Abnormal lipid and apolipoprotein composition of major lipoprotein density classes in patients with chronic renal failure

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1 Nephrol Dial Transplant (1996) 11: Original Artile Nephrology Dialysis Transplantation Abnormal lipid and apolipoprotein omposition of major lipoprotein density lasses in patients with hroni renal failre P.-O. Attman 1, P. Alapovi 2, M. Tavella 2 and C. Knight-Gibson 2 'Department of Nephrology, Sahlgrenska University Hospital, University of Goteborg, Goteborg, Sweden and 2 Lipid and Lipoprotein Laboratory, Oklahoma Medial Researh Fondation, Oklahoma City, Oklahoma, USA Abstrat Bakgrond and methods. To haraterize the abnormalities of lipoprotein omposition in patients with hroni renal failre (CRF), the lipid and apolipoprotein (apo) onentrations and omposition of major lipoprotein density lasses were determined in 2 sbjets with moderate to advaned renal failre (GFR 5-59 ml/min) and nine ontrols. Patients were divided into 14 normotriglyeridaemi (NTG) sbjets with triglyeride (TG) levels < 1.7 mmol/1 (15 mg/dl) and six hypertriglyeridaemi (HTG) sbjets with TG ^1.7 mmol/1. Lipoproteins were isolated by preparative ltraentrifgation: very low density (VLDL), intermediate density (IDL), low density (LDL) and high density (HDL) lipoproteins. Reslts. Althogh all density lasses were haraterized by abnormal onentration and omposition of some lipid and apo onstitents, the most profond hanges orred in IDL and HDL. Cholesterol levels were elevated in VLDL and IDL with little hange in LDL and reded in HDL. TG levels were inreased in all density lasses. ApoB levels were inreased in VLDL, IDL and LDL of all reahing the signifiane levels in VLDL and IDL of HTG (P<.l). In IDL, the levels of apoc-peptides and apoe were inreased (P<.1). ApoC-peptides and apo E were also elevated in VLDL of NTG and HTG, bt their inrease was only signifiant in HTG (P<.1). In LDL, the onentration of apoc-ii and apoc-iii was signifiantly inreased (P<.5). However, in HDL there was signifiant (P<.1) redtion of apoa-i, apoa-ii and apoc-peptides in both patient grops. The major ompositional hange was a signifiant inrease in the relative ontents of apoc-ii and apoc- III in VLDL, IDL and LDL (P<.1). Conlsions. Reslts indiate that the harateristi featre of dyslipoproteinemia in CRF is the amlation of partially delipidized TG-rih apob-ontaining lipoproteins enrihed in apoc-peptides and distribted harateristially in the IDL density- irrespetive of fasting TG onentrations. Inreased levels of these 'remnant lipoproteins' and reded levels of HDL may represent risk fators for atherogenesis and progressive renal disease. Key words: apolipoproteins; hroni renal failre; lipids; lipoproteins Introdtion Chroni renal failre (CRF) is haraterized by speifi ompositional and metaboli abnormalities of plasma lipoproteins [1]. The renal dyslipoproteinaemia may be manifested by elevated plasma lipid onentrations. However, speifi ompositional alterations of lipoproteins an also be deteted in normolipidaemi patients as refleted by abnormal onentration and omposition of apolipoproteins [2]. We have earlier shown that this dyslipoproteinaemi ondition is present not only in advaned renal failre and dring dialysis bt also in asymptomati earlier stages of renal insffiieny when the glomerlar filtration rate (GFR) is reded below 5 ml/min [2 4]. The harateristi plasma apolipoprotein abnormalities inlde inreased onentrations of apolipoprotein (apo) B and apocpeptides and dereased onentrations of apoa-i and apoa-ii [4,5]. The prpose of the present stdy was to frther explore the altered lipoprotein omposition in patients with both moderate and advaned renal failre. The speifi aim was to determine the abnormalities in the lipid and apolipoprotein onentrations of major lipoprotein density lasses in these patients. A frther objetive was to investigate whether these abnormalities are fond both in normolipidaemi and hyperlipidaemi patients. Sbjets and methods Patients Correspondene and offprint reqests to: Per-Ola Attman MD, Department of Nephrology, Sahlgrenska University Hospital, S Goteborg, Sweden Eropean Dialysis and Transplant Assoiation-Eropean Renal Assoiation Twenty adlt patients (11 men, 9 women, mean age years) with hroni renal insffiieny (GFR 5-59ml/min/1.73 m 2 BSA) were investigated.

2 64 Table 1. Clinial harateristis of patients with hroni renal failre Nmber of patients Mean age (years) (years) Sex Males Females Mean body mass index Mean glomerlar filtration rate (ml/min/1.73m 2 BSA) Diagnosis Chroni glomerlonephritis Chroni interstitial nephritis Polyysti kidney disease Other Mean serm protein onentration (n= 19) (g/1) Mean serm albmin onentration (n=13) (g/1) Mean 24-h rinary protein exretion (n = 16) (g) Beta-bloker treatment (n) Plasma triglyerides Nmber of patients (n) Mean age (years) (years) Mean body mass index (kg/m 2 ) Mean glomerlar filtration rate (ml/min/1.73 m 2 BSA) ^* ^ 1.7 mmol/ > 1.7 mmol/ Clinial harateristis of these patients are presented in Table 1. For ertain analyses the patients were separated into two grops: 14 normotriglyeridaemi (NTG) and six hypertriglyeridaemi (HTG) patients with plasma triglyeride (TG) onentration 1.7 mmol/1 (15mg/dl) as the t-off point. The patients attended the Department of Nephrology at the Sahlgrenska University Hospital, GSteborg, Sweden. The patients were treated with antihypertensive drgs, diretis, sodim biarbonate, and phosphate-binding drgs as appropriate. No patient was treated with ortiosteroids, immnosppressive drgs, or drgs known to signifiantly inflene lipoprotein metabolism. The patients reeived no dietary onselling prior to the stdy. Control sbjets Nine healthy, normolipidaemi, Caasian sbjets (4 men, 5 women, age 44.7 ± 17. years), employees of University of GSteborg and Oklahoma Medial Researh Fondation, served as ontrols. Methodology Blood samples were obtained from antebital venepntre after an overnight fast. Plasma samples ontained EDTA (1 mg/ml) and e-aminoaproi aid (1.3 mg/ml) as preservatives. Samples were immediately shipped by air freight to P.-O. Attman et al. Oklahoma City for analysis within 3-4 days of sampling. Lipoprotein density lasses were isolated by seqential preparative ltraentrifgation sing Qik-Seal tbes (Bekman, Palo Alto, CA) by a previos desribed proedre [6]. The very low density lipoproteins (VLDL, d< 1.6 g/ml), intermediate density lipoproteins (IDL, d g/ml), low density lipoproteins (LDL, d g/ml) and high density lipoproteins (HDL, d g/ml) were isolated at soltion densities 1.6 g/ml, 1.19 g/ml, 1.63 g/ml and 1.21 g/ml respetively. All lipoprotein density lasses were dialysed against.15 M NaCl ontaining.5% EDTA (ph 7.). The reovery of lipids d between 85 and 95% of plasma vales and that of apolipoproteins d between 75 and 8% for apocpeptides and 8 and 9% for apolipoproteins A-I, A-H, B, and E. Lipid and apolipoprotein vales of VLDL, IDL, LDL, and HDL were adjsted to those of whole plasma. Total holesterol (TC) and TG ontents were determined by enzymati methods as previosly desribed [7]. The perentage omposition of holesterol esters (CE), free holesterol (FC), and TG in lipoprotein density lasses was determined by gas hromatography [8]. Conentrations of apolipoproteins A-I, A-H, B, C-I, C-II, C-III, and E were measred by eletroimmnoassays as previosly desribed [5,6,9]. The isolation of antigens and the preparation of monospeifi antisera were desribed in detail and reported in several pbliations from this laboratory [5,6,9]. The lipid mass refers to the sm of individally determined total holesterol and triglyeride onentrations and apolipoprotein mass to the sm of individally determined levels of apolipoproteins A-I, A-H, B, C-L C-II, C-III, and E in eah of the major lipoprotein density lasses. Statistial methods Conventional statistial methods were sed to desribe the salient featres of the reslts. Stdent's npaired two-tailed t test was sed to test the signifiane of differenes between means. Reslts Plasma lipid and apolipoprotein onentrations Plasma TG onentrations, bt not TC onentrations, were signifiantly inreased in the (Table 2) and were signifiantly orrelated to GFR vales (r= -.45, P<.5). In the NTG patients there was a slight inrease in the levels of TG ompared to ontrol sbjets. However, in HTG patients there was a nearly threefold inrease of plasma TG and an inrease of plasma TC levels. Apolipoproteins A-I and A-II were signifiantly reded in both NTG and HTG patients. ApoB onentrations were signifiantly elevated only in the HTG patients, whereas a signifiant inrease in apoc-iii levels was fond in all CRF patients. In addition the HTG patients had inreased onentrations of apoc-i and apoc-ii, bt no hange in the onentration of apoe. Conseqently, the apoa- I/apoC-III ratio and the apoa-i/apob were signifiantly reded in all together with a signifiantly inreased apoc-iii/apoe ratio.

3 o Lipoproteins in renal disease 65 oi U^ <2 e oni ith ien d O. O H I 'E d -o 8 ~aa C iype o d a Hẕ non O d 3 a o. '3. apolipo d pids (*_ trat 8 U V.2 a t*. ins 1 polipo -«: '5. (/I 1/E C-I I A-I/B III 6 j _ CQ - < H O H ( %rnso«ottv-jooo Oo O O^NO o o ^1 ; (N W -~. *3\ O (N ""»/^ O -^- m > so r- <N 1 fn OO SO t O^ O *N Os ^^ ~m l/~^ OO ^O OO ^^ ^ I Tt Tt TT I oo VI ^" (N TJ 1 o r^ O\ 6 > (N O (N OO O OO ^ O r^i O ro *N ^- Q Q Q Q 6 a: o o E E CEDE UHUH o. O o..... V Vg *. V Is.52 '-5 3-S C IP "2 I Iz o e 2 o o I ao Si Lipid and apolipoprotein onentrations in lipoprotein density lasses Althogh the onentrations of lipids and apolipoproteins B, C-I, C-II, C-III, and E in VLDL were higher in the patient grop than in ontrols, the statistially signifiant inreases were only reahed in HTG patients (Table 3). However, the differenes in the levels of lipids and apolipoproteins between CRF patients and ontrols were expressed more signifiantly in IDL than VLDL. Signifiantly higher levels of TC, apoc-peptides and apoe were observed in the entire patient poplation as well as in NTG and HTG patients (Table 3). The TG levels were also inreased in all patient grops. The apob onentrations were signifiantly higher in the entire patient grop and HTG patients. There were no differenes in the levels of apoa-i and apoa-ii between patients and ontrols. In LDL, the most harateristi differenes between patient grops and ontrols inlded signifiantly inreased onentrations of TG, apoc-ii and apoc- III (Table 3). In ontrast, the onentrations of apob and apoe were similar in patients and ontrols. The levels of apoa-i and apoa-ii were lower in patients than ontrols. In HDL of all patient grops, there were signifiant dereases in the onentrations of apoa-i, apoa-ii, apoc-i and apoc-ii and inreases in the levels of apob (Table 3). Dereased levels of TC were statistially signifiant in the entire patient poplation and HTG patients. The apoc-iii and apoe onentrations were slightly dereased and the TG onentrations were slightly inreased in all patient grops in omparison with ontrols. The differenes in the lipid and apolipoprotein onentrations between and ontrols were learly refleted in the lipid and apolipoprotein masses of their orresponding lipoprotein density lasses (Figre 1). The most affeted lipoprotein density lasses of were IDL and HDL. In omparison with normal ontrols, were haraterized by a signifiant twofold inrease in the total lipoprotein mass of IDL (77.5 ±52.3 vs mg/dl; / ) <.5) and a signifiant redtion of that of HDL (217.5±55.9 vs 32.1 ±6.4; P<.1). Signifiantly inreased levels of apolipoprotein masses of IDL and reded apolipoprotein masses of HDL were harateristi of both NTG and HTG patients. Althogh the lipid and apolipoprotein masses of VLDL and LDL were elevated in CRF patients when ompared to ontrols, the statistial signifiane was only reahed in HTG patients. The proportional inrease of apolipoprotein mass in IDL and derease in HDL were greater than those of lipid mass in both NTG and HTG patients. Distribtion of lipids and apolipoproteins in lipoprotein density lasses Changes in the apolipoprotein mass of lipoprotein density lasses in are losely assoiated with the redistribtion of apolipoproteins B, C and E between HDL and IDL and LDL. In,

4 66 Table 3. Conentrations of lipids and iipolipoproteins (HTG) patients with hroni renal failre (CRF) in major lipoprotein density lasses of normo- (NTG) and P.-O. Attman et at. hypertriglyeridaemi Sbjets Lipids (mmol/1) TG TC Apolipoproteins (mg/dl) A-I A-II B C-I C-II -m E VLDL IDL LDL HDL.31 (.23) 6 (.37).38 (.22).98^ (.3).17 (.2).29 (.16).21 (.8).48 w (.13).26 (.14) 7 (.25).39" (.12).8" (.26).14 (.8).21 (.16).18 (.11).27 (.22).28 (.23).6 (3).39 (.22) 1.12 bf (.71).28 (.13).76' (.62) 7* (.32) 1.22 b - d (.92) 3.4 (.66) 3.1 (.67) 2.96 (.47) 3.42 (.98) 1.61 (6) 1.21* (.38) 1.27 (.39) 1.6* (.35) (.8) (.7) (.6).7 (.8).7 () 1.4 (1.7).9 (.7) 2.5 (2.8) 7.5 (5.3) 5.1 (3.8) 4.3 (3.4) 7. (4.1) (29.) 9.2* (27.) 94.9* (28.1) 79.4 C (22.7).4 (.7).2.1 (.1).3 (.6).1.6 (1.8).2 (.1) 1.7 (3.3) 4. (2.6) 2." (1.4) 1.9* (1.1) (1.3) 44.7" (12.8) 45.5" (12.7) 42.8" (14.1) 4.1 (4.) 6.7 (5.3) 4.7 (3.1) 11.6" (6.5) 5.2 (4.4) 13.3' (9.5) 9.3 (5.1) 22.7" (11.2) 84.1 (16.1) 85.6 (3.8) 8.9 (23.) 96.5 (45.) 1.8 (2.6) 5.9" (3.7) 5.3' (3.5) 7.4" (3.9) (.3).9.6 (.3) 2.1" (1.6).3 1.*.7' 2.2"-«(1.5) (1.4) 5.4».d (2.9) 7.5 (1.9) 3.8 s (2.5) 4.1" (2.4) 2.7" (3.).7 \.2 J.1 (.1).7" (.6).4 1.3" (.8) 1.3* 1.* 2." d (1.3) 2.1 (.8) 1." (.8) 1.".8" (.7) Signifiane of differene between patients and ontrol sbjets is indiated: */ > <.5; "P<.1; / > <.1. Signifiane of differene between and patients is indiated: d P<.5; */»<.1; r P<.1..9 (.6) 2. (1.7) b -*.4 3.3* (4.) 1.8" (1.3) 6.8"' e (6.1) 2.1 (1.) 6.5" (3.8) 5.3" (2.5) 9.6 d (4.8) (3.4) 4.4 (3.4) 4.4 (3.9) (1.9) 1.6 (1.) 3.3*.7 2.2' (1.7) 1.6* (1.) 3.5"- d (2.2) (1.5) 2.2 (1.3) 2.5 (2.2) 6.2 (2.) 4.3 (3.) 5. (3.2) 2.5" (1.6) VLDL IDL LDL HDL VLDL IDL LDL HDL Fig. 1. Lipid and apolipoprotein mass in major lipoprotein density lasses in normo- (NTG) and hypertriglyeridaemi (HTG) patients with hroni renal failre expressed in perentage of ontrol vales (Hi NTG, E5 HTG patients). Asterisks denote signifiane of differene from ontrol vales (V<.5, **P<.1, ***/'<.1). 1.7% of total apob, 1.7% of apoc-i, 17.1% of apoc-ii, 17.6% of apoc-iii and 19.1% of apoe were present in IDL ompared to 5.5%, 2.8%, 3.2%, 4.9% and 7.% of orresponding total apolipoprotein ontents in IDL of ontrol sbjets. There was a twofold inrease in the perentage distribtion of apocpeptides in LDL of when ompared to ontrols, bt no differene in the perentage distrib-

5 Lipoproteins inrenaldisease VLDL IDL LDL HDL Fig. 2. Conentrations (mean±se) of apolipoprotein C-III in major lipoprotein density lasses in normo- (NTG) and hypertriglyeridaemi (HTG) patients with hroni renal failre and ontrol sbjets (D ontrol, 8 all patients, NTG, HTG). Asterisks denote signifiane of differene from ontrol vales (*/ > <.5, */ > <.1, ***7»<.1). tion of apoe. In ontrast, the perentage distribtion of total apoc-peptides and apoe in HDL of CRF patients was signifiantly reded (4-6%, P<.1-P<.1). The hanges in the perentage distribtion of total TG, TC, apoa-i and apoa-h were non-signifiant. The altered distribtion of apoc-iii among major lipoprotein density lasses of is illstrated in Figre 2. The signifiantly inreased onentration of apoc-iii in whole plasma is refleted in inreases of apoc-iii in VLDL, IDL, and LDL bt not HDL. Plasma onentration of apoc-iii was signifiantly orrelated with IDL-apoC-III (r =.72, P<.l) and LDL-apoC-III (r =.48, P<.5). The proportionally greater inrease of apoc-iii than those of apob and apoe was fond in all density lasses of. The apoc-iii/apoe ratio was inreased more than twofold in IDL and 3-5-fold in LDL. Frthermore, there were signifiant dereases of apob/apoc-iii and apob/apoe ratios in VLDL and IDL. Composition oflipids and apolipoproteins in lipoprotein density lasses The most harateristi ompositional differenes in VLDL, IDL and LDL between and ontrols relate to the relative ontents of holesterol esters, TG and apolipoproteins C-II and C-III. In VLDL, had a signifiantly higher perentage of holesterol esters (36.4 ±1.6 vs 23.1 ± 1.3%; /><.1) and a lower perentage of TG (53.1 ±11.3 vs 66.9±15.2%; P<.5) than ontrols. Also in IDL, the perentage ontent of holesterol ester was signifiantly higher (54.3 ±9. vs 41.3 ± 1.3%; / ) <.1) and that of TG signifiantly lower ( vs 51.5± 16.3%; /><.1) in patients than ontrols. In ontrast, there was no differene between and ontrols in the relative ontents of free holesterol in VLDL and IDL. The perentages 67 of individal netral lipids in LDL of were similar to those of ontrols, exept for a signifiantly higher relative ontent of TG (21.3 ±6. vs 15.1 ±7.4%; / ) <.1) and a lower relative ontent of holesterol esters (68.2 ±4.4 vs 69.6 ±7.1%; P<.5) in HTG patients. There was no signifiant differene in the apolipoprotein omposition of VLDL between patients and ontrols, althogh the relative ontents of apolipoproteins B, C-III and E tended to be slightly higher in the former than in the latter sbjets. However, in IDL of the perentages of apoc-ii (3.3 ± 1.6 vs 1.3±1.1%; P<.1) and apoc-iii (13.3±5.3 vs 5.6 ±2.4%; P<.1) were signifiantly higher than in ontrols with insignifiant hanges in the relative ontents of other apolipoproteins; these ompositional differenes orred in both NTG and HTG patients. The LDL omposition of was also haraterized by signifiantly higher perentages of apoc-i ( vs 1.3±.8%; / ) <.5), apoc-ii 1.3 ±.6 vs ±.2%; / > <.1) and apoc-iii (6.1 ±3. vs %; P<.1) than that of ontrol sbjets. As in IDL, these differenes were observed in both NTG and HTG patients. There were no signifiant differenes in the proportions of LDL-apoB and apoe between patients and ontrols. The netral lipid omposition of HDL did not differ between patients and ontrols. Both the NTG and HTG patients had signifiantly reded relative ontents of apoa-i (59.6±4.9 and vs %; P<.1 and P<.5 respetively) and inreased perentages of apoa-ii (28.9 ±4.1 and 31.3 ±9.7 vs 24.3 ±2.4%; / > <.5) and apob (3.4±2.1 and 4.8 ±2.6 vs.8 ±1.4%; / > <.1). However, there were no ompositional differenes in apoc-peptides and apoe between patients and ontrols. Disssion Reslts of this stdy have shown that eah of the major lipoprotein density lasses from predialysis patients with CRF is haraterized by abnormal onentration, distribtion, and omposition of at least some lipid and apolipoprotein onstitents. By inlding both the lipid and apolipoprotein measrements, this stdy extends previos observations whih had been mainly onerned with the abnormal lipid profiles of lipoprotein density lasses in on maintenane haemodialysis [1-12]. Present findings have demonstrated that lipid abnormalities of lipoprotein density lasses from predialysis are very similar to those fond in dialysed patients. Additionally, they have established that altered apolipoprotein onentration profiles of lipoprotein density lasses are harateristi of predialyti CRF patients irrespetive of their plasma lipid onentrations [2,4]. Bease of a negative orrelation between GFR vales and TG vales, one may onlde that patients with advaned renal failre resemble more losely hypertriglyeridaemi than normotriglyerida-

6 68 emi patients regarding their levels of lipids and apolipoproteins in density lasses and vie versa. It appears that one of the main nderlying reasons for the omposition abberation of all lipoprotein density lasses in is the amlation of omplex apob-ontaining lipoproteins partially depleted of TG and enrihed with holesterol esters, apoc-peptides and apoe [13,14]. This ors in HTG patients in an exaggerated form. Althogh present to varying extent in VLDL and LDL, these omplex apob-ontaining lipoproteins amlate mainly in the IDL density (Table 3; Figre 1) [12,15-2]. The most harateristi ompositional featre of these lipoproteins is that their relative and absolte ontents of apoc-iii are greater than those of apoc-i, apoc-ii and apoe in NTG and, espeially, HTG patients (Table 3; Figre 2). It is qite possible that this ompositional abnormality is mainly responsible for the inreased prevalene of the so-alled late pre-beta or broad-beta lipoproteins in the eletrophoreti pattern of normo- and hypertriglyeridaemi [15,17,18,21]. Reslts from this and other laboratories have established that major lipoprotein density lasses do not onsist of hemially and metabolially homogeneos lipid-protein omplexes, bt represent mixtres of polydisperse lipoprotein families of partiles haraterized by similar density properties bt distint apolipoprotein omposition [22]. The determination of apobontaining lipoprotein families in whole plasma and VLDL, IDL, and LDL of predialysis patients with CRF has shown that in omparison with ontrols the inreased onentration and abnormal omposition of apob-ontaining lipoproteins are mainly de to elevated levels of triglyeride-rih lipoprotein B:C (LP-B:C) and lipoprotein B:C:E (LP-B:C:E) with no signifiant hange in the levels of holesterol-rih lipoprotein B (LP-B) [23]. What are the potential metaboli and pathogeneti onseqenes of inreased onentrations of LP-B:C:E and, espeially, LP-B:C partiles? It has been shown that LP-B:C and LP-B:C:E partiles are effiient sbstrates for lipoprotein lipase [24]. However, the reded ativities of lipoprotein lipase and hepati trigjyeride lipase and/or the presene of an inhibitor of lipoprotein lipase in may trigger an ineffiient lipolyti degradation of LP-B:C and LP-B:C:E partiles and ase their amlation in partially delipidized form [ 1 ]. Partial or total inhibition of LP-B:C:E and LP-B:C binding and ptake by LDL reeptor [25] may frther ontribte to their amlation in irlation. These metaboli abnormalities may be attribted to the inreased onentrations of apoc- III shown to be a potential inhibitor of both lipoprotein lipase ativity [26] and lipoprotein binding to LDL reeptor [25,27]. ApoE on the other hand promotes the hepati ptake of TG-rih lipoproteins (27). The inreased apoc-iii:e ratios in indiate the extent of the inhibition of TG-rih lipoprotein ptake. However, sh lipoprotein partiles may bind to marophages by reeptors distint from the LDL P.-O. Attman et al. reeptor [28]. There is inreasing evidene from linial trials [29-34] sggesting that partially delipidized triglyeride-rih lipoproteins ('remnant lipoproteins') may have atherogeni potential eqal to or greater than that of holesterol-rih lipoproteins. Ths, inreased onentrations of apoc-iii-enrihed lipoproteins of IDL size may be onsidered as a signifiant risk fator for oronary artery disease so prevalent in. Moreover there is some evidene that inreased onentrations of these lipoprotein partiles may also ontribte to the progression of renal insffiieny [35]. Reded onentrations of apoa-i and apoa-ii may be either a onseqene of abnormal amlation of partially delipidized omplex apob-ontaining lipoproteins and/or a separate metaboli abberation [12,27]. Reent findings sggest that the reded levels of these two apolipoproteins are ased by reded formation of lipoprotein A-LA-II (LP-A-LA-II) rather than lipoprotein A-I (LP-A-I) [36]. Inreased onentration of apob in HDL may be de either to elevated levels of LP-B partiles of higher density and/or lipoprotein (a) previosly reported to be inreased in patients with CRF [13,37]. In smmary, the lipid transport in CRF is haraterized by abnormalities in the metabolism of triglyeriderih lipoproteins of lower densities and of HDL, both of whih may be manifested at the early stages of renal insffiieny and may not be refleted in elevated plasma lipid onentrations. There is some indiation that the former abnormality may be de to the amlation of a partially metabolized TG-rih lipoprotein of hepati and/or intestinal origin (remnant lipoprotein), the strtral make-p of whih prevents its normal degradation and removal bt presmably enhanes its atherogeni potential. The natre and signifiane of the metaboli abnormality of HDL remains obsre exept for the generalization that reded onentration of these lipoprotein partiles rede their non-atherogeni apaity. The prognosti signifiane of these metaboli abnormalities and their effet on progression of renal disease and its vaslar manifestations remain to be explored. Aknowledgements. This stdy was spported by the Swedish Medial Researh Conil (B A), Henning & Johan Throne Hoists Stiftelse far Vetenskaplig Forskning, University of GSteborg, Riksforbndet far Njrsjka, Njrsjkas FOrning i Vastsverige, Sweden, and by a grant (HR1-5) from the Oklahoma Center for Advanement of Siene and Tehnology, State of Oklahoma, USA, and by the resores of the Oklahoma Medial Researh Fondation. Referenes 1. Attman P-O, Samelsson O, Alapovi P. Lipoprotein metabolism and renal failre. Am J Kidney Dis 1993; 21: Samelsson O, Attman P-O, Knight-Gibson C et al. Lipoprotein abnormalities withot hyperlipidaemia in moderate renal insffiieny. Nephrol Dial Transplant 1994; 9: Grtzmaher P, M3rz W, Peshke B, Gross W, Shoeppe W. Lipoproteins and apolipoproteins dring the progression of hroni renal disease. Nephron 1988; 5:

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