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Clinical Chemistry 43: 1223-1231, 1997;
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(Clinical Chemistry. 1997;43:1223-1231.)
© 1997 American Association for Clinical Chemistry, Inc.

Articles

Plasma protein abnormalities in nephrotic syndrome: effect on plasma colloid osmotic pressure and viscosity

Jorge Joven1,a, Xavier Clivillé1, Jordi Camps1, Eugenia Espinel2, Jose Simó1, Elisabet Vilella1 and Angel Oliver3

1 Centre de Recerca Biomedica. Unitat de Recerca Clínico Experimental, Hospital Universitari de Sant Joan/Facultad de Medicina de Reus, Universitat Rovira i Virgili. Calle Sant Joan s/n, 43201, Reus, Spain.

2 Hospital Valle de Hebrón, Barcelona, Spain.

3 Hospital Joan XXIII, Tarragona, Spain.
a Author for correspondence. Fax +3477312569; e-mail ala{at}fmcs.urv.es


   Abstract
Top
 Abstract
Introduction
 Patients and Methods
 Results
 Discussion
 References
 
The concentrations of 25 plasma proteins were measured in 22 patients with membranous nephropathy. For some large proteins, the plasma concentrations were increased; there were also large proteins with low plasma concentrations, but small or medium-sized proteins showed uniformly lower plasma concentration than the controls. Plasma colloid osmotic pressure ({pi}) and viscosity ({eta}) were not interrelated but showed positive and significant correlations with plasma concentrations of small and medium-sized proteins ({pi}) and plasma concentrations of large proteins ({eta}), respectively. Nephrotic plasma is not efficient in maintaining plasma {pi} but highly efficient in maintaining plasma {eta}. High plasma fibrinogen concentrations and low antithrombin III concentrations may predispose to thrombosis, and low IgG concentrations may account for the higher predisposition to bacterial infection. The relative composition of nephrotic plasma is heavily dependent on the size of the different proteins. Plasma {pi} and {eta} are also maintained by the relative preponderance of different plasma proteins.


Key Words: indexing terms: hypoalbuminemia • lipoproteins • membranous nephropathy • oncotic pressure • proteinuria • rheology


   Introduction
Top
 Abstract
 Introduction
Patients and Methods
 Results
 Discussion
 References
 
Although extremely complex, nephrotic syndrome may be described as the combination of proteinuria, edema, hypoalbuminemia, and hyperlipoproteinemia. The filtration of individual proteins through normal glomerular basement membranes depends on their size and charge, and is roughly 0% at 70 kDa and 100% at <10 kDa (1). Proteins that cross this membrane are absorbed and catabolized in tubular cells or excreted with the urine (2)(3). In nephrotic syndrome, the function of this barrier is severely disrupted and small, medium-sized, and even very large proteins are massively lost into urine, thereby causing changes in the plasma composition (2)(4). However, the nature of most of the plasma protein abnormalities has not previously been considered in a homogeneous group of patients. The assessment of individual proteins may be useful for understanding their mutual relations, for designing potential treatment protocols, and for determining the pathophysiological consequences of proteinuria, such as the response of the liver to the altered plasma composition. Little else is known about this response except that it is quantitatively important and rapid (5). Likewise, little is known about the role of other tissues, but their role cannot be discarded. The synthesis of some proteins increases while for others it stays the same or even decreases. For most proteins the rate of synthesis remains undetermined (4)(5)(6)(7)(8)(9)(10)(11). What triggers this hepatic response is not known, but several different authors have suggested that it might be hypoalbuminemia, with the consequent decrease in low plasma colloid osmotic pressure ({pi}) or low plasma viscosity ({eta}) (12)(13)(14)(15)(16). However, the signal is probably complex and multifactorial. In the present study, we have attempted to determine the plasma protein composition in untreated nephrotic syndrome patients who had normal renal functions and no confusing metabolic disorders. We have also explored the possible effect of albumin and nonalbumin proteins on plasma {pi} and {eta}.


   Patients and Methods
Top
 Abstract
 Introduction
 Patients and Methods
Results
 Discussion
 References
 
study subjects and samples
The procedures followed were in accordance with the ethical standards of the Hospital de Sant Joan. Of the 84 patients with biopsy-proved membranous nephropathy in our follow-up protocols (9)(17), active since 1986, we selected 22 patients with creatinine clearance >=75 mL/min · 1.73 m2, urinary protein excretion >=3.5 g/24 h, and plasma albumin concentration <31 g/L. For purposes of comparison, we also studied 22 healthy normolipemic controls matched for sex, age (within 5 years), and weight (within 6 kg). A complete clinical and laboratory evaluation of patients and controls was performed, including the plasma determination of C-reactive protein, rheumatoid factor, circulating antinuclear antibodies, and immunoelectrophoresis. We had no knowledge of immunosupressive treatment, recent infectious complications, or signs of inflammation. None had a systemic illness, liver disease, obesity, thyroid dysfunction, diabetes mellitus, or abused alcohol. To avoid possible misinterpretations, patients had been free of any medication during the 3 months before sampling except for furosemide, calcium-channel antagonists, or both. After an overnight fast, blood was drawn from all patients and controls into tubes containing either EDTA or citrate. Plasma was separated without delay by centrifugation at 4 °C and immediately processed or stored at -70 °C without subsequent thawing until the assay. Patients and controls were also instructed to collect 24-h urine in sterile containers.

lipoprotein fractionation
Plasma was subjected to sequential preparative ultracentrifugation as previously described (18). VLDL were isolated at a density of <1.006 kg/L, IDL between 1.006 and 1.019 kg/L, and LDL between 1.019 and 1.063 kg/L. The cholesterol and triglyceride measured in the infranatant liquid of this last spin were considered to represent HDL (9). Plasma lipoprotein(a) was measured as described (17).

protein quantification
Plasma apoproteins (apo) AI, AII, B, CII, CIII, and E were measured as described (9). We used either a Monarch 2000 (Instrumentation Laboratory, Milan, Italy) or a Hitachi 704 (Boehringer Mannheim, Mannheim, Germany) automated analyzer for turbidimetric measurements, and reagents from BioKit (immunoglobulins G, A, and M, C-reactive protein, rheumatoid factor; Barcelona, Spain), Orion (transferrin, haptoglobin, complement C3 and C4; Espoo, Finland), Ape associates ({alpha}2-macroglobulin, ceruloplasmin; Ghislenghien, Belgium), and Boehringer Mannheim ({alpha}1-microglobulin, antithrombin III). Ferritin was measured as described (19). For nephelometric measurements (fibrinogen, {alpha}1-antitrypsin, hemopexin, orosomucoid, transthyretin) we used an Array 360 nephelometer (Beckman Instruments, Brea, CA), with reagents supplied by the manufacturer and Behring (Marburg, Germany). We prepared our own reference material for the measurement of apoproteins and we used the standard WHO 1STIS 80/602 for the measurement of ferritin and the reference international calibrator CRM 470 for the other proteins measured. To study the analytical variables we used control specimens provided by the Generalitat de Catalunya (Barcelona, Spain), Baxter Dade (Basel, Switzerland), Beckman Instruments, and Boehringer Mannheim, the values of which had been assigned according to the reference values of the IFCC. For each variable, all samples were run within the same assay. The intraassay imprecision (12 replicates) ranged between 0.6% and 5.7% for low values, 0.3% and 4.1% for medium values, and from 1.3% to 8.6% for high values.

plasma {pi} measurement
Plasma {pi} was measured in a Wescor 4400 colloid osmometer (Wescor, Logan, UT). The instrument contains two chambers, the sample chamber and the saline-filled reference chamber, separated by a semipermeable membrane that has a molecular mass cutoff of 30 kDa. A transducer measures the increase in hydrostatic pressure in the sample chamber at equilibrium. The instrument was calibrated with a water manometer and the {pi} of the control material provided by the manufacturer. We found an intra- and interassay CV of <1% and 3.1%, respectively.

plasma {eta} measurement
According to accepted recommendations (20), blood for measuring plasma {eta} was obtained in a separate tube and centrifuged at 1500g for 5 min. Then, the plasma was immediately pipetted off under sterile conditions. Analyses were performed within 24 h in a Brookfield digital rheometer, Model DV-III (Brookfield, Stoughton, MA), at 37 °C and shear rates of 150, 200, 250, 350, and 450 s-1. Rheocalc® software was used to analyze the data and the value assigned to plasma {eta} was the mean of the measurements performed. The intra- and interassay CVs were 1.9% and 3.8%, respectively.

other laboratory procedures
Total protein, albumin, creatinine, cholesterol, and triglyceride were measured in plasma, isolated lipoprotein fractions, or urine as described (21). The selectivity of protein excretion was determined in 24-h urine specimens as reported by Stierle et al. (22).

statistical analyses
Values are expressed as mean (SD) or median. Data were initially analyzed with Snedecor's F-test of homogeneity of variances. Differences between groups were then assessed with the Student t-test or the Mann–Whitney U-test following the indications of the F-test. Levels of P <=0.05 were considered statistically significant.

Correlations were determined by linear regression analysis. Stepwise multiple regression and nonlinear regression analyses were performed, with either plasma {pi} or {eta} as the dependent variable, to assess the interrelations among variables. We used graphic methods to assess goodness of distributional fit and the appropriateness of gaussian assumptions regarding the errors of measurement in the model (23).


   Results
Top
 Abstract
 Introduction
 Patients and Methods
 Results
Discussion
 References
 
clinical data and lipoproteins
Patients were statistically indistinguishable from controls as far as sex, age, and body mass index were concerned. In contrast to controls, nephrotic patients showed lower plasma {pi} and {eta} (Table 1 ). No differences were observed in the variables measured between males and females or between those taking antihypertensives, and no subgroups were considered. Nephrotic patients showed hypercholesterolemia, hypertriglyceridemia, and high concentrations of lipoprotein(a) compared with controls. There was no difference in HDL cholesterol and triglyceride between nephrotic patients (1.43 ± 0.32 mmol/L and 0.21 ± 0.11 mmol/L, respectively) and controls (1.40 ± 0.22 mmol/L and 0.15 ± 0.05 mmol/L, respectively). Mean plasma VLDL, IDL, and LDL cholesterol concentrations were significantly (P <0.05) increased in nephrotic patients (1.19 ± 0.66, 0.91 ± 0.61, and 7.30 ± 2.41 mmol/L, respectively) compared with controls (0.38 ± 0.16, 0.23 ± 0.10, and 3.87 ± 0.69 mmol/L, respectively). A similar distribution was observed for mean plasma VLDL, IDL, and LDL triglyceride (2.11 ± 1.12, 1.10 ± 0.61, and 0.56 ± 0.36 mmol/L for nephrotics and 0.61 ± 0.20, 0.24 ± 0.08 and 0.25 ± 0.10 mmol/L for controls). In nephrotics, but not in controls, plasma albumin concentration was positively correlated with plasma {pi} (r = 0.681, P = 0.009) and inversely correlated with plasma {eta} (r = -0.514, P = 0.024) and the 24-h urinary protein (r = -0.530, P = 0.017). Plasma cholesterol was inversely correlated with plasma albumin (r = -0.524, P = 0.013) and positively correlated with plasma {eta} (r = 0.733, P < 0.0001). This correlation was also significant for LDL cholesterol and LDL apo B. Other lipoprotein fractions and the plasma triglyceride concentration were not significantly correlated with plasma {pi} or {eta}. Likewise, plasma {pi} and {eta} were not correlated.


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  		Table 1. Clinical and basic laboratory data of the study population.

plasma protein composition
The plasma concentration of 25 proteins is shown in Table 2 , which quantitatively represents most of the plasma protein composition (101.7% ± 6.4% in nephrotics and 102.1% ± 5.7% in controls). Ranges for the control subjects may be divergent from previously published data, which is probably due to the different distribution in age and gender and the reference material used as the target. The relative abundance of albumin is much lower in nephrotic patients than in controls (36% vs 57%); fibrinogen and {alpha}2-macroglobulin increased most with respect to controls. Except for six proteins (apoproteins AI and CII, IgM, transthyretin, C-reactive protein, and ferritin), the differences in the mean plasma concentration of the selected proteins were statistically significant. Some proteins (n = 9) showed a significant increase in mean plasma concentration in nephrotics, and their molecular masses (actual or bound to lipoproteins) were higher than that of albumin in all cases. In contrast, with the exception of transthyretin, the plasma concentration of those proteins with similar or lower molecular mass than albumin (transferrin, {alpha}1-antitrypsin, orosomucoid, hemopexin, and antithrombin III) was significantly lower in nephrotic patients than in controls. There were also proteins with high molecular mass (IgG, complement C3, and apo AII) that showed lower values in nephrotics than in controls (Table 2 ). In controls, there was no significant correlation among the proteins measured and plasma albumin concentration. However, in nephrotics, there were positive (Fig. 1 , n = 5) and negative (Fig. 2 , n = 6) correlations and there was a significant degree of autocorrelation among them. Again, those proteins showing positive correlations have a similar or lower molecular mass than albumin, and those with negative correlations have a higher molecular mass than albumin. Except for {alpha}2-macroglobulin (r = -0.455, P = 0.033), no correlation was found among proteins whose molecular mass was higher than albumin and plasma {pi}. The proteins in Fig. 1 with similar or lower molecular masses than albumin all showed significant and positive correlations with plasma {pi}. However, for plasma {eta} these proteins did not show significant correlations except for antithrombin III, which was negative (r = -0.565, P = 0.012). All the proteins shown in Fig. 2 also had significant but positive correlations with plasma {eta}. The exceptions (i.e., {alpha}2-macroglobulin and antithrombin III) could be explained in terms of shape rather than molecular mass. Moreover, there is a significant shift in the average molecular mass of plasma proteins. Those proteins with molecular mass >80 kDa, excluding apoproteins, represent 31% of the total protein in control plasma (22.7 g/L, roughly half of the plasma albumin concentration) and 52% in nephrotics (27.3 g/L, or 8 g/L higher than plasma albumin concentration).


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  		Table 2. Plasma protein composition in 22 nephrotic patients and matched controls.



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  		Figure 1. Plasma albumin concentration in 22 nephrotic patients and its relation with five plasma proteins [(a) transferrin, (b) hemopexin, (c) antithrombin III, (d) transthyretin, (e) orosomucoid] showing positive and significant correlations.



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  		Figure 2. Plasma albumin concentration in 22 nephrotic patients and its relation with six plasma proteins [(a) haptoglobin, (b) C3, (c) C4, (d) apo B, (e) fibrinogen, (f) {alpha}2-macroglobulin] showing negative and significant correlations.

plasma {pi}
The relation between plasma {pi} and plasma protein concentration (qualitatively identical if plotted against plasma albumin) is shown in Fig. 3 . There was no overlapping between controls and nephrotics. Individual values are shown together with lines prepared according to the normogram described by Nitta et al. (24), representing solutions of pure albumin, pure globulin, and a 50% mixture of each (panel A). The data points in controls fall above the line relating plasma {pi} and the mixture of albumin and globulin, whereas in nephrotics they mostly fall below it. The nephrotic plasma is also much less effective than the control plasma in supporting plasma {pi} in terms of {pi} per gram of plasma protein (panel B). In the multiple stepwise linear regression analysis, only plasma albumin and total nonalbumin concentrations were selected as being the most significantly related to plasma {pi}. No other individual protein significantly added to the fit of the model. The obtained model to predict plasma {pi} did not differ much from another published one (25) except for the values of {alpha} and ß coefficients and our lower multiple correlation coefficients (71.1% vs 99.5% in controls and 69.4% vs 97.2% in nephrotics):



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  		Figure 3. Relation between plasma {pi} and plasma protein concentration.

(A) Relation in nephrotic patients (•) and controls (•). Lines a and b represent the predicted relation for a solution of pure albumin and pure globulin, respectively. The broken line represents the relation for a solution of a mixture of 50% albumin and 50% globulin (24). (B) Relation found for a serially diluted pool (n = 12) of control (c) and nephrotic plasmas (n).

{pi} = {alpha} (nonalbumin proteins)2 + ß (albumin ·nonalbumin proteins)

For the controls, {alpha} was negative (-0.12) and for nephrotics it was positive (+0.09), indicating that in controls a higher concentration of nonalbumin proteins may decrease plasma {pi}, but in nephrotics, these proteins play a role in its maintenance. The ß coefficients were positive both in controls (+0.32) and nephrotics (+0.22). However, this model cannot replace direct measurement of plasma {pi} because, although predictive, it was not accurate and the prediction errors, albeit in the gaussian distribution, were between -8 and + 10 mmHg. Surprisingly, this model was not better than one that had been previously described (26), which was derived from rats and based on total protein concentration only.

plasma {eta}
Although nephrotic patients showed lower values of plasma {eta} than controls, there is a clear overlapping of the individual values (Fig. 4 , panel A), and the nephrotic plasma is more effective in generating plasma {eta} per gram of protein (panel B). Therefore, the altered plasma composition has a positive effect on supporting plasma {eta}. The multiple stepwise linear regression analysis showed that only plasma albumin and total protein concentrations were significantly related to plasma {eta} but with a multiple correlation coefficient of 48.5%. Surprisingly, plasma fibrinogen did not add significance to the model. We did not find better nonlinear prediction models for plasma {eta}. The linear model (constant = 0.37) showed a negative B coefficient for albumin in nephrotics (B = -0.011, t = -3.361) but a positive one for controls (B = 0.15, t = 4.293) and for total protein concentration (B = 0.015, t = 3.836 for nephrotics and B = 0.21, t = 5.49 for controls). Again, the prediction model was not accurate, and prediction errors ranged between -0.3 and +0.5 mPa · s, but the Figures indicate that in nephrotics, a higher concentration of nonalbumin proteins might increase plasma {eta}.



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  		Figure 4. Relation between plasma {eta} and plasma protein concentration.

(A) Relation in nephrotic patients (•) and controls (•). Lines a and b represent the relation found for fibrinogen and albumin respectively. (B) Relation found for a serially diluted pool (n = 12) of control (c) and nephrotic plasmas (n).


   Discussion
Top
 Abstract
 Introduction
 Patients and Methods
 Results
 Discussion
References
 
plasma protein composition
Despite the exceptions noted, the size of the protein seems to be highly determinant in the relative composition of nephrotic plasma, a concept that is reinforced by the correlations among these proteins and the plasma albumin concentration. Albumin is the only protein that has been extensively investigated in nephrotic syndrome. The amount of albumin lost daily in the urine of nephrotic patients is usually lower than the normal daily hepatic synthesis of albumin, and thus albuminuria is a necessary but not sufficient contributor to the development of hypoalbuminemia. Therefore, either an increase in the catabolism or an insufficient increase in the synthetic rate of albumin has been proposed (27)(28). According to our data, similar reasoning should be applied to a number of proteins of similar or lower molecular masses that are low in nephrotic plasma in roughly the same proportion and that show significant interrelations. This might also explain why urinary protein losses correlate with the plasma albumin concentration, but only rather crudely. In nephrotic plasma, the relative abundance of albumin is substituted by a predominant presence of proteins of higher molecular mass (and radius) than albumin. Some of these proteins show an inverse relation; the lower the plasma albumin concentration, the higher their concentration. These proteins are obviously restricted from passing into the glomerular ultrafiltrate, and although even very large proteins may be found in urine, their daily urinary excretion is usually a small percentage of the total plasma protein pool (29)(30). This could explain the increased plasma concentration of these proteins in nephrotic patients but not the significant inverse correlations found. Metabolic derangements, increased synthesis, or delayed catabolism, already described for apo B (9)(31), might be explanations of this finding. There is much evidence to suggest that the signal (or signals) for these metabolic alterations is low plasma {pi} and (or) low plasma {eta} (15)(32)(33), although a minor but distinct contribution by proteinuria per se cannot be discarded (16)(34).

plasma {pi} and {eta}
Plasma {pi} and plasma {eta} appear to be maintained in nephrotic plasma by different proteins. Plasma {pi} and {eta} are not interrelated but may be predicted from total plasma protein and albumin concentrations, suggesting a relation that is dependent on the relative abundance of albumin and nonalbumin proteins. Nephrotic plasma is not efficient at maintaining plasma {pi}, which is mostly correlated with the plasma concentration of proteins with similar or lower molecular mass than albumin. In contrast, nephrotic plasma with high concentrations of large and very large proteins is highly efficient at maintaining plasma {eta}. Low plasma {pi} is invariably seen in overt nephrotic syndrome, but we confirm data from Appel et al. (12) that plasma {eta} in nephrotic patients may be normal or even high. This finding has been used as an argument against the proposed role of low plasma {eta} in generating a metabolic response. In our opinion, this argument cannot be sustained because one may presume that a final metabolic balance is reached in the overt nephrotic syndrome after a variable length of time. In the initial stages, conceivably there is no increase in the plasma concentration of large proteins and therefore low plasma {eta} values can be predicted.

nephrotic hyperlipidemia
Nephrotic hyperlipidemia occurs as a result of both increased hepatic synthesis and decreased lipoprotein clearance, although the relative contribution of each and the actual molecular mechanism are controversial. The influence of low plasma {pi} in the generation of nephrotic hyperlipidemia seems to be firmly established (13)(14), but there is little evidence as regards low plasma {eta}. In contrast to Appel et al. (12), we found no correlation between plasma {pi} and plasma cholesterol but we did find a strong and positive correlation between plasma {eta} and plasma cholesterol and consequently LDL cholesterol and LDL apo B. The discrepancy may be well explained because we used plasma instead of serum, thus introducing the influence of plasma fibrinogen in these measurements. However, this cannot reinforce the idea that low plasma {eta} is a mediator of enhanced lipoprotein production because if this were the case, an inverse correlation would be expected. Moreover, there is a marked hyperlipidemia in nephrotic patients and plasma apoproteins represent 7.4% of the total amount of proteins (vs 4.5% in controls), factors that could make some contribution to the plasma {eta}. Although controversial, nephrotic hyperlidemia may increase the likelihood of atherosclerosis (35), but the protein alterations described, especially the high plasma concentrations of fibrinogen (36) and the low antithrombin III concentrations (37), definitely predispose to thrombosis.

hepatic response
The fact that the main metabolic response is mediated by the liver may be exemplified by analyzing plasma immunoglobulin concentration. Plasma immunoglobulins represent 21.8% of total plasma protein in controls, a similar figure to the one found in nephrotics (22.5%), quantitatively second only to liver-derived proteins. Plasma IgG significantly decreases as a consequence of urinary losses because of the absence of any counterregulatory response in the form of increased IgG synthesis (28)(38)(39), and this may account for a higher predisposition to bacterial infection (40). IgM plasma concentrations were normal and IgA concentrations were higher than in controls, which probably reflects the immunologic basis of the renal disease (41). We should recognize, however, that we have selected the two extremes, healthy controls and overt nephrotic syndrome, but there are many cases with evolving nephrotic syndrome in which the hepatic response and the consequences in plasma may be different.

In summary, our findings indicate that the plasma protein abnormalities found in nephrotic syndrome are responsible for changes in plasma {pi} and {eta} in close dependence on the molecular mass of the proteins considered, small and medium-sized proteins influencing plasma {pi} and large or very large proteins, including lipoproteins, influencing plasma {eta}. All this is indicative of complex and nonuniform hepatic responses to albuminuria that should be further investigated.


   Acknowledgments
 
This work was supported by grants from the Fondo de Investigaciones de la Seguridad Social and the Comissionat per a Universitats i Recerca de la Generalitat de Catalunya. We are indebted to Laboratorios Cerba and Boehringer Mannheim for technical assistance in the measurement of some laboratory values.


   References
Top
 Abstract
 Introduction
 Patients and Methods
 Results
 Discussion
 References
 

  1. Brenner BM, Hostelter TH, Humes HD. Molecular basis of proteinuria of glomerular origin. N Engl J Med 1978;298:826-833. [Web of Science][Medline] [Order article via Infotrieve]
  2. Peterson PA, Evrin PE, Berggard I. Differentiation of glomerular, tubular and normal proteinuria: determination of urinary excretions of beta2-microglobulin, albumin and total protein. J Clin Invest 1969;48:1189-1198.
  3. Maack TH, Johnson V, Dau ST, Figueirido J, Sigulem D. Renal filtration transport and metabolism of low molecular weight proteins: a review. Kidney Int 1979;16:251-270. [Web of Science][Medline] [Order article via Infotrieve]
  4. Gitlin D, Janeway CA, Farr LE. Studies on the metabolism of plasma proteins in nephrotic syndrome. I. Albumin, gamma-globulin and iron binding globulin. J Clin Invest 1956;35:44-55.
  5. Sun X, Martin V, Weiss RH, Kaysen GA. Selective transcriptional augmentation of hepatic gene expression in the rat with Heymann nephritis. Am J Physiol 1993;264:F441-F444. [Abstract/Free Full Text]
  6. Kaysen GA, Gambertoglio J, Jiménez I, Jones H, Hutchinson FN. Effect of dietary protein intake on albumin homeostasis in nephrotic patients. Kidney Int 1986;29:572-577. [Web of Science][Medline] [Order article via Infotrieve]
  7. Marshall JF, Apostolopoulos JJ, Brack CM, Howlett GJ. Regulation of apolipoprotein gene expression and plasma high density lipoprotein composition in experimental nephrosis. Biochim Biophys Acta 1990;1042:271-279. [Medline] [Order article via Infotrieve]
  8. Sun X, Jones H, Joles JA, van Tol A, Kaysen GA. Apolipoprotein gene expression in analbuminemic rats and in rats with Heymann nephritis. Am J Physiol 1992;262:F755-F761. [Abstract/Free Full Text]
  9. Joven J, Villabona C, Vilella E, Masana L, Albertí R, Vallés M. Abnormalities of lipoprotein metabolism in patients with the nephrotic syndrome. N Engl J Med 1990;323:579-584. [Abstract]
  10. Marsh JB. Lipoprotein metabolism in experimental nephrosis. J Lipid Res 1984;25:1619-1623. [Web of Science][Medline] [Order article via Infotrieve]
  11. Kaysen GA. Nonrenal complications of the nephrotic syndrome. Annu Rev Med 1994;45:201-210. [Web of Science][Medline] [Order article via Infotrieve]
  12. Appel GB, Blum CB, Chien S, Kunis CL, Appel AS. The hyperlipidemia of the nephrotic syndrome. N Engl J Med 1985;312:1544-1548. [Abstract]
  13. Baxter JH, Goodman HC, Allen JC. Effect of infusion of serum albumin on serum lipids and lipoproteins in nephrosis. J Clin Invest 1961;40:490-498.
  14. Allen JC, Baxter JH, Goodman HC. Effects of dextran, polyvinylpyrrolidone and gamma globulin on the hyperlipidemia of experimental nephrosis. J Clin Invest 1961;40:499-508.
  15. Yedgar S, Weinstein DB, Patsch W, Schonfeld G, Casanada FE, Steinberg D. Viscosity of culture medium as a regulator of synthesis and secretion of very low density lipoproteins by cultured hepatocytes. J Biol Chem 1982;257:2188-2192. [Abstract/Free Full Text]
  16. Joven J, Espinel E, Simó JM, Vilella E, Camps J, Oliver A. The influence of hypoalbuminemia in the generation of nephrotic hyperlipidemia. Atherosclerosis 1996;126:243-252. [Web of Science][Medline] [Order article via Infotrieve]
  17. Joven J, Simó JM, Vilella E, Camps J, Espinel E, Villabona C. Accumulation of atherogenic remnants and lipoprotein(a) in the nephrotic syndrome: relation to remission of proteinuria. Clin Chem 1995;41:908-913. [Abstract/Free Full Text]
  18. Joven J, Vilella E, Costa B, Turner P, Richart C, Masana L. Concentrations of lipids and apolipoproteins in patients with well-controlled insulin-dependent and non-insulin dependent diabetes. Clin Chem 1989;35:813-816. [Abstract/Free Full Text]
  19. Simó JM, Joven J, Clivillé X, Sans T. Automated latex agglutination immunoassay of serum ferritin with a centrifugal analyzer. Clin Chem 1994;40:625-629. [Abstract/Free Full Text]
  20. International Committee for Standardization in Haemotology: recommendation for a selected method for the measurement of plasma viscosity. J Clin Pathol 1984;37:1147–52..
  21. Simó J, Bertran N, Juanpere M, Camps J, Joven J. Evaluación preliminar del analizador automático Monarch 2000. Quim Clin 1989;8:329-335.
  22. Stierle HE, Oser B, Boesken WH. Improved classification of proteinuria by semiautomated ultrathin SDS polyacrylamide gel electrophoresis. Clin Nephrol 1990;33:168-173. [Web of Science][Medline] [Order article via Infotrieve]
  23. Domenech JM, Riba MD. Métodos estadísticos. Modelo lineal de regresión. Barcelona, Spain: Editorial Herder, 1985..
  24. Nitta A, Ohnuki T, Kazuhiro O, Nakada T, Staub NC. The corrected protein equation to estimate plasma colloid osmotic pressure and its development on a normogram. Tohoku J Exp Med 1981;135:43-49. [Web of Science][Medline] [Order article via Infotrieve]
  25. Canaan-Kühl S, Venkatraman ES, Ernst SI, Olshen RA, Myers BD. Relationships among protein and albumin concentrations and oncotic pressure in nephrotic plasma. Am J Physiol 1993;264:F1052-F1059. [Abstract/Free Full Text]
  26. Deen WM, Robertson CR, Brenner BM. A model of glomerular ultrafiltration in the rat. Am J Physiol 1972;223:1178-1183. [Free Full Text]
  27. Kaysen GA, Jones H, Martin V, Hutchinson FN. Low-protein diet restricts albumin synthesis in nephrotic rats. J Clin Invest 1987;83:1623-1629.
  28. Kaysen GA, Al Bander H. Metabolism of albumin and immunoglobulins in the nephrotic syndrome. Am J Nephrol 1990;10(Suppl 1):36-42.
  29. Shore VG, Forte T, Licht H, Lewis SB. Serum and urinary lipoproteins in the human nephrotic syndrome: evidence for renal catabolism of lipoproteins. Metabolism 1982;31:258-268. [Web of Science][Medline] [Order article via Infotrieve]
  30. Rydzewsky A, Myslielec M, Soszka J. Concentration of three thrombin inhibitors in the nephrotic syndrome in adults. Nephron 1986;42:200-203. [Web of Science][Medline] [Order article via Infotrieve]
  31. Warwick GL, Caslake MJ, Boulton-Jones JM, Dagen M, Packard CJ, Shepherd J. Low-density lipoprotein metabolism in the nephrotic syndrome. J Metabolism 1990;39:187-192.
  32. Dich J, Hansen SE, Thieden H. Effect of albumin concentration and colloid osmotic pressure on albumin synthesis in the perfused rat liver. Acta Physiol Scand 1973;89:352-358. [Web of Science][Medline] [Order article via Infotrieve]
  33. Appel G. Lipid abnormalities in renal disease. Kidney Int 1991;39:169-183. [Web of Science][Medline] [Order article via Infotrieve]
  34. Davies RW, Staprans I, Hutchison FN, Kaysen GA. Proteinuria, not altered albumin metabolism, affects hyperlipidemia in the nephrotic rat. J Clin Invest 1990;86:600-605.
  35. Mallick NP, Short CD. The nephrotic syndrome and ischaemic heart disease. Nephron 1981;27:54-57. [Web of Science][Medline] [Order article via Infotrieve]
  36. Llach F, Arieff AI, Massry SG. Renal vein thrombosis and nephrotic syndrome: a prospective study of 36 adult patients. Ann Intern Med 1975;83:8-14.
  37. Kauffman RH, Veltkamp JJ, Van Tilburg NH, Van Es LA. Acquired antithrombin III deficiency and thrombosis in the nephrotic syndrome. Am J Med 1978;65:607-613. [Medline] [Order article via Infotrieve]
  38. Deen WM, Bridges CR, Brenner BM, Myers BD. Heteroporous model of glomerular size selectivity: application to normal and nephrotic humans. Am J Physiol 1985;249:F374-F389.
  39. Giangiacomo J, Cleary TG, Cole BR, Hoffsten P, Robson AM. Serum immunoglobulins in the nephrotic syndrome. A possible cause of minimal-change nephrotic syndrome. N Engl J Med 1975;293:8-12. [Abstract]
  40. Yokoyama H, Kida H, Tani Y, Abe T, Tomosugi N, Koshino Y, Hattori N. Immunodynamics of minimal change nephrotic syndrome in adults' T and B lymphocyte subsets and serum immunoglobulin levels. Clin Exp Immunol 1985;61:601-607. [Web of Science][Medline] [Order article via Infotrieve]
  41. Beale MG, Nash GS, Bertovich MJ, MacDermott RP. Immunoglobulin synthesis by peripheral blood mononuclear cells in minimal change nephrotic syndrome. Kidney Int 1983;23:380-386. [Web of Science][Medline] [Order article via Infotrieve]




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