Proteins from the lipocalin family play significant roles during the transport of chemical signals. These globular proteins (molecular mass: 17,7 - 21,7 kDa) are able to bind a wide spectrum of volatile ligands. Since they decay continuously, the scent impact is prolonged. Major urinary proteins (MUPs) are lipocalins, typically found in the urine and used during olfactory communication in the house mouse. But the urine is not the only source of chemical signals. Many species of mammals perform selfgrooming - a technique in which saliva is transported into the fur. The goal of the thesis is to identify main proteins that are involved in chemical communication by selected species of the genus Apodemus, and to discover the source of production (i.e. saliva or urine). The Experion capillary electrophoresis system was used to confirm the absence of lipocalins in the urine in two Apodemus species (A. uralensis, A. sylvaticus). Furthermore, a lot of lipocalins is present in the saliva of above-mentioned species. The quantity and types of salivary lipocalins was identified by 2D electrophoresis along with mass spectrometry analyses (MALDI MS/MS) in three species of the genus Apodemus (A. uralensis, A. sylvaticus and A. flavicollis). The conclusion of this inter-specific comparison suggests, that sociality...

Made available in DSpace on 2017-07-10T14:17:06Z (GMT). No. of bitstreams: 1 Ademar Cunha Junior.pdf: 5907577 bytes, checksum: d4f5656226f906835cfbc7f0cb6c2a2a (MD5) Previous issue date: 2014-02-14 / Acute kidney injury (AKI) in patients receiving cisplatin is common, therefore the evaluation of renal function in patients on use of nephrotoxic drugs is fundamental. Objective: To evaluate the incidence of AKI and the role of lipocalin associated to neutrophil gelatinase (NGAL) in the monitoring of renal function in patients with head and neck cancer (HNC) who received cisplatin. Methods: We prospectively studied 50 patients with HNC treated with three sessions of cisplatin. Blood and urine were collected 24 h before cisplatin, 24 h after infusion, 48 h after each application and 35 days after the end of treatment (urine NGAL, C-reactive protein, creatinine, glomerular filtration rate, plasma lactate dehydrogenase and magnesium). Results: AKI was observed in 78 % of patients. There was increase in creatinina, and decrease in GFR after each cycle of cisplatin, and increased urine NGAL. Positive association was observed between the levels of NGAL, creatinine and C-reactive protein. It was observed an increase in creatinine, NGAL, C-reactive protein and decreased GFR in AKI patients compared to patients without AKI. Conclusion: AKI was noted in 78 % of patients with HNC treated with cisplatin and showed the correlation of NGAL with creatinine and GFR in demonstrating renal injury. NGAL levels may be elevated compared to baseline levels, even before the use of cisplatin / A injúria renal aguda (IRA) em pacientes que recebem a cisplatina é comum. Portanto, a avaliação da função renal em pacientes que utilizam drogas nefrotóxicas é fundamental. Objetivo: Avaliar a incidência da IRA e o papel da lipocalina associada à gelatinase neutrofílica (NGAL) na avaliação da função renal em pacientes com câncer de cabeça e pescoço (CCP) que receberam a cisplatina. Métodos: Foram avaliados prospectivamente 50 pacientes com CCP, tratados com três sessões de cisplatina. Foram coletados sangue e urina 24 h antes da cisplatina, 24 h após a infusão, 48 h após cada aplicação e 35 dias após o término do tratamento (NGAL urinária, proteína C reativa, creatinina e taxa de filtração glomerular, desidrogenase lática e magnésio plasmáticos). Resultados: A IRA foi observada em 78% dos pacientes. Houve aumento na creatinina, ureia e queda na TFG após cada ciclo de cisplatina, e aumento da NGAL urinária. Foi observada associação positiva entre os níveis de NGAL e a creatinina e PCR. Evidenciou-se um aumento dos níveis de creatinina, NGAL, PCR e diminuição da TFG nos pacientes com IRA em relação aos pacientes sem IRA. Conclusão: Observamos IRA em 78% dos pacientes avaliados com CCP tratados com a cisplatina e ao final do estudo 32% ainda apresentavam TFG abaixo de 60ml/min com potencial para cronificação do quadro. Observamos correlação da NGAL com a creatinina e a TFG em demonstrar lesão renal e sua concentração esteve elevada em relação a concentração basal, mesmo antes da utilização da cisplatina

Made available in DSpace on 2014-06-11T19:32:16Z (GMT). No. of bitstreams: 0 Previous issue date: 2010-11-12Bitstream added on 2014-06-13T20:03:24Z : No. of bitstreams: 1 stafuzza_nb_dr_jabo.pdf: 3950530 bytes, checksum: 7762a1b85de88115c5c16380df8c26e1 (MD5) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / O crescimento da população bubalina em território brasileiro está relacionado ao interesse dos produtores nesse animal, como uma alternativa para a produção de carne, leite e seus derivados. Diante deste panorama, torna-se necessário o aprimoramento de programas de melhoramento genético, visando a seleção de animais geneticamente superiores para a reprodução. Por essa razão, o conhecimento do genoma da espécie é de extrema valia para o setor, uma vez que gera informações necessárias à identificação e avaliação de genes associados com características de interesse econômico. Desse modo, o presente trabalho envolveu a construção de uma nova ferramenta genômica para búfalo, denominada biblioteca BAC, a qual permitirá um novo direcionamento nos estudos moleculares do genoma bubalino, destacando-se a definição da estrutura e organização de genes de interesse econômico, fornecendo informações em nível de seqüência de DNA para o entendimento dos mecanismos e regulação dos mesmos. Com a disponibilidade dessa ferramenta, as primeiras regiões a serem caracterizadas serão aquelas que contêm genes de interesse econômico, as quais se destacam as regiões com genes relacionados com produção e qualidade do leite, regiões com genes relacionados com resposta imune e adaptativa, e regiões com genes da família das lipocalinas, os quais estão envolvidos com características de produção e reprodução. Porém, para que esses genes possam ser caracterizados por meio da biblioteca BAC de búfalo, há a necessidade de gerar marcadores para identificar e isolar clones específicos para esses genes. Marcadores derivados do genoma bovino têm sido utilizados com sucesso em estudos de mapeamento do genoma bubalino, os quais podem ser uma fonte importante de marcadores. Porém, para famílias gênicas, há a necessidade da geração de marcadores específicos para búfalo... / The increase of the buffalo population in Brazil is the result of the great interest of the producers as an alternative source for the production of meat, milk and dairy products. Thus, it becomes necessary genetic improvement programs more effective, in order to select genetically superior animals for breeding. The knowledge of the buffalo genome is valuable in this regard, since it generates information to identify and evaluate genes associated with economically traits. In this project we constructed a new genomic tool for buffalo - a genomic BAC library - which can be used in molecular studies of buffalo genome especially those related with the definition of the molecular structure and organization of economically important genes. Once this genomic tool is available, the first target regions of the buffalo genome to be characterized are those containing genes related to milk production, adaptive and innate immune response, and regions lipocalin genes involved in reproduction and production traits. However, to characterize these regions using the BAC library is necessary to have molecular markers to be able to identify and isolate the specific clones. Markers derived from the bovine genome have been successfully used in buffalo genome mapping studies, showing to be an important source of markers. On the another hand, for those genes found in the genome as gene families, there is a need for buffalo specific markers. The evaluation of new markers will contribute to the characterization of those target regions of the buffalo genome, providing information about the genomic architecture of this specie when compared with other bovid

The aim of my thesis was to identify proteins involved in chemical communication and especially those that are involved in sexual signalling. Volatile chemical signals are transported with lipocalins in their beta-barrel structure to present their ligands to receptors or out of the body. Thus, I focused on the identification of these proteins in saliva and vaginal secretion of the house mouse using proteomic and transcriptomic approaches. Due to a cyclic manner of reproduction and its hormonal control, I have also focused on the role of estradiol on sperm phenotype in the laboratory mouse. We have identified an elevated sexual dimorphism in several lipocalins (i.e. 10 out of 20) in the saliva proteome where they may play a role in sexual signalling (i.e. similar to their described roles in the mouse urine). Interestingly, vaginal secretion also contains lipocalins and they rise from proestrus to estrus and remain steady during metestrus. Such variation provides evidence that they serve sexual signalling, however, due to their elevated levels during metestrus it is most likely that their ligands function as signals and not the proteins themselves. On the level of sperm phenotype, we have provided evidence, that experimental concentrations of estradiol have differential effects on sperm. This is due...

Sexually dimorphic behaviour of the house mouse (Mus musculus musculus) relies on various physical and chemical cues, however, chemical signals are the most essential cues for individual recognition and in causing various priming effects on reproductive behaviour of the receiver. House mice belong to macrosmatic mammals, and thus, their sense of smell is highly developed and is able to recognize a wide spectrum of ligands from other individuals and from their surrounding environment. Volatile signals belong to organic compounds that are produced by most tissues, and may have harmfull effects on cells, and thus they are transported out of the body with lipocalin transporters where some of them may function as signals. These volatile signals are able to stimulate chemosensory neuronal receptors, and thus, yield particular responses in neural circuits. The ligand sensing has a differential effect upon males and females, however, it has not been shown yet in wild mice whether these differences are also caused by the variation in receptors and neural processing, or rather by differential expression of signals typical for each sex. The aim of this thesis was to perform comparative analysis of orofacial mucosal tissues to determine the specificity of expression of particular lipocalins. For the first time...

<p>Primarni glomerulonefritisi predstavljaju inflamatorna oboljenja bubrega, kod kojih su primarno zahvaćeni glomerulusi, ali promene na tubulointersticijumu imaju veliki značaj za tok i prognozu bolesti. Pored kliničko-laboratorijskih ispitivanja, perkutana biopsija bubrega zauzima značajno mesto u dijagnostici posebnih oblika glomerulonefritisa. Lipokalin vezan za neutrofilnu gelatinazu (NGAL) zauzima značajno mesto medju novijim biomarkerima u nefrologiji. Osnovna funkcija mu je transport gvoždja, ali ima ulogu i u regulaciji metabolizma gvoždja, regulaciji inflamacije, dok u masnom tkivu utiče na razvoj insulinske rezistencije i dijabetesa. Cilj ispitivanja je utvrditi nivo lipokalina 2 u serumu i urinu bolesnika sa primarnim glomerulonefritisom, te utvrditi postojanje korelacije izmedju nivoa lipokalina 2 i patohistolo&scaron;kog oblika glomerulonefritisa, stepenom bubrežne insuficijencije i brzinom progresije bubrežne insuficijencije. Takodje, cilj ispitivanja je bio analizirati povezanost lipokalina 2 sa odogovorom na primenjenu terapiju glomerulonefritisa. Ispitivanje je sprovedeno na 60 bolesnika sa dijagnozom primarnih glomerulonefritisa. Nivo lipokalina 2 je odredjivan pri postavljanju dijagnoze i nakon minimalno &scaron;est meseci lečenja. Rezultati studije ukazuju da bolesnici sa primarnim glomerulonefritisom imaju značajno veće nivoe lipokalina 2 u odnosu na zdrave osobe. Bolesnici sa proliferativnim oblicima primarnih glomerulonefritisa imaju veće nivoe NGAL-a u serumu i odnosa uNGAL/kreatinin, ali razlika nije statistički značajna. Nije utvrdjeno postojanje značajne razlike u prosečnim nivoima NGAL-a u serumu, niti urinu, pri postavljanju dijagnoze, izmedju bolesnika sa pozitivnim i negativnim efektom lečenja primarnog glomerulonefritisa. Utvrdjeno je postojanje korelacije izmedju nivoa NGAL-a u serumu i vrednosti kreatinina, ureje, mokraćne kiseline, klirensa kreatinina i broja leukocita, dok je sa nivoom NGAL-a u urinu utvrdjena korelacija sa klirensom kreatinina, dnevnom proteinurijom i serumskim albuminima. Utvrdjeno je postojanje statistički značajne razlike u prosečnim nivoima NGAL-a u serumu u zavisnosti od stadijuma bubrežne insufijencije. Nije utvrdjeno postojanje značajne razlike u prosečnim nivoima NGAL-a u serumu pri postavljanju dijagnoze, izmedju bolesnika sa povoljnim i nepovoljnim efektom lečenja na bubrežnu funkciju.</p> / <p>The primary glomerulonephritis are inflammatory kidney diseases. Glomerulus are primarily affected, but tubulointerstitial changes are very important for course and prognosis of the disease. In addition to clinical and laboratory testing, percutaneous renal biopsy has an important place in the diagnosis of specific forms of glomerulonephritis. Neutrophil gelatinaseassociated lipocalin (NGAL) occupies an important place among the newer biomarkers in nephrology. The main function of NGAL is transport of iron, whether it has a role in the regulation of iron metabolism, regulation of inflammation, while in adipose tissue affects the development of insulin resistance and diabetes. The aim of this study was to determine the level of lipocalin 2 in serum and urine of patients with primary glomerulonephritis and determine the existence of a correlation between the level of lipocalin 2 and histological forms of glomerulonephritis, the degree of renal insufficiency and speed of progression of renal insufficiency. Also, the aim of this study was to analyze the association of lipocalin 2 with the effect of therapy for glomerulonephritis. The study was conducted on 60 patients diagnosed with primary glomerulonephritis. The levels of lipocalin 2 were determined at diagnosis and after a minimum of six months of treatment. The study results show that patients with primary glomerulonephritis have significantly higher levels of lipocalin 2 compared to healthy people. Patients with proliferative forms of primary glomerulonephritis have higher levels of NGAL in serum and ratio uNGAL/creatinine, but the difference was not statistically significant. There was no significant differences in average levels of NGAL in serum or urine at the beginning, between patients with positive and negative effects of the treatment of primary glomerulonephritis. Correlation was found between the level of NGAL in serum and creatinine, urea, uric acid, creatinine clearance and the number of leukocytes, while the level of NGAL in urine correlated with creatinine clearance, the daily proteinuria and serum albumin. Statistically significant differences in mean levels of NGAL in serum depending on the severity of renal insufficiency were found. No evidence of significant differences in average levels of NGAL in serum at the beginning, among patients with favorable and unfavorable effects of treatment on renal function were found.</p>

Dans les conditions naturelles, les plantes sont soumises à des conditions environnementales très variées qui peuvent conduire à un excès d'énergie dans les chloroplastes, résultant en une production d'espèces réactives de l'oxygène (ERA). Pour faire face à ces ERA, les plantes ont développé différents mécanismes de protection, comme des alkénal réductases, des peroxyrédoxines et des lipocalines. Le travail présenté dans cette thèse a pour but de caractériser et de déterminer leur importance dans la protection des contre les stress oxydants. Une analyse préliminaire de mutants d'Arabidopsis a mis en évidence le rôle important des peroxyrédoxines à 2 cystéines et des lipocalines dans la tolérance au stress photooxydant. Cette thèse s'est surtout concentrée sur les lipocalines. Deux lipocalines ont été récemment identifiées chez les plantes, TIL (lipocaline thermoinduite) et CHL (chloroplastique), toutes les deux induites par des conditions de stress. Chez Arabidopsis, chaque lipocaline semble être spécialisée dans la réponse à des conditions différentes: chaleur (AtTIL) et fortes lumières (AtCHL). Le double mutant AtCHL KO × AtTIL KO est plus sensible à la chaleur et la forte lumière que les simples mutants. La mutation de AtCHL a augmenté fortement la photosensibilité de mutants (vte1, npq1) affectés dans des mécanismes de protection des lipides (tocopherols, zéaxanthine), confirmant ainsi le rôle des lipocalines dans la protection contre la peroxydation lipidique. Les résultats obtenus dans cette thèse montrent que les lipocalines AtTIL and AtCHL ont des fonctions redondantes dans la protection des lipides qui sont essentielles à la résistance des plantes au stress. / Under field conditions, plants are exposed to various environmental conditions that can lead to an excess of energy in the chloroplasts, resulting in the production of toxic reactive oxygen species (ROS). To cope with the harmful effects of ROS, plants have developed various protection mechanisms, such as alkenal-reductases, peroxiredoxins and lipocalins. The work performed in this thesis aimed at understanding their importance in the protection against lipid peroxidation. A first screening of Arabidopsis mutants lacking one of those mechanisms brought into light that 2-Cys PRX and lipocalins are important for the tolerance against photooxidative stress. This thesis is focused mainly on lipocalins, a group of proteins recognized as carriers of small lipophilic molecules. However, two true lipocalins have been recently identified in plants, the temperature-induced lipocalin (TIL) and the chloroplastic lipocalin (CHL), their expression beeing induced by various abiotic stresses. Each lipocalin appeared to be specialized in the responses to specific stress conditions in Arabidopsis, with AtTIL and AtCHL playing a protective role against heat and high light, respectively. The double mutant AtCHL KO × AtTIL KO deficient in both lipocalins was more sensitive to temperature, drought and light stresses than the single mutants. Seeds of the AtCHL KO × AtTIL KO double mutant were very sensitive to natural and artificial aging, and again this phenomenon was associated with the oxidation of polyunsaturated lipids. The results obtained in this thesis show that AtTIL and AtCHL have overlapping functions in lipid protection which are essential for stress resistance and survival.

Orientador: Maria Elisabete Jorge Amaral / Banca: Humberto Tonhati / Banca: Vera Fernanda Martins Hossepian de Lima / Banca: Beatriz da Costa Aguiar Alves Reis / Banca: Luciane Madureira de Almeida / Resumo: O crescimento da população bubalina em território brasileiro está relacionado ao interesse dos produtores nesse animal, como uma alternativa para a produção de carne, leite e seus derivados. Diante deste panorama, torna-se necessário o aprimoramento de programas de melhoramento genético, visando a seleção de animais geneticamente superiores para a reprodução. Por essa razão, o conhecimento do genoma da espécie é de extrema valia para o setor, uma vez que gera informações necessárias à identificação e avaliação de genes associados com características de interesse econômico. Desse modo, o presente trabalho envolveu a construção de uma nova ferramenta genômica para búfalo, denominada biblioteca BAC, a qual permitirá um novo direcionamento nos estudos moleculares do genoma bubalino, destacando-se a definição da estrutura e organização de genes de interesse econômico, fornecendo informações em nível de seqüência de DNA para o entendimento dos mecanismos e regulação dos mesmos. Com a disponibilidade dessa ferramenta, as primeiras regiões a serem caracterizadas serão aquelas que contêm genes de interesse econômico, as quais se destacam as regiões com genes relacionados com produção e qualidade do leite, regiões com genes relacionados com resposta imune e adaptativa, e regiões com genes da família das lipocalinas, os quais estão envolvidos com características de produção e reprodução. Porém, para que esses genes possam ser caracterizados por meio da biblioteca BAC de búfalo, há a necessidade de gerar marcadores para identificar e isolar clones específicos para esses genes. Marcadores derivados do genoma bovino têm sido utilizados com sucesso em estudos de mapeamento do genoma bubalino, os quais podem ser uma fonte importante de marcadores. Porém, para famílias gênicas, há a necessidade da geração de marcadores específicos para búfalo... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: The increase of the buffalo population in Brazil is the result of the great interest of the producers as an alternative source for the production of meat, milk and dairy products. Thus, it becomes necessary genetic improvement programs more effective, in order to select genetically superior animals for breeding. The knowledge of the buffalo genome is valuable in this regard, since it generates information to identify and evaluate genes associated with economically traits. In this project we constructed a new genomic tool for buffalo - a genomic BAC library - which can be used in molecular studies of buffalo genome especially those related with the definition of the molecular structure and organization of economically important genes. Once this genomic tool is available, the first target regions of the buffalo genome to be characterized are those containing genes related to milk production, adaptive and innate immune response, and regions lipocalin genes involved in reproduction and production traits. However, to characterize these regions using the BAC library is necessary to have molecular markers to be able to identify and isolate the specific clones. Markers derived from the bovine genome have been successfully used in buffalo genome mapping studies, showing to be an important source of markers. On the another hand, for those genes found in the genome as gene families, there is a need for buffalo specific markers. The evaluation of new markers will contribute to the characterization of those target regions of the buffalo genome, providing information about the genomic architecture of this specie when compared with other bovid / Doutor

Fertilization is a multiple step process leading to fusion of female and male gametes resulting in a formation of a zygote. Besides direct gamete interaction via binding receptors localized on both oocyte and sperm surface, fertilization also involves communication based on chemical molecules triggering various signalling pathways. This work is aimed to characterize chemical communication of gametes of a model organism Mus musculus. For this purpose, modern proteomic and visualisation methods like nano-liquid chromatography tandem mass spectrometry (nLC-MS/MS), selected reaction monitoring (SRM) and immunofluorescent microscopy were used. Lipocalins were identified as candidate proteins involved in communication including those from major urinary proteins (MUPs), LCN lipocalins and fatty acid binding proteins (FABPs). For the first time, we report their presence in the sperm acrosome. Based on lipocalins capacity to bind and transport other molecules, we propose that these proteins have a protective and/or signalling role for gametes. Furthermore, chemical communication between sperm and oocyte is based on chemotaxis which enables their interaction before their fusion. In this work, we detected that spermatozoa show chemotactic responses in the presence of L-glutamate. This amino acid naturally...

INTRODUÇÃO E OBJETIVO: A estenose de junção ureteropélvica (EJUP) é importante causa de obstrução do trato urinário e pode levar a deterioração progressiva da função renal. Há espaço para o aprimoramento de novos métodos diagnósticos capazes de discriminar hidronefrose e uropatia obstrutiva. Acredita-se que os biomarcadores urinários podem fornecer indícios de lesão renal precoce na obstrução urinária. Neste contexto, KIM-1 pode elevar-se na urina por lesão tubular proximal, NGAL por lesão no túbulo proximal, distal ou alça de Henle, CA19-9 por produção excessiva no túbulo obstruído e ?2-microglobulina (beta2M) por injúria ao glomérulo ou ao túbulo proximal. O objetivo do presente estudo foi avaliar as propriedades diagnósticas dos biomarcadores urinários citados em adultos com EJUP, sendo o primeiro estudo na literatura a avaliar tais moléculas nesta população. MÉTODOS: Foram estudados de modo prospectivo pacientes consecutivos acima de 18 anos com diagnóstico de EJUP submetidos a pieloplastia videolaparoscópica de dezembro de 2013 a fevereiro de 2015. Foram excluídos do estudo pacientes com EJUP bilateral, rim contralateral patológico, EJUP em rim único, antecedentes de tratamento cirúrgico para estenose de JUP ou taxa de filtração glomerular inferior a 60 ml/min/1,73m2. Cada paciente forneceu quatro amostras de urina para medição de biomarcadores, uma no pré-operatório e outras com 1, 3 e 6 meses de seguimento pós-operatório. O grupo controle foi constituído por voluntários saudáveis sem hidronefrose à ultrassonografia. RESULTADOS: Foram incluídos 47 pacientes com idade média de 38,6 ± 12,7 anos (intervalo 19 a 64 anos), sendo 17 (36,2%) do sexo masculino e 30 (62,8%) do sexo feminino. O grupo controle foi composto por 40 indivíduos semelhantes ao grupo com EJUP no que concerne idade (p = 0,95) e sexo (p = 0,82). KIM-1 foi o marcador com melhores propriedades diagnósticas, apresentando área sob a curva (AUC) de 0,79 (95% CI 0,70 a 0,89). O NGAL, por sua vez, teve AUC de 0,71 (95% CI 0,61 a 0,83), CA19- 9 teve AUC de 0,70 (95% CI 0,60 a 0,81) e (beta2M) apresentou AUC de 0,61 (95% CI 0,50 a 0,73), sendo o único biomarcador com propriedades inadequadas neste cenário. O KIM-1 foi o marcador mais sensível com o ponto de corte 170,4 pg/mg de creatinina (sensibilidade 91,4%, especificidade 59,1%) e o CA 19-9 o mais específico para o ponto de corte de 51,3 U/mg de creatinina (sensibilidade 48,9%, especificidade 88,0%), enquanto o NGAL foi o que apresentou maior queda após desobstrução, com 90,0% dos pacientes apresentando clareamento superior a 50%. CONCLUSÕES: A avaliação dos biomarcadores urinários é útil no diagnóstico de obstrução em adultos com EJUP submetidos a pieloplastia videolaparoscópica. O KIM-1 foi o marcador mais sensível e o CA 19-9 o mais específico, enquanto o NGAL foi o que apresentou maior que com a desobstrução. Houve queda das concentrações dos marcadores após pieloplastia no período estudado. O papel exato dos biomarcadores urinários no cenário de obstrução em adultos deve ser mais amplamente investigado / INTRODUCTION AND OBJECTIVE: Ureteropelvic junction obstruction (UPJO) is an important cause of urinary tract obstruction and can lead to progressive deterioration of renal function. Thus the development of novel non-invasive methods capable of discriminating obstruction and hydronephrosis may be useful. Elevation of urinary biomarkers may provide early evidence of kidney damage in urinary obstruction. In this scenario, urinary concentrations of KIM-1 may be elevated following proximal tubular injury, while NGAL may increase as result of injury to proximal or distal tubule as well as to loop of Henle, CA19-9 after overproduction in the obstructed tubule and ?2 microglobulin (beta2M) after injury to the glomerulus or the proximal tubule. The aim of this study was to evaluate the diagnostic properties of these urinary biomarkers in adults with UPJO. METHODS: We prospectively studied consecutive patients older than 18 years diagnosed with UPJO undergoing laparoscopic pyeloplasty from December 2013 to February 2015 in our institution. Exclusion criteria included patients with bilateral UPJO, unilateral UPJO with contralateral pathologic kidney, solitary kidney, history of previous surgical treatment for UPJO or glomerular filtration rate below 60 ml/min/1,73m2. Each patient provided four voided urine samples for biomarker measurement, one at preoperative consultation and the others at 1, 3 and 6 months of postoperative follow-up. Healthy individuals with no hydronephrosis on ultrasound evaluation constituted our control group. RESULTS: We included 47 patients with a mean age of 38.6 ± 12.7 years (range 19-64 years), from which 17 (36.2%) were males and 30 (62.8%) were females. The control group consisted of 40 subjects with no statistical difference to the study group regarding age (p = 0.95) and gender (p = 0.82). KIM-1 had an area under the curve (AUC) of 0.79 (95% CI 0.70 to 0.89) and was the biomarker with the best diagnostic properties. CA19-9 had an AUC of 0.70 (95% CI 0.60 to 0.81), NGAL had an AUC of 0.71 (95% CI 0.61 to 0.83) and beta2M had an AUC of 0.61 (95% CI 0.50 to 0.73). KIM-1 was the most sensitive marker with a cutoff of 170.4 pg/mg creatinine (sensitivity 91.4%, specificity 59.1%) whereas CA 19-9 as the most specific one, displaying a cutoff of 51.3 U/mg creatinine (sensitivity 48.9%, specificity 88.0%). NGAL showed the greatest decrease in urinary concentrations after pyeloplasty, in which 90.0% of patients had a clearance greater than 50% in comparison to preoperative values. CONCLUSIONS: The evaluation of urinary biomarkers is useful in the assessment of UPJO in adults undergoing laparoscopic pyeloplasty. Urinary concentrations of CA 19-9, NGAL and KIM-1 were elevated in patients with UPJO and significantly decreased after pyeloplasty. The exact role of those biomarkers in the setting of obstruction in adults should be further evaluated