Causal link between neonatal hydronephrosis and later development of hypertension

Abstract

1. Although congenital ureteral obstruction is a common disorder in infants, its pathophysiology remains poorly understood and its clinical management continues to be debated. During the past decade, the surgical management of non-symptomatic hydronephrosis in children has become more conservative, but the long-term physiological consequences of this new policy are unclear. 2. In experimental models with complete ureteral obstruction, tubular atrophy and interstitial inflammation occur rapidly. Although this type of obstruction is very rare in clinical practice, it is often referred to in clinical discussions. New studies, using a model with chronic partial ureteral obstruction, have demonstrated that hydronephrosis is associated with renal injuries and is causally related to hypertension. 3. The mechanisms underlying the development of hypertension in experimental hydronephrosis are complex and involve changes in both the renin-angiotensin system and renal sympathetic nerve activity. Furthermore, oxidative stress and nitric oxide deficiency in the diseased kidney, with consequent resetting of the tubuloglomerular feedback mechanism, appear to play a pivotal role in the development and maintenance of hyper-tension. 4. In view of the new knowledge regarding the long-term effects of partial ureteral obstruction, today's non-operative management of hydronephrosis should be reconsidered to prevent obstructive nephropathy and hypertension in later life.

Impaired EphA4 signaling leads to congenital hydronephrosis, renal injury, and hypertension

“…At present, no systematic prospective study has been conducted to investigate the long-term consequences of the conservative treatment strategy in children with congenital hydronephrosis. However, there are several case reports on adult patients with hypertension that is obviously caused by hydronephrosis, as they became normotensive following nephrectomy or pyeloplasty (4). Recently, a retrospective study evaluated the proportion of children with ureteropelvic junction obstruction who were diagnosed with hypertension preoperatively and how blood pressure changed after relief of the obstruction (14).…”

“…Studies have demonstrated that kidney function, in terms of renal perfusion and glomerular filtration remains, rather well preserved during infancy in hydronephrosis (3,15,34). These observations have led to a worldwide trend towards nonoperative management in children with nonsymptomatic unilateral hydronephrosis, but the long-term physiological consequences of this new policy are unclear (4). We have previously demonstrated that experimentally induced hydronephrosis, after completed nephrogenesis, is associated with renal injuries and is causally related to hypertension in both rats (5,9) and mice (6,8).…”

Surgical treatment reduces blood pressure in children with unilateral congenital hydronephrosis

“…This observation has led to a worldwide trend towards conservative management. The long-term physiological consequences of this new treatment policy are not known, but recent experimental studies have clearly shown an increased cardiovascular risk later in life [6,7,11].…”

Current perspectives on congenital obstructive nephropathy

“…Regardless of the specific lesion, unilateral upper urinary tract obstructive disease rarely results in proteinuria or azotemia, so conservative management of these patients is usually recommended. However, some authors have raised concern about the possibility of increased long-term risk for hypertension as a result of ureteral obstruction [42]. Bilateral upper urinary tract obstruction or obstruction of a solitary functional kidney is far more ominous and often requires prompt surgical intervention and careful medical management to minimize and monitor renal injury.…”