title: Transferrin synthesis is increased in nephrotic patients insufficiently to replace urinary losses.
abstract: The urinary loss of transferrin is sufficient to reduce plasma transferrin concentrations in the nephrotic syndrome. Hypotransferrinemia may lead to iron loss and microcytic anemia. The mechanism responsible for the hypotransferrinemia in the nephrotic syndrome is, however, unknown. In the present study, synthesis rate of transferrin was measured in vivo in nephrotic patients (n = 7) compared with control subjects (n = 6) using L-[1-(13)C]-valine. Plasma transferrin and iron concentration in the patients were significantly lower than in control subjects (transferrin, 1.39 +/- 0.08 versus 2.57 +/- 0.11 g/L, P < 0.0001; iron, 10.2 +/- 0.8 versus 21.1 +/- 4.5 micromol/L, P = 0.02). Furthermore, albuminuria correlated with transferrinuria (r(2) = 0.901, P = 0.001). The absolute synthesis rate of transferrin was increased in the patients (10.0 +/- 1.1 versus 7.4 +/- 0.7 mg/kg per d, P = 0.07), although this value failed to achieve significance. C-reactive protein, plasma iron, and proteinuria did not correlate with transferrin synthesis. In contrast, transferrin synthesis correlated with albumin synthesis (r(2) = 0.648, P = 0.03; n = 7). The present study indicates that increased transferrin synthesis occurs in nephrotic patients but is insufficient to compensate for urinary losses. Because, overall, no significant relationship was found between transferrin synthesis and either C-reactive protein or iron, it is unlikely that inflammation suppresses or that iron deficiency stimulates increased transferrin synthesis in these patients. The correlation between transferrin synthesis and albumin synthesis suggests that transferrin synthesis is a component of a general response in hepatic protein synthesis in the nephrotic syndrome. This suggests that a therapeutic approach to maximize plasma transferrin concentrations in nephrotic patients should be aimed primarily at reducing urinary protein excretion.
authors.affiliation: Department of Vascular Medicine and Metabolism, University Medical Center Utrecht, Utrecht, The Netherlands.|Department of Clinical Chemistry, University Medical Center Utrecht, Utrecht, The Netherlands.|Department of Metabolic Diseases, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Berthil H C M T
authors.initials: BHCMT
authors.lastname: Prinsen
authors.affiliation: Department of Metabolic Diseases, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Monique G M DE Sain-VAN DER
authors.initials: MGMS
authors.lastname: Velden
authors.affiliation: Department of Medicine, Division of Nephrology, University of California-Davis, Davis, and Department of Veterans Affairs Northern California System of Clinics, Mather, California.
authors.forename: George A
authors.initials: GA
authors.lastname: Kaysen
authors.affiliation: Department of Metabolic Diseases, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Helma W H C
authors.initials: HWHC
authors.lastname: Straver
authors.affiliation: Department of Clinical Chemistry, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Herman J M VAN
authors.initials: HJMV
authors.lastname: Rijn
authors.affiliation: Department of Nutrition and Metabolism, University Hospital Groningen, Groningen, The Netherlands.
authors.forename: Frans
authors.initials: F
authors.lastname: Stellaard
authors.affiliation: Department of Metabolic Diseases, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Ruud
authors.initials: R
authors.lastname: Berger
authors.affiliation: Department of Vascular Medicine and Metabolism, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Ton J
authors.initials: TJ
authors.lastname: Rabelink
mesh_terms: D000328:Adult; D000418:Albumins / Q000096:biosynthesis; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007501:Iron / Q000097:blood; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D009404:Nephrotic Syndrome / Q000150:complications / Q000378:metabolism* / Q000652:urine; D011507:Proteinuria / Q000209:etiology / Q000378:metabolism; D014168:Transferrin / Q000096:biosynthesis* / Q000652:urine
chemical_list: D000418:Albumins; D014168:Transferrin; D007501:Iron