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Molecular pathology of murine ureteritis causing obstructive uropathy with hydronephrosis.

ABSTRACT: Primary causes of urinary tract obstruction that induces urine retention and results in hydronephrosis include uroliths, inflammation, and tumors. In this study, we analyzed the molecular pathology of ureteritis causing hydronephrosis in laboratory rodents.F2 progenies of C57BL/6 and DBA/2 mice were studied histopathologically and by comprehensive gene expression analysis of their ureters. Incidence of hydronephrosis was approximately 5% in F2 progenies. Histopathologically, this hydronephrosis was caused by stenosis of the proximal ureter, which showed fibrosis and papillary malformations of the proliferative epithelium with infiltrations of B-cell-dominated lymphocytes. Additionally, CD16-positive large granular leukocytes and eosinophils infiltrated from the ureteral mucosa to the muscular layer. Eosinophilic crystals were characteristically observed in the lumen of the ureter and the cytoplasm of large granular leukocytes, eosinophils, and transitional epithelial cells. Comprehensive gene profiling revealed remarkably elevated expression of genes associated with hyperimmune responses through activation of B cells in diseased ureters. Furthermore, diseased ureters showed dramatically higher gene expression of chitinase 3-like 3, known as Ym1, which is associated with formation both of adenomas in the transitional epithelium and of eosinophilic crystals in inflammatory conditions. The Ym1 protein was mainly localized to the cytoplasm of the transitional epithelium, infiltrated cells, and eosinophilic crystals in diseased ureters.We determined that the primary cause of hydronephrosis in F2 mice was ureteritis mediated by the local hyperimmune response with malformation of the transitional epithelium. Our data provide a novel molecular pathogenesis for elucidating causes of aseptic inflammation in human upper urinary tracts.

SUBMITTER: Ichii O

PROVIDER: S-EPMC3218045 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature

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Molecular pathology of murine ureteritis causing obstructive uropathy with hydronephrosis.

Ichii Osamu O Otsuka Saori S Namiki Yuka Y Hashimoto Yoshiharu Y Kon Yasuhiro Y

PloS one 20111116 11

Primary causes of urinary tract obstruction that induces urine retention and results in hydronephrosis include uroliths, inflammation, and tumors. In this study, we analyzed the molecular pathology of ureteritis causing hydronephrosis in laboratory rodents.F2 progenies of C57BL/6 and DBA/2 mice were studied histopathologically and by comprehensive gene expression analysis of their ureters. Incidence of hydronephrosis was approximately 5% in F2 progenies. Histopathologically, this hydronephrosis ...[more]

PMID: 22114694

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Project description:The treatment of asymptomatic hydronephrosis due to ureteropelvic junction obstruction (UPJO), as well as the timing and indications for surgical intervention, remain controversial. Diabetes insipidus (DI) is a rare disease in infants that is known to cause non-obstructive hydronephrosis, while its association with obstructive hydronephrosis has not been reported. Some studies have found that increased water intake is a predisposing risk factor of developing hydronephrosis. However, there are no studies or guidelines that indicate the specific follow-up intervals and surgical indications for mild hydronephrosis if predisposing risk factors persist. A 46-month-old boy was admitted to our Urology Department with a history of Society of Fetal Urology (SFU) Grade 2 prenatal left hydronephrosis, which was stable at SFU Grade 1-2 at regular postnatal follow-ups. The patient developed polydipsia and polyuria three months prior to admission, then he was considered as primary polydipsia by endocrinology and was treated with fluid restriction while the examination was negative. Renal ultrasound at follow-up demonstrated severe left hydronephrosis with an anterior-posterior diameter (APD) of 6.25 cm three months after symptom onset. Diuretic renography (DR) revealed a renal function of 13.7% with a glomerular filtration rate (GFR) of 11.25 mL/min. The patient was otherwise asymptomatic without any abdominal pain or vomiting. He underwent left pyelostomy immediately as well as laparoscopic left dismembered ureteropelvioplasty after three months, and a diagnosis of UPJO was confirmed. The patient had an uncomplicated postoperative recovery and the result of follow-up renal ultrasound was stable. However, the symptoms of polydipsia and polyuria did not improve significantly. He underwent pituitary magnetic resonance imaging (MRI) and pathological examination, the results of which were consistent with central DI caused by Langerhans cell hyperplasia four months postoperatively. This case indicates the need to pay attention to children with mild hydronephrosis undergoing regular observation and conservative treatment, as a sudden aggravation of the hydronephrosis and a rapid decline of renal function may occur if DI persists.

Dataset Information

Molecular pathology of murine ureteritis causing obstructive uropathy with hydronephrosis.

Publications

Molecular pathology of murine ureteritis causing obstructive uropathy with hydronephrosis.

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