A pilot clinical study to evaluate changes in urine osmolality and urine cAMP in response to acute and chronic water loading in autosomal dominant polycystic kidney disease.
OBJECTIVE
Autosomal dominant polycystic kidney disease (ADPKD) leads to kidney failure in half of those affected. Increased levels of adenosine 3':5'-cyclic monophosphate (cAMP) play a critical role in disease progression in animal models. Water loading, by suppressing arginine vasopressin (AVP)-stimulated cAMP production, is a proposed therapy for ADPKD.


METHODS
The effects of acute and sustained water loading on levels of urine osmolality (Uosm) and cAMP in 13 subjects with ADPKD and 10 healthy controls were studied. Uosm and cAMP concentrations were measured before and after water loading.


RESULTS
Urine [cAMP] indexed to Uosm significantly decreased with acute water loading in both groups (58% in controls and 35% in ADPKD). Chronic water loading resulted in a nonsignificant 13% decrease in 24-hour urine cAMP excretion in ADPKD participants, despite an increase in 24-hour urine volume by 64% to 3.14 +/- 0.32 L and decrease in mean Uosm by 46%, to below that of plasma (270 +/- 21 mOsm/L).


CONCLUSIONS
Increased water intake of 3 L per day decreased Uosm in most ADPKD subjects. While urine [cAMP] accurately reflects changes in Uosm during acute water loading in ADPKD subjects, chronic water loading did not lower 24-hour urine cAMP excretion, although subjects with higher baseline [cAMP] (>2 nmol/mg Cr) responded best. Decreases in urine [cAMP] and osmolality are consistent with decreased AVP activity. These results support the need for a larger study to evaluate the effect of chronic water loading on ADPKD progression.
Barash
Irina
I
Department of Medicine, Division of Nephrology, 550 First Avenue, New York, NY 10016, USA. irina.barash@nyumc.org
Ponda
Manish P
MP
Goldfarb
David S
DS
Skolnik
Edward Y
EY
D000328:Adult; D001127:Arginine Vasopressin / Q000378:metabolism; D015415:Biomarkers / Q000652:urine; D000242:Cyclic AMP / Q000652:urine*; D018450:Disease Progression; D015536:Down-Regulation; D004326:Drinking; D005260:Female; D005440:Fluid Therapy; D006801:Humans; D008297:Male; D009994:Osmolar Concentration; D010865:Pilot Projects; D016891:Polycystic Kidney, Autosomal Dominant / Q000503:physiopathology / Q000628:therapy* / Q000652:urine; D013997:Time Factors; D016896:Treatment Outcome; D014882:Water-Electrolyte Balance
D015415:Biomarkers; D001127:Arginine Vasopressin; D000242:Cyclic AMP