Wearable Devices for Blood Purification: Principles, Miniaturization, and Technical Challenges Paolo Armignacco,* Anna Lorenzin,* Mauro Neri,* Federico Nalesso,*† Francesco Garzotto,*† and Claudio Ronco*† *International Renal Research Institute, Vicenza, Italy, and †Department of Nephrology Dialysis and Transplantation, St. Bortolo Hospital, Vicenza, Italy ABSTRACT The prevalences of end-stage renal disease (ESRD) and renal replacement therapy (RRT) continue to increase across the world imposing staggering costs on providers. Therefore, strategies to optimize the treatment and improve survival are of fundamental importance. Despite the benefits of daily dialysis, its implementation is difficult and wearable hemodialysis might represent an alternative by which frequent treatments can be delivered to ESRD patients with much less interference in their routines pro- moting better quality of life. The development of the wearable artificial kidney (WAK) requires incorporation of basic components of a dialysis system into a wearable device that allows mobility, miniaturization, and above all, patient-oriented management. The technical require- ments necessary for WAK can be divided into the follow- ing broad categories: dialysis membranes, dialysis regeneration, vascular access, patient monitoring systems, and power sources. Pumping systems for blood and other fluids are the most critical components of the entire device. Chronic Kidney Disease and Hemodialysis in the World Chronic kidney disease (CKD) has a median prev- alence of 7.2% in persons aged 30 years or older, and in persons aged 64 years or older, it varies from 23.4% to 35.8% (1). Moreover, the prevalences of CKD, end-stage renal disease (ESRD), and renal replacement therapy (RRT) are increasing across the world (2,3). The recent reports from the USRDS (2012) and ANZDATA (2013) reported respectively, 3.3% increase in number of incident dialysis patients and 3.7% increase in prevalent dialysis patients (4,5). The reported prevalence (per million patients) of ESRD patients on RRT in Europe is 730 and 1665 in the United States (4,6). In the current eco- nomic times, the annual costs of providing hemodi- alysis (HD) are staggering and have been estimated to be in the range of 35 billion US$ (Medicare and non-Medicare costs) (4). Unfortunately, despite the vast resources used and various technological advances, the survival and quality of life of hemodi- alysis patients is poor, mainly because of increased cardiovascular risk (7). Though concerted efforts to reduce cardiovascular disease (CVD) have mani- fested in declining rates of CVD in dialysis patients, the cardiovascular mortality is still substantial with 84.7 deaths per 1000 patients years at risk (4). Strategies to optimize the treatment and improve survival are of fundamental importance. Increasing the dose of dialysis, by increasing the frequency of the treatments, appears to be a more physiological approach for fluid and solute removal (8). More frequent dialysis has been shown to improve weight and blood pressure control, decrease left ventricular hypertrophy, erythropoietin resistance and serum inflammatory mediators, and contribute to a better nutritional status, calcium/phosphorus metabolism, and quality of life (9–12). Despite the benefits of daily dialysis, its implementation is difficult, and wearable hemodialysis might represent an alterna- tive by which more frequent treatments can be delivered to CKD patients with much less interfer- ence in their routines promoting better quality of life (13). The wearable artificial kidney (WAK) was reported for the first time in the 1970s (14) and thanks to the advances in technology, the miniaturi- zation of the portable devices became possible. The safety and efficiency of WAK was firstly assessed in animal models (15), but in 2007, Davenport et al. (16) analyzed the performance of this device in eight CKD patients. Their results show that the device performed well in removing fluid without any car- diovascular adverse event, no adverse changes in Address correspondence to: Claudio Ronco MD, Institute Ospedale San Bortolo Vicenza, Ospedale “S. Bortolo” Azienda Ulss 6, Viale Rodolfi 37, Vicenza 36100, Italy, Tel.: 390444753869, Fax: 011390444753949, or e-mail: cronco@goldnet.it. Conflict of Interest: None. Seminars in Dialysis—2015 DOI: 10.1111/sdi.12346 © 2015 Wiley Periodicals, Inc. 1 VIEWS, VISIONS AND VISTAS IN DIALYSIS