51 THE ROLE OF URINARY TRACT AQUAPORINS IN PELVI-URETERIC JUNCTION OBSTRUCTION.
Laura Jackson1,2, Richard Coward1,2, Gavin Welsh2, Mark Woodward1,2
1Bristol Royal Hospital for Children, Bristol, United Kingdom. 2University of Bristol, Bristol, United Kingdom

Abstract

Aim of the Study:

Determining the mechanisms underpinning antenatally detected pelvi-ureteric junction obstruction (PUJO) is important as distinguishing which children need a pyeloplasty can be challenging, and delayed treatment causes morbidity. This research investigates the role of aquaporin (AQP) water channels in the pathobiology of PUJO.

Methods:

Following ethical approval (Licences:I57B0BE74, 30/2787), partial unilateral ureteric obstruction (n=12) or sham procedure (n=6) was performed in neonatal rats. At 5 weeks of age intra-renal pelvis pressure was assessed and bilateral nephroureterectomy performed. Kidney and renal pelvis AQP isoform expression was evaluated by qRT-PCR, Western Blotting and Immunohistochemistry. Urine AQP1 excretion at 4 weeks was analysed by ELISA.

Main Results:

Moderately hydronephrotic kidneys demonstrated increased pressure (8.3 +/- 2.9mmHg vs sham 0.5 +/- 0.1mmHg, p<0.05) and normal histology. Severely hydronephrotic kidneys displayed reduced glomeruli/field of view (1.6 +/- 0.7 vs sham 4.1 +/- 0.2, p<0.05) and increased interstitial fibrosis (27.3 +/- 13% per section vs sham 0.2 +/- 0.1%, p<0.05).

Renal AQP1 (0.32+0.137/-0.096 fold of sham, p<0.05), AQP2 (0.21+0.175/-0.095 fold of sham, p<0.05) and AQP6 (0.35+0.295/-0.160 fold of sham, p<0.05) mRNA relative expression, and AQP4 protein expression (optical density 5976 +/-2188 vs sham 18400 +/-3046, p<0.05), were downregulated in severe hydronephrosis.

AQP1 and 3 were localised to the vasculature and urothelium of normal renal pelvis respectively. Relative mRNA expression of both isoforms was reduced in moderate (AQP1 0.63+0.046/-0.043 fold of sham, p<0.05, AQP3 0.48+0.050/-0.046 fold of sham, p<0.05) and severe hydronephrosis (AQP1 0.48+0.042/-0.039 fold of sham, p<0.05, AQP3 0.34+0.035/-0.032 fold of sham, p<0.05).

Urinary AQP1 excretion was not significantly changed in any hydronephrotic state.

Conclusion:

Urothelial renal pelvis AQP expression is diminished in hydronephrotic states. Mechanistically this is detrimental as it will not allow hydrostatic pressure release. Increasing expression could be therapeutically beneficial.


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