|This article needs to be updated. (March 2011)|
Artificial kidney is often a synonym for hemodialysis, but may also, more generally, refer to renal replacement therapies (with exclusion of kidney transplantation) that are in use and/or in development. This article deals with bioengineered kidneys/bioartificial kidneys that are grown from renal cell lines/renal tissue.
Kidneys are paired vital organs located behind the abdominal cavity, at about the level of the bottom of the ribcage, corresponding to the levels T12-L3 of the spine vertebrae. They perform about a dozen physiologic functions, and are fairly easily damaged. Some of these functions include: filtration and excretion of metabolic waste products; regulation of necessary electrolytes, fluids, stimulation of red blood cell-production. These organs routinely filter about 120 to 150 quarts of blood a day to produce about 1 to 2 quarts of urine, composed of wastes and extra fluid.
Kidney failure results in the slow accumulation of nitrogenous wastes, salts, water, and disruption of the body's normal pH balance. This failure commonly occurs over a long period of time, and when the patient's renal function declines enough over the course of the disease, is commonly known as end stage renal disease (ESRD; which is also known as Level 5 or 6 kidney disease, depending on whether dialysis or renal replacement therapy is used). Detecting kidney disease before the kidney's start to shut down is uncommon, with high blood pressure and decreased appetite being the sort of symptoms that indicate a problem. Until the Second World War, kidney failure generally meant death for the patient. Several insights into kidney function and acute kidney failure were made during the war, not least of which would be Bywaters and Beall's descriptions of pigment-induced nephropathy drawn from their clinical experiences during the London Blitz.
Need for a bioartificial kidney
Over 300,000 Americans are dependent on hemodialysis as treatment for kidney failure, but according to data from the 2005 USRDS 452,000 Americans have end-stage kidney disease (ESKD). Intriguing investigations from groups in London, Ontario and Toronto, Ontario have suggested that dialysis treatments lasting two to three times as long as, and delivered more frequently than, conventional thrice weekly treatments may be associated with improved clinical outcomes. Implementing six-times weekly, all-night dialysis would overwhelm existing resources in most countries. This, as well as scarcity of donor organs for kidney transplantation has prompted research in developing alternative therapies, including the development of a wearable or implantable device.
Hemodialysis is a method for removing waste products such as creatinine and urea,as well as free water from the blood when the kidneys are in kidney failure. The mechanical device used to clean the patients blood is called a dialyser, also known as an artificial kidney. The other name for artificial kidney is also called a dialysis machine. Modern dialysers typically consist of a cylindrical rigid casing enclosing hollow fibers cast or extruded from a polymer or copolymer, which is usually a proprietary formulation. The combined area of the hollow fibers is typically between 1-2 square meters. Intensive research has been conducted by many groups to optimize blood and dialysate flows within the dialyser, in order to achieve efficient transfer of wastes from blood to dialysate.
Wearable artificial kidney
A wearable artificial kidney is a wearable dialysis machine that a person with end-stage kidney disease could use daily or even continuously. A wearable artificial kidney (WAK) is not currently available, but some research teams are in the process of developing such a device. The FDA has approved the first human clinical trial in the United States for a wearable artificial kidney designed by Blood Purification Technologies Inc. of Beverly Hills, California. The present prototype of the WAK is a 10-pound device, powered by nine-volt batteries, which connects to a patient via a catheter. It is designed to run continuously on batteries
Implantable Renal Assist Device (IRAD)
However, manufacturing a membrane that mimics the kidney's ability to filter blood and subsequently excrete toxins while reabsorbing water and salt would allow for a wearable and/or implantable artificial kidney. Developing a membrane using microelectromechanical systems (MEMS) technology is a limiting step in creating an implantable, bioartificial kidney.
The BioMEMS and Renal Nanotechnology Laboratories at the Cleveland Clinic's Lerner Research Institute have focused on advancing membrane technology to develop an implantable or wearable therapy for end-stage kidney disease (ESKD). Current dialysis cartridges are too large and require superphysiologic pressures for blood circulation, and pores in current polymer membranes have too broad of a size distribution and irregular features. Manufacturing a silicon, nanoporous membrane with narrow pore size distributions improves the membrane's ability to discriminate between filtered and retained molecules. It also increases hydraulic permeability by allowing the mean pore size to approach the desired cutoff of the membrane. Using a batch-fabrication process allows for strict control over pore size distribution and geometry.
In recent studies, human kidney cells were harvested from donated organs unsuitable for transplantation, and grown on these membranes. The cultured cells covered the membranes and appear to retain features of adult kidney cells. The differentiated growth of renal epithelial cells on MEMS materials suggests that a miniaturized device suitable for implantation may be feasible.
A UCSF-led effort to create an implantable artificial kidney for dialysis patients has been selected as one of the first projects to undergo more timely and collaborative review at the Food and Drug Administration.
The FDA announced on April 9, 2012 that it had chosen three renal device projects to pilot a new regulatory approval program called Innovation Pathway 2.0, intended to bring breakthrough medical device technologies to patients faster and more efficiently.
The artificial kidney project, which is targeted for clinical trials in 2017, was selected for its transformative potential in treating end stage kidney disease and for its potential to benefit from early interactions with the FDA in the approval process.
The FDA effort will involve close contact between the federal agency and device developers early in the development process to identify and address potential scientific and regulatory hurdles and create a roadmap for project approval. The goal is to improve the projects’ overall chance of success, while reducing the time and cost of FDA review and maintaining safety. Lessons, the agency said, will inform approvals in other areas.
- Artificial organ
- Tissue engineering
- Wearable artificial kidney
- Microelectromechanical Systems
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