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Significance of urinary complement components in various glomerular diseases
K Sakakibara1, T Urano, Y Takada
1Department of Physiology, Hamamatsu University, School of Medicine, Shizuoka-ken, Japan.
Insights
Urinary C1q and C3 levels indicate complement system activation in glomerular diseases. Elevated levels correlate with immune complex deposits, aiding diagnosis.
Area of Science:
- Nephrology
- Immunology
- Clinical Chemistry
Background:
- The complement system plays a crucial role in immune responses and kidney diseases.
- Assessing complement component levels in urine may offer insights into glomerular pathology.
Purpose of the Study:
- To investigate the urinary excretion of complement components C1q and C3 in patients with glomerulonephritis.
- To correlate urinary C1q and C3 levels with intraglomerular immune complex deposition and disease activity.
Main Methods:
- Enzyme immunoassay was used to measure C1q and C3 concentrations in urine and blood.
- Fractional clearance ratios relative to neutral dextran were calculated.
- Urinary C1q and C3 excretion patterns were analyzed in normal subjects and patients with various glomerulonephritis types.
Main Results:
- Urinary C1q and C3 excretion significantly increased in active lupus nephritis, membranoproliferative glomerulonephritis, membranous glomerulonephritis, and IgA nephropathy with capillary deposits.
- Lower urinary levels were observed in minimal lesion nephrotic syndrome, mild proliferative glomerulonephritis, inactive lupus nephritis, and diabetic nephropathy.
- Urinary C1q and C3 excretion correlated with intraglomerular immune complex deposition, particularly along the glomerular capillary wall.
Conclusions:
- Urinary C1q and C3 excretion reflects complement fixation by intraglomerular immune complexes.
- Measurement of urinary complement components offers a novel diagnostic approach for glomerular diseases.
- This method provides valuable clues for the investigation and diagnosis of various kidney conditions.
Abstract:
The concentrations of two components of the complement system (C1q and C3) were measured in the urine and blood in 10 normal subjects and 134 patients with primary and secondary glomerulonephritis by using a highly sensitive enzyme immunoassay. The values of urinary excretion of C1q and C3 were well correlated to the ratios of fractional clearance of these complement proteins to that of neutral dextran of 55 A, which was used to minimize the influences of glomerular sieving because of their comparable molecular size to these complement components. The rate of renal tubular reabsorption of C1q and C3 were at least 89.2 and 93.4% of filtrated C1q and C3, respectively. Urinary C1q and C3 were excreted significantly in cases of membranoproliferative glomerulonephritis (MPGN), membranous glomerulonephritis, IgA nephropathy with both mesangial and capillary immune complex (IC) deposit and also in case of active lupus nephritis. On the other hand, the concentrations of these complement components were low in case of minimal lesion nephrotic syndrome, mild proliferative glomerulonephritis, inactive lupus nephritis and diabetic nephropathy without any immune staining. There was a significant correlation between the urinary excretion of C1q or C3 and intraglomerular IC deposition, especially IC deposition along the glomerular capillary wall. However, the degree of the excretion of these proteins was not correlated to the degree or permselectivity of proteinuria. The correlations between urinary C1q and C3 were observed in cases of IgA nephropathy with both mesangial and capillary deposit and MPGN, although we couldn't see the correlation in the other glomerular diseases. It is suggested that urinary excretion of such complement components represents the fixation of complement by deposited intraglomerular IC. The measurement of urinary concentration of these complement components provides a new clue to investigation or diagnosis of glomerular diseases.