Wada T, Yokoyama H, Su, S, Mukaida N, Iwano M, et al
Monitoring urinary levels of chemotactic and activating factor
reflects disease activity of lupus nephritis
(Mar) 49:761-767 1996
Nephrologists caring for patients with lupus nephritis (LN) are yet to
find a reliable noninvasive laboratory test to monitor disease
activity. ESR, antinuclear antibodies, anti-dsDNA levels have been
found not to be useful . Although complement levels may be more
reliable, they are of no benefit in patients with hereditary
complement deficiency states. Wada et al have evaluated whether
urinary and serum levels of monocyte chemotactic and activating factor
(MCAF), also known as monocyte chemotactic protein (MCP-1), and of IL
- 8 can fulfill the promise of being reliable markers of active LN.
Forty two patients with various lesions of LN and 22 volunteers were
entered into the study. Eight patients with minimal change disease
served as controls with noninflammatory lesions. Urinary and serum
MCAF and IL-8 levels were measured by ELISA.
Urinary MCAF levels were significantly higher in patients with active
diffuse LN (class IV) compared to control volunteers. Although
patients with class IVb and c lesions had higher urinary MCAF levels
than patients with other LN lesions, the differences did not achieve
statistical significance. Serum levels of MCAF were higher in LN
patients, regardless of the activity of the lesions.
Immunohistochemistry and in-situ hybridization with MCAF probe
localized the protein and mRNA to tubular epithelium, endothelium of
interstitial blood vessels and tubulointerstitial macrophages;
surprisingly, glomerular cells were not involved.
Urinary IL-8 levels were increased in patients with active LN but did
not correlate with urinary MCAF levels. Steroid therapy resulted in
decrease in urinary levels of both MCAF and IL-8.
Comment: Although the data are interesting because these
chemokines have received so much attention recently, several issues
need to be resolved before MCAF assay can be considered for patient
monitoring. The variability of the urinary and serum levels of the
chemokine are too large. Although as a group the patients with active
lesions had higher MCAF levels in the urine whether this would hold
for the individual patient is doubtful. The response of the urinary
levels of MCAF to steroids in the group IV patients was also variable
with nearly half the patients not showing any differences.
Furthermore, despite localization of the protein and mRNA transcript
to the tubulointerstitium, the urinary levels of MCAF did not
correlate with severity of interstitial nephritis. Additionally,
there was no glomerular localization of the probes despite a diffuse
nephritic process, raising issue with the ability of these probes to
predict glomerular inflammation. (B.S. Kasinath, M.D., University
of Texas as San Antonio)