Küchle, Claudius

Lang, Susanne M.

Schiffl, Helmut

English

Universität München: Elektronischen Publikationen

Effect of dialysate buffer on serum beta-2-microglobulin levels in chronic hemodialysis

Open Access LMU ( Ludwig-Maximilians-Univ. München)

Letter to the EditorNephron 1998;79:99–100Effect of Dialysate Buffer on SerumBeta-2-Microglobulin Levels inChronic HemodialysisC. KüchleS.M. LangH. SchifflMedizinische Klinik, Klinikum Innenstadt,Universität München, DeutschlandClaudius Küchle, MDMedizinische KlinikKlinikum Innenstadt, Universität MünchenZiemssenstrasse 1D–80336 Munich (Germany)ABCFax + 41 61 306 12 34E-Mail karger@karger.chwww.karger.com© 1998 S. Karger AG, Basel0028–2766/98/0791–0099$15.00/0This article is also accessible online at:http://BioMedNet.com/kargerDear Sir,In patients with end-stage renal diseasedialysis-related amyloidosis (DRA), alsotermed AB-amyloidosis referring to its pre-cursor protein ß2-microglobulin (ß2m), hasbeen identified as an important cause ofmorbidity. The pathogenesis of DRA re-mains largely obscure. Uremia is undoubted-ly a major precondition for this disorder, butnon-transplant renal replacement therapyalso affects precipitation of the disease. Thepathophysiological process underlying amy-loidogenesis cannot be explained solely onthe basis of simple retention and depositionof amyloid, but may also involve cell activa-tion and generation of inflammatory media-tors which consequently alter processing ofß2m and favor its osteoarticular deposition[1].There is growing evidence that the bioin-compatibility of maintenance hemodialysisprocedures is important in the pathogenesisof DRA. Cuprophane dialysis membranesare known to activate complement and cells,to cause increased production of ß2m and toaugment uremic ß2m body burden [2]. Onthe other hand highly permeable and bio-compatible membranes eliminate ß2m, re-duce circulating ß2m concentrations [3] andpostpone the development of the major clini-cal manifestations of DRA [4]. In addition,use of ultrapure dialysate has been shown tolower the incidence of the ensuing carpaltunnel syndrome [5]. The question, whetheror not the chemical composition of the dialy-sate affects the pathogenesis of DRA, has notbeen investigated in clinical studies. Thepresent prospective, randomized compari-son was aimed to elucidate the effect of dif-ferent dialysate buffers on circulating ß2mconcentrations in patients undergoing main-tenance hemodialysis. Forty-one stablechronic hemodialysis patients with end-stagerenal disease of different etiologies, main-tained on acetate hemodialysis utilizing thelow-flux cellulose acetate membrane for atleast 2 years, were randomly assigned to 4study groups: group A continued hemodialy-sis on acetate dialysate and cellulose acetatemembranes (FB130, surface area 1.3 m2,Baxter, Ill., USA); group B remained on ace-tate dialysate but changed to a high flux poly-sulfone membrane (F60, surface area 1.25m2, Fresenius, Oberursel, Germany); groupC changed to bicarbonate dialysate but re-mained on a low-flux cellulose acetate mem-brane, and group D was treated with bicar-bonate dialysate and a high-flux polysulfonemembrane. Hemodialysis was performedthree times a week for 4–5 h (MTS A 2008 Cdelivery system, Fresenius); nominal dialy-sate flow rate was 500 ml/min, blood flowrates ranged from 200 to 250 ml/min, fluidremoval rate was adjusted to clinical needs.The chemical composition of the dialysatesused were identical in terms of calcium,magnesium, and glucose concentration, butcontained either acetate (35 mmol/l) or bi-carbonate (32 mmol/l). The sodium and po-tassium concentrations were adjusted to thepatient’s values. Throughout the study theindividual hemodialysis regime remainedunchanged. Serum levels of ß2m were deter-mined using routine laboratory methods.There were no statistically significant dif-ferences in the demographic characteristicsof the 4 groups of anuric patients at recruit-ment (table 1). Circulating ß2m levels weremarkedly elevated in all patients at baseline,but they took different courses during thestudy period of 1 year follow-up. Continua-tion of the previous regimen of acetate dialy-sate and cellulose acetate membrane resultedin constant ß2m levels. The introduction ofhigh-flux polysulfone membranes to patientsreceiving acetate dialysis caused a significantreduction in serum ß2m. A more pro-nounced fall in serum ß2m was noted inpatients treated with polysulfone mem-branes. However, by comparison with pa-tients receiving bicarbonate dialysis, pa-tients treated with acetate dialysates had sig-nificantly higher serum ß2m levels (table 2).Our investigation demonstrates that thechoice of dialysate buffer affects circulatingß2m levels independent of the biocompati-bility and permeability of the dialyzer mem-brane used. The previously published notionthat exposure of patient’s blood to acetatedialysate for 1 or 6 weeks resulted in elevatedserum ß2m concentrations [6] is confirmedand extended by our data. Higher circulatingß2m levels in response to acetate dialysatemay be explained at least by two differentcauses. Under the condition of hemodialysisthese mechanisms may not operate separate-AA100 Nephron 1998;79:99–100 Küchle/Lang/SchifflTable 1. Characteristics of patients at recruitmentGroup Membrane DialysatebufferNumber(f/m)Age,years(range)Time on HD1months (range)Urine volume1ml/day (range)CA acetate 9 (6/3) 50.3 (29–72) 43.7B13.8 (26–62) 52.2B35.2 (0–100)B CA bicarbonate 10 (6/4) 51.8 (35–66) 43.3B15.4 (26–72) 23.6B33.3 (0–100)C PS acetate 11 (6/5) 52.4 (28–71) 40.5B19.8 (19–81) 36.4B37.5 (0–100)D PS bicarbonate 11 (7/4) 52.8 (36–66) 39.7B11.8 (19–56) 27.3B40.0 (0–100)CA = Cellulose acetate; PS = polysulfone; HD = hemodialysis.1 Mean B SD.Table 2. Serum ß2m levels (mean b SD)in the 4 treatment groups: effects of porosityof dialysis membrane and of dialysatebufferGroup Membrane DialysatebufferSerum ß2m levels, mg/l0 months 6 months 12 monthsCA acetate 50.2B7.5 51.6B5.8 51.7B5.8B CA bicarbonate 49.8B8.7 46.5B7.3 46.2B9.9*C PS acetate 50.1B8.5 39.2B6.5 41.6B8.5D PS bicarbonate 48.8B7.9 33.5B6.9 31.7B7.2*CA = Cellulose acetate; PS = polysulfone.* p ! 0.05 vs. corresponding values of patients on acetate dialysate.ly but synergistically. First, Sonikian et al.[6] performed in vitro and in vivo studiesindicating that metabolic acidosis enhancesß2m generation and release. Secondly, ace-tate may exert a direct effect on monocytesor lymphocytes or may induce the liberationof inflammatory mediators such as cytokinesor growth factors, which stimulate ß2m syn-thesis by these cells [7–10].Our observations have clinical implica-tions, because at present there is no causaltherapy for established DRA. It would beprudent to recommend the use of highlypermeable, biocompatible dialyzer mem-branes in combination with sterile bicarbon-ate dialysate to postpone DRA in those pa-tients at increased risk of this disorder:namely all patients who have no chance ofreceiving a kidney transplant and patientsover 55 years.OOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOReferences1 Floege J, Ehlerding G: Beta-2-microglobulin-associated amyloidosis. Nephron 1996;72:9–26.2 Hakim RM, Wingard RL, Husni L, Parker RA,Parker TF III: The effect of membrane biocom-patibility on plasma B2-microglobulin levels inchronic hemodialysis patients. J Am Soc Neph-rol 1996;7:472–478.3 Schiffl H, Küchle C, Held E: Beta-2-microglo-bulin removal by different hemodialysis mem-branes; in Maeda K, Shinzato T (eds): Dialysis-Related Amyloidosis. International Sympo-sium, Nagoya, May 1994. Contrib Nephrol.Basel, Karger, 1995; vol 112, pp 156–163.4 Küchle C, Fricke H, Held E, Schiffl H: Highflux hemodialysis postpones clinical manifesta-tion of dialysis related amyloidosis. Am JNephrol 1996;16:484–488.5 Baz M, Durand C, Ragon A, Jaber K, AndrieuD, Merzouk T, Purgus R, Olmer M, ReynierJP, Berland Y: Using ultrapure water in hemo-dialysis delays carpal tunnel syndrome. Int JArtif Organs 1991;14:681–685.6 Sonikian M, Gogusev J, Zingraff J, Loric S,Quednau B, Bessou G, Siffert W, Drueke TB,Reusch HP, Luft FC: Potential effect of meta-bolic acidosis on beta-2-microglobulin genera-tion: In vivo and in vitro studies. J Am SocNephrol 1996;7:350–356.7 Carozzi S, Nasini MG, Caviglia PM, SchelottoC, Santoni O, Atti M: Acetate free biofiltration.Effects on peripheral blood monocyte activa-tion and cytokine release. ASAIO Trans 1992;38:52–54.8 Port FK, Van De Kerkove KM, Kunkel SL:Release of IL1 during hemodialysis: Effect ofdialysate (abstract). Kidney Int 1986;29:221.9 Bingel M, Lonnemann G, Koch KM, DinarelloCA, Shaldon S: Human interleukin-1 produc-tion is enhanced by sodium acetate. Lancet1987;i:14–16.10 Nachbaur K, Toppmeyer J, Bieling P, KotlanB, König P, Huber CH: Cytokines in the con-trol of beta-2-microglobulin release. I. In vitrostudies on various hematopoietic cells. Immu-nobiology 1988;177:55–65.

Acetate free biofiltration. Effects on peripheral blood monocyte activation and cytokine release.

Beta-2-microglobulin removal by different hemodialysis membranes; in Maeda K, Shinzato T (eds): DialysisRelated Amyloidosis. International Symposium,

De Kerkove KM, Kunkel SL: Release of IL1 during hemodialysis: Effect of dialysate (abstract).

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FC: Potential effect of metabolic acidosis on beta-2-microglobulin generation: In vivo and in vitro studies.

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Huber CH: Cytokines in the control of beta-2-microglobulin release. I. In vitro studies on various hematopoietic cells. Immunobiology

III: The effect of membrane biocompatibility on plasma B2-microglobulin levels in chronic hemodialysis patients.

Shaldon S: Human interleukin-1 production is enhanced by sodium acetate.

Using ultrapure water in hemodialysis delays carpal tunnel syndrome.

C. Küchle

S.M. Lang

H. Schiffl

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Effect of Dialysate Buffer on Serum Beta-2-Microglobulin Levels in Chronic Hemodialysis

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Effect of dialysate buffer on serum beta-2-microglobulin levels in chronic hemodialysis

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