Present Status and Perspective of the Development of a Bioartificial Kidney for Chronic Renal Failure Patients

Abstract

A bioartificial tubule device was applied for the treatment of 10 acute renal failure and multiple organ failure patients by Humes et al. A bioartificial kidney for chronic renal failure patients, however, has never been applied. In order to develop a bioartificial kidney for preventing and treating long-term complications of maintenance dialysis patients, we have to overcome difficulties such as antithrombogenic issue of hemofilters and development of long functioning tubule devices in the context of economical and easy treatment. Continuous hemofilters should modify with an antithrombogenic material on the inner surfaces of membranes to get more hemocompatible characteristics. We are developing an antithrombogenic continuous hemofilter coating with methacryloyloxyethyl phosphorylcholine polymer which will mimic phospholipid layers of human cell membrane on the inner surface of a hemofilter. The transportability of H2O, Na+, and glucose of bioartificial tubule devices using polysulfone hollow fiber modules and porcine proximal tubular epithelial cells LLC-PK1 were evaluated using two kinds of circuits of different medium inside and outside of the cell-attached hollow fiber membrane. Transport of H2O, Na+, and glucose were significantly increased when 2.5 g/dL of albumin was added, and plateaued on the eight day and then decreased thereafter until the 13th day. Transfection of a specific gene into human tubular epithelial cells might be required to keep contact inhibition in order to maintain a confluent monolayer for longer duration.

Renal replacement therapy review

“…A biofilm of renal tubule cells attached to a semi-permeable membrane has beneficial fluid transport properties, and a small osmotic gradient creates sufficient transfer of isosmotic fluid across the tubule cells. 153 This reclamation process allows therapy to be delivered without large volume fluid replacement, freeing the patient from water sources. Membrane characteristics have also been altered to alter solute transfer properties, thus allowing for selective hemofiltration.…”

“…151 Investigational cell lines have been utilized, specifically MadinDarby canine kidney (MDCK) cells and Lewis lung cancerporcine kidney 1 (LLC-PK 1 ) cells. 152,153 Renal tubule cells are cultured on an ultrastructure, typically an existing hollow fiber membrane or a newer engineered membrane. The Renal Assist Device (RAD) utilizes human tubule cells, which are attached to a polysulfone high-flux membrane coated with pronectin-L. 150 Others have used nanopore silicone membranes with collagen coating to attach human renal tubule cells.…”

The use of bioreactors as in vitro models in pharmaceutical research

“…Humes et al [67] utilised commercially available haemofiltration cartridges, with polysulfone (PSF) based fibres seeded with human PTCs (hPTCs). Although confluent monolayers of cells were observed within the fibres [65], Saito et al, concurring with Zink et al [68] has commented on the lack of biocompatibility of PSF and PSF-based membranes for generating a confluent monolayer of cells [66]. The clinical trial undertaken with the BAK device from Humes's group has also been critically assessed, noting the lack of documentation on expected effect size, the incompletion of treatment of patients assigned to CVVH + RAD treatment and the lack of statistical significance of the primary results with comparisons performed as an as-treated rather than an as-randomised intention to treat sample [69].…”

“…Humes et al developed a device to treat patients with acute renal failure and multiple organ failure with a degree of success, while Saito et al focused on the prevention and treatment of long term complications in patients on maintenance dialysis [66]. Both devices however utilise the same bioartificial component, hollow fibre modules seeded with proximal tubule cells (PTCs), and pass ultrafiltered blood through the module before administering back into the patient (Fig 2).…”

The Long Road to Wearable Blood-Cleansing Devices

“…Also, the differentiated growth of renal tubular cells on nanostructured silicon and silicon-related membranes, as shown by Fissel et al, is encouraging in this aspect [33] . With regard to thrombogenic properties of current membranes, the developments of new polymers such as methacryloyloxyethyl phosphorylcholine, which mimic the cells' phospholipid layer, hold promise for an extended filter life of wearable extracorporeal devices [27] .…”