Advances in Autosomal Dominant Polycystic Kidney Disease: A Clinical Review

Abstract

Polycystic kidney disease (PKD) is a multiorgan disorder resulting in fluid-filled cyst formation in the kidneys and other systems. The replacement of kidney parenchyma with an ever-increasing volume of cysts eventually leads to kidney failure. Recently, increased understanding of the pathophysiology of PKD and genetic advances have led to new approaches of treatment targeting physiologic pathways, which has been proven to slow the progression of certain types of the disease. We review the pathophysiologic patterns and recent advances in the clinical pharmacotherapy of autosomal dominant PKD. A multipronged approach with pharmacologic and nonpharmacologic treatments can be successfully used to slow down the rate of progression of autosomal dominant PKD to kidney failure.

Keywords: ADH; ADPKD; Polycystic kidney disease; TKV; autosomal dominant polycystic kidney disease; tolvaptan.

Figure 1

Pathophysiology and genetics of autosomal dominant polycystic kidney disease (ADPKD) show the multiple abnormal signaling pathways. Abbreviations: AC6, adenylate cyclase 6; Ca²⁺, calcium ions; cAMP, cyclic adenosine monophosphate; Cl⁻, chloride ions; Gs, g protein; H₂0, water molecules (entry via aquaporins); MAPK, mitogen activated protein kinase; MEK, dual threonine and tyrosine recognition kinase; mTOR, mammalian target of rapamycin; PC1, polycystin 1; PC2, polycystin 2; PDE1, phosphodiesterase 1; PDE3, phosphodiesterase 3; PKA, protein kinase A; V2R, vasopressin 2 receptor.