The clinical significance of chronic pro-inflammatory reactions in hemodialysis patients due to exposure to endotoxins has become a central issue in nephrology in recent years. The European Renal Association urges the routine use of ultrapure dialysate with bacteria and endotoxin levels < 0.1 cfu/ml and < 0.03 EU/ml, respectively. The American Association for the Advancement of Medical Instrumentation (AAMI) considered making similar recommendations for the United States, but chose not to do so at the time since many dialysis clinics would not be able to achieve this high level of dialysate purity without major changes in equipment and operating procedures. Recently, AAMI reduced its recommended levels of dialysate bacteria level from 2000 cfu/ml to 200 cfu/ml, and introduced an endotoxin limit of 2 EU/ml. The comparable European levels are 100 cfu/ml and 0.25 EU/ml for bacteria and endotoxins, respectively. To consistently achieve such high-purity levels in dialysate, two major challenges need to be overcome by dialysis clinics, namely: i) prevention of biofilm formation on surfaces of water systems in contact with liquids used to make the dialysate, and ii) ability to adhere to a standardized maintenance protocol to satisfy such low level of contamination. During the Phase I study, we developed a new technology based on the turbulent two-phase flow cleaning method that proved to remove more than 99% of mature biofilm from the distribution loops of a simulated dialysis center water system (DCWS), and with complete killing of any remaining surface bacteria. In the Phase II study, we propose to complete the development of the two-phase cleaning process and to develop an automated clean-inplace/ sanitize-in-place (CIP/SIP) system capable of delivering a validated cleaning/disinfecting cycle to all the components of the DCWS, including: RO distribution loop, bicarbonate distribution loop, connections to dialysis machines, RO-membrane unit and storage tanks. According to our plan, the distribution loops and connection tubing to dialysis machines will be cleaned and disinfected with the two-phase flow process, while storage tanks will be cleaned with a spray system, but without the need to fill such tanks. The entire cleaning/disinfection will be performed with the automated CIP/SIP system. The proposed system will perform a validated maintenance protocol with minimal labor requirements and in shorter times.
The Specific Aims are:
Aim 1 - To develop the cleaning procedure and analytical methodologies for each component of the DCWS using the simulated system developed in the Phase I study;
Aim 2 - To develop an automated clean-in-place/sanitize-in-place (CIP/SIP) system, including: flow and chemical control, cycle steps and sequence, process indicators and parameters;
Aim 3 - To validate the cleaning procedure for each dialysis water system component, including: distribution loops, connections to dialysis machines, storage tanks, and RO-membrane unit;
Aim 4 - To verify the validated cleaning process and protocol in the clinical setting;
and Aim 5 - To define water system designs and cleaning/disinfecting protocols necessary to consistently deliver high quality dialysate in the clinical setting.
