Plasma α2 macroglobulin is increased in nephrotic patients as a result of increased synthesis alone

Monique G M De Sain-Van Der Velden, Ton J. Rabelink, Dirk Jan Reijngoud, Mireille M. Gadellaa, Hieronymus A M Voorbij, Frans Stellaard, George A. Kaysen

Research output: Contribution to journalArticlepeer-review

41 Scopus citations

Abstract

Background. α2 Macroglobulin (α2M), a protease inhibitor, is often increased in plasma of patients with the nephrotic syndrome. Although it has been speculated that synthesis is increased, no direct measurements have been performed. Methods. α2M synthesis in both normal subjects (N = 4) and nephrotic patients (N = 7) were measured using endogenous labeling with 13C valine in order to establish the mechanism of increased plasma level in the nephrotic syndrome and the relationship between α2M synthesis rate and plasma concentration over a wide range of plasma concentration values. A primed (15 μmol/kg)/continuous (15 μmol/kg/hr) infusion was administered for six hours. Blood samples were collected at different intervals and at each time point α2M was isolated from EDTA plasma using immunoprecipitation and SDS-polyacrylamide gel electrophoresis (PAGE). Care was taken to ensure that the α2M used for combustion had not been subjected to proteolysis. The rate of appearance of 13C valine derived from the isolated α2M was measured by gas chromatography combustion isotope ratio mass spectrometry. Results. Plasma α2M was significantly elevated in nephrotic subjects (3.13 ± 0.33 g/liter) versus controls (1.64 ± 0.15 g/liter; P = 0.012). The α2M fractional synthesis rate [(FSR), which is equal to fractional catabolic rate (FCR) in steady state] was the same in the two groups: 2.70 ± 0.18%/day for the nephrotic patients versus controls 2.74 ± 0.21%/day. However, the α2M absolute synthesis rate (ASR) was significantly (P = 0.012) increased in the patients (3.69 ± 0.33 mg/kg/day) versus controls (2.06 ± 0.35 mg/kg/day). Plasma α2M concentration correlated directly to its ASR (r2 = 0.821; P = 0.0001; N = 11). Conclusions. Increased plasma α2M concentration in nephrotic patients is therefore a result of increased synthesis alone.

Original languageEnglish (US)
Pages (from-to)530-535
Number of pages6
JournalKidney International
Volume54
Issue number2
DOIs
StatePublished - 1998

Keywords

  • α macroglobulin
  • Analbuminemia
  • FCR
  • Gas chromatography combustion isotope ratio mass spectrometry
  • Nephrotic syndrome
  • Protein
  • Stable isotopes
  • Valine tRNA pool

ASJC Scopus subject areas

  • Nephrology

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