as a noninvasive biomarker of IF/TA.


Asunto(s)
Rechazo de Injerto/genética , Enfermedades Renales/genética , Trasplante de Riñón/efectos adversos , Riñón/química , Riñón/cirugía , Glicoproteínas de Membrana/genética , ARN Mensajero/análisis , Receptores Virales/genética , Atrofia , Biopsia , Femenino , Fibrosis , Marcadores Genéticos , Rechazo de Injerto/patología , Rechazo de Injerto/orina , Receptor Celular 1 del Virus de la Hepatitis A , Humanos , Inmunosupresores/efectos adversos , Riñón/efectos de los fármacos , Riñón/patología , Enfermedades Renales/inducido químicamente , Enfermedades Renales/patología , Enfermedades Renales/orina , Masculino , Glicoproteínas de Membrana/orina , Necrosis , Valor Predictivo de las Pruebas , ARN Mensajero/orina , Reacción en Cadena en Tiempo Real de la Polimerasa , Resultado del Tratamiento , Urinálisis
7.
Biomarkers ; 17(5): 385-93, 2012 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-22515481

RESUMEN

Over the past few years and with the use of innovative genomic and proteomic tools, several molecules that their urinary concentration is modified during acute kidney injury have been identified and proposed as biomarkers. Among the most studied biomarkers are neutrophil gelatinase-associated lipocalin-2, kidney injury molecule-1, interleukin-18, cystatin C, N-acetyl-ß-D-glucosaminidase, liver fatty-acid binding protein, and heat shock protein 72. Here, we reviewed and compared the sensitivity and specificity of each biomarker for the appropriate diagnosis of acute kidney injury, as well as its ability to stratify renal injury and to monitor a renoprotective pharmacologic strategy.


Asunto(s)
Lesión Renal Aguda/diagnóstico , Lesión Renal Aguda/orina , Biomarcadores/orina , Acetilglucosaminidasa/orina , Proteínas de Fase Aguda/orina , Cistatina C/orina , Proteínas de Unión a Ácidos Grasos/orina , Proteínas del Choque Térmico HSP72/orina , Receptor Celular 1 del Virus de la Hepatitis A , Humanos , Interleucina-18/orina , Lipocalina 2 , Lipocalinas/orina , Glicoproteínas de Membrana/orina , Proteínas Proto-Oncogénicas/orina , Receptores Virales , Sensibilidad y Especificidad
8.
J Pediatr ; 161(2): 270-5.e1, 2012 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-22424940

RESUMEN

OBJECTIVE: To identify urine biomarkers predictive of acute kidney injury (AKI) in infants admitted to level 2 and 3 neonatal intensive care units with birth weight >2000 g and 5-minute Apgar score ≤ 7. STUDY DESIGN: A nested case-control study was performed comparing 8 candidate urine AKI biomarkers in infants with AKI (defined as a rise in serum creatinine of at least 0.3 mg/dL or a serum creatinine elevation ≥ 1.7 mg/dL persisting for 3 days) and 24 infants from the described cohort without AKI. Urine was analyzed for neutrophil gelatinase-associated lipocalin, osteopontin, cystatin C, albumin, ß(2) microglobulin, epithelial growth factor, uromodulin (UMOD), and kidney injury molecule 1. RESULTS: Compared with the infants without AKI, those with AKI had higher levels of urine cystatin C (1123 pg/mL [95% CI, 272-4635 pg/mL] vs 90 pg/mL [95% CI, 39-205 pg/mL]; P < .004; area under the receiver operating characteristic curve [AUC] = 0.82), lower levels of UMOD (11.0 pg/mL [95% CI, 5.7-21.4 pg/mL] vs 26.2 pg/mL [95% CI, 17.4-39.4 pg/mL]; P < .03; AUC = 0.77), and lower levels of epithelial growth factor (6.7 pg/mL [95% CI, 4.0-11.3 pg/mL] vs 17.4 pg/mL [95% CI, 12.7-23.8 pg/mL; P = .003; AUC = 0.82). Although the differences were not statistically significant, levels of urine neutrophil-associated gelatinase lipocalin, kidney injury molecule 1, and osteopontin trended higher in infants with AKI. CONCLUSION: Urinary biomarkers can predict AKI in neonates admitted to level 2 and 3 neonatal intensive care units.


Asunto(s)
Lesión Renal Aguda/diagnóstico , Biomarcadores/orina , Proteínas de Fase Aguda/orina , Biomarcadores/sangre , Estudios de Casos y Controles , Creatinina/sangre , Cistatina C/orina , Factor de Crecimiento Epidérmico/orina , Femenino , Receptor Celular 1 del Virus de la Hepatitis A , Humanos , Recién Nacido , Lipocalina 2 , Lipocalinas/orina , Masculino , Glicoproteínas de Membrana/orina , Osteopontina/orina , Valor Predictivo de las Pruebas , Proteínas Proto-Oncogénicas/orina , Receptores Virales , Uromodulina/orina
9.
EMBO Mol Med ; 3(1): 5-20, 2011 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-21204265

RESUMEN

This study was designed to assess whether heat shock protein Hsp72 is an early and sensitive biomarker of acute kidney injury (AKI) as well as to monitor a renoprotective strategy. Seventy-two Wistar rats were divided into six groups: sham-operated and rats subjected to 10, 20, 30, 45 and 60 min of bilateral ischemia (I) and 24 h of reperfusion (R). Different times of reperfusion (3, 6, 9, 12, 18, 24, 48, 72, 96 and 120 h) were also evaluated in 30 other rats subjected to 30 min of ischemia. Hsp72 messenger RNA (mRNA) and protein levels were determined in both kidney and urine. Hsp72-specificity as a biomarker to assess the success of a renoprotective intervention was evaluated in rats treated with different doses of spironolactone before I/R. Renal Hsp72 mRNA and protein, as well as urinary Hsp72 levels, gradually increased relative to the extent of renal injury induced by different periods of ischemia quantified by histomorphometry as a benchmark of kidney damage. Urinary Hsp72 increased significantly after 3 h and continued rising until 18 h, followed by restoration after 120 h of reperfusion in accord with histopathological findings. Spironolactone renoprotection was associated with normalization of urinary Hsp72 levels. Accordingly, urinary Hsp72 was significantly increased in patients with clinical AKI before serum creatinine elevation. Our results show that urinary Hsp72 is a useful biomarker for early detection and stratification of AKI. In addition, urinary Hsp72 levels are sensitive enough to monitor therapeutic interventions and the degree of tubular recovery following an I/R insult.


Asunto(s)
Lesión Renal Aguda/diagnóstico , Proteínas del Choque Térmico HSP72/metabolismo , Lesión Renal Aguda/metabolismo , Proteínas de Fase Aguda/orina , Animales , Biomarcadores/metabolismo , Biomarcadores/orina , Creatina/sangre , Proteínas del Choque Térmico HSP72/genética , Proteínas del Choque Térmico HSP72/orina , Receptor Celular 1 del Virus de la Hepatitis A , Humanos , Interleucina-18/orina , Isquemia/metabolismo , Isquemia/patología , Lipocalina 2 , Lipocalinas/orina , Glicoproteínas de Membrana/orina , Proteínas Proto-Oncogénicas/orina , Ratas , Ratas Wistar , Receptores Virales , Daño por Reperfusión/metabolismo , Daño por Reperfusión/patología , Espironolactona/toxicidad , Factores de Tiempo
10.
Transpl Immunol ; 16(2): 73-80, 2006 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-16860708

RESUMEN

BACKGROUND: Monitoring recipient's alloreactivity has shown to be critical for limiting overimmunosuppression besides allowing preemptive treatment of acute rejection (AR). METHODS: Flow cytometry and real time RT-PCR were performed in urine of kidney transplant recipients with AR (n = 13) and compared with pyelonephritis (n = 10), chronic allograft nephropathy (n = 13), acute tubular necrosis (n = 13) and stable graft function (n = 11). Expression of CD3, CD4, CD8, HLA-DR, Fas-L, ICAM-1 and CD25 were assessed using flow cytometry. mRNA of perforin, granzyme B and Fas-L were quantified by real time RT-PCR. RESULTS: Frequencies of CD3+, HLA-DR+, Fas-L+, ICAM-1+ and CD25+ cells were significantly higher in AR group (p < 0.05). ROC curves showed sensitivity from 70% to 91% and specificity from 30% to 100%, whereas the highest sensitivity and specificity was 91% and 100% respectively, for Fas-L+ cells. Levels of mRNA of perforin, granzyme B and Fas-L were significantly augmented in AR, while the sensitivity and specificity ranged from 85% to 88% and from 55% to 100%, respectively. CONCLUSIONS: Analyses of immune activation markers by flow cytometry and real time RT-PCR are equally useful for noninvasive monitoring kidney allografts.


Asunto(s)
Rechazo de Injerto/orina , Trasplante de Riñón , Femenino , Citometría de Flujo , Rechazo de Injerto/inmunología , Granzimas , Humanos , Enfermedades Renales/inmunología , Enfermedades Renales/orina , Trasplante de Riñón/efectos adversos , Trasplante de Riñón/inmunología , Masculino , Glicoproteínas de Membrana/inmunología , Glicoproteínas de Membrana/orina , Monitoreo Fisiológico , Perforina , Proteínas Citotóxicas Formadoras de Poros , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Serina Endopeptidasas/inmunología , Serina Endopeptidasas/orina
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