1. Hemodialysis membrane

Challenges and Advance in innovation membrane for better Dialysis Hemodialysis membrane : Histories perspective, current state and future prospect. Suchada Boonkaew, MSN (Nursing and Administration) Presidents of The Nephrology Nurses Association of Thailand

Outline •Histories perspective •current state and future prospect.

Outline •Histories perspective •current state and future prospect.

Highlights in History of Hemodialysis Frist patient Single pass surviving due machine for all types of dialyzers to dialysis Frist chronic HD First animal dialysis programme Diffusive membrane transport 1850 1860 1870 1880 1890 1900 1910 1920 1930 1940 1950 1960 1970 1980 1990 2000 First anticoagulant First human (hirudin) dialysis Natural occurring EPO mammalian anticoagulant First high flux dialyzer & (heparin) for medical related machine application

1854: The Scientific Basis for Dialysis Thomas Graham “... might be applied to medicine ...” 1805 - 1869 Script of Graham´s Bakerian Lecture, 1854

1913: First “Artificial Kidney” burette with hirudin solution John Jacob Abel \"... by which the blood of a living animal may be submitted to dialysis outside the body, 1857 - 1939 and again returned to the natural circulation without exposure to air, infection by micro- organisms or any alteration which would necessarily be prejudicial to life.\" Abel JJ, Rowntree LG, Turner BB: On the removal of diffusible substances from the circulating blood by means of dialysis. Trans Ass Am Physicians 28:51, 1913

From the past to present Thomas Graham, 1861 W. J. KOLFF, 1944 Diffusion Rotating drum kidney https://www.nationalww2museum.org/war/articles/medical-innovations-dialysis https://hackaday.com/2019/10/09/willem-kolffs-artificial-organs/ https://advancedrenaleducation.com/wparep/article/history-of-hemodialysis/ https://royalsocietypublishing.org/doi/pdf/10.1098/rstl.1861.0011

1945 - 1960: Technical Progress C. Moeller, Hamburg (1957) Alwall dialyzer (1947) Academic hospital Stuivenberg (1956)

Kiil Flatbed

Early C-DAK 1.3 Extracorporeal ExP-700 Lundia Coil 1.2m² C-DAK dialyzer family Stewart RD, Lipps BJ, Baretta ED, Piering WR, Roth DA, Sargent JA: Short-term hemodialysis with the capillary kidney. Trans Am Soc Artif Intern Organs 1968;14:121-5 Stewart RD, Cerny JC, Lipps BJ, Holmes GW: Hemodialysis with the capillary Efficient Single Use Dialyzers kidney. Univ Mich Med Cent J 1968 Mar-Apr;34(2):80-3

1969: The First Highflux Dialyzer Capable but ... ... also highly permeable for water. Rhone-Poulenc RP 6 Funck-Brentano JL, Sausse A, Vantelon J, Granger A, Zingraff J, Man NK: A new disposable plate-kidney. Trans Am Soc Artif Intern Organs 1969;15:127-30

1983: Polysulfone

Outline •Histories perspective •current state and future prospect.

From the past to present Flat Plate dialyzer, 1970 Coil dialyzer, 1956 high blood compartment Hollow Fiber dialyzer resistances [high TMPs] Unpredictable UF http://www.virtualmuseum.ca/edu/ViewLoitDa.do;jsessionid=98C34490F4CA9F515656B2D2508D7147?method=preview&lang=EN&id=4116 https://homedialysis.org/home-dialysis-basics/machines-and-supplies/dialysis-museum

Type of Membrane •Cellulose •Substituted (modified) cellulose •Synthetic membrane

Membrane transport Pore Membrane Blood characteristics characteristics components Pore size Pore density Pore size distribution Ronco, C., Clark, W.R. Haemodialysis membranes. Nat Rev Nephrol 14, 394–410 (2018)

Membrane transport Pore Membrane Blood characteristics characteristics components Pore size Pore density Pore size distribution Ultrafiltration Solute clearance Ronco, C., Clark, W.R. Haemodialysis membranes. Nat Rev Nephrol 14, 394–410 (2018)

Membrane transport Pore Membrane Blood characteristics characteristics components Thickness Surface area Hydrophilic/ hydrophobic Protein adsorption membrane urea Benefit: Absorb endotoxin Con: Reduce efficacy of small molecule clearance Azar A.T. (2013) Dialyzer Performance Parameters. In: Azar A. (eds) Modelling and Control of Dialysis Systems. Studies Ronco, C., Clark, W.R. Haemodialysis membranes. Nat Rev in Computational Intelligence, vol 404. Springer, Berlin, Heidelberg. Nephrol 14, 394–410 (2018)

Solutes Property and Membrane Transport Clearance Electrical charge Hydrophilicity Membrane cut off Protein-bound Log (Molecular size)

Type of Dialyzer (>10 years ago) Efficiency Flux Small molecules UF coefficient No KoA Yes Middle > 450 ml/min molecules Low High Kuf > 14 ml/mmHg/hr efficiency efficiency ß2-microglobulin clearance > 20 ml/min No Yes Low flux High flux

New Membrane Innovation • High cut-off membrane • Medium cut-off membrane

High Cut-off Membrane Albumin Small molecule Middle molecule Protein bound Dalton 500 66.5K Advances in Chronic Kidney Disease, Vol 18, No 3 (May), 2011: pp 180-187180

High Cut-off membrane Sieving Coefficient MRWO MRWC *MRWO, molecular weight retention onset *MRWC, molecular weight cut-off Advances in Chronic Kidney Disease, Vol 18, No 3 (May), 2011: pp 180-187180

Medium Cut-off Membrane New sciences such as microfluidics and nanotechnology may further contribute to significant progress in this direction Ronco, C. The rise of expanded hemodialysis. Blood Purif.44, I–VIII (2017). )

Medium Cut-off Membrane Ronco, C. The rise of expanded hemodialysis. Blood Purif.44, I–VIII (2017). )