Anionic versus Cationic Immunoglobulin Clearance in Normal Subjects: A Novel Approach to the Evaluation of Charge Permselectivity

Abstract

The excretion of proteins differing in charge (the different immunoglobulin subclasses) and/or size (albumin, immunoglobulins) were investigated in normal subjects in a number of physiological conditions aiming at the evaluation of renal charge permselectivity. In 101 randomly selected normal subjects the urinary excretion rates of albumin, IgG₄ (anionic proteins) and of total IgG (mostly cationic) were evaluated in basal conditions; the protein/creatinine urinary ratio and protein clearances were assessed in part of them. In addition, the intra- and interday variations of protein excretion were evaluated. Protein clearances were measured in a sample group after standardized physical exercise, after an amino acid load, and in orthostatism. Albumin, IgG₄ and IgG were assayed using sensitive methods developed in our laboratories. The excretion rate values of albumin, IgG₄ and total IgG (median, interquartile range) were 4.36 µg/min, (2.58–6.59), 4.25 ng/min (2.6–7.6), and 1.47 µg/min (0.85–2.44), respectively. The clearances of the three proteins (mean ± SD) were 0.13 ± 0.07, 0.017 ± 0.012 and 0.14 ± 0.08 ml/ min × 10 ³, respectively. The IgG₄/IgG ratio averaged 0.1 and was always below 0.25. Protein excretion rates showed a noticeable variation during the day and from day to day. Physical exercise, the change of posture and the amino acid load significantly increased proteinuria but did not significantly modify the anionic/cationic immunoglobulin ratio. Thus, the anionic/cationic immunoglobulin ratio of about one tenth, substantially stable during dynamic tests, in normal subjects may be considered an index of physiological renal protein charge permselectivity.

Charge Selectivity of Proteinuria in Type I Diabetes Explored by Ig Subclass Clearance

“…Several studies in limited cohorts of dia-betic patients have confirmed the potentiality of this approach and the validity of the hypothesis (21,(24)(25)(26). Sensitive methods to detect the tiny amounts of urinary IgGs had to be developed (29,30), and clearances have been calculated to take into account possible individual variations in protein blood concentrations (29,32). Previous work in nondiabetic subjects has shown that the clearance of anionic IgGs is lower than that of neutral/ cationic IgGs (32), thus confirming in humans the restricted filtration of anionic proteins seen in animal studies and that the anionic-cationic Ig ratio is not influenced by individual protein clearance changes in physiological conditions.…”

Charge and size selectivity of proteinuria in children with idiopathic nephrotic syndrome

“…Charge selectivity was assessed by studying the albumin/ transferrin and the IgG4/IgG1 clearance ratios [13]. The molecular radii and pI of the proteins measured were: albumin 3.8 nm, pI range 4.6 -6; transferrin 3.6 nm, pI 5.9; IgG1 5.5 nm, pI range 7 -9; IgG4 5.5 nm, pI 56.0.…”

Multivalent Poly(ethylene glycol)-Containing Conjugates for In Vivo Antibody Suppression

“…The domain 1 polypeptide is positively charged due to an excess of positively charged amino acids, and it is well-known that charge can affect clearance from circulation. The glomerular filtration rate of anionic IgG has been shown to be slower than that of cationic IgG (28). Similarly, it has been demonstrated that the kidney filtration rate of dextran depends on charge, with positively charged molecules clearing faster than negatively charged molecules (29).…”