RESUMO
INTRODUCTION: posterior urethral valves represent an important cause of childhood chronic kidney disease. The identification of biomarkers that indicate early kidney damage and even adequate clearance could reduce how many patients head towards kidney failure. OBJECTIVE: this study evaluated how this easy-analysis biomarker (CA 19-9) could help identifying potential renal damage and adequate clearance in obstructive uropathies. METHODS: 46 female Wistar rats were divided into 5 groups, with different patterns of partial urinary tract obstruction: group control; group OIV: infravesical obstruction; group OIVd: infravesical obstruction with reversion, obstruction relief 7 postoperative days later; group OUu: unilateral ureteral obstruction; group OUb: bilateral ureteral obstruction. The CA 19-9s performance was compared to another biomarker: Ngal. Determination of basal CA 19-9 and Ngal in urine and blood and serum creatinine levels was performed in the rats prior to surgery (T0) and after 14 days (T1). Group OIVd underwent intermediate (Ti) collection before clearance. RESULTS: the urinary concentration of CA 19-9 increased in groups OIV, OIVd and OUb; elevation at T1 and Ti, reached statistical significance compared to the T0 value (p<0,05). Changes in urinary CA 19-9 were more expressive in infravesical obstruction groups (AUC 0.81). Obstruction relief in group OIVd promoted significant urinary CA 19-9 reduction (p<0,05) in the final evaluation. CONCLUSIONS: CA 19-9 urinary concentration increased in partial urinary tract obstruction. Its best performance was in the bladder neck obstruction group, in which the elevation was detected early (6 days after infravesical obstruction) and the CA19-9 urinary concentration declined after clearance.
Assuntos
Obstrução Ureteral , Animais , Antígeno CA-19-9/urina , Feminino , Lipocalina-2 , Prognóstico , Ratos , Ratos Wistar , Obstrução Ureteral/diagnóstico , Obstrução Ureteral/cirurgia , Obstrução Ureteral/urinaRESUMO
Renal damage due to urinary tract obstruction accounts for up to 30% of acute kidney injury in paediatrics and adults. Bilateral ureteral obstruction (BUO) is associated with polyuria and reduced urinary concentrating capacity. We investigated the renal handling of water and electrolytes together with the renal expression and the urinary excretion of the Na-K-Cl cotransporter (NKCC2) after 1 (BUO-1), 2 (BUO-2), and 7 (BUO-7) days of release of BUO. Immunoblotting and immunohistochemical studies showed that NKCC2 expression was upregulated in apical membranes both from BUO-2 and from BUO-7 rats. The apical membrane expression, where NKCC2 is functional, may be sufficient to normalize water, potassium, sodium, and osmolytes tubular handling. NKCC2 abundance in homogenates and mRNA levels of NKCC2 was significantly decreased in almost all groups suggesting a decrease in the synthesis of the transporter. Urinary excretion of NKCC2 was increased in BUO-7 groups. These data suggest that the upregulation in the expression of NKCC2 in apical membranes during the postobstructive phase of BUO could contribute to improving the excretion of sodium and consequently also the excretion of potassium, osmolytes, and water. Moreover, the increase in urinary excretion of NKCC2 in BUO-7 group could be a potential additional biomarker of renal function recovery.
Assuntos
Nefropatias/metabolismo , Nefropatias/urina , Rim/metabolismo , Simportadores/urina , Obstrução Ureteral/metabolismo , Obstrução Ureteral/urina , Animais , Imuno-Histoquímica , Rim/patologia , Córtex Renal/metabolismo , Córtex Renal/patologia , Nefropatias/sangue , Masculino , Concentração Osmolar , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos Wistar , Simportadores/genética , Ureia/sangue , Cotransportadores de K e Cl-RESUMO
OBJECTIVE: To assess the role of transforming growth factor-beta1 (TGF-beta1) in congenital ureteropelvic junction obstruction at diagnosis and during postoperative follow-up. MATERIALS AND METHODS: We conducted a case-control study including 19 patients with a mean age of 6.7 years and 19 matched controls. All patients presented negative voiding cystourethrography, obstructive diuretic renogram and underwent dismembered pyeloplasty. Urinary TGF-beta1 and other markers were measured pre-, intra- and postoperatively. RESULTS: The mean bladder urine TGF-beta1 concentration in obstructed patients prior to pyeloplasty was higher than in controls (92.5 pg/mL +/- 16.8 vs. 35.8 pg/mL +/- 16.2; p = 0.0001). The mean renal pelvic urine TGF-beta1 concentration in the hydronephrotic kidney was higher than in the preoperative bladder urine sample (122.3 pg/mL +/- 43.9 vs. 92.5 pg/mL +/- 16.8; p = 0.036). Postoperative mean TGF-beta1 concentration was significantly lower than preoperative TGF-beta1 (48.7 pg/mL +/- 13.1 vs. 92.5 pg/mL +/- 16.8; p = 0.0001). CONCLUSION: TGF-beta1 is a cytokine leading to renal fibrosis. The measurement of urinary TGF-beta1 could become a useful tool for the diagnosis of obstructive hydronephrosis and the evaluation of the parenchyma function status, pre and postoperatively.
Assuntos
Hidronefrose/diagnóstico , Fator de Crescimento Transformador beta1/urina , Obstrução Ureteral/diagnóstico , Biomarcadores/urina , Estudos de Casos e Controles , Criança , Feminino , Seguimentos , Humanos , Hidronefrose/urina , Pelve Renal , Masculino , Período Perioperatório , Sensibilidade e Especificidade , Resultado do Tratamento , Obstrução Ureteral/congênito , Obstrução Ureteral/cirurgia , Obstrução Ureteral/urina , Bexiga Urinária/metabolismo , Refluxo Vesicoureteral/diagnósticoRESUMO
OBJECTIVE: To assess the role of transforming growth factor-β1 (TGF-β1) in congenital ureteropelvic junction obstruction at diagnosis and during postoperative follow-up. MATERIAL AND METHODS: We conducted a case-control study including 19 patients with a mean age of 6.7 years and 19 matched controls. All patients presented negative voiding cystourethrography, obstructive diuretic renogram and underwent dismembered pyeloplasty. Urinary TGF-β1 and other markers were measured pre-, intra- and postoperatively. RESULTS: The mean bladder urine TGF-β1 concentration in obstructed patients prior to pyeloplasty was higher than in controls (92.5 pg/mL ± 16.8 vs. 35.8 pg/mL ± 16.2; p = 0.0001). The mean renal pelvic urine TGF-β1 concentration in the hydronephrotic kidney was higher than in the preoperative bladder urine sample (122.3 pg/mL ± 43.9 vs. 92.5 pg/mL ± 16.8; p = 0.036). Postoperative mean TGF-β1 concentration was significantly lower than preoperative TGF-β1 (48.7 pg/mL ± 13.1 vs. 92.5 pg/mL ± 16.8; p = 0.0001). CONCLUSION: TGF-β1 is a cytokine leading to renal fibrosis. The measurement of urinary TGF-β1 could become a useful tool for the diagnosis of obstructive hydronephrosis and the evaluation of the parenchyma function status, pre and postoperatively.
Assuntos
Criança , Feminino , Humanos , Masculino , Hidronefrose/diagnóstico , Fator de Crescimento Transformador beta1/urina , Obstrução Ureteral/diagnóstico , Biomarcadores/urina , Estudos de Casos e Controles , Seguimentos , Hidronefrose/urina , Pelve Renal , Período Perioperatório , Sensibilidade e Especificidade , Resultado do Tratamento , Obstrução Ureteral/congênito , Obstrução Ureteral/cirurgia , Obstrução Ureteral/urina , Bexiga Urinária/metabolismo , Refluxo Vesicoureteral/diagnósticoRESUMO
BACKGROUND: Urinary tract obstruction is a common cause of renal failure. In this study, we evaluated the time course of P-aminohippurate (PAH) renal excretion and the cortical expression of organic anion transporters (Oat1 and Oat3) at 1 (BUO-1), 2 (BUO-2) and 7 (BUO-7) days after release of 24-hour bilateral ureteral obstruction (BUO) in the rat. METHODS: Conventional clearance technique, differential centrifugation, semiquantitative immunoblotting and immunohistochemical techniques have been employed. RESULTS: These studies showed that Oat1 and Oat3 in basolateral membranes were downregulated both at BUO-1 and BUO-2. Concomitantly, the rats developed a reduction in PAH renal elimination. In contrast, total recovery in PAH renal excretion and in the expression of Oat1 and Oat3 were observed at BUO-7, as compared with the sham group. A direct correlation was observed between the secretory clearance of PAH and Oat1 (r(2) = 0.88) and Oat3 (r(2) = 0.83) expression in basolateral membranes. CONCLUSION: These results indicate that the differential expression of organic anion transporters is one of the main molecular mechanisms contributing to the organic anion excretion modifications observed during the time course of obstructive nephropathy. This study provides evidence regarding the importance of adjusting the dose regimens of negatively charged drugs during the different time phases of this pathology.
Assuntos
Rim/metabolismo , Proteína 1 Transportadora de Ânions Orgânicos/urina , Transportadores de Ânions Orgânicos Sódio-Independentes/urina , Recuperação de Função Fisiológica/fisiologia , Obstrução Ureteral/urina , Animais , Ânions/urina , Masculino , Taxa de Depuração Metabólica , Compostos Orgânicos/urina , Ratos , Ratos WistarRESUMO
Congenital obstructive nephropathy is the primary cause of end-stage renal disease in children. Rapid diagnosis and initiation of the treatment are vital to preserve function and/or to slow down renal injury. Obstructive uropathy effects -decline in the plasmatic renal flow and glomerular filtration rate, interstitial infiltrate of leukocytes, significant decrease of the urine concentration, loss of the capacity to concentrate urine as well as fibrosis and apoptosis- are a consequence of a variety of factors that work in complex ways and are still not fully understood. Mediators as angiotensin II, transforming growth factor-beta (TGF-beta) and nitric oxide (NO) have been implicated in congenital obstructive nephropathy. The renin-angiotensin system is regulated in different ways, affecting both renal structure and function, and that it in turn depends upon the duration of the obstruction. On the other hand, the role of nitric oxide in renal injury remains somewhat controversial due to the fact that it can exert opposite effects such as cytoprotective and prooxidant / proapoptotic efects as well as proinflammatory and anti-inflammatory effects. In addition, reactive oxidative species (ROS) might contribute to the progression of renal disease. During unilateral ureteral obstruction induced uncoordinated and aberrant growth may lead to the loss of cellular phenotype and apoptosis. Promoting inflammatory responses, the oxidizers can regulate the adherence of certain molecules and proinflammatory mediators, transcription factors and fibrogenic cytokines, that are clearly involved in the progression of renal disease. The congenital obstructive nephropathy is characterized by tubular atrophy, cellular proliferation, apoptosis and fibrosis; immature kidney is more susceptible than adult kidney to showing the above mentioned alterations. Apoptosis seems to be the principal mechanism that leads to tubular atrophy during the neonatal unilateral ureteral obstruction (UUO). Considering the significant role of the apoptosis in UUO, we believe of big interest the study of the regulatory factors of apoptosis in the renal obstruction neonatal. The complex biochemical and molecular events during the development, maintenance and progression of the renal injury in unilateral ureteral obstruction require further major studies to better understand the alterations mentioned above.
Assuntos
Falência Renal Crônica/metabolismo , Falência Renal Crônica/patologia , Obstrução Ureteral/fisiopatologia , Adulto , Angiotensina II/metabolismo , Angiotensina II/urina , Animais , Apoptose , Proteínas Reguladoras de Apoptose/metabolismo , Proteínas Reguladoras de Apoptose/urina , Biomarcadores/metabolismo , Criança , Humanos , Molécula 1 de Adesão Intercelular/metabolismo , Molécula 1 de Adesão Intercelular/urina , Falência Renal Crônica/urina , Óxido Nítrico/metabolismo , Óxido Nítrico/urina , Estresse Oxidativo , Espécies Reativas de Oxigênio/metabolismo , Espécies Reativas de Oxigênio/urina , Renina/metabolismo , Renina/urina , Obstrução Ureteral/metabolismo , Obstrução Ureteral/urinaRESUMO
Congenital obstructive nephropathy is the primary cause of end-stage renal disease in children. Rapid diagnosis and initiation of the treatment are vital to preserve function and/or to slow down renal injury. Obstructive uropathy effects -decline in the plasmatic renal flow and glomerular filtration rate, interstitial infiltrate of leukocytes, significant decrease of the urine concentration, loss of the capacity to concentrate urine as well as fibrosis and apoptosis- are a consequence of a variety of factors that work in complex ways and are still not fully understood. Mediators as angiotensin II, transforming growth factor-beta(TGF-beta) and nitric oxide (NO) have been implicated in congenital obstructive nephropathy. The renin-angiotensin system is regulated in different ways, affecting both renal structure and function, and that it in turn depends upon the duration of the obstruction. On the other hand, the role of nitric oxide in renal injury remains somewhat controversial due to the fact that it can exert opposite effects such as cytoprotective and prooxidant / proapoptotic efects as well as proinflammatory and anti-inflammatory effects. In addition, reactive oxidative species (ROS) might contribute to the progression of renal disease. During unilateral ureteral obstruction induced uncoordinated and aberrant growth may lead to the loss of cellular phenotype and apoptosis. Promoting inflammatory responses, the oxidizers can regulate the adherence of certain molecules and proinflammatory mediators, transcription factors and fibrogenic cytokines, that are clearly involved in the progression of renal disease. The congenital obstructive nephropathy is characterized by tubular atrophy, cellular proliferation, apoptosis and fibrosis; immature kidney is more susceptible than adult kidney to showing the above mentioned alterations.
Assuntos
Humanos , Animais , Criança , Adulto , Angiotensina II/metabolismo , Angiotensina II/urina , Falência Renal Crônica/metabolismo , Falência Renal Crônica/patologia , Molécula 1 de Adesão Intercelular/metabolismo , Molécula 1 de Adesão Intercelular/urina , Óxido Nítrico/metabolismo , Óxido Nítrico/urina , Proteínas Reguladoras de Apoptose/metabolismo , Proteínas Reguladoras de Apoptose/urina , Apoptose , Espécies Reativas de Oxigênio/metabolismo , Espécies Reativas de Oxigênio/urina , Biomarcadores/metabolismo , Estresse Oxidativo , Obstrução Ureteral/fisiopatologia , Obstrução Ureteral/metabolismo , Obstrução Ureteral/urinaRESUMO
Congenital obstructive nephropathy is the primary cause of end-stage renal disease in children. Rapid diagnosis and initiation of the treatment are vital to preserve function and/or to slow down renal injury. Obstructive uropathy effects -decline in the plasmatic renal flow and glomerular filtration rate, interstitial infiltrate of leukocytes, significant decrease of the urine concentration, loss of the capacity to concentrate urine as well as fibrosis and apoptosis- are a consequence of a variety of factors that work in complex ways and are still not fully understood. Mediators as angiotensin II, transforming growth factor-beta(TGF-beta) and nitric oxide (NO) have been implicated in congenital obstructive nephropathy. The renin-angiotensin system is regulated in different ways, affecting both renal structure and function, and that it in turn depends upon the duration of the obstruction. On the other hand, the role of nitric oxide in renal injury remains somewhat controversial due to the fact that it can exert opposite effects such as cytoprotective and prooxidant / proapoptotic efects as well as proinflammatory and anti-inflammatory effects. In addition, reactive oxidative species (ROS) might contribute to the progression of renal disease. During unilateral ureteral obstruction induced uncoordinated and aberrant growth may lead to the loss of cellular phenotype and apoptosis. Promoting inflammatory responses, the oxidizers can regulate the adherence of certain molecules and proinflammatory mediators, transcription factors and fibrogenic cytokines, that are clearly involved in the progression of renal disease. The congenital obstructive nephropathy is characterized by tubular atrophy, cellular proliferation, apoptosis and fibrosis; immature kidney is more susceptible than adult kidney to showing the above mentioned alterations.(AU)