Prostaglandins as potential targets for the treatment of polycystic kidney disease.

Polycystic kidney disease (PKD) is characterized by the proliferation of fluid-filled kidney cysts that enlarge over time, causing damage to the surrounding kidney and ultimately resulting in kidney failure. Both increased cell proliferation and fluid secretion are stimulated by increased cyclic adenosine monophosphate (cAMP) in PKD kidneys, so many treatments for the disease target cAMP lowering. Prostaglandins (PG) levels are elevated in multiple animal models of PKD and mediate many of their effects by elevating cAMP levels. Inhibiting the production of PG with cyclooxygenase 2 (COX2) inhibitors reduces PG levels and reduces disease progression. However, COX inhibitors also block beneficial PG and can cause nephrotoxicity. In an orthologous model of the main form of PKD, PGD2 and PGI2 were the two PG highest in kidneys and most affected by a COX2 inhibitor. Future studies are needed to determine whether specific blockage of PGD2 and/or PGI2 activity would lead to more targeted and effective treatments with fewer undesirable side-effects.