Blanc, E.

Pascual, M.

Schifferli, J. A.

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LettersHCV-RNA, is not yet routinely available and is limited byfalse-positive or false-negative results.Meanwhile, in order to reduce the incidence of HCVinfection, strict adherence to the universal precautions (CDC,Atlanta) must be carried out. According to current knowledgethe application of these measures of hygiene is probablysufficient to prevent HCV spread in the dialysis setting, andthe isolation of positive patients is not warranted.Department of Nephrology and M. BeccariDialysis,Fatebenefratelli and OftalmicoHospital,Milan,Italy1. Sungur C. Is HCV a nosocomial infection in haemodialysispatients? Nephrol Dial Transplant 1994; 9(7): 875-8762. Mclntyre PG, McCruden EAB, Dow BC et al. Hepatitis C virusinfection in renal dialysis patients in Glasgow. Nephrol DialTransplant 1994; 9(3): 291-2953. Jadoul M, Cornu C, van Ypersele de Strihou C, UCLCollaborative Group. Incidence and risk factors for hepatitis Cseroconversion in hemodialysis: a prospective study. Kidney Int1993; 44: 1322-13264. Allander T, Medin C, Jacobson SH, Grillner L, Persson MAA.Hepatitis C transmission in a hemodialysis unit: molecular evid-ence for spread of virus among patients not sharing equipment.J Med Virol 1993; 43: 415-4195. Caramelo C, Navas S, Alberola ML, Bermejillo T, Reyero A,Carrefio V. Evidence against transmission of hepatitis C virusthrough hemodialysis ultrafiltrate and peritoneal fluid. Nephron1994; 66: 470-473Sir,I read Dr Beccari's contribution on the issue of nosocomialspread of hepatitis C virus (HCV) infection amonghaemodialysis patients with interest. He stresses anothercontroversial aspect of the problem; the isolation policy forHCV-infected patients in dialysis units, and concludes thatif universal precautions are followed strictly, there is no needfor such an isolation policy.I agree with Dr Beccari that adherence to universal precau-tions is an essential measure in the prevention of nosocomialblood-borne viral infections, but on the other hand I thinkit is hard to draw a concrete conclusion about isolationpolicies for the following reasons:1. Molecular biological studies which show the presenceof viral genetic material in the haemodialysis ultrafiltraterather than the ones which fail to detect the viral RNAshould be regarded as important microbiological find-ings. Apart from methodological differences anderrors, the degree of viraemia of a patient is probablyan important factor in the contamination of theultrafiltrate.2. Haemodialysis treatment itself is a well-established riskfactor for acquiring HCV infection [1], especially if thesame machine is shared by more than four patients [2].3. In the previous decade isolation policies for hepatitis Bvirus (HBV) infection, which shares common routes oftransmission with HCV, has been successful in reducingthe nosocomial transmission of HBV infection in dialysisunits, and isolation policies for HBV-infected dialysispatients are mandatory.4. The risk of acquiring nosocomial HCV infection isstrikingly different in units with a low rate of infectionfrom those in which 50-70% of chronic dialysis patientsare infected.14755. The issue becomes more complex when one remembersthe lack of protective effect of anti-HCV antibodies,different infectivity and pathogenicity potentials of dis-tinct HCV strains, and studies showing dialysis patientsinfected with more than one strain of HCV [3,4].The answer to this controversy probably resides in thedata which will be derived from the molecular epidemiolog-ical studies. Demonstration of a particular strain of HCV ininfected patients sharing the same machine and/or dialysisunit will be an invaluable additional finding in favour ofnosocomial transmission. Unfortunately, as Dr Beccaripoints out most of these molecular diagnostic tools areinaccessible to the majority of physicians taking care ofdialysis patients.I believe that isolation policies for HCV-infected dialysispatients should be developed according to the prevalenceand rate of infection in a particular unit, and every effortshould be undertaken to prevent spread of infection to newlyadmitted cases.Bayindir Medical Center, Cem SungurTR-06520 SQgutozu,Ankara,Turkey1. Jadoul M, Cornu C, van Ypersele de Strihou C. UCLCollaborative Study Group. Incidence and risk factors for hepat-itis C seroconversion in hemodialysis: a prospective study. KidneyInt 1993; 44: 1322-13262. Wagner A, Kocaman A, Gessman M, Debusman E, Philipp T,Traenhart O. Epidemiology of HCV-infection in patients onchronic hemodialysis (abstract). J Am Soc Nephrol 1993; 4: 394A3. Yoshida C, Vanderborght B, Stuyver L, Rouzere C, Maertens G.Tracing non-transfusional transmission of HCV infection throughgenomic typing of HCV in hemodialysis unit (abstract). In: XllthInternational Congress of Nephrology, 1993, Jerusalem, 3944. Martin P. Hepatitis C genotypes: the key to pathogenicity? AnnIntern Med 1995; 122: 227-228Complement activation by LDL-apheresis usingdextran sulphateSir,LDL-apheresis (LDL-aph) using dextran sulphate (DS)adsorption has been used successfully as a therapeutic toolto reduce LDL-cholesterol in familial hypercholesterolaemia[1]. Anaphylactoid reactions have been reported in patientstreated with LDL-aph using DS columns [2]. These reactionshave been attributed to the release of bradykinin, a potentvasodilator. However, artificial biomaterials can also activatethe complement system, which may play a major role in suchanaphylactoid reactions. We studied the effects of LDL-aphwith DS (Kaneka LA 15 Liposorber) on the complementsystem during three apheresis sessions, in a 25-year-oldpatient with familial hypercholesterolaemia.Plasma samples were collected in EDTA before, during,and after each procedure. Complement activation productsC4d, Bb, and SC5b-9 were measured with commercial kits(Quidel). The concentrations of several proteins, CH50 andAP50 were reduced after LDL-aph (see Table 1). As shownin Figure 1, complement activation products Bb and SC5b-9significantly increased at the end of LDL-aph (Bb, in ug/ml,from 0.95 + 0.05 to 34.4+1.1; SC5b-9, inng/ml, from25.0 + 4.5 to 830 + 334); however, there was no significantincrease in C4d. Of note, plasma samples coming out of theDS column were practically devoid of factor H, and hadincreased concentrations of Bb and SC5b-9. There was also1476 LettersTable 1. Complement measurements after LDL-apheresis in apatient with familial hypercholesterolaemia"ProteinC3Factor BDHIClqClrClsC l inhibitorC4C9CH50<AP5OCTotal proteinAlbuminAfter LDL-apheresisb (%)69.3 + 1.765.3 + 9.345.6 + 2.329.0+1.583.1 ±7.324.0 + 4.924.847.770.3 + 7.778.6±3.361.0+12.145.0 + 2.541.5±0.585.2 + 1.287.0±2.3"Antigenic concentrations, except for factor D, CH50, AP50(haemolytic assays). All values were in the normal range beforeapheresis. Total protein and albumin are used as controls.b Values are expressed as the percentage of the pre-apheresis levels.Each value represents the mean + SEM from three different apheresissessions, except for Clr and Cls (single values).c Standard haemolytic assays assessing classical pathway (CH50) andalternative pathway (AP50) of complement.SC5b-9(ng/ml)180016001200BXi100.80.60.40.20.0.factor HhSCSb-9/ // /Q Bb fragment\ \ ,\ y ^Bb50 '40 .« 30 '20 •10 .^ o—1 2 3 4 5 6plasma samplesFig. 1. Changes in the concentration of complement activation prod-ucts Bb and SC5b-9, and of complement inhibitory protein factorH, during LDL-apheresis with DS. Each value represents the meanfrom two different apheresis sessions. Plasma samples: 1. Beforestarting LDL-aph. 2. After separation of plasma from whole bloodwith filter made of polysulphone, before DS column. 3. Plasmacoming out of DS column. 4. At the end of LDL-aph. 5. Two hoursafter the end of LDL-aph. 6. Twenty-four hours after the end ofLDL-aph.a marked C3c formation (C3 conversion to C3c) as assessedby double immunodiffusion (from <1% to 28.6 + 3.5%, atthe end of LDL-aph). Twenty-four hours after a normalLDL-aph session, no C3c was detectable in plasma, andCH50, AP50 had increased to 72 and 86%, respectively.In two sessions of LDL-aph, the neutrophil count (permicrolitre) declined from 3875 + 31 to 1645±11 after 2 h ofLDL-aph.The main finding of this study was the strong activationof the alternative pathway (AP) of complement during LDL-aph using DS, probably due to its deregulation in the fluidphase because of the reduction of factor H. We could notdemonstrate activation of the classical pathway. The signi-ficant reduction in factor H (and Clq) was due to adsorption,since more than 90% of these proteins were recovered in theeluates from the DS columns. In vitro, previous work hasshown that the interaction of human serum with negativelycharged polystyrene sulphonate results in massive comple-ment activation by the AP due to an immediate adsorptionof factor H [3]. Factor H is an essential inhibitory proteinof the AP under normal conditions; thus its adsorption orin-vivo blockade results in hypercatabolism of the AP [3,4].The resulting strong complement activation by the AP maycause anaphylactoid reactions. Nafamostat mesilate, whichinhibits both complement activation and the release of brady-kinin, may be the anticoagulant of choice for LDL-aph usingDS, in order to avoid potential life-threatening reactions [5].Renal Unit, Massachusetts General M. PascualHospital, E. BlancBoston, USA J.A. SchifferliHospital of Sion, Sion,SwitzerlandDepartment of Medicine,Kantonsspital,Basel, Switzerland1. Mabuchi H, Michishita I, Takeda M et al. A new low densitylipoprotein apheresis system using two dextran sulfate cellulosecolumns in an automated column regenerating unit (LDLcontinuous apheresis). Atherosclerosis 1987; 68: 19-252. Keller C, Grutzmacher P, Bahr F et al. LDL-apheresis withdextran sulphate and anaphylactoid reactions to ACE inhibitors.Lancet 1993; 341: 60-613. Pascual M, Piastre O, Montdargent B, Labarre D, Schifferli JA.Specific interactions of polystyrene biomaterials with factor D ofhuman complement. Biomaterials 1993; 14: 665-704. Veerhuis R, Van Es LA, Daha MR. In vivo modulation of ratcomplement activities by infusion of anti-H antibodies.Immunobiology 1985; 170: 133-1455. ICojima S, Harada-Shiba M, Nomura S et al. Effect of nafamostatmesilate on bradykinin generation during low-density lipoproteinapheresis using a dextran sulfate cellulose column. ASAIO Trans1991; 37: 644-648ACE inhibitors do not decrease rHuEpo response inpatients with end-stage renal failureSir,Angiotensin-converting enzyme (ACE) inhibitors have beensuccessfully utilized to reduce haemoglobin concentrationsin patients with post-transplant erythrocytosis [1,2]. Someauthors have suggested that ACE inhibitors could decreaseserum erythropoietin levels [3] and bone-marrow erythro-poiesis in ESRD [4]. In this way Walter [5] has suggestedthat ACE inhibitors could reduce the efficacy of rHuEpo inESRD patients. However, other studies were unable to findany effect of ACE inhibitors on haematocrit or rHuEpodose [6].We have studied 252 patients on haemodialysis from 17units; 48 of them were treated with ACE inhibitors. Allpatients had been treated with rHuEpo for at least 6 months,and to be included in the study a patient's haemoglobin hadto be over 9 g/dl in the 3 previous months. Age, sex, monthson rHuEpo treatment, months on HD, haemoglobin, haem-atocrit, iron metabolism, iPTH, aluminium, B2-microglobulinand Ul/kg/week of rHuEpo were monitored. The grouptreated with ACE inhibitors was younger (51 + 14 versus57+16 years, /><0.05), but both groups were similar in

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