Binswanger, U.

Probst, W.

Záruba, J.

RERO DOC Digital Library

Nephrol Dial Transplant 1994: Lettersinvolvement and with the following laboratory findings ofblood and urine examinations: BUN, creatinine, complementcomponent C3, and immunoglobulins. Seven cases (46.6%)had renal involvement with microscopic haematuria (n = 4),acute nephritic syndrome (n = 2), macroscopic haematuriaand nephrotic syndrome (n= 1).MHC antigens were determined by tissue typing laboratoryusing standard microlymphocytotoxicity assay [3]. Therelative risks for each HLA antigen for HSP were calculatedby means of ratios of study and control groups (relativerisk = (antigen + patient% x antigen — control%)/(antigen— patient% x antigen + control%)). Confidence interval of99% was 0.767-3.000 for these relative risk values.In HSP patients, HLA-A3, HLA-A9, HLA-Bw35 withrelative risks higher than 99% maximum confidence limit(3.000) showed the strongest association with HSP (Table 1).We have been unable to find an association between MHCantigens and the studies in first-degree relatives, becauserelative risks of all antigens in each locus were below 3.000.No common haplotype was found in both patient andfamily studies.HSP has been linked to HLA Bw35 and HLA-DR4 bysome authors, although several investigators have beenunable to find an association [1]. There has been still muchspeculation on the relation between HSP and MHC antigens.Our results agree in part with previous findings by others,but also include differences from recent studies such as thesignificance of HLA-A3 and HLA-A9.All these observations demonstrate that disease susceptibil-ity genes may play a role in the pathogenesis of HSP. Wehave described some genetic markers for HSP in Turkishpopulation and tried to compare them with previous findings.Ege University, The Medical School,Dept of Pediatric NephrologyBornova-Izmir, TurkeyS. MirN. KutukculerM. CokerA. Keskinoglu1. Bergstein JM. Henoch-SchOnlein purpura. In: Behrman RE,Vaughan CV, ed. Nelson Textbook of Pediatrics. 13th edn. WBSaunders, Philadelphia, 1987; 1123-11242. Muller CA, Markovic-Lipkovski J, Risler T, Bohle A, MullerGA. Expression of HLA-DQ.-DR and DP antigens in normalkidney and glomerulonephritis. Kidney Int 1989; 35: 116-1243. Colombe BW. Histocompatibility testing. In: Stites DP, Terr AI,ed. Basic and Clinical Immunology. 7th edn. Prentice HallInternational, London, 1991, pp. 295-311Table 1. The relative risks of HLA antigens in Turkish children withHenoch-SchOnlein purpuraHLA-A1 :0.9A2 :0.4A3 :3.6*A9 :3.1*A3(hl.2A 10:0.4B5 :1.8B8 :1.2B12 :1.3B14 :1.3B17 :1.8B21 :1.2Bw35:3.8*Bw73:2.5Bw4 :0.2Bw6 :0.6B7 :0.6B13 :0.6B40 :0.6B27 :0.2B37 :0.2Cw2:1.3Cw3:0.4Cw4:1.5Cw6:0.2DR1DR2DR3DR4DR5DR7DR11:0.3:0.3:0.6:0.9:0.4:0.3:0.2DRw53:0.2*99% confidence interval: 0.767-3.000.587L-carnitine improves vascular refilling in haemodialysispatients during ultrafiltrationSir,Patients on maintenance haemodialysis are reported toexhibit disturbed carnitine metabolism and carnitine defi-ciency [1]. There are reports that carnitine supplementationin patients undergoing chronic haemodialysis may lead tothe amelioration of uraemic anaemia and improved exercisetolerance. Recently carnitine was also found to reducethe rate of intradialytic hypotensive episodes and musclecramps [2].Carnitine is a peptide synthesized in liver, kidney, andbrain from the essential amino acids lysine and methionine.It facilitates the entry of long-chain fatty acids into mitochon-dria and therefore serves as an important metabolic cofactor.Skeletal and cardiac muscle and the kidneys rely primarilyon fatty acids as an energy substrate. Recently it has beenhypothesized that carnitine also has a vascular mechanismof action [3]. According to this hypothesis 'external' carnitineplays a role in metabolic fine regulation at a cellular level bypromoting local blood flow under conditions of metabolicstress through changes in vascular endothelial and smoothmuscle cells.During haemodialysis excess accumulated body water isremoved from haemodialysis patients by using ultrafiltration.During this process fluid is first removed from the vascularcompartment. There are various compensatory haemo-dynamic mechanisms to counteract this depletion of bloodvolume in order to preserve blood pressure and tissue perfu-sion. They include decreased venous capacitance, increasedcardiac rate and contractility, and increased vascular resist-ance. In addition a shift of fluid is initiated from theextravascular to the vascular compartment. An imbalancebetween the rate of this vascular refilling and the ultrafiltra-tion rate can result in clinically overt hypovolaemia [4].It has been suggested that L-carnitine might improvetolerance to ultrafiltration. In order to study the mechanismbehind this, we measured vascular refilling during haemodia-lysis. Ten patients undergoing maintenance haemodialysiswere studied prior to carnitine supplementation and after 4weeks of carnitine therapy. One gram of L-carnitine wasadministered i.v. after each dialysis session. All patients weredialysed thrice weekly with high-flux dialysers, the dialysistime being 7.5 or 9 h per week, according to the patientsKt/V values. Eight patients were on acetate and two onbicarbonate dialysis. All patients were normotensive at thetime of the study, and nine were on antihypertensive medica-tion (calcium-channel blockers and/or ACE inhibitors, onepatient was on beta blockers). Patients with diabetic nephro-pathy were excluded.The rate constant of vascular refilling was calculated fromthe change in blood volume and colloid-osmotic pressureand was normalized for 50-kg lean body mass (Lp =ml x min"1 x mmHg"1 x 50kg"1) [5]. The relative change inblood volume was monitored continuously by means ofultrasound velocity and the change in colloid-osmotic pres-sure was calculated from plasma protein concentrations. Atthe beginning of the dialysis session the patients were sub-jected to an 'ultrafiltration pulse' for 20 min. The volumeultrafiltered during this 'pulse' was equivalent to the neces-sary ultrafiltration-volume per hour to reach the patientsideal predialysis weight. After 4 weeks of carnitinesupplementation the serum free carnitine increased in allpatients from 43.6±11.3 to 149.8 ± 58.9 umol/1 (M±SD,paired t test, P<0.02). Lp increased significantly in six of58810 patients from 4.54±0.95 to 9.09±2.45 (M±SD,P<0.002, paired t test). This corresponded to a meanincrease of more than 100%. In the remaining four patientswe observed a decrease in Lp of 5.62±0.56 to 3.36±1.34(M±SD). There were no differences in pre- and post-supplementation caraitine, other laboratory findings, bloodpressure, interdialytic weight gain, medication, and dialysismodality between the two groups.This study has shown that a majority (60%) of patientshave increased vascular refilling after carnitine therapy. Inselected patients L-carnitine might contribute to better ultra-filtration tolerance during haemodialysis. This might be dueto an improved regional blood flow distribution, through itsextracellular functions apart from its role in fatty acidmetabolism [6]. These may lead to the promotion of localblood flow and an increased vascular refilling rate. We wereunable to identify any different characteristics in thenon-responders. Further research is needed to determine thesubgroup of patients who benefit from carnitinesupplementation and whether this leads to long-term haemo-dynamic stability on dialysis.Nephrol Dial Transplant 1994: LettersDivision of Nephrology,Department of Internal Medicine,University Hospital Zurich,SwitzerlandJ. ZarubaW. ProbstU. Binswanger1. Wanner Ch, HOrl WH. Carnitine abnormalities in patients withrenal insufficiency. Pathophysiological and therapeutical aspects.Nephron 1988; 50: 89-1022. Ahmad S, Robertson Th, Golper ThA et al. Multicenter trial ofL-carnitine in maintenance hemodialysis patients. II. Clinical andbiochemical effects. Kidney Int 1990; 38: 912-9183. Dubelaar ML, Lucas CMHB, Hfllsmann WC. The effect ofL-carnitine on force development of the latissimus dorsi musclein dogs. / Cardiol Surg 1991; 6: 270-2754. Keshaviah PR, Ilstrup KM, Shapiro FL. Dynamics of vascularrefilling. Progr Artif Organs 1983; 506-5105. Schneditz D, Roob J, Oswald M et al. Nature and rate of vascularrefilling during hemodialysis and ultrafiltration. Kidney Int 1992;42: 1425-14336. HQlsmann WC, Dubelaar ML. Carnitine in metabolism of pacedcardiac and skeletal muscles: prevention of acidosis and improve-ment of vascular flow. In: Ferrari R, ed. L-camitine and its Rolein Medicine: From function to therapy. 1992: 345-358

L-carnitine improves vascular refilling in haemodialysis patients during ultrafiltration

Abstract

Similar works

Full text

Available Versions

RERO DOC Digital Library