In-Depth Review A Case for Water in the Treatment of Polycystic Kidney Disease

Autosomal dominant polycystic disease (ADPKD) is an inherited disorder characterized by the development within renal tubules of innumerable cysts that progressively expand to cause renal insufficiency. Tubule cell proliferation and transepi-thelial fluid secretion combine to enlarge renal cysts, and 3-5-cyclic adenosine monophosphate (cAMP) stimulates that growth. The antidiuretic hormone, arginine vasopressin (AVP), operates continuously in ADPKD patients to stimulate the formation of cAMP, thereby contributing to cyst and kidney enlargement and renal dysfunction. Studies in animal models of ADPKD provide convincing evidence that blocking the action of AVP dramatically ameliorates the disease process. In the current analysis, the authors reason that increasing the amount of solute-free water drunk evenly throughout the day in patients with ADPKD and normal renal function will decrease plasma AVP concentrations and mitigate the action of cAMP on the renal cysts. Potential pitfalls of increasing fluid intake in ADPKD patients are considered, and suggestions for how physicians may prudently implement this therapy are offered. Clin J Am Soc Nephrol 4: 1140–1150, 2009. doi: 10.2215/CJN.00790209 C onvergent findings in the last decade have establishedthat 3-5-cyclic adenosine monophosphate (cAMP)stimulates mural epithelial cell proliferation and se-cretion of fluid into cysts of patients with autosomal dominant polycystic kidney disease (ADPKD), contributing to massive renal enlargement and dysfunction (1). AVP promotes cAM