artificial kidney

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Artificial kidney is often a synonym for hemodialysis, but may also, more generally, refer to renal replacement therapies (with exclusion of renal 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.

Renal Failure

Kidneys are paired vital organs located behind the abdominal cavity, at about the level of the bottom of the ribcage. They perform about a dozen physiologic functions, and are fairly easily damaged. Kidney failure results in the slow accumulation of nitrogenous wastes, salts, water, and disruption of the body's normal pH balance. Until the Second World War, kidney failure generally meant death for the patient. Several insights into renal function and acute renal 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.^[1]

Artificial Kidney

Dialyser used in hemodialysis

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 renal failure. The mechanical device used to clean the patients blood is called a dialyser, also known as an artificial kidney. 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.

Need for a bioartificial kidney

Over 300,000 Americans are dependent on hemodialysis as treatment for renal failure, but according to data from the 2005 USRDS 452,000 Americans have end-stage renal disease (ESRD).^[2] 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^[3] 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.^[4]

Bioengineered kidneys

Currently, no viable bioengineered kidneys exist. Although a great deal of research is underway, numerous barriers exist to their creation.^[5][6][7]

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 renal disease (ESRD). 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.^[8]

In recent studies, human kidney cells were harvested from donated organs unsuitable for transplatation, 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.

See also

• Artificial organ
• Kidney
• Dialysis
• Tissue engineering
• Wearable artificial kidney
• Microelectromechanical Systems
• Nanotechnology
• Hemodialysis

References

1. ^ Bywaters EGL, Beall D (1941). "Crush injuries with impairment of renal function.". British Medical Journal 1 (4185): 427–32. doi:10.1136/bmj.1.4185.427. PMC 2161734. PMID 20783577. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2161734. 
2. ^ Fissell WH, Humes HD, Fleischman AJ, Roy S (2007). "Dialysis and Nanotechnology: Now, 10 years, or Never?". Blood Purification 25 (1): 12–17. doi:10.1159/000096391. PMID 17170531. 
3. ^ Lindsay RM, Leitch R, Heidenham AP, Kortas C. (2003). "The London daily/nocturnal Hemodialysis study: Study design, morbidity, and mortality results.". Am J Kidney Dis. 42 Supp 1: S5–S12. doi:10.1016/S0272-6386(03)00531-6. 
4. ^ Fissell W, Manley S, Westover A, Humes HD, Fleischman AJ, Roy S (2006). "Differentiated Growth of Human Renal Tubule Cells on Thin-Film and Nanostructured Materials". ASAIO Journal 2006 52 (3): 221–227. doi:10.1097/01.mat.0000205228.30516.9c. PMID 16760708. 
5. ^ Saito A, Aung T, Sekiguchi K, Sato Y, Vu D, Inagaki M, Kanai G, Tanaka R, Suzuki H, Kakuta T (2006). "Present status and perspectives of bioartificial kidneys". J Artif Organs 9 (3): 130–5. doi:10.1007/s10047-006-0336-1. PMID 16998696. 
6. ^ Saito A, Aung T, Sekiguchi K, Sato Y (2006). "Present status and perspective of the development of a bioartificial kidney for chronic renal failure patients". Ther Apher Dial 10 (4): 342–7. doi:10.1111/j.1744-9987.2006.00387.x. PMID 16911187. 
7. ^ Wang P, Takezawa T (2005). "Reconstruction of renal glomerular tissue using collagen vitrigel scaffold". J Biosci Bioeng 99 (6): 529–40. doi:10.1263/jbb.99.529. PMID 16233828. 
8. ^ Fissell W, Fleischman AJ, Roy S, Humes HD (2007). "Development of continuous implantable renal replacement: past and future". Translational Research 150 (6): 327–336. doi:10.1016/j.trsl.2007.06.001. PMID 18022594. 

External links

• Tissue engineering and kidneys - umich.edu.
• BioMEMS & Nanotechnology -lerner.ccf.org/bme/mems/