Congenital Urinary Tract Obstruction: The Long View

Abstract

Maldevelopment of the collecting system resulting in urinary tract obstruction (UTO) is the leading identifiable cause of CKD in children. Specific etiologies are unknown; most cases are suspected by discovering hydronephrosis on prenatal ultrasonography. Congenital UTO can reduce nephron number and cause bladder dysfunction, which contribute to ongoing injury. Severe UTO can impair kidney growth in utero, and animal models of unilateral ureteral obstruction show that ischemia and oxidative stress cause proximal tubular cell death, with later development of interstitial fibrosis. Congenital obstructive nephropathy therefore results from combined developmental and obstructive renal injury. Due to inadequacy of available biomarkers, criteria for surgical correction of upper tract obstruction are poorly established. Lower tract obstruction requires fetal or immediate postnatal intervention, and the rate of progression of CKD is highly variable. New biomarkers based on proteomics and determination of glomerular number by MRI should improve future care. Angiotensin inhibitors have not been effective in slowing progression, although avoidance of nephrotoxins and timely treatment of hypertension are important. Because congenital UTO begins in fetal life, smooth transfer of care from perinatologist to pediatric and adult urology and nephrology teams should optimize quality of life and ultimate outcomes for these patients.

The molecular mechanisms of hemodialysis vascular access failure

“…EC morphology, gene and protein expression, as well as protein release are all strongly affected by different WSS patterns. 105 , 106 …”

Ultrasound evaluation for prediction of outcomes and surgical decision in fetal hydronephrosis

“…HY is more frequently diagnosed in fetuses of male gender and those in a unilateral position (5). Studies have demonstrated that vesicoureteral reflux and tract obstruction, particularly at the ureteropelvic junction, are the leading causes of HY, while HY caused by duplex renal system or hydroureteronephrosis is rare (6,7). HY may be divided into physiological and pathological types based on the post-partum conditions.…”

Anatomy, Applied Embryology, and Pathogenesis of Congenital Anomalies of the Kidney and Urinary Tract

“…Experimental obstruction of the developing urinary tract has been known to generate typical morphology of renal malformations for over 40 years, and molecular analyses confi rm similarities with human CAKUT [ 27 ]. Lower urinary tract issues are considered in detail elsewhere in this book, but it is worth noting that the pathology in human CAKUT contains a mixture of primary and secondary effects with a direct reduction in nephron number and later bladder dysfunction, which contributes to ongoing injury via ischemia and oxidative stress which promote proximal tubular cell death and interstitial fi brosis [ 28 ]. There are also confl icting data on whether correcting the obstruction is effective, with good results in large animals but poorer outcomes in mice and rats.…”