Selective Decrease in Urinary Aquaporin 2 and Increase in Prostaglandin E2 Excretion Is Associated with Postobstructive Polyuria in Human Congenital Hydronephrosis

Abstract

Abstract. This study was undertaken to determine the role of aquaporin 2 (AQP2) in the impaired urinary concentrating capacity observed in patients who underwent pyeloplasty because of congenital unilateral hydronephrosis as a result of pyeloureteral junction disease. Twelve children (mean age, 8 Ϯ 2 mo) were examined in the study. From day 1 to day 5 after surgery, the urine was collected separately from pyelostomy draining only from the postobstructed kidney and from the bladder catheter draining mostly from the contralateral kidney used as internal control. After pyeloplasty, the postobstructed kidney was characterized by a reduced urinary excretion of AQP2 (~54%) associated with polyuria that persisted from day 1 to day 5 (433 Ϯ 58 versus 310 Ϯ 74 ml/24 h at day 1; 326 Ϯ 44 versus 227 Ϯ 26 ml/24 h at day 5). In parallel, urine osmolality from the postobstructed kidney was significantly reduced compared with the contralateral kidney (111 Ϯ 12 versus 206 Ϯ 49 at day 1; 136 Ϯ 24 versus 235 Ϯ 65 mOsm/kg at day 5). Creatinine clearance from the postobstructed kidney was not significantly different compared with the contralateral kidney throughout the 4 d after surgery. However, on day 5, creatinine clearance from the postobstructed kidney became significantly lower. Prostaglandin E2 in the urine from postobstructed kidneys was found to be twofold higher than in the contralateral samples (26.0 Ϯ 6.7 versus 13.5 Ϯ 2.5 at day 5). It is concluded that (1) the selective downregulation of AQP2 in postobstructed kidney may account for the higher excretion of hypotonic urine, and (2) the local increase in prostaglandin E2 synthesis in postobstructed kidney may be involved in AQP2 downregulation and in maintaining a GFR similar to that of the contralateral kidney.Developmental renal and urinary tract abnormalities are responsible for 54% of chronic renal insufficiency in children, with a prevalence of congenital obstructive nephro-uropathies (1). Among them, ureteral obstruction (UO), with or without concomitant renal failure, is associated with long-term impairment of the ability to concentrate urine. The pathophysiologic mechanisms of postobstructive polyuria and of the defective urinary concentrating capacity, which requires an adequate treatment of the patient, have still to be elucidated in humans. Studies in animal models suggest that the pathophysiology behind the loss of urinary concentrating ability is complex and involves different tubular segments (2,3). These studies have shown impaired water reabsorption at the collecting duct level during bilateral ureteral obstruction (BUO) and massive vasopressin-insensitive polyuria after relief of obstruction, suggesting that BUO can be considered a form of nephrogenic diabetes insipidus (NDI) (4).The vasopressin-sensitive water channel aquaporin 2 (AQP2) is the chief target for the regulation of collecting duct water permeability (5,6). AQP2 is translocated from intracellular vesicles to the apical membrane of collecting duct cells after vasopressin stimulation and is d...

Diabetes Insipidus: A Review

“…This is thought to be due to a variety of factors including decreased AQP expression, ischemic renal tubular damage and impaired ENaCs [94]. Increased PGE2 may play a role in the decreased AQP2 expression [95,96]. These defects, combined with decreased urinary concentrating capability, increased ANP, and the supernormal volume of fluid and solute, leads to dieresis [95].…”

Sildenafil Citrate Can Reduce Pathological Post-obstructive Diuresis in a Rat Model ofBilateral Ureteral Obstruction

“…The vasopressin is an antidiuretic agent that acts on the receptors of basolateral membrane of kidney collecting duct cells, which causes the fusion of vesicles containing aquapurins into apical cells of the collecting ducts. As a consequence, an impermeable membrane converts into a waterpermeable membrane, through the action of aquapurins AQP2, AQP3, and AQP4 (8)(9)(10).…”

“…Moreover, expression of aquaporin is downregulated after long lasting bilateral ureteral obstruction (BUO), suggesting a contribution to long-term polyuria and impairment of urinary concentrating capacity that happen after relief of OU (2)(3)(4)(5)(6)(7)(8)(9)(10).…”

Nephrogenic Diabetes Insipidus Due to Urinary Tract Obstruction: A Systematic Review

“…One study examined 12 children who underwent pyeloplasty due to congenital unilateral hydro-nephrosis, as a result of pyeloureteral junction disease [11]. In this study, AQP 2 levels in post-obstructed kidneys were compared to non-obstructed kidneys for 5 days.…”

“…Moreover, in one study, while examining AQP 2, an increase in prostaglandins E-2 (PGE-2) was observed in the urine from the obstructed kidney. The authors hypothesized that increased PGE-2 (rho activation and subsequent formation of f-actin stress fibers) [12] may also be responsible for downregulation of AQP channels [11].…”