A chronic intermittent haemodialysis pig model for functional evaluation of dialysis membranes

Abstract

Performance evaluation of new dialysis membranes is primarily performed in vitro, which can lead to differences in clinical results. Currently, data on dialysis membrane performance and safety are available only for haemodialysis patients. Herein, we aimed to establish an in vivo animal model of dialysis that could be extrapolated to humans. We created a bilateral nephrectomy pig model of renal failure, which placed a double-lumen catheter with the hub exposed dorsally. Haemodialysis was performed in the same manner as in humans, during which clinically relevant physiologic data were evaluated. Next, to evaluate the utility of this model, the biocompatibility of two kinds of membranes coated with or without vitamin E used in haemodiafiltration therapy were compared. Haemodialysis treatment was successfully performed in nephrectomized pigs under the same dialysis conditions (4 h per session, every other day, for 2 weeks). In accordance with human clinical data, regular dialysis alleviated renal failure in pigs. The vitamin E-coated membrane showed a significant reduction rate of advanced oxidation protein products during dialysis than non-coated membrane. In conclusion, this model mimics the pathophysiology and dialysis condition of patients undergoing haemodialysis. This dialysis treatment model of renal failure will be useful for evaluating the performance and safety of dialysis membranes.

Keywords

Haemodialysis animal models pig acute renal failure vitamin E-coated membrane dialysis membrane

Get full access to this article

View all access options for this article.

References

Kolff

Berk

ter Welle

, et al. The artificial kidney: a dialyser with a great area. 1944. J Am Soc Nephrol 1997; 8(12): 1959–1965.

Ronco

Clark

WR.

Haemodialysis membranes. Nat Rev Nephrol 2018; 14(6): 394–410.

Pstras

Ronco

Tattersall

Basic physics of hemodiafiltration. Semin Dial 2022; 35(5): 390–404.

Boschetti-de-Fierro

Beck

, et al. Membrane innovation in dialysis. Contrib Nephrol 2017; 191: 100–114.

Chen

Lin

CC.

Influence of dialysis membranes on clinical outcomes: from history to innovation. Membranes 2022; 12(2): 152.

Kohlová

Amorim

Araújo

, et al. The biocompatibility and bioactivity of hemodialysis membranes: their impact in end-stage renal disease. J Artif Organs 2019; 22(1): 14–28.

Sakiyama

Yamamoto

Ishimori

, et al. Performance evaluation of developed polysulfone membrane hemodiafilters, ABH-F and ABH-P, in post- and pre-dilution hemodiafiltration. J Artif Organs 2015; 18(4): 330–337.

Hirano

Yamamoto

Matsuda

, et al. Evaluation of dialyzer jacket structure and hollow-fiber dialysis membranes to achieve high dialysis performance. Ther Apher Dial 2011; 15(1): 66–74.

Eatroff

Langston

Chalhoub

, et al. Long-term outcome of cats and dogs with acute kidney injury treated with intermittent hemodialysis: 135 cases (1997–2010). J Am Vet Med Assoc 2012; 241(11): 1471–1478.

10.

Lemoine

Fournier

Kocevar

, et al. Intracellular phosphate dynamics in muscle measured by magnetic resonance spectroscopy during hemodialysis. J Am Soc Nephrol 2016; 27(7): 2062–2068.

11.

Hayashi

Uesato

Aisaka

Effects of activated factor X inhibitor, JTV-803, in a pig model of hemodialysis. Thromb Res 2002; 107(6): 351–356.

12.

Rutai

Zsikai

Tallósy

, et al. A Porcine sepsis model with numerical scoring for early prediction of severity. Front Med 2022; 9: 867796.

13.

Hunter

Hosgood

Patel

, et al. Effects of hydrogen sulphide in an experimental model of renal ischaemia-reperfusion injury. Br J Surg 2012; 99(12): 1665–1671.

14.

Frithiof

Bandert

Larsson

, et al. Central venous line and dialysis catheter position affects drug clearance during continuous renal replacement therapy in an animal model. ASAIO J 2019; 65(4): 408–413.

15.

Lafever

SNF

Santiago

Lopez

, et al. Hemodynamic effects of connection to continuous renal replacement therapy in a pediatric animal model. Artif Organs 2018; 42(6): 640–646.

16.

Bower

Holbert

Pearson

, et al. Chronic hemodialysis in the anephric goat. Nephron 1980; 25(1): 34–39.

17.

Pils

Draibe

Liard

, et al. Parenteral nutrition and repeated hemodialysis of bilaterally nephrectomized conscious dogs. I. Experimental model. Res Exp Med 1980; 177(2): 119–124.

18.

Rotmans

JI.

Animal Models for studying pathophysiology of hemodialysis access. Open Urol Nephrol J 2014; 7: 14–21.

19.

Yin

Yang

, et al. Pig models on intestinal development and therapeutics. Amino Acids 2017; 49(12): 2099–2106.

20.

Kanwar Nasir

Gordon

Carl

LA.

Chapter 47 kidney. In: Wanda

Colin

Matthew

(eds) Haschek and Rousseaux’s handbook of toxicologic pathology. 3rd ed. Cambridge: Academic Press, 2013, pp.1667–1773.

21.

Ben-David

Ahmed

Faroja

, et al. Irreversible electroporation: treatment effect is susceptible to local environment and tissue properties. Radiology 2013; 269(3): 738–747.

22.

Stasi

Franzin

Divella

, et al. PMMA-based continuous hemofiltration modulated complement activation and renal dysfunction in LPS-induced acute kidney injury. Front Immunol 2021; 12: 605212.

23.

Fiorentino

La Fergola

De Rosa

Medium cut-off dialyzer for middle molecular uremic toxins in AKI and chronic dialysis. J Nephrol 2024; 37(1): 23–37.

24.

Floridi

Piroddi

Pilolli

, et al. Analysis method and characterization of the antioxidant capacity of vitamin E-interactive polysulfone hemodialyzers. Acta Biomater 2009; 5(8): 2974–2982.

25.

Koga

Fujieda

Meguro

, et al. Biocompatibility of polysulfone hemodialysis membranes and its mechanisms: involvement of fibrinogen and its integrin receptors in activation of platelets and neutrophils. Artif Organs 2018; 42(9): E246–E258.

26.

Okada

Michiwaki

Mori

, et al. Removal performance of pre- and post-dilution online hemodiafiltration using identical hemodiafilters in the same patients. J Artif Organs 2023; 26(4): 309–315.

27.

Kiaii

Aritomi

Nagase

, et al. Clinical evaluation of performance, biocompatibility, and safety of vitamin E-bonded polysulfone membrane hemodialyzer compared to non-vitamin E-bonded hemodialyzer. J Artif Organs 2019; 22(4): 307–315.

28.

Piroddi

Pilolli

Aritomi

, et al. Vitamin E as a functional and biocompatibility modifier of synthetic hemodialyzer membranes: an overview of the literature on vitamin E-modified hemodialyzer membranes. Am J Nephrol 2012; 35(6): 559–572.

29.

Yang

Xiao

, et al. Effects of vitamin E-coated dialyzer on oxidative stress and inflammation status in hemodialysis patients: a systematic review and meta-analysis. Ren Fail 2014; 36(5): 722–731.

30.

D’Arrigo

Baggetta

Tripepi

, et al. Effects of vitamin E-coated versus conventional membranes in chronic hemodialysis patients: a systematic review and meta-analysis. Blood Purif 2017; 43(1–3): 101–122.

31.

Locatelli

Andrulli

Viganò

, et al. Evaluation of the impact of a new synthetic vitamin E-bonded membrane on the hypo-responsiveness to the erythropoietin therapy in hemodialysis patients: a multicenter study. Blood Purif 2017; 43(4): 338–345.

32.

Morimoto

Nakao

Fukuoka

, et al. Long-term use of vitamin E-coated polysulfone membrane reduces oxidative stress markers in haemodialysis patients. Nephrol Dial Transplant 2005; 20(12): 2775–2782.

33.

Sasaki

Development of vitamin E-modified polysulfone membrane dialyzers. J Artif Organs 2006; 9(1): 50–60.

34.

Panichi

Rosati

Paoletti

, et al. A vitamin E-coated polysulfone membrane reduces serum levels of inflammatory markers and resistance to erythropoietin-stimulating agents in hemodialysis patients: results of a randomized cross-over multicenter trial. Blood Purif 2011; 32(1): 7–14.

35.

Sanaka

Mochizuki

Kinugasa

, et al. Randomized controlled open-label trial of vitamin e-bonded polysulfone dialyzer and erythropoiesis-stimulating agent response. Clin J Am Soc Nephrol 2013; 8(6): 969–978.

36.

Lines

Carter

Dunn

, et al. A randomized controlled trial evaluating the erythropoiesis stimulating agent sparing potential of a vitamin E-bonded polysulfone dialysis membrane. Nephrol Dial Transplant 2014; 29(3): 649–656.

37.

Colombo

Reggiani

Astori

, et al. Advanced oxidation protein products in nondiabetic end stage renal disease patients on maintenance haemodialysis. Free Radic Res 2019; 53(11–12): 1114–1124.

38.

Rodríguez-Ayala

Anderstam

Suliman

, et al. Enhanced RAGE-mediated NFkappaB stimulation in inflamed hemodialysis patients. Atherosclerosis 2005; 180(2): 333–340.

39.

Zhou

Zhang

Chen

, et al. Association between serum advanced oxidation protein products and mortality risk in maintenance hemodialysis patients. J Transl Med 2021; 19(1): 284.

40.

Matsumoto

Mukai

Arihara

, et al. Ethylene-vinyl alcohol copolymer dialyzer membrane reduces protein oxidation in hemodialysis patients. Ren Fail 2011; 33(4): 382–387.

41.

Ward

Ouseph

McLeish

KR.

Effects of high-flux hemodialysis on oxidant stress. Kidney Int 2003; 63(1): 353–359.

42.

El-Wakil

Abou-Zeid

El-Gohary

, et al. Relation of middle molecules levels and oxidative stress to erythropoietin requirements in high-flux versus low-flux hemodialysis. Saudi J Kidney Dis Transpl 2013; 24(5): 930–937.

Supplementary Material

Please find the following supplemental material available below.

For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.

For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.

0.00 MB

0.26 MB