Management of autosomal-dominant polycystic kidney disease-state-of-the-art

Abstract

Autosomal-dominant polycystic kidney disease (ADPKD) is the most frequent genetic cause of end-stage renal disease in adults. Affected individuals and families face a significant medical and psychosocial burden due to both renal and extrarenal manifestations. Consequently, interventions that ameliorate the course of the disease and specifically slow down the loss of kidney function are of special interest. Major research efforts in both the clinical and pre-clinical setting in the last two decades resulted in a number of pivotal clinical trials aimed to ameliorate the disease. These studies have underlined the important role of specific supportive measures and provided the basis for first targeted pharmacological therapies. Very recently, the concept of repurposing drugs approved for other conditions for a use in ADPKD has gained increasing attention. Here, we review the current best-practice management of ADPKD patients with a focus on interventions that have reached clinical use to maintain kidney function and give an outlook on future trials and potential novel treatment strategies.

Keywords: ADPKD; clinical trials; management; tolvaptan.

FIGURE 1

Renal and extrarenal manifestations in ADPKD. The clinical diagnosis of ADPKD is primarily based upon imaging of the kidneys showing bilateral kidney enlargement with cysts dispersed throughout the entire parenchyma (A). Importantly, this phenotype has to be distinguished from other polycystic diseases such as nephronophthisis (B), tumor syndromes accompanied by kidney cysts (Birt-Hogg-Dubé syndrome syndrome in C, image modified from Bartram et al. [16]) and hydronephrosis due to postrenal obstruction (D). Furthermore, typical renal symptoms (listed below the images) and typical extrarenal manifestations (listed below the images) help in making the diagnosis. Example images from ADPKD patients: polycystic liver disease (E), splenic cyst (F), ICAs (G) and cardiac phenotypes including coronary dissections (H: left ventricular aneurysm due to left anterior descending artery obstruction by dissection in 30-year-old female patient). Images kindly provided by Thorsten Persigehl, Department of Radiology, University of Cologne.