Plasma α2 macroglobulin is increased in nephrotic patients as a result of increased synthesis alone
| Autor: | Monique G.M. de Sain-van der Velden, Mireille M. Gadellaa, Ton J. Rabelink, Dirk-Jan Reijngoud, George A. Kaysen, Frans Stellaard, H.A.M. Voorbij |
|---|---|
| Rok vydání: | 1998 |
| Předmět: |
Adult
Male medicine.medical_specialty α2 macroglobulin stable isotopes gas chromatography combustion isotope ratio mass spectrometry alpha-2-Macroglobulin Valine Internal medicine medicine Humans alpha-Macroglobulins Gel electrophoresis biology nephrotic syndrome Chemistry Albumin FCR Glomerulonephritis Liter medicine.disease Endocrinology analbuminemia Nephrology biology.protein Female Steady state (chemistry) protein Nephrotic syndrome valine tRNA pool |
| Zdroj: | Kidney International. 54:530-535 |
| ISSN: | 0085-2538 |
| DOI: | 10.1046/j.1523-1755.1998.00018.x |
| Popis: | Plasma α 2 macroglobulin is increased in nephrotic patients as a result of increased synthesis alone. Background α 2 Macroglobulin (α 2 M), 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 α 2 M synthesis in both normal subjects ( N = 4) and nephrotic patients ( N = 7) were measured using endogenous labeling with 13 C valine in order to establish the mechanism of increased plasma level in the nephrotic syndrome and the relationship between α 2 M 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 α 2 M was isolated from EDTA plasma using immunoprecipitation and SDS-polyacrylamide gel electrophoresis (PAGE). Care was taken to ensure that the α 2 M used for combustion had not been subjected to proteolysis. The rate of appearance of 13 C valine derived from the isolated α 2 M was measured by gas chromatography combustion isotope ratio mass spectrometry. Results Plasma α 2 M was significantly elevated in nephrotic subjects (3.13 ± 0.33g/liter) versus controls (1.64 ± 0.15g/liter; P = 0.012). The α 2 M 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 α 2 M absolute synthesis rate (ASR) was significantly ( P = 0.012) increased in the patients (3.69 ± 0.33mg/kg/day) versus controls (2.06 ± 0.35mg/kg/day). Plasma α 2 M concentration correlated directly to its ASR ( r 2 = 0.821; P = 0.0001; N = 11). Conclusions Increased plasma α 2 M concentration in nephrotic patients is therefore a result of increased synthesis alone. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|