HDCN Article Review/Hyperlink

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

Kidney Int (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)