Mechanism and Treatment of Renal Fibrosis: Identification of transcripts associated with renal damage due to ureteral obstruction as candidate urinary biomarkers

摘要

Renal obstruction is a common cause of renal failure in adults and children and is suspected when hydronephrosis is detected on imaging. Because not all cases of hydronephrosis are associated with renal damage, biomarkers are needed to guide intervention to relieve obstruction. We performed gene expression profiling on the kidneys from adult mice over a detailed time course after obstruction and compared these data with a neonatal model of bilateral high-grade obstruction induced by conditional deletion of the calcineurin β1 gene. Having identified a set of 143 transcripts modulated in both adult and neonatal obstruction, we tested their expression in a model of short-term obstruction (1 day), where renal damage is transient and reversible, and long-term obstruction (5 days), where significant renal damage is permanent. A significant number of transcripts increased early after obstruction, and later normalized, while 26 transcripts remained elevated 10 and 28 days after relief of 5 days of ureteral obstruction. With the use of qPCR, elevated levels of several of these candidate RNA biomarkers of renal damage were detected in urine from obstructed mice. In addition, several of these candidate RNA biomarkers of damage resulting from obstruction were detectable in catheterized urine samples from children undergoing surgery for ureteropelvic junction obstruction. Measurement of urinary transcripts modulated in response to renal obstruction could serve as biomarkers of renal damage with important clinical applications.