Abstract
The charge selectivity (CS) function in human renal disease has not been unequivocally demonstrated to date. However, the clearance ratio of IgA to IgG may be theoretically useful in estimating CS in humans, since IgA and IgG have similar sizes and tertiary structures, but distinct isoelectric points (3.5–5.5 [IgA] and 4.5–9.0 [IgG]), and Stokes-Einstein radius: 61 Å (IgA) and 49–60 Å (IgG). Two-dimensional electrophoresis with the following immunoblotting revealed that the considerably anionic portion (isoelectric points [pI] <4.0) of IgA, visible in serum, was absent in the urine in steroid-sensitive nephrotic syndrome (SSNS) but present in the same during IgA nephropathy (IgAN) and membranoproliferative glomerulonephritis (MPGN). A latex assay revealed the CS index (CSI) was significantly low in patients with podocyte disease (group A), including SSNS, focal and segmental glomerulosclerosis (FSGS) and Finnish-type congenital nephrotic syndrome (FCNS), but high in those with Alport syndrome (AS), IgAN, Henoch-Schönlein purpura nephritis (HSPN), and MPGN (group B). The linear regression analysis of the IgA size selectivity index (IgA SSI; clearance ratio of IgA to transferrin) and SSI (clearance ratio of IgG to transferrin), which represents the clearance ratio of IgA to IgG referring to the transferrin clearance, revealed the influence of the charge more accurately. Indeed, the slope of the regression lines of IgA SSI (y) to SSI (x) were concluded to be y = 0.39x (group A) and y = 1.05x (group B), respectively. These results suggested that the charge selective barrier among podocyte diseases (group A) is preserved to some degree, but lost in cases of nephritis and AS (group B).
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Abbreviations
- AS:
-
Alport syndrome
- CSI:
-
charge selectivity index
- FCNS:
-
Finnish-type congenital nephrotic syndrome
- FSGS:
-
focal and segmental glomerulosclerosis
- GBM:
-
glomerular basement membrane
- GCW:
-
glomerular capillary wall
- IgAN:
-
IgA nephropathy
- IgA SSI:
-
IgA size selectivity index
- MPGN:
-
membranoproliferative glomerulonephritis
- SSNS:
-
steroid-sensitive
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This work was supported by a Grant-in-Aid from the Japanese Society for Promotion of Science (17591118 to S. Takahashi).
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Takahashi, S., Watanabe, S., Wada, N. et al. Charge Selective Function in Childhood Glomerular Diseases. Pediatr Res 59, 336–340 (2006). https://doi.org/10.1203/01.pdr.0000196733.47083.81
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DOI: https://doi.org/10.1203/01.pdr.0000196733.47083.81
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