Early alteration of urinary exosomal aquaporin 1 and transforming growth factor β1 after release of unilateral pelviureteral junction obstruction

Abstract

Background/purpose: Down-regulation of aquaporin 1 (AQP1) and up-regulation of transforming growth factor β(1) (TGF-β(1)) in the renal parenchyma have been demonstrated in children who underwent pyeloplasty for pelviureteral junction obstruction. However, no information about urinary exosomal AQP1 and TGF-β(1) during postobstructive polyuria in children with congenital unilateral hydronephrosis is available. The aim of the present study is to evaluate the urine concentration of exosomal AQP1 and TGF-β(1) on the first and the second day after surgery in children who underwent pyeloplasty.

Methods: Twenty-two patients (age, 36.2 ± 17.1 months) with unilateral pelviureteral junction obstruction were examined in the study. For the first 2 days after the operation, the urine was collected separately from pyelostomy draining only from the postobstructed kidney and from the bladder catheter draining mostly from the contralateral kidney, which was used as an internal control. Urinary output, urinary osmolality, sodium, β(2)-microglobulin (β(2)-MG), and creatinine, as well as urinary exosomal AQP1 and TGF-β(1) excretion, were tested in each sample.

Results: After pyeloplasty, a significantly decreased urinary excretion of exosomal AQP1 (≈ 64%) was found in the postobstructed kidney. The patients developed polyuria (807 ± 216 mL/24 h vs 484 ± 144 mL/24 h at day 1, 1021 ± 348 mL/24 h vs 603 ± 228 mL/24 h at day 2; P < .01) and reduced urine osmolality (115 ± 44 mOsm/kg vs 282 ± 61 mOsm/kg at day 1, 139 ± 39 vs 303 ± 46 mOsm/kg at day 2; P < .01) that persisted for 48 hours. In parallel, urinary TGF-β(1) and β(2)-MG (normalized for creatinine) from the postobstructed kidney were significantly higher compared with the contralateral kidney. The urine output and urinary sodium concentration from the postobstructed kidney elevated significantly on the second day after the release of obstruction compared with those on the first day. The contralateral kidney also showed same trends.

Conclusions: The down-regulation of urinary exosomal AQP1 in the postobstructed kidney may account for the polyuria, hypotonic urine, and elevated urinary β(2)-MG. The urinary TGF-β(1) level locally increased in the postobstructed kidney may be involved in renal AQP1 down-regulation.