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1 Institute of Experimental Clinical Research, Aarhus University, DK-8200, Aarhus N, Denmark; The Water and Salt Research Center, Aarhus University, DK-8000, Aarhus C, Denmark
2 Institute of Experimental Clinical Research, Aarhus University, DK-8200, Aarhus N, Denmark
3 Institute for Basic Psychiatric Research, Department of Biological Psychiatry, Aarhus University Hospital, DK-8240, Risskov, Denmark
4 Laboratory of Kidney and Electrolyte Metabolism, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA
5 The Water and Salt Research Center, Aarhus University, DK-8000, Aarhus C, Denmark; Institute of Anatomy, Aarhus University, DK-8000, Aarhus C, Denmark
6 Institute of Experimental Clinical Research, Aarhus University, DK-8200, Aarhus N, Denmark; The Water and Salt Research Center, Aarhus University, DK-8000, Aarhus C, Denmark; Department of Clinical Physiology, Aarhus University Hospital, DK-8200, Aarhus N, Denmark
* To whom correspondence should be addressed. E-mail: jf{at}iekf.au.dk.
The incidence of congenital hydronephrosis is about 1% and often associated with renal insufficiency. It is currently unknown if early release is essential to prevent deterioration of renal function. Partial unilateral ureteral obstruction (PUUO) was performed in rat at postnatal day 2. The obstruction was either unreleased or released after 1 or 4 weeks of obstruction. Renal blood flow (RBF) and kidney size were measured sequentially during 24 weeks using magnetic resonance imaging (MRI). In unreleased rats, RBF of the obstructed kidney was progressively reduced to 0.92 ± 0.17 vs. 1.79 ± 0.12 ml.min-1.100g bw-1, P<0.05 after 24 weeks. Likewise GFR of the obstructed kidney was severely reduced at 24 weeks (172 ± 36 vs 306 ± 42 µl.min-1.100g bw-1, P<0.05). These changes were preceded by development of severe hydronephrosis and obstructive nephropathy with a reduction in total protein content (45 ± 3 vs. 58 ± 4 mg . kidney-1). Moreover, non-released PUUO caused a marked natriuresis (0.32±0.07 vs. 0.11±0.02 µmol/min/100g bwt, P<0.05) and impairment in solute free water reabsorption (TcH2O; 0.47±0.16 vs. 2.71±0.74 µl/min/100g bwt, P<0.05) consistent with a significant downregulation of Na-KATPase to 62±7%, AQP1 to 53±3% and AQP3 to 53±7% of sham levels. Release after 1 week completely prevented the development of hydronephrosis, the reduction in RBF and GFR, and the downregulation of renal transport proteins whereas release after 4 weeks had no effect. This suggests that early release of neonatal obstruction provides a dramatically better protection of renal function than release of obstruction after the maturation process is completed.
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