Original Article
Abnormalities of Lipoprotein Metabolism in Patients with the Nephrotic Syndrome
N Engl J Med 1990; 323:579-584August 30, 1990
- Abstract
- Abstract
Background and Methods.
Patients with the nephrotic syndrome characteristically have multiple abnormalities of lipoprotein metabolism, but the cause and exact nature of these abnormalities are uncertain. In this study, we measured serum lipids and apoproteins in 57 patients with the nephrotic syndrome. We also determined the kinetic indexes of low-density lipoprotein (LDL) metabolism in six patients, and again in three of the six after recovery.
Results.
The patients with the nephrotic syndrome had elevated serum concentrations of cholesterol, triglycerides, and phospholipids, which were confined to the lipoproteins containing apoprotein B. The serum concentrations of high-density lipoproteins and the associated A-I and A-II apoproteins were similar in the patients with the nephrotic syndrome and normal subjects. The relative proportions of lipids and their positive association with the increased serum concentrations of apoproteins B, C-II, C-III, and E suggest quantitative rather than qualitative differences in the lipoproteins. All the patients had lipiduria, which probably reflected the excretion of high-density lipoproteins, although no intact immunoreactive apoprotein A-I was found in urine. Serum albumin concentrations were inversely related to serum lipid concentrations in the patients, the severity of the hypoalbuminemia corresponding to the degree of change in serum lipoprotein concentrations. The kinetic studies of lipoprotein metabolism revealed an overproduction of LDL apoprotein B that returned to normal after recovery.
Conclusions.
The elevated serum concentrations of LDL cholesterol, other lipids, and apoprotein B in patients with uncomplicated nepnrotic syndrome are due to reversible increases in lipoprotein production. (N Engl J Med 1990; 323:579–84.)
Media in This Article
Figure 1
Mean Cholesterol, Triglyceride, and Phospholipid Distribution in the Lipoprotein Fractions of Serum of Normal Subjects and Patients with the Nephrotic Syndrome.Figure 2
LDL Apoprotein B Fractional Catabolic Rate and the Rate of Production in Patients with the Nephrotic Syndrome (●) with Proteinuria and after Recovery.Article Activity
- Article
HYPERLIPIDEMIA is a striking feature of the nephrotic syndrome. It is a matter of debate, however, whether this hyperlipidemia leads to an increased risk of coronary heart disease and, if so, whether hypolipidemic therapy is indicated.1 2 3 In addition, there are conflicting data regarding the distribution of cholesterol among the serum lipoproteins in patients with the nephrotic syndrome,4 5 6 7 and the different lipoprotein fractions have not been measured in a large group of such patients. This is probably because in most patients the nephrotic syndrome is accompanied by renal failure or other metabolic disorders such as diabetes mellitus (or both), or because the patients are receiving treatment, such as corticosteroids, that has a confounding effect on the lipoprotein patterns.
We attempted to determine prospectively the pattern of hyperlipoproteinemia in patients with untreated nephrotic syndrome who had normal renal function and no confounding metabolic disorders. In addition, because indirect evidence suggested that increased hepatic synthesis of low-density lipoprotein (LDL) was the primary cause of hypercholesterolemia in these patients,7 8 9 10 we carried out kinetic studies of LDL metabolism before and after recovery.
Methods
Patient Selection
We studied 57 patients with the nephrotic syndrome without complications and with no other illnesses. They were recruited from eight different hospitals over a three-year period. Their ages ranged from 15 to 81 years (mean [±SD], 44.8±22.7); 37 were male and 20 were female. All had serum creatinine levels of less than 110 μmol per liter. They were selected from a group of 119 patients, among whom we excluded 39 because they had renal insufficiency, 10 because they had diabetes mellitus, and 13 because they had other disorders, including systemic lupus erythematosus, alcohol abuse, liver disease, obesity, familial hyperlipidemia, thyroid dysfunction, Cushing's syndrome, Addison's disease, and pheochromocytoma. None of the study patients were taking oral contraceptives, corticosteroids, cytotoxic drugs, or anticoagulant drugs, but 41 were taking furosemide in doses ranging from 40 to 120 mg per day. As a group, these 41 patients had serum lipid and lipoprotein concentrations similar to those in the 16 patients not taking furosemide.
The nephrotic syndrome was defined as the excretion of more than 3.5 g of protein per day in the urine; serum albumin and total protein concentrations below 30 and 60 g per liter, respectively; and the presence of edema without other apparent cause. The mean (±SD) levels of the measured variables were as follows: serum creatinine, 86.7±21.4 μmol per liter; serum albumin, 22.5±5.4 g per liter; serum total protein, 47.0±7.4 g per liter; and 24-hour urinary excretion of protein, 7.15±8.52 g. Forty-five patients were studied when the diagnosis was first made, and 12 were studied at the time of a recurrence.
Percutaneous renal biopsies were performed in 55 patients. Twelve patients had minimal-change glomerulopathy, 18 membranous nephropathy, 7 membranoproliferative glomerulonephritis, 5 renal amyloidosis, 9 focal glomerulosclerosis, 3 mesangial proliferative glomerulonephritis, and 1 acute glomerulonephritis. None of the patients with renal amyloidosis had any preexisting or coexisting illness. We also studied 57 normal subjects (37 men and 20 women) as a control group. These subjects were matched with the patients for sex, age within five years, and weight within 5 kg. None were taking any medications or had proteinuria, and all had normal renal function. The study was approved by the regional medical research committee, and all subjects gave informed consent.
Kinetic Studies
The rate of production and the fractional catabolic rate of LDL were studied in six patients when they had all the manifestations of the nephrotic syndrome and in three of the six after recovery. Their serum creatinine levels ranged from 75 to 89 μmol per liter. Complete remission, defined as the absence of any clinical or laboratory manifestations of the nephrotic syndrome, was achieved spontaneously in two patients, whereas the third had received corticosteroid therapy for 45 days. The second kinetic study was undertaken two months after recovery and after all drugs had been discontinued.
For the LDL kinetic studies, 50 ml of blood was drawn after an overnight fast, with 1 mg of EDTA added per milliliter as an anticoagulant. LDL (density, 1.019 to 1.063 kg per liter) was isolated from plasma by preparative ultracentrifugation11 and labeled with iodine-125 (Amersham, Buckinghamshire, United Kingdom).12 , 13 After dialysis for 24 hours with 25 liters of 0.15 M sodium chloride and 0.01 percent EDTA (pH 7.5) to remove unreacted 125I, 10 μCi of the autologous LDL was passed through a 22-μm filter (Millipore, Velizy, France) and injected into the donor through an antecubital vein.
Ten-milliliter blood samples were collected from the contralateral arm 15 minutes after the injection of the 125I-labeled LDL and then daily for 10 to 14 days. Radioactivity was determined in 1-ml aliquots and the counts expressed as a percentage of the count in the 15-minute sample. Plasma radioactivity—decay curves were constructed, and the fractional catabolic rate — defined as the fraction of total LDL apoprotein B removed per unit of time — was calculated from the biexponential curves according to the curve-peeling technique of Matthews.14 The rate of production of LDL apoprotein B, standardized for body weight, was calculated as the fractional catabolic rate times the size of the pool. The size of the pool was calculated as the serum LDL apoprotein B concentration times the volume of plasma. Serum LDL apoprotein B was measured with the 1,1,3,3-tetramethylurea—precipitation technique of Kane et al.15 The precipitate was extracted, dried in the presence of nitrogen, solubilized in 0.1 M sodium hydroxide, and the protein assayed by the method of Lowry et al.16 For illustrative purposes, the results of the LDL kinetic studies in the patients with the nephrotic syndrome were compared with those in normal subjects and patients with hypercholesterolemia whom we had studied previously.17 , 18
Other Studies
The patients and normal subjects were studied after an overnight fast of at least 12 hours. The blood samples were centrifuged immediately after collection and the serum transported on ice to the Hospital de Sant Joan for analysis. The measurements were performed in fresh serum or in serum stored at − 20°C, in which case the samples were analyzed in batches to minimize interassay variation. Twenty-four-hour urine samples were collected from all patients and normal subjects, sodium azide was added (final concentration, 2 mg per liter) to prevent bacterial growth, and 50-ml aliquots were frozen for later analysis.
Total protein, albumin, creatinine, cholesterol, triglycerides, phospholipid, and apoproteins A-I, A-II, and B were measured in fresh serum by standard procedures, as was urinary protein in aliquots of 24-hour collections, in an autoanalyzer (2000 IL, Monarch, Milan, Italy).19 An aliquot of the serum was subjected to sequential preparative ultracentrifugation11 to separate very-low-density lipoprotein (VLDL; density <1.006 kg per liter) and LDL, and the tube was sliced to isolate the fractions quantitatively. High-density lipoprotein (HDL) was measured in the subnatant of the isolated LDL. Apoproteins C-II, C-III, and E were measured as previously described20 by single radial immunodiffusion on plates purchased from Daiichi Pure Chemicals (Tokyo, Japan). The interassay coefficient of variation for all measurements was less than 5 percent.
The urine samples underwent dialysis with phosphate-buffered saline, were concentrated 10-fold under pressure with use of an ultrafiltration membrane with a mean pore radius of 2.4 nm (24 Å) (Amicon, Danvers, Mass.), and then concentrated 25-fold in a standard filtration system (Millipore). Apoprotein A-I, cholesterol, triglycerides, and phospholipids were measured in the samples as described above. The limit of sensitivity for apoprotein A-I ranged from 15 to 20 μg per liter. Sodium dodecyl sulfate–polyacrylamide-gel gradient (8 to 25 percent) electrophoresis was performed in prepared gels with use of the Phast System (Pharmacia, Uppsala, Sweden), and the resulting bands were identified by silver staining. The apparent molecular weight of each band was calculated from a calibration curve established with use of the low-molecular-weight calibration-kit proteins (Pharmacia). Trypsin was used as a control.
Statistical Analysis
The unpaired Student t-test was used to compare values in the patients with the nephrotic syndrome with those in the normal subjects and in the men and women, respectively. The paired Student t-test was used to compare the values in the patients with active nephrotic syndrome with the values in the same patients after recovery. P values of less than 0.05 were considered to indicate statistical significance. Pearson's correlation coefficients were calculated to evaluate the degree of linear association between measured variables.
Results
Nineteen patients (33.3 percent) had increased serum LDL and normal serum VLDL concentrations (Type IIa hyperlipoproteinemia, according to the World Health Organization's description of lipoprotein phenotypes21), 34 (59.6 percent) had increased LDL and VLDL concentrations (Type IIb), and 4 (7 percent) had normal LDL and increased VLDL concentrations (Type IV). No patient had hyperchylomicronemia. The mean cholesterol, triglyceride, and phospholipid concentrations in serum and in the isolated lipoprotein fractions in all 57 patients are shown in Table 1Table 1
Lipid and Apoprotein Concentrations in Patients with the Nephrotic Syndrome and Matched Normal Subjects. and Figure 1Figure 1Mean Cholesterol, Triglyceride, and Phospholipid Distribution in the Lipoprotein Fractions of Serum of Normal Subjects and Patients with the Nephrotic Syndrome.. Although no patient had normal levels of both cholesterol and triglycerides, the range of values was wide (cholesterol, 4.8 to 20.4 mmol per liter; and triglyceride, 0.9 to 5.0 mmol per liter). The mean values for all three lipid components in serum and in the LDL and VLDL fractions were significantly higher in men and women with the nephrotic syndrome than in normal men and women. The increase in lipid components was greatest in the VLDL fraction (VLDL cholesterol, 3.9-fold increase; VLDL triglycerides, 2.5-fold; and VLDL phospholipids, 3.1-fold). In the LDL fraction, cholesterol was 1.8-fold, triglyceride 2.3-fold, and phospholipid 2.0-fold higher in the patients with the nephrotic syndrome than in the normal subjects. In contrast, the concentrations of HDL lipids were only marginally elevated. There were no significant differences in the relative proportions of lipids in the lipoprotein fractions between the patients with the nephrotic syndrome and the normal subjects.There were significant inverse linear correlations between the serum concentrations of albumin and cholesterol (r = −0.55; P<0.001), triglycerides (r = −0.29; P<0.05), phospholipids (r = −0.51; P<0.001), and LDL cholesterol (r = −0.53; P<0.01). There was no correlation between the 24-hour urinary excretion of protein and any of the lipoproteins measured.
Among the apoproteins, the mean serum apoprotein B, C-II, C-III, and E concentrations were higher in the patients with the nephrotic syndrome than in the normal subjects, for both men and women (Table 1). The largest percent increase was in serum apoprotein B (115 percent in men and 86 percent in women), and the increase in apoprotein B values correlated well with the increased LDL cholesterol values (r = 0.61; P<0.001). The serum apoprotein A-I concentrations in the patients with the nephrotic syndrome (Table 1) were significantly correlated with their HDL cholesterol values (r = 0.68; P<0.001). The serum apoprotein C-II and VLDL triglyceride levels (r = 0.26; P<0.05) and apoprotein C-III and apoprotein C-II levels (r = 0.79; P<0.001) were also positively correlated in the patients with the nephrotic syndrome, and the ratio between apoproteins C-III and C-II was significantly higher (P<0.01) in the patients than in the normal subjects.
To determine whether the abnormal lipoprotein profiles bore any relation to the degree of hypoalbuminemia, we divided the patients arbitrarily into two groups — those with serum albumin levels of 21 g per liter or higher (18 men and 15 women; group 1), and those with levels below 21 g per liter (19 men and 5 women; group 2) (Table 2Table 2
Lipid and Apoprotein Concentrations in Patients with the Nephrotic Syndrome Grouped Arbitrarily According to Degree of Hypoalbuminemia.*). The mean serum and LDL cholesterol, triglyceride, and phospholipid concentrations were significantly higher in group 2 than in group 1, as was the VLDL phospholipid concentration. Among the apoproteins, only serum apoprotein B levels were significantly higher in group 2 than in group 1. We found no relation between the histologic findings and any of the lipoprotein patterns.All the patients but none of the normal subjects had lipiduria. The values for 24-hour excretion in the patients were as follows: cholesterol, 15.2± 10.8 μmol per day (range, 1.2 to 36.1); triglycerides, 6.1±5.9 μmol per day (range, 0.6 to 21.2); and phospholipids, 16.3±9.9 μmol per day (range, 0.6 to 55.0). The relative proportions of cholesterol, triglycerides, and phospholipids (0.41:0.16:0.43) were similar to their proportions in the serum HDL fraction (0.37:0.08:0.55). This result prompted us to measure urinary apoprotein A-I. No immunoreactive apoprotein A-I was detectable. When the urine was subjected to electrophoresis, however, 49 patients had a band corresponding to a molecular weight of approximately 27,000. We did not identify this band as apoprotein A-I, but its size suggested that it was an apoprotein A-I—like protein.
The results of the kinetic studies of LDL metabolism are shown in Table 3Table 3
LDL Apoprotein B Kinetic Indexes in Patients with the Nephrotic Syndrome before and after Recovery, Patients with Two Types of Hypercholesterolemia, and Normal Subjects* and Figure 2Figure 2LDL Apoprotein B Fractional Catabolic Rate and the Rate of Production in Patients with the Nephrotic Syndrome (●) with Proteinuria and after Recovery.. The size of the LDL apoprotein B pool in the patients with the nephrotic syndrome was higher than that in the normal subjects. This increase was due to an increased rate of production; the fractional catabolic rate was similar to that of the normal subjects. The rate of LDL production in the patients with the nephrotic syndrome was higher than that in the two groups of patients with hypercholesterolemia. The fractional catabolic rate was similar in the patients with the nephrotic syndrome and those with polygenic hypercholesterolemia, whereas it was much lower in the patients with homozygous familial hypercholesterolemia. The serum lipid and apoprotein concentrations as well as the kinetic values were normal in the three patients studied after recovery.Discussion
We measured the serum lipid concentrations and lipoprotein kinetics in carefully selected patients with the nephrotic syndrome who had normal glomerular function and no complicating diseases such as diabetes and who were not receiving any therapy other than furosemide. In agreement with previous studies,4 5 6 , 22 , 23 our patients had increased concentrations of cholesterol, triglycerides, and phospholipids in serum and in the VLDL and LDL fractions of serum, but the proportions of the individual components in the serum and lipoprotein fractions were similar to those in the normal subjects. These results, in combination with the increases in apoproteins, suggest that the abnormalities in serum lipoproteins in patients with the nephrotic syndrome are due to increased numbers of particles rather than abnormal particles, as have been described in children with the nephrotic syndrome.6 In contrast to the findings of Newmark et al.,5 none of our patients had hyperchylomicronemia.
Although most investigators have found increased concentrations of VLDL and LDL in patients with the nephrotic syndrome, the results of HDL measurements have been contradictory, with high,22 , 24 low,25 and normal26 , 27 levels of HDL cholesterol being reported. The presence or absence of chronic renal failure is a plausible explanation for this variation. Our patients had a selective increase in cholesterol in the apoprotein B—rich VLDL and LDL lipoprotein fractions. The mechanism of this selectivity is unclear, but it has been postulated that HDL cholesterol does not increase in these patients because it is lost in the urine. This possibility cannot be excluded in our study. However, we found no immunoreactive, intact apoprotein A-I in the urine of our patients, and the calculated 24-hour urinary losses of cholesterol, triglycerides, and phospholipids represented only 0.29, 0.78, and 0.39 percent, respectively, of the total circulating HDL lipids.
We found an absolute increase in serum apoproteins C-III and C-II in the patients with the nephrotic syndrome, together with an increased ratio of C-III to C-II consistent with a relative predominance of lipoprotein lipase inhibitor (apoprotein C-III) over activator (apoprotein C-II). These results, together with the previously reported decreases in lipoprotein lipase activity in patients with the nephrotic syndrome,28 suggest that VLDL catabolism is decreased in these patients. The finding of increased serum apoprotein E concentrations suggests an accumulation of apoprotein E-enriched particles of VLDL.
Increases in serum LDL concentrations, as found in patients with the nephrotic syndrome, could be due to overproduction, impaired catabolism, or both. Possible alterations in kinetic indexes are difficult to assess in case–control studies, because of the variations in such measurements and the near impossibility of achieving exact matching. These problems are obviated by serial studies conducted before and after recovery in individual patients. Our finding of an increased rate of production and normal fractional catabolic rate of LDL apoprotein B supports the work of others10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 indicating that overproduction of these lipoproteins is the chief cause of increased LDL concentrations in patients with the nephrotic syndrome. The normalization of serum LDL apoprotein B levels after recovery was due to diminished production; the fractional catabolic rate did not change. Different results were recently reported by Warwick et al.,30 who found that LDL apoprotein clearance by way of the LDL-receptor pathway was decreased. The subjects in the two studies were similar, although some of the patients of Warwick et al.30 had mild renal insufficiency. Further studies are therefore needed to clarify this point.
The stimulus that triggers the increased production of apoprotein B is not clear. Hypoalbuminemia, low plasma oncotic pressure, and low plasma viscosity have been proposed as possible mechanisms.26 , 31 Our data support indirectly the pivotal role of hypoalbuminemia in the development of hyperlipoproteinemia. We hypothesize that decreased serum albumin levels are accompanied by a compensatory increase in LDL synthesis, particularly of the large, oncotically more effective apoprotein B. Further decreases in serum albumin may be accompanied by compensatory increases in other apoproteins that — particularly with respect to C-III and its inhibitory effect on lipoprotein lipase — could result in the accumulation of VLDL in the circulation.
In conclusion, patients with the nephrotic syndrome and hyperlipidemia appear to have a selective increase in LDL apoprotein B synthesis and normal catabolism of this lipoprotein. The normal serum levels of HDL and apoproteins A-I and A-II and the negligible urinary losses of apoprotein A-I make it unlikely that HDL metabolism is altered in patients with the nephrotic syndrome. These findings suggest that treatment directed toward inhibiting LDL synthesis (with the hydroxymethylglutaryl—coenzyme A reductase inhibitors, for example) would be appropriate.
Supported by grants from the Fondo de Investigaciones de la Seguridad Social and the Fundación Juan Abelló Pascual.
We are indebted to the clinical and laboratory staffs of the Hospital Valle de Hebrón de Barcelona, Hospital Clínico y Provincial de Barcelona, Fundación Puigvert, Hospital de Bellvitge de Hospitalet de Llobregat, Hospital de San Andrés de Manresa, Hospital Germans Trias y Pujol de Badalona, Hospital de Sant Joan de Reus, and Hospital Juan XXIII de Tarragona.
Source Information
From the Centre de Recerca Biomedica del Hospital de Sant Joan, Reus (J.J., C.V.); the Unitat de Recerca de Lipids, Reus (E.V., L.M.); the Hospital Germans Trias y Pujol, Badalona (R.A.); and the Hospital Valle de Hebrón. Barcelona (M. V.), all in Spain. Address reprint requests to Dr. Joven at the Hospital de Sant Joan, calle Sant Joan s/n, 43201 Reus, Spain.
- References
References
1
Wass
CrossRef | Web of Science | Medline2
Mallick
CrossRef | Medline3
Kannel
Web of Science | Medline4
Baxter
CrossRef | Web of Science | Medline5
Newmark
Web of Science | Medline6
Gherardi
CrossRef | Web of Science | Medline7
Golper
CrossRef | Web of Science | Medline8
McKenzie
CrossRef | Web of Science | Medline9
Joven
CrossRef | Web of Science | Medline10
Vega
CrossRef | Web of Science | Medline11
Havel
CrossRef | Web of Science | Medline12
McFarlane
CrossRef | Web of Science | Medline13
Langer
CrossRef | Web of Science | Medline14
Matthews
CrossRef | Web of Science | Medline15
Kane
CrossRef | Web of Science | Medline16
Lowry
Web of Science | Medline17
Masana
Web of Science | Medline18
International Collaborative Study Group
Web of Science | Medline19
Simo 20
Joven
Web of Science | Medline21
Beaumont
Web of Science | Medline22
Ohta
CrossRef | Web of Science | Medline23
Chopra
CrossRef | Web of Science | Medline24
Jensen
CrossRef | Web of Science | Medline25
Alexander
Web of Science | Medline26
Appel
Full Text | Web of Science | Medline27
Joven
Medline28
Kashyap
CrossRef | Web of Science | Medline29
Gitlin
CrossRef | Web of Science | Medline30
Warwick
CrossRef | Web of Science | Medline31
Allen
CrossRef | Web of Science | Medline
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Citing Articles
1
Abdelgawad Ali Fahmi, Dawoud Fakhry Habib, Naglaa Mohamed Kholousy, Ahmed Ibrahim Amin, Mostafa Shalaby, Mohamed Mahmoud Ahmed, Asem Metwally Abo Shanab. (2012) Renal leptin in experimental nephrotic syndrome. Journal of Genetic Engineering and Biotechnology
CrossRef2
N. D. Vaziri, P. Gollapudi, S. Han, G. Farahmand, J. Yuan, A. Rahimi, H. Moradi. (2011) Nephrotic syndrome causes upregulation of HDL endocytic receptor and PDZK-1-dependent downregulation of HDL docking receptor. Nephrology Dialysis Transplantation 26:10, 3118-3123
CrossRef3
P. K. Nigam. (2011) Serum Lipid Profile: Fasting or Non-fasting?. Indian Journal of Clinical Biochemistry 26:1, 96-97
CrossRef4
Zuhier Awan, Dana Bailey, Anouar Hafiane, Jacques Genest. (2009) Acquired severe hypercholesterolemia and hypoalphalipoproteinemia. Journal of Clinical Lipidology 3:6, 393-397
CrossRef5
Michal Chmielewski, Boleslaw Rutkowski, Bengt Lindholm. (2009) Mechanisms and clinical implications of lipid disorders in chronic kidney disease. Clinical Lipidology 4:4, 449-456
CrossRef6
Silvestre García-de-la-Puente, José Luis Arredondo-García, Pedro Gutiérrez-Castrellón, Aurora Bojorquez-Ochoa, Edith Reyna Maya, María Del Pilar Pérez-Martínez. (2009) Efficacy of simvastatin in children with hyperlipidemia secondary to kidney disorders. Pediatric Nephrology 24:6, 1205-1210
CrossRef7
Doris T. Chan, Ashley B. Irish, Gursharan K. Dogra, Gerald F. Watts. (2008) Dyslipidaemia and cardiorenal disease: mechanisms, therapeutic opportunities and clinical trials. Atherosclerosis 196:2, 823-834
CrossRef8
Robert D. Toto, Gloria Lena Vega, Scott M. Grundy. 2008. Cholesterol Management in Patients with Chronic Kidney Disease. , 715-724.
CrossRef9
Bertram L. Kasiske, Ajay K. Israni. 2008. Cardiovascular Complications after Renal Transplantation. , 469-491.
CrossRef10
Choong H. Kim, Hyun J. Kim, Masato Mitsuhashi, Nosratola D. Vaziri. (2007) Hepatic tissue sterol regulatory element binding protein 2 and low-density lipoprotein receptor in nephrotic syndrome. Metabolism 56:10, 1377-1382
CrossRef11
Jeffrey M. Saland, Henry N. Ginsberg. (2007) Lipoprotein metabolism in chronic renal insufficiency. Pediatric Nephrology 22:8, 1095-1112
CrossRef12
Chunni Zhang, Min Yao, Xiangdong Wang, Yiyi Zhuang, Zhenkun Xia, Yuhua Yang, Yong Li, Xiaozhuan Liu, Ke Li, Junjun Wang. (2007) Effect of hypoalbuminemia on the increased serum cholesteryl ester transfer protein concentration in children with idiopathic nephrotic syndrome. Clinical Biochemistry 40:12, 869-875
CrossRef13
Sahar B Hachem, Arshag D Mooradian. (2006) Familial Dyslipidaemias. Drugs 66:15, 1949-1969
CrossRef14
Michele Buemi, Lorena Nostro, Eleonora Crascì, Antonio Barillà, Vincenzo Cosentini, Carmela Aloisi, Tito Sofi, Susanna Campo, Nicola Frisina. (2005) Statins in nephrotic syndrome: A new weapon against tissue injury. Medicinal Research Reviews 25:6, 587-609
CrossRef15
Abhijit V. Kshirsagar, David A. Shoham, Heejung Bang, Susan L. Hogan, Ross J. Simpson, Romulo E. Colindres. (2005) The Effect of Cholesterol Reduction With Cholestyramine on Renal Function. American Journal of Kidney Diseases 46:5, 812-819
CrossRef16
L. Vogt. (2005) Cellular cholesterol efflux to plasma from proteinuric patients is elevated and remains unaffected by antiproteinuric treatment. Nephrology Dialysis Transplantation 21:1, 101-106
CrossRef17
André J. Tremblay, Jean Bergeron, Jean-Marc Gagné, Claude Gagné, Patrick Couture. (2005) Influence of apolipoprotein E genotype on the reliability of the Friedewald formula in the estimation of low-density lipoprotein cholesterol concentrations. Metabolism 54:8, 1014-1019
CrossRef18
F KRONENBERG. (2005) Dyslipidemia and nephrotic syndrome: Recent advances. Journal of Renal Nutrition 15:2, 195-203
CrossRef19
R. Boldova Aguar, A. Cenarro Lagunas, M.C. Gonzalvo Liarte, P. González García. (2004) Hiperlipidemias secundarias. Mecanismos etiopatogénicos. Impacto vascular y tisular de las hiperlipidemias. Historia natural. Medicine - Programa de Formación Médica Continuada Acreditado 9:18, 1105-1114
CrossRef20
André J Tremblay, Hugo Morrissette, Jean-Marc Gagné, Jean Bergeron, Claude Gagné, Patrick Couture. (2004) Validation of the Friedewald formula for the determination of low-density lipoprotein cholesterol compared with β-quantification in a large population. Clinical Biochemistry 37:9, 785-790
CrossRef21
Nosratola D. Vaziri, Choong H. Kim, Dennis Phan, Sara Kim, Kaihui Liang. (2004) Up-regulation of hepatic Acyl CoA: Diacylglycerol acyltransferase-1 (DGAT-1) expression in nephrotic syndrome. Kidney International 66:1, 262-267
CrossRef22
B. Kasiske, F.G. Cosio, J. Beto, K. Bolton, B.M. Chavers, R. Grimm, A. Levin, B. Masri, R. Parekh, C. Wanner, D.C. Wheeler, P.W.F. Wilson. (2004) Clinical practice guidelines for managing dyslipidemias in kidney transplant patients: a report from the Managing Dyslipidemias in Chronic Kidney Disease Work Group of the National Kidney Foundation Kidney Disease Outcomes Quality Initiative. American Journal of Transplantation 4:s7, 13-53
CrossRef23
Nosratola D. Vaziri, Kaihui Liang. (2004) Effects of HMG-CoA Reductase Inhibition on Hepatic Expression of Key Cholesterol-Regulatory Enzymes and Receptors in Nephrotic Syndrome. American Journal of Nephrology 24:6, 606-613
CrossRef24
L. Vogt. (2004) Lipid management in the proteinuric patient: do not overlook the importance of proteinuria reduction. Nephrology Dialysis Transplantation 19:1, 5-8
CrossRef25
Nosratola D Vaziri. (2003) Molecular mechanisms of lipid disorders in nephrotic syndrome. Kidney International 63:5, 1964-1976
CrossRef26
Nosratola D Vaziri, Tadashi Sato, Kaihui Liang. (2003) Molecular mechanisms of altered cholesterol metabolism in rats with spontaneous focal glomerulosclerosis. Kidney International 63:5, 1756-1763
CrossRef27
(2003) REFERENCES. American Journal of Kidney Diseases 41, S77-S91
CrossRef28
Pedro VALDIVIELSO, Manuel MOLIZ, Alfonso VALERA, Miguel A CORRALES, Miguel A SANCHEZ-CHAPARRO, Pedro GONZALEZ-SANTOS. (2003) Atorvastatin in dyslipidaemia of the nephrotic syndrome. Nephrology 8:2, 61-64
CrossRef29
Maurizio Bruschi, Paolo Catarsi, Giovanni Candiano, Maria Pia Rastaldi, Luca Musante, Francesco Scolari, Mary Artero, Michele Carraro, Alba Carrea, Gianluca Caridi, Cristina Zennaro, Simone Sanna-Cherchi, Fabio Battista Viola, Franco Ferrario, Francesco Perfumo, Gian Marco Ghiggeri. (2003) Apolipoprotein E in idiopathic nephrotic syndrome and focal segmental glomerulosclerosis. Kidney International 63:2, 686-695
CrossRef30
Jeffrey M. Saland, Henry Ginsberg, Edward A. Fisher. (2002) Dyslipidemia in pediatric renal disease: epidemiology, pathophysiology, and management. Current Opinion in Pediatrics 14:2, 197-204
CrossRef31
Lynda Anne Szczech, Donal N Reddan, William F Owen, Robert Califf, Michael Racz, Robert H Jones, Edward L Hannan. (2001) Differential survival after coronary revascularization procedures among patients with renal insufficiency. Kidney International 60:1, 292-299
CrossRef32
Hubert Scharnagl, Matthias Nauck, Heinrich Wieland, Winfried März. (2001) The Friedewald Formula Underestimates LDL Cholesterol at low Concentrations. Clinical Chemistry and Laboratory Medicine 39:5, 426-431
CrossRef33
Manuel T. Velasquez, Sam J. Bhathena. (2001) Dietary phytoestrogens: A possible role in renal disease protection. American Journal of Kidney Diseases 37:5, 1056-1068
CrossRef34
Christopher J Deighan, Muriel J Caslake, Michael Mcconnell, J Michael Boulton-Jones, Christopher J Packard. (2000) Patients with nephrotic-range proteinuria have apolipoprotein C and E deficient VLDL1. Kidney International 58:3, 1238-1246
CrossRef35
Wu Zhao-Long, Wang Xiao-Xia, Cheng Wei-Ying. (2000) Inhibitory effect ofCordyceps sinensis andCordyceps militaris on human glomerular mesangial cell proliferation induced by native LDL. Cell Biochemistry and Function 18:2, 93-97
CrossRef36
UF Mondorf, R Schmidt, J Siegers, W Gross, H Geiger, EH Scheuermann. (2000) Lipid hydroperoxides: Elevated levels in patients on haemodialysis and patients with chronic renal failure. Nephrology 5:1-2, 65-70
CrossRef37
Anna-Lena Berg, Peter Nilsson-Ehle, Margret Arnadottir. (1999) Beneficial effects of ACTH on the serum lipoprotein profile and glomerular function in patients with membranous nephropathy. Kidney International 56:4, 1534-1543
CrossRef38
Martin Haas, Dontscho Kerjaschki, Gert Mayer. (1999) Lipid-lowering therapy in membranous nephropathy. Kidney International 56:S71, 110-112
CrossRef39
Davide Noto, Carlo M. Barbagallo, Armida Lo Cascio, Angelo B. Cefalu, Giovanni Cavera, Rosalia Caldarella, Giuseppina Marino, Salvatore Travali, Ignazio Cutaia, Silvio Maringhini, Alberto Notarbartolo, Maurizio Averna. (1999) Lipoprotein(a) levels in relation to albumin concentration in childhood nephrotic syndrome. Kidney International 55:6, 2433-2439
CrossRef40
Thomas Demant, Christoph Mathes, Katja Gütlich, Andrea Bedynek, Hjalmar B Steinhauer, Thomas Bosch, Christopher J Packard, Graham L Warwick. (1998) A simultaneous study of the metabolism of apolipoprotein B and albumin in nephrotic patients1. Kidney International 54:6, 2064-2080
CrossRef41
Orth, Stephan R., Ritz, Eberhard, . (1998) The Nephrotic Syndrome. New England Journal of Medicine 338:17, 1202-1211
Full Text42
Pernille M. Hansen, Tonny Jensen, Jo/rn Egeberg, Hans Lithell, Allen Kofoed-Enevoldsen, Torsten Deckert. (1997) Skeletal Muscle Lipoprotein-Lipase Activity in Insulin-Dependent Diabetic Patients With and Without Albuminuria. Journal of Diabetes and its Complications 11:4, 230-235
CrossRef43
Kaihui Liang, Nosratola D Vaziri. (1997) Acquired VLDL receptor deficiency in experimental nephrosis. Kidney International 51:6, 1761-1765
CrossRef44
Kaihui Liang, Nosratola D Vaziri. (1997) Down-regulation of hepatic lipase expression in experimental nephrotic syndrome. Kidney International 51:6, 1933-1937
CrossRef45
Guohua Ding, Harry Van Goor, Sharon D Ricardo, Janis M Orlowski, Jonathan R Diamond. (1997) Oxidized LDL stimulates the expression of TGF-β and fibronectin in human glomerular epithelial cells. Kidney International 51:1, 147-154
CrossRef46
Jorge Joven, Eugenia Espinel, José M Simó, Elisabet Vilella, Jordi Camps, Angel Oliver. (1996) The influence of hypoalbuminemia in the generation of nephrotic hyperlipidemia. Atherosclerosis 126:2, 243-252
CrossRef47
Gen Yoshino, Tsutomu Hirano, Tsutomu Kazumi. (1996) Dyslipidemia in diabetes mellitus. Diabetes Research and Clinical Practice 33:1, 1-14
CrossRef48
Robin P.F. Dullaart, Ron T. Gansevoort, Wim J. Sluiter, Dick de Zeeuw, Paul E. de Jong. (1996) The serum lathosterol to cholesterol ratio, an index of cholesterol synthesis, is not elevated in patients with glomerular proteinuria and is not associated with improvement of hyperlipidemia in response to antiproteinuric treatment. Metabolism 45:6, 723-730
CrossRef49
Nosratola D Vaziri, Kai Hui Liang. (1995) Hepatic HMG-CoA reductase gene expression during the course of puromycin-induced nephrosis. Kidney International 48:6, 1979-1985
CrossRef50
R Frankel. (1995) Xanthelasmas and xanthomas — cutaneous clues to systemic lipid disorders. Clinical Eye and Vision Care 7:3, 117-128
CrossRef51
Clinton D. Brown, Neal Azrolan, Lorraine Thomas, Kathleen G. Roberts, Andrew Bostom, Zhong H. Zhao, E.A. Friedman. (1995) Reduction of lipoprotein(a) following treatment with lovastatin in patients with unremitting nephrotic syndrome. American Journal of Kidney Diseases 26:1, 170-177
CrossRef52
A. J. JENKINS, J. D. BEST. (1995) The role of lipoprotein(a) in the vascular complications of diabetes mellitus. Journal of Internal Medicine 237:4, 359-365
CrossRef53
Tsutomu Hirano, Seiichi Furukawa, Munekazu Kurokawa, Tetsu Ebara, Joseph L Dixon, Seishi Nagano. (1995) Intracellular apoprotein B degradation is suppressed by decreased albumin concentration in Hep G2 cells. Kidney International 47:2, 421-431
CrossRef54
Gloria Lena Vega, Robert D Toto, Scott M Grundy. (1995) Metabolism of low density lipoproteins in nephrotic dyslipidemia: Comparison of hypercholesterolemia alone and combined hyperlipidemia. Kidney International 47:2, 579-586
CrossRef55
Manuel Júdice Halpern. (1995) Lipids and atherosclerosis. Molecular Aspects of Medicine 16:6, 509-710
CrossRef56
Papasani V. Subbaiah, Roger A. Rodby. (1994) Abnormal acyltransferase activities and accelerated cholesteryl ester transfer in patients with nephrotic syndrome. Metabolism 43:9, 1126-1133
CrossRef57
Elisabeth F. Gröne, Autar K. Walli, Hermann-Josef Gröne, Bernd Miller, Dietrich Seidel. (1994) The role of lipids in nephrosclerosis and glomerulosclerosis. Atherosclerosis 107:1, 1-13
CrossRef58
Tsutomu Hirano, Tetsu Ebara, Seiichi Furukawa, Seishi Nagano, Terumi Takahashi. (1994) Mechanism of hypertriglyceridemia in dahl salt-sensitive rats, an animal model of spontaneous nephrotic syndrome. Metabolism 43:2, 248-256
CrossRef59
Annette Krämer, Matthias Nauck, Hermann Pavenstädt, Susanne Schwedler, Heinrich Wieland, Peter Schollmeyer, Christoph Wanner. (1993) Receptor-mediated uptake of IDL and LDL from nephrotic patients by glomerular epithelial cells. Kidney International 44:6, 1341-1351
CrossRef60
D. BUGGY, A. BREATHNACH, B. KEOGH, T. COOKE, J. FEELY. (1993) Lipoprotein(a) and treatment of chronic renal disease. Journal of Internal Medicine 234:5, 453-455
CrossRef61
Mark E Thomas, Kevin P G Harris, C Ramaswamy, Jane M Hattersley, David C Wheeler, Zac Varghese, John D Williams, John Walls, John F Moorhead. (1993) Simvastatin therapy for hypercholesterolemic patients with nephrotic syndrome or significant proteinuria. Kidney International 44:5, 1124-1129
CrossRef62
Matti K Salo, Olli Jaakkola, Tiina Solakivi, Seppo Ylä-Herttuala. (1993) Severe hyperlipoproteinemia in congenital nephrotic syndrome of the Finnish type: effect of dialysis and kidney transplantation. Acta Paediatrica 82:10, 768-772
CrossRef63
Robin PF Dullaart, Ron T Gansevoort, Bert D Dikkeschei, Dick de Zeeuw, Paul E de Jong, Arie van Tol. (1993) Role of elevated lecithin: Cholesterol acyltransferase and cholesteryl ester transfer protein activities in abnormal lipoproteins from proteinuric patients. Kidney International 44:1, 91-97
CrossRef64
A. B. Haaber, M. Deckert, S. Stender, T. Jensen. (1993) Increased urinary loss of high density lipoproteins in albuminuric insulin-dependent diabetic patients. Scandinavian Journal of Clinical & Laboratory Investigation 53:2, 191-196
CrossRef65
G. L. WARWICK, C. J. PACKARD, J. P. STEWART, T. D. G. WATSON, L. BURNS, J. M. BOULTON-JONES, J. SHEPHERD. (1992) Post-prandial lipoprotein metabolism in nephrotic syndrome. European Journal of Clinical Investigation 22:12, 813-820
CrossRef66
A. J. Jenkins, J. S. Steele, E. D. Janus, J. D. Santamaria, J. D. Best. (1992) Plasma apolipoprotein (a) is increased in Type 2 (non-insulin-dependent) diabetic patients with microalbuminuria. Diabetologia 35:11, 1055-1059
CrossRef67
T. Kodama, T. Tomiyama, T. Ishizaki, T. Baba. (1992) Vascular risk factors in Japanese non-insulin-dependent diabetic patients with microalbuminuria. Journal of Diabetes and its Complications 6:2, 70-76
CrossRef68
Graham L Warwick, Christopher J Packard, Thomas Demant, Dorothy K Bedford, J Michael Boulton-Jones, James Shepherd. (1991) Metabolism of apolipoprotein B-containing lipoproteins in subjects with nephrotic-range proteinuria. Kidney International 40:1, 129-138
CrossRef69
(1991) Abnormalities of Lipoprotein Metabolism in the Nephrotic Syndrome. New England Journal of Medicine 324:10, 697-698
Full Text70
Keane, William F., Kasiske, Bertram L., . (1990) Hyperlipidemia in the Nephrotic Syndrome. New England Journal of Medicine 323:9, 603-604
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