Plasma IgG pool is not defended from urinary loss in nephrotic syndrome.
In the nephrotic syndrome, the plasma level of some proteins of hepatic origin is partially defended by an increase in their synthetic rate. The plasma levels of several liver-derived proteins, as well as immunoglobulin G (IgG) are increased in one condition where plasma albumin concentration and oncotic pressure (II) are reduced, i.e., hereditary analbuminemia. To determine whether the urinary loss of IgG, a protein derived from the immune system, is compensated for by an increased synthetic rate, we measured IgG synthesis in normal Sprague-Dawley rats (SD); two models of the nephrotic syndrome: Heymann nephritis (HN) and Adriamycin treatment; and in Nagase analbuminemic rats (NAR), a model of decreased II without urinary protein loss. Plasma IgG and total IgG mass were significantly reduced in both HN and Adriamycin, yet IgG synthesis was nearly identical in HN, Adriamycin, and SD. In contrast, plasma and total IgG and IgG synthesis were all markedly increased in NAR. We derived a pathogen-free colony of NAR by Caesarean section and found that plasma IgG was not increased in pathogen-free NAR, despite reduced II. Thus, unlike proteins of hepatic origin (e.g., albumin) where synthesis increases following urinary loss, no compensatory increase in IgG synthesis occurs. Increased plasma IgG as well as IgG synthesis in the NAR is not a compensatory response to the absence of albumin or reduction in II, but rather is due to subclinical infection. Profound hypogammaglobulinemia of nephrotic syndrome occurs in part because no compensatory synthetic mechanisms balance urinary loss, and alteration in plasma II does not modulate IgG synthesis.
al-Bander
H A
HA
Department of Medicine, Veterans Affairs Medical Center, Martinez, California 94553.
Martin
V I
VI
Kaysen
G A
GA
D000818:Animals; D004195:Disease Models, Animal; D004317:Doxorubicin / Q000633:toxicity; D005921:Glomerulonephritis / Q000097:blood* / Q000276:immunology / Q000652:urine; D006706:Homeostasis; D007075:Immunoglobulin M / Q000378:metabolism* / Q000652:urine; D008297:Male; D009404:Nephrotic Syndrome / Q000097:blood* / Q000276:immunology / Q000652:urine; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D012709:Serum Albumin / Q000172:deficiency*
D007075:Immunoglobulin M; D012709:Serum Albumin; D004317:Doxorubicin