Effect of increasing serum albumin on serum lipoprotein(a) concentration in patients receiving CAPD

Effect of Increasing Serum Albumin on Serum Lipoprotein(a) Concentration in Patients Receiving CAPD Won Seok Yang, MD, Won Ki Min, MD, Jung Sik Park, MD, and Soon Bae Kim, MD 0 Lipoprotein(a) [Lp(a)], an independent risk factor for atherosclerotic cardiovascular disease in the general population, is known to be elevated in patients with renal disease accompanied by hypoalbuminemia such as nephrotic syndrome and end-stage renal disease. In this study, the role of hypoalbuminemia in the elevation of serum Lp(a) was investigated in 20 continuous ambulatory peritoneal dialysis (CAPD) patients with serum albumin below 3.5 g/dL. The patients were divided into two groups. In group 1 (n = lo), fasting serum Lp(a) and albumin were measured before, after repeated infusion of 20% albumin 100 mL three times per week for 2 weeks, and 4 weeks after withdrawal of albumin infusion. In group 2 (n = lo), serum albumin and Lp(a) were measured similarly without albumin infusion. C-reactive protein was monitored in both group as an indicator of acute-phase reactant. Serum Lp(a) was also measured in 20 age- and sex-matched normal controls. Apolipoprotein(a) [ape(a)] phenotype was determined in all the subjects. CAPD patients as a whole (n = 20; median, 70.2 mg/dL; interquartile range, 45.0 to 88.2 mg/dL) had higher serum Lp(a) than normal controls (n = 20; median, 9.9 mg/dL; interquartile range, 2.4 to 24.3 mg/dL) (P < O.OOOl), although the distribution of ape(a) phenotype was similar. Serum albumin in group 1 increased from 2.8 t 0.5 g/dL to 3.5 5 0.0 g/dL (P < O.ooo5) at the end of repeated infusion of albumin, whereas serum Lp(a) decreased from 73.7 mg/dL (range, 43.2 to 89.0 mg/dL) to 25.0 mg/dL (range, 10.7 to 71.7 mg/dL) (P < 0.01). Four weeks after withdrawal of albumin infusion, serum albumin decreased again to 2.9 -r- 0.5 g/dL (P < O.OOl), whereas serum Lp(a) increased to 85.2 mg/dL (range, 43.3 to 108.0 mg/dL) (P < 0.05). Serum albumin in group 2 was 2.8 + 0.8 g/dL, 3.0 5 0.4 g/dL, and 2.9 + 0.7 g/dL, respectively. The change of serum Lp(a) was not significant (87.0 mg/dL [range, 48.8 to 84.8 mg/dL], 82.8 mg/dL [range, 45.1 to 81.0 mg/dL], and 83.0 mg/dL [range, 44.7 to 74.0 mg/dL]). C-reactive protein was stable during the study period in both groups. These findings support the hypothesis that hypoalbuminemia is one of the important trigger factors in the elevation of serum Lp(a) in CAPD patients. 0 1997

by the

National

Kidney

Foundation,

INDEX WORDS: Albumin; apolipoprotein(a) low-density lipoprotein cholesterol.

Inc.

phenotype;

L

apolipoprotein

B; end-stage

renal disease;

lipoprotein(a);

netic factors. However, the factor(s) or mechanism(s) responsible for the increased serum Lp(a) in these patients has not been elucidated. In a previous study,‘* we found a significant inverse relationship between serum albumin and Lp(a) concentrations in ESRD patients on hemodialysis; this also was demonstrated in a multicenter study13 of a large number of hemodialysis and continuous ambulatory peritoneal dialysis (CAPD) patients. However, the possible cause-effect relationship between these two parameters has not been investigated. In this study, to evaluate the role of hypoal-

IPOPROTEIN(A) [Lp(a)], a low-density lipoprotein-like particle in which apolipoprotein(a) [ape(a)] is linked to apo BlOO by a disulfide bridge,’ is an independent risk factor for atherosclerotic cardiovascular disease.* High serum concentration of Lp(a) has been found to be associated with an increased risk of coronary artery disease, stroke, and saphenous vein bypass graft stenosis. 3-5The serum Lp(a) levels are distributed widely, ranging from less than 1.0 mg/ dL to greater than 100 mg/dL, and are influenced by genetically determined ape(a) polymorphism, ie, there is an inverse relationship between serum Lp(a) concentration and the size of ape(a) isoform6 The results of several studies7-9 have demonstrated that the serum Lp(a) level was elevated approximately twofold to threefold in end-stage renal disease (ESRD) patients compared with normal subjects. The analysis of frequency distribution of ape(a) isoforms did not show a significant difference between the two groups,‘o311 indicating that the elevation of serum Lp(a) level in ESRD patients is caused by other factors related to renal insufficiency or dialysis rather than ge-

From the Departments of Internal Medicine and Clinical Pathology, Asan Medical Center, College of Medicine, University of Ulsan, Seoul, Korea, Received October 18, 1996; accepted in revised form June 13, 1997. Supported by the Asan Institute for Life Sciences (S.B. Kim) and the Ministry of Health and Welfare (J.S. Park). Address reprint requests to Soon Bae Kim, MD, Department of Internal Medicine, College of Medicine, University of Ulsan, Song-Pa PO Box 145, Seoul 138-736, Korea. 0 1997 by the National Kidney Foundation, Inc. 0272-6386/97/3004-0010$3.00/O

American

1997:

Journal

of Kidney

Diseases,

Vol 30, No 4 (October),

pp 507-513

507

508

YANG

buminemia in the elevation of serum Lp(a), we measured serum Lp(a) before, at the end, and after withdrawal of repeated infusions of albumin in CAPD patients with hypoalbuminemia. MATERIALS

AND

METHODS

Subjects Twenty patients with ESRD (13 men and seven women with a mean age of 58 + 12 [SD] years) who had been receiving CAPD and who had a serum albumin level less than 3.5 g/dL were included in this study after their informed consent was obtained. The underlying renal diseases were diabetic nephropathy (n = 13), chronic glomerulonephritis (n = 2). lupus nephritis (n = l), hypertensive nephrosclerosis (n = I), and small kidneys of unknown etiology (n = 3). Patients with liver cirrhosis or those taking corticosteroids or lipid-lowering drugs were excluded from this study. The median duration of CAPD before this study was 4 months (range, 1 to 29 months). Peritoneal dialysis was performed with four daily exchanges of 2-L solutions containing 1.5% or 4.25% glucose, depending on the need for ultrafiltration. For comparison of basal lipid values, 20 age- and sexmatched normal subjects (13 men and seven women with a mean age of 57 2 12 [SD] years) were selected among normal persons who visited Asan Medical Center for routine examinations.

Infusion of Albumin The CAPD patients were divided into two groups. Group 1 (n = 10) received repeated infusions of albumin, and group 2 (n = 10) were received no infusions of albumin. One hundred milliliters of 20% albumin solution was administrated three times per week for 2 weeks in the group 1 patients. Serum albumin, hematocrit, blood urea nitrogen (BUN), creatinine, lipid parameters including Lp(a), and C-reactive protein were measured before, at the end of repeated infusion of albumin, and after 4 weeks of the washout period. In group 2, the same parameters were measured similarly three times with no infusion of albumin. The individual regimens of dialysis and medications were maintained without significant change during the study period in every patient. Three patients in group 1 and four patients in group 2 who had been on recombinant erythropoietin therapy before this study received their maintenance dose.

Analysis of Lipoprotein

and Other Parameters

Blood samples were obtained after an overnight fast. Serum cholesterol and triglyceride were measured by enzymatic methods using a Hitachi 736-40 autoanalyzer (Hitachi Ltd, Tokyo, Japan). High-density lipoprotein cholesterol (HDLC) was analyzed enzymatically after precipitation of other lipoproteins with heparin and MnC& . The low-density lipoprotein cholesterol (LDLC) level was calculated by the Friedewald formula: LDLC = total cholesterol - HDLC - triglyceride/ 5.14Apolipoprotein A-I (apo A-I) and apolipoprotein B (apo B) were measured by imrnunonephelometry using a Beckman Array Protein System Analyzer (Beckman Instruments, Brea, CA). Serum albumin, BUN, and serum creatinine were mea-

ET AL

sured by the bromcresol green method, the urease method, and the Jaffe method, respectively, using a Hitachi 736-40 autoanalyzer. Hematocrit was also measured. C-reactive protein was measured by nephelometty. Serum samples for the Lp(a) analysis were stored at -70°C for assay in batches, which was performed within 1 week. Lp(a) was measured by sandwich enzyme-linked immunosorbent assay using a monospecific, polyclonal anti-ape(a) antibody and a second monospecific, monovalent anti-apo (a) antibody coupled with a peroxidase (Immunozym Lp(a); Immuno AG, Vienna, Austria). The intra-assay and interassay coefficients of variation were 4.0% and 9.0%, respectively.

Ape(a) Isoform Determination Ape(a) phenotype was determined by immunoblotting technique using the commercially available kits, including the PhastSystem (Pharmacia Biotech, Uppsala, Sweden) and the Lp(a) phenotype kit (Immuno AG). Briefly, the serum sample was reduced with 6% sodium dodecyl sulfate (SDS), 5% glycerol, 0.06 mol/L Tris/HCl, 0.002% bromophenol blue, and 2-mercaptoethanol. The reduced specimens were applied to sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) in a 4% to 15% gradient polyacrylamide gel. The separated proteins were transferred to a nitrocellulose membrane and then incubated with sheep antihuman Lp(a) as the first antibody and rabbit anti-sheep immunoglobulin G(Fc)-alkaline phosphatase conjugate as the second antibody. Subsequent treatment with substrate visualized the Lp(a) bands. Ape(a) isoforms were categorized into F, B, Sl, S2, S3, S4, and S5 according to Utermann’s standardized nomenclature”; the number of kringle IV repeats for each of these isoforms is 11 to 13, 14 to 16, 17 to 19, 20 to 22, 23 to 25, 26 to 28, and 29 to 42, respectively. To identify the position of the Lp(a) bands of the serum specimen, two standard samples were included in each gel. The ape(a) phenotype standard consisted of five known isoforms: B, Sl, S3, S4, and S5, whose kringle IV numbers were 14, 19, 23, 27, and 35, respectively. Those bands that migrated &35 were assigned as S5.

Statistical Analysis The values of Lp(a) are presented as the median and interquartile range. Other lipid and chemical parameters are presented as mean values ? SD. Comparisons of the baseline values between the CAPD patients and the normal subjects were performed by Mann-Whitney U test or Student’s r-test, as appropriate. The changes in serum Lp(a) or albumin with repeated infusion of albumin or after withdrawal of albumin administration were evaluated by the Wilcoxon signed-rank test or the paired r-test. P < 0.05 was considered statistically significant. RESULTS

Serum Lipoproteins in CAPD Patients and Normal Subjects The serum albumin levels of CAPD patients and normal subjects were 2.7 k 0.5 g/dL and 4.4

ALBUMIN AND LIPOPROTEIN(A) IN CAPD PATIENTS Table 1. Lp(a) Level and ape(a) Phenotype Patients and Normal Subjects

No. Age W Sex (M:F) Albumin (g/dL) Cholesterol (mg/dL) Triglyceride (mg/dL) HDLC (mg/dL) LDLC (mg/dL) Apo A-l (mg/dL) Apo 6 (mg/dL) LP(4 O-wW Ape(a) phenotype BlS2 SlS5 s3 s3s5 s4 s4s4 s4s5 s5 s5s5

of CAPD

CAPD Patients

Normal Subjects

20 58 t 12 13:7 2.7 t 0.5 196 t 54 177 2 123 39% 14 122 t 43 107 t 29 120 t 51 70.2 (45.0-86.2)t

20 57 2 12 13:7 4.4 k 0.4 178 ? 27 152 2 94 452 10 103 2 27 134 ? 23 115 2 26 9.9 (2.4-24.3)

1 1 2 2 4 1 3 7

1

1 4 5 5 3

* P < 0.005 compared with normal subjects. T P < 0.0001 compared with normal subjects.

+ 0.4 g/dL, respectively (Table 1). The serum Lp(a) concentration of CAPD patients (n = 20; 70.2 mg/dL; range, 45.0 to 86.2 mg/dL) was significantly elevated compared with that of normal subjects (n = 20; 9.9 mg/dL range, 2.4 to 24.3 mg/dL) (P < 0.0001). Both CAPD patients and normal subjects had ape(a) phenotypes mainly of high molecular weight, such as S3, S4, and S5. The distribution of ape(a) phenotype was not different between the two groups. The difference in total cholesterol, HDLC, triglyceride, LDLC, and apo B between the two groups was not significant, but Apo AI was significantly lower in CAPD patients. Effect of Increasing Serum Albumin on Serum Lipoproteins The clinical characteristics of groups 1 and 2 are shown in Table 2. The changes of serum albumin and lipoproteins including Lp(a) before, after repeated infusion of albumin, and after withdrawal of albumin are summarized in Table 3. In group 1, serum albumin increased from 2.6

509

2 0.5 g/dL to 3.5 2 0.6 g/dL (P < 0.0005) at the end of repeated infusion of albumin, whereas serum Lp(a) decreased from 73.7 mg/dL (range, 43.2 to 89.0 mg/dL) to 25.6 mg/dL (range, 10.7 to 71.7 mg/dL) (P < 0.01). Four weeks after withdrawal of albumin infusion, serum albumin decreased again to 2.9 + 0.5 g/dL (P < O.OOl), whereas serum Lp(a) increased to 65.2 mg/dL (range, 43.3 to 106.0 mg/dL) (P < 0.05) (Fig 1). The changes of total cholesterol, LDLC, and apo B were not statistically significant, although there was a tendency to decrease or increase in response to infusion or withdrawal of albumin, respectively. No change was seen in HDLC and apo A-I. During the period of infusion of albumin, hematocrit decreased from 26.7% + 4.4% to 24.4% + 4.1% (P < 0.05). There was no correlation between the decrease in serum Lp(a) and the decrease in hematocrit. Serum Lp(a) corrected with the change of hematocrit for possible hemodilution was 30.6 mg/dL (range, 13.1 to 78.6 mg/dL) at the end of repeated infusion of albumin (P < 0.05 compared with baseline) and 68.8 mg/dL (range, 50.1 to 115.8 mg/dL) 4 weeks after withdrawal of albumin infusion (P < 0.05 compared with week 2).

Table 2. Clinical and Laboratory Characteristics of CAPD Patients Group

No. Age W

Sex (M:F) Duration of CAPD 0-W Underlying renal disease Diabetes Glomerulonephritis Hypertensive Lupus nephritis Unknown Albumin (g/dL) Wa) Owl) Ape(a) phenotype 81 S2 s3 s3s5 s4 s4s4 s4s5 s5

1

10 57 2 10 7:3

Group

10 582 15 6:4

4 (l-25)

3 (l-29)

7 1

6 1

1 2.6 2 0.5 73.7 (43.2-89.0)

2

2 2.8 2 0.6 67.0 (46.8-84.8)

1 1 2

1 1 2

3 2

5

510

YANG Table

3. The

Changes

of Lp(a)

and

Other

Lipoproteins

in CAPD

Patients

With

or Without

Group 1 Baseline

Albumin (g/dL) Hematocrit (%) BUN (mg/dL) Creatinine (mg/dL) Cholesterol (mg/dL) Triglyceride (mg/dL) HDLC (mg/dL) LDLC (mg/dL) Apo A-l (mg/dL) Apo B (mg/dL) b(a) (mg/dL) P TP $ P $ P 11P

l

< < < < <

2.6 + 0.5 26.7 t 4.4 50 k 20 7.0 2 4.4 199 k 68 204 2 133 34 e-14 124 c 53

962

2.9 2 ? k ? rt 159 -+ 38211 134 2 99 2 130 2

24.5 52 8.0 204

4.2 55

110 12

lOOk 51 97 2 23 107 2 34

19

135 t 58 73.7 (43.2-89.0)

Week 6

0.6" 4.1$

25.65 (10.7-71.7)

0.5t 2.8

11 3.7 57

94

50 23 43 65.211 (43.3-106.0)

Baseline

Week 2

2.8 k 0.6 26.8 2 3.8 52% 17 7.9 t 2.8

193 + 150 k 44 k 120 2

40

114 14 33 1182 34 105k 40 67.0 (46.8-84.8)

3.0 26.6 51 8.2 188 115 48 116 130 105 62.8

L 2 2 -t T + f k e 2

0.4

2.9

20 3.3 36 86 14 32 33 30 (45.1-81.0)

Week 6

2.9 + 0.7 25.3 -c 52 -c 8.8 2 173232 148 -c 432

5.2 20 3.6

134

17 20 117? 28 102 + 33 63.0 (44.7-74.0)

lOOk

0.0005 compared with baseline value. 0.001 compared with week 2. 0.05 compared with baseline value. 0.01 compared with baseline value. 0.05 compared with week 2.

In group 2, serum albumin at baseline, week 2, and week 6 was 2.8 2 0.6 g/dL, 3.0 + 0.4 gl dL, and 2.9 + 0.7 g/dL, respectively. The change of serum Lp(a) was not significant: 67.0 mg/dL (range, 46.8 to 84.8 mg/dL) at baseline, 62.8 mg/ dL (range, 45.1 to 81.0 mg/dL) at week 2, and 63.0 mg/dL (range, 44.7 to 74.0 mg/dL) at week 6. Other lipoproteins, including apolipoproteins and hematocrit, also showed no significant changes. The changes of BUN and creatinine were not significant during the study period in both groups (Table 3). The median C-reactive protein at baseline, week 2, and week 6 was 0.7 mg/dL (range, < 0.2 to 3.8 mg/dL), 1.2 mg/dL (range, < 0.2 to 3.7 mg/dL), and 0.8 mg/dL (range, < 0.2 to 5.6 mg/dL) in group 1 and 0.4 mg/dL (range, < 0.2 to 4.0 mg/dL), 0.5 mg/dL (range, < 0.2 to 2.8 mg/dL), and 1.7 mg/dL (range, < 0.2 to 3.9 mg/dL) in group 2, respectively.

27.0 -

200 = s g 0 4

Infusion

Group 2

Week 2

3.5 + 24.4 T 49+17 7.7 ? 171 + 173 f 36 k

Albumin

ET AL

wo-

160 -

140 -

120 -

100 -

60 -

60 -

40 -

DISCUSSION

20 -

0

week2

Group

week6

I

0

week2

Group

week6

II

Fig 1. Changes of serum Lp(a) concentration CAPD patients with (group 1) and without (group repeated infusion of albumin for 2 weeks. *Infusion albumin.

in 2) of

Serum Lp(a) was significantly elevated in CARD patients with hypoalbuminemia. Repeated infusions of albumin resulted in a marked decrease in serum Lp(a) level. Furthermore, with withdrawal of albumin infusion, serum Lp(a) concentrations rebounded toward baseline values. Infusion of albumin may cause an increase in plasma volume, which results in the dilution of serum lipoprotein concentrations. Although the

ALBUMIN AND LIPOPROTEIN(A) IN CAPD PATIENTS

plasma volume was not measured in this study, the changes of hematocrit that might reflect those of plasma volume revealed a small reduction with infusion of albumin. After correction with hematocrit, however, the changes in serum Lp(a) were still significant. In addition, considering the prominent change, the decrease in serum Lp(a) cannot be explained by the dilutional effect alone. Little is known about the mechanism of elevation of serum Lp(a) in CAPD patients. Proteinuria has been suggested as a surrogate marker for the loss of unidentified liporegulatory substance(s) in patients with nephrotic syndrome.r6 In patients with proteinuria, the reduction of proteinuria by administration of angiotensin-converting enzyme inhibitor or a nonsteroidal anti-inflammatory drug was associated with a decrease in serum Lp(a) concentration.“~‘* Angiotensin-converting enzyme inhibitor, however, did not have a significant effect on serum Lp(a) level in patients who did not respond in terms of proteinuria.” Thus, urinary loss of unidentified liporegulatory substance(s) also can be a possible cause for the elevation of serum Lp(a) in patients with proteinuria. Likewise, this could be the case in CAPD patients in view of the significant loss of protein into dialysate, usually exceeding more than 5 g/d.l’ A positive correlation between the amount of total protein loss or albumin clearance and serum Lp(a) concentration was also reported in CAPD patients.” It may be possible that infusion of albumin decreases the loss of such liporegulatory substance(s) into dialysate fluid. In a recent stndy,2o however, it was found that infusion of albumin in CAPD patients increases peritoneal albumin transport as well as solute clearance. In addition, infusion of albumin in patients with proteinuria caused increased fractional excretions of immunoglobulin G (IgG), transfetin, and alburnin2’ Therefore, the decrease in serum Lp(a) with repeated infusion of albumin in this study does not seem to be explained by the reduced loss of unidentified liporegulatory substance(s) into dialysate fluid or urine. Elevated serum Lp(a) is a common finding in patients with renal disease accompanied by hypoalbuminemia, such as nephrotic syndrome,22 and in ESRD patients receiving hemodialysis10V11’23or CAPD.9,23 A significant inverse correlation was also found between these two parameters in studies 12.13of larger numbers of hemodialysis and

511

CAPD patients. The findings of marked reduction of serum Lp(a) with infusion of albumin and elevation of serum Lp(a) toward baseline with withdrawal of albumin infusion in this study suggest that hypoalbuminemia is involved in the pathogenesis of the increased serum Lp(a) of CAPD patients. The mechanism whereby hypoalbuminemia leads to increased serum Lp(a) is not yet clear. With the findings of previous studies, however, several speculative mechanisms can be considered. First, hypoalbuminemia induces decreased serum oncotic pressure, which is known to stimulate hepatic synthesis of albumin and other liverderived proteins, including apolipoproteins.24925 Ape(a), which is the apolipoprotein unique to Lp(a), is also synthesized mainly in the liver.26 Likewise, low serum albumin might trigger the increased hepatic synthesis of APO(a).’ Second, several studies27,28 using Hep G2 cells have shown that free fatty acids stimulate apo B secretion into the culture medium. However, the stimulatory effect was manifested only in a low albumin concentration of the media and was suppressed by increased concentration of albumin.29 In a similar study3’ using hepatocyte from normal human donors, the secretion of ape(a) was also found to increase twofold to threefold when the cells were incubated with oleate albumin complex in a high molar ratio (4:l). Therefore, in the presence of hypoalbuminemia, the relative increase in free fatty acid on albumin may lead to increased secretion of ape(a) from the hepatocyte. Third, the impaired catabolism of Lp(a) in the presence of hypoalbuminemia is also conceivable. Although repeated infusions of albumin resulted in significant reductions in the serum Lp(a) levels of our patients, the relative changes of serum Lp(a) in relation to those of albumin concentration were different among the patients. The reason for such different responses is not clear, but this may be the result of the complex interactions with other unknown regulatory factors in the metabolism of Lp(a). Lp(a) has been shown to respond as an acutephase reactant in a few studies.31V32In this study, C-reactive protein was also monitored as an index of acute-phase reactant, and the changes of C-reactive protein during the study period were not significant, suggesting that the changes in

YANG

512

serum Lp(a) of our patients were not the result of acute-phase response. Of the other lipid parameters, the changes of total cholesterol, LDLC, and apo B also showed the same tendency with that of Lp(a) in response to infusion or withdrawal of albumin, although these were not statistically significant. Further study with a larger group of patients will be required to evaluate the effects of increasing serum albumin on these lipid or lipoproteins. In conclusion, the results of this study support the hypothesis that hypoalbuminemia is one of the important trigger factors for the elevation of serum Lp(a) in CAPD patients. ACKNOWLEDGMENT The authors thank Chun Hee Kim for her technical assistance. REFERENCES 1. Berg K: A new serum type system in man-The Lp system. Acta Path01 Microbial Stand 59:369-382, 1963 2. Rader DJ, Brewer HB: Lipoprotein (a)-Clinical approach to a unique atherogenic lipoprotein. JAMA 267:11091112, 1992 3. Schaefer EJ, Lamon-Fava S, Jenner JL, McNamara JR, Grdovas JM, Davis CE, Abolafia JM, Lippel K, Levy RI: Lipoprotein(a) levels and risk of coronary heart disease in men. The lipid research clinics coronary primary prevention trial. JAMA 271:999-1003, 1994 4. Zenker G, Koltringer P, Bone G, Niederkom K, Pfeiffer K, Jurgens G: Lipoprotein(a) as a strong indicator for cerebrovascular disease. Stroke 17:942-945, 1986 5. Hoff HF, Beek GJ, Skibinski CI, Jurgens G, O’Neil J, Kramer J, Lytle B: Serum Lp(a) level as a predictor of vein gratt stenosis after coronary artery bypass surgery in patients. Circulation 77:1238-1244, 1988 6. Utetmamt G: The mysteries of lipoprotein(a). Science 246:904-910, 1989 7. Parra I-U, Mezdour H, Cachera C, Dracon M, Tacquet A, Fruchart JC: Lp(a) lipoprotein in patients with chronic renal failure treated by hemodialysis. Clin Chem 33:721, 1987 (letter) 8. Parsy D, Dracon M, Cachera C, Parra HJ, Vanhoutte G, Tacquet A, Fmchart JC: Lipoprotein abnormalities in chronic hemodialysis patients. Nephrol Dial Transplant 351-56, 1988 9. Shoji T, Nishizawa Y, Nishitani H, Yamakawa M, Morii H: High serum lipoprotein(a) concentrations in uremic patients treated with continuous ambulatory peritoneal dialysis. Clin Nephrol 38:271-276, 1992 10. Dieplinger H, Lackner C, Kronenberg F, Sandholzer C, Lhotta K, Hoppichler F, Graf H, Konig P: Elevated plasma concentrations of lipoprotein(a) in patients with end-stage renal disease are not related to the size polymorphism of apolipoprotein(a). J Clin Invest 91:397-401, 1993 11. Hirata K, Kikuchi S, Saku K, Jimi S, Zhang B, Naito S, Hamaguchi H, Arakawa K: Apolipoprotein(a) phenotypes

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and serum lipoprotein(a) levels in maintenance hemodialysis patients with/without diabetes mellitus. Kidney Int 44: 10621070, 1993 12. Yang WS, Kim SB, Min WK, Park S, Lee MS, Park JS: Atherogenic lipid profile and lipoprotein(a) in relation to serum albumin in haemodialysis patients. Nephrol Dial Transplant 10:1668-1671, 1995 13. Kronenberg F, Kijnig P, Neyer U, Auinger M, Pribasnig A, Lang U, Reitinger J, Pinter G, Utermann G, Dieplinger H: Multicenter study of lipoprotein(a) and apolipoprotein(a) phenotypes in patients with end-stage renal disease treated by hemodialysis or continuous ambulatory peritoneal dialysis. J Am Sot Nephrol6:110-120, 1995 14. Friedwald WT, Levy RI, Fredrickson DS: Estimation of concentration of low density lipoprotein cholesterol in plasma without use of the ultracentrifuge. Clin Chem 18:449502, 1972 15. Utermann G: Lipoprotein(a), in Striver CR, Beaudet AL, Sly WS, Valle D (eds): The Metabolic and Molecular Bases of Inherited Disease. New York, NY, McGraw-Hill, 1995, pp 1887-1912 16. Davis RW, Staprans I, Hutchinson FN, Kaysen GA: Proteinuria, not altered albumin metabolism, affects hyperlipidemia in the nephrotic rat. J Clin Invest 86:600-605, 1990 17. Keilani T, Schleuter WA, Levin ML, Gatlle DC: Improvement of lipid abnormalities associated with proteinuria using fosinopril, an angiotensin-converting enzyme inhibitor. Ann Intern Med 118:246-254, 1993 18. Gansevoort RT, Heeg JE, Dikkeschei FD, de Zeeuw D, de Jong PE, Dullaart RPF: Symptomatic antiproteinuric treatment decreases serum lipoprotein(a) concentration in patients with glomerular proteinuria. Nephrol Dial Transplant 9:244-250, 1994 19. Wanner C, Battens W, Walz G, Nauck M, Schollmeyer P: Protein loss and genetic polymorphism of apolipoprotein(a) modulate serum lipoprotein(a) in CAPD patients. Nephrol Dial Transplant 10:75-81, 1995 20. Worrall J, Macdougall IC, Raine AEG, Dawnay A: Effect of acutely raising the serum albumin on peritoneal transport and ultrafiltration in CAPD patients. J Am Sot Nephrol 6:568, 1995 (abstr) 21. Branten AJW, Wetzels JIM: The effect of albumin infusion on the urinary excretion of b2microglobulin in patients with proteinuria. J Am Sot Nephrol 7:1329, 1996 (abstr) 22. Wanner C, Rader D, Bartens W, Kramer J, Brewer HB, Schollmeyer P, Wieland H: Elevated plasma lipoprotein(a) in patients with the nephrotic syndrome. Ann Intern Med 119:263-269, 1993 23. Webb AT, Reaveley DA, O’Donnell M, O’Connor B, Seed M, Brown EA: Lipoprotein(a) in patients on maintenance haemodialysis and continuous ambulatory peritoneal dialysis. Nephrol Dial Transplant 8:609-613, 1993 24. Baxter JH, Goodman HC, Allen JC: Effects of infusion of serum albumin on serum lipids and lipoproteins in nephrosis. J Clin Invest 40:490-498, 1961 25. Yamauchi A, Fukuhara Y, Yamamoto S, Yano F, Takenaka M, Imai E, Noguchi T, Tanaka T, Kamada T, Ueda N: Oncotic pressure regulates gene transcriptions of albumin and apolipoprotein B in cultured rat hepatoma cells. Am J Physiol 263:C397-C404, 1992

ALBUMIN

AND

LIPOPROTEIN(A)

IN CAPD

PATIENTS

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