HPE HPE 85 – Spring 2017 - Page 59

Issue 85 | Spring 2017 Practical therapeutics Management of ADPKD in the era of tolvaptan Autosomal dominant polycystic kidney disease is the most common hereditary renal disease and the fourth leading cause of end-stage renal disease, affecting millions of people worldwide. Here we discuss the first targeted therapy available Polina Todorova MD Claudia Witte MD Franziska Grundmann MD Roman-Ulrich Mueller MD Department II of Internal Medicine and Center for Molecular Medicine Cologne, University of Cologne, Germany The hallmark of autosomal dominant polycystic kidney disease (ADPKD) is numerous, fluid-filled cysts that derive from the entire nephron located throughout the entire parenchyma. The cystic transformation of the kidneys is accompanied by a progressive loss of renal function. Mutations in two genes lead to ADPKD – PKD1 and PKD2. 1 They both encode for proteins that concentrate in primary cilia – a hallmark of proteins mutated in cystic kidney diseases that are consequently considered to be ciliopathies. 2 Loss of function in one of the two proteins leads to increased proliferation, defects in planar cell polarity and hyper-secretion of renal tubular cells. However, with cilia being present on nearly every cell of the human body it is clear that the phenotype in ADPKD is not limited to the kidney but accompanied by extra-renal symptoms such as cysts in other organs, intracranial aneurysms, diverticulosis and heart valve defects. 1 ADPKD follows an autosomal dominant inheritance. Consequently, affected families will have individuals suffering from ADPKD in every generation. Diagnosis Even though ADPKD is a genetic disease, the diagnosis does not require a genetic exam in the vast majority of patients but is based on clinical criteria. In patients Figure 1 T2-weighted MRI shows the massive enlargement of both kidneys with cysts distributed throughout the entire parenchyma as typical in ADPKD accompanying polycystic liver disease – as shown here – is one of the most common extra-renal manifestations of the disease. Image courtesy of Thorsten Persigehl MD, Department of Radiology, University of Cologne. hospitalpharmacyeurope.com 57