A New Polymethylmethacrylate Membrane for Hemodialysis

Abstract

High molecular weight (MW) solutes are not removed during conventional hemodialysis (HD), and their accumulation is thought to play a role in some long-term HD complications (anemia, bone and joint pain, neuropathy, itching). The present trial was conducted to evaluate the removal capacity during in vivo HD of a new polymethylmethacrylate (PMMA) membrane (Filtryzer BK-F, 1.3 m²) compared to conventional PMMA (BK-P, 1.6 m²) and to cellulose acetate (CA, 1.3 m²). BK-F dialyzers, with a pore size of 100 A° and 62% porosity, are designed to remove high MW substances. Ten stable anuric RDT patients (53 ± 13 years) were treated for one week with each membrane in a randomized sequence. Plasma concentrations of creatinine, BUN and beta₂-microglobulin (beta₂-M) were measured before (b) and after (a) HD to determine the reduction rate for these substances (%). Beta₂-M concentration after HD was corrected for changes in distribution volume. Samples of spent dialysate were collected after 3 minutes, 120 minutes and at the end of HD sessions, and appropriately treated and concentrated for HPLC analysis. The reduction rate for BUN and creatinine was similar for the 3 membranes. BK-F showed a higher beta₂-M reduction rate than BK-P (p<0.005) or CA (p<0.0001). HPLC analysis of dialysate showed prevalent peaks < 4 kilodaltons (kDa) throughout HD for BK-P and CA. Solutes > 10 kDa were infrequently detected. Peak profile during HD with BK-F was quite different, showing a predominant peak > 50 kDa which also included albumin. However, albumin loss significantly decreased after 120 minutes and at the end of dialysis compared with the 3-minute values, and was lower than that reported in CAPD patients. With BK-F a peak of MW > 500 kDa was also detected which previous studies indicated as a range characterized by the presence of erythropoiesis inhibitors. Use of the BK-F membrane in HD could afford satisfactory removal of high MW substances, thereby preventing or controlling some long-term HD complications such as anemia or beta₂-M amyloid formation.

Keywords

High performance liquid chromatography Polymethylmethacrylate membrane High molecular weight solutes Hemodialysis

Get full access to this article

View all access options for this article.

References

Geiyo

, Yamada

, Odani

. A new form of amyloid protein associated with chronic hemodialysis was identified as beta₂-microglobulin. Biochem Biophys Res Commun 1985; 129: 701–6.

Massry

S.G.

. The toxic effects of parathyroid hormone in uremia. Semin Nephrol 1983; 3: 306–28.

Horl

W.H.

, Haag-Weber

, Georgopoulos

, Block

L.H.

. Physiochemical characterization of a polypeptide present in uremic serum that inhibits the biological activity of polymorphonuclear cells. Proc Natl Acad Sci USA 1990; 87: 6353–7.

Haag-Weber

, Mai

, Cohen

, Horl

W.H.

. GIP and DIP: a new view of uraemic toxicity. Nephrol Dial Transplant 1994; 9: 346–7.

Niwa

, Aiuchi

, Nakaya

, Emoto

, Miyazaki

, Maeda

. Inhibition of mitochrondrial respiration by furancarboxylic acid accumulated in uremic serum in its albumin-bound and non-dialyzable form. Clin Nephrol 1993; 39: 92–6.

Tanaka

. Quality of membrane. Contrib Nephrol 1993; 103: 112–24.

Sakai

, Tanzawa

. Poly (methyl Methacrylate) membranes. J Appl Scie 1978; 22: 1805–18.

Arakawa

Niigata Research Programme for beta₂-M removal membrane. Long-term multicentre study on beta₂-microglobulin removal by PMMA BK membrane.

Nephrol Dial Transplant 1991; Suppl 2: 69–74.

Hakim

R.M.

, Fearon

D.T.

, Lazarus

J.M.

. Biocompatibility of dialysis membranes: effects of chronic complement activation. Kidney Int 1984; 26: 194–200.

10.

Tetta

, Camussi

, Turello

. Production of cytokines in hemodialysis. Blood Purif 1990; 8: 337–46.

11.

Jindal

K.K.

, McDougall

, Woods

, Nowakowski

, Goldstein

M.B.

. A study of the basic principles determining the performance of several high-flux dialyzers. Am J Kidney Dis 1989; 14: 507–11.

12.

Bergstrom

, Wehle

. No change in corrected beta₂-microglobulin concentration after cuprophane haemodialysis. Lancet 1987; 1: 628–9.

13.

Daugirdas

J.T.

. The post:pre dialysis plasma urea nitrogen ratio to estimate KT/V and NPCR: validation. Int J Artif Organs 1989; 12: 420–7.

14.

Nensel

, Rockel

, Hillenbrandt

, Bartel

. Dialyzer permeability for low-molecular weight proteins. Blood Purif 1994; 12: 128–34.

15.

Vanholder

, Van Loo

, Dhondt

A.M.

, Glorieux

, De Smet

, Ringoir

. Second symposium on uraemic toxicity. Nephrol Dial Transplant 1995; 10: 414–8.

16.

Klinke

, Rockel

, Abdelhamid

, Fiegel

, Walb

. Transmembranous transport and adsorption of beta-2-microglobulin during hemodialysis using polysulfone, polyacrylonitrile, polymethilmethacrylate and cuprammonium rayon membranes. Int J Artif Organs 1989; 12: 697–702.

17.

Kobayashi

, Ono

, Yamamoto

. Removal of high molecular weight substances with large-pore-size membrane (BK-F). Kidney and Dialysis 1993; 34(suppl): 154–7.

18.

Gorevic

P.D.

, Munoz

P.C.

, Casey

T.T.

. Polymerization of intact beta₂-microglobulin in tissue causes amyloidosis in patients on chronic hemodialysis. Proc Natl Acad Sci USA 1986; 83: 7908–12.

19.

Casey

T.T.

, Stone

W.J.

, Di Raimond

C.R.

. Tumoral amyloidosis of bone of beta-2-microglobulin origin in association with long-term hemodialysis: a new type of amyloid disease. Human Pathol 1985; 17: 731–8.

20.

Nakazawa

, Azuma

, Suzuki

. Elimination effects of beta₂-microglobulin with adsorbent column: ocular fundus for early marker of dialysis amyloidosis. Nephrol Dial Transplant 1992; 7: 752 (Abstract).

21.

Vincent

, Pozet

, Revillard

. Plasma beta₂-microglobulin turnover in renal insufficiency. Acta Clin Belg 1983; 35(S10): 2–13.

22.

Vandenbroucke

J.M.

, Jadaul

, Maldague

. Possible role of dialysis membrane characteristics in amyloid osteoarthropathy. Lancet 1986; V. 1210–11.

23.

Saito

, Naito

, Hirohata

. Dialytic removal of middle molecular and low molecular weight proteins. In: Atsumi

, Maekawa

, Ota

, eds. Progress in Artificial Organs. Cleveland: ISAO Press, 1983; 412–6.

24.

Naito

, Miyazaki

. Haemodialysis with protein permeable membranes. Nephrol Dial Transplant 1989; 4(suppl): 78–82.

25.

Niwa

, Yazawa

, Kodama

, Uehara

, Maeda

, Yamada

. Efficient removal of albumin-bound furancarboxylic acid, an inhibitor of erythropoiesis, by continous ambulatory peritoneal dialysis. Nephron 1990; 56: 241–5.

26.

Niwa

, Takeda

, Maeda

, Shibata

, Tatematsu

. Accumulation of furancarboxylic acids in uremic serum as inhibitors of drug binding. Clin Chim Acta 1988; 173: 127–38.

27.

Mabuchi

, Nakahashi

. Inhibition of hepatic glutathione S-transferases by a major endogenous ligand substance present in uremic serum. Nephron 1988; 49: 281–3.

28.

Costigan

M.G.

, Yaqoob

, Lindup

W.E.

. Effects of haemodialysis and continous ambullatory peritoneal dialysis on the plasma clearance of an albumin-bound furan dicarboxylic acid. Nephrol Dial Transplant 1995; 10: 648–52.

29.

Bosch

, Schmidt

, Samtleben

, Gurland

H.J.

. Effect of protein absorption on diffusive and convective transport through polysulfone membranes. Contrib Nephrol 1985; 46: 14–22.

30.

Wallner

S.F.

, Vautrin

R.M.

. Evidence that inhibition of erythropoiesis is important in the anemia of chronic renal failure. J Lab Clin Med 1981; 97: 170–8.

31.

McGonigle

R.J.S.

, Husserl

, Wallin

J.D.

, Fisher

J.W.

. Hemodialysis and continuous ambulatory peritoneal dialysis effects on erythropoiesis in renal failure. Kidney Int 1984; 25: 430–6.

32.

Kawano

, Takaue

, Kuroda

. Improved EPO therapy in patients with renal anemia by a protein permeable membrane (BK-F) that filtrates erythropoietic inhibitor. Nephrol Dial Transplant 1995; 10: 1048 (Abstract).