Session Information
Session Type: Abstract Submissions (ACR)
Background/Purpose: Vascular cell adhesion molecule-1 (VCAM-1), an adhesion molecule, is involved in the progression of glomerular and tubulointerstitial injury. High levels of VCAM-1 have been found in the urine of patients with active lupus nephritis. Angiostatin, due to its anti-inflammatory action, has been shown to improve kidney function in murine models. Over expression of angiostatin inhibits leukocyte and macrophage migration and recruitment. We investigated both VCAM-1 and angiostatin as potential biomarkers for lupus nephritis.
Methods:
VCAM-1 and angiostatin were measured during 2 to 16 clinic visits in 17 SLE patients (82% female, 42% African-American, 45% Caucasian, and 13% others) for a total of 88 visits by ELISA (R&D). Mean age was 38 years. We analyzed the relationship between these potential urine biomarkers and the urine protein/creatinine ratio (urine Pr/Cr), the SLICC Renal Activity Score, SLEDAI renal descriptors and other clinical variables.
Results:
Table 1: Mean (SD) Log-transformed and Normalized (by urine creatinine) VCAM-1 and Angiostatin, by Clinical Variables at Each Visit
|
|
Clinical Variables at Each Visit |
VCAM-1 |
Angiostatin |
||
|
Mean (SD) |
P-value* |
Mean (SD) |
P-value* |
||
|
Age, years
|
21-44 (n=65) 45-70 (n=23) |
9.1 (2.4) 9.2 (1.2) |
0.99
|
5.1 (1.6) 6.1 (1.8) |
0.019 |
|
Sex
|
Female (n=72) Male (n=16) |
9.2 (2.3) 8.9 (1.1) |
0.63 |
5.4 (1.6) 5.5 (2.1) |
0.77 |
|
Ethnicity
|
Caucasian (n=40) African American (n=37) Other (n=11) |
8.4 (2.7) 9.7 (1.1) 9.9 (1.0) |
0.086 |
4.7 (1.5) 6.0 (1.6) 5.8 (2.2) |
0.21 |
|
Physician’s Global Assessment |
≥1.5 (n=64) <1.5 (n=24) |
9.7 (1.1) 7.5 (3.2) |
0.0069 |
5.9 (1.6) 4.1 (1.3) |
<0.0001 |
|
Hematuria
|
Present (n=14) Absent (n=74) |
9.2 (1.4) 9.1 (2.2) |
0.12 |
5.0 (1.6) 5.5 (1.7) |
0.65 |
|
Proteinuria
|
Present (n=26) Absent (n=62) |
9.9 (1.1) 8.8 (2.4) |
0.089 |
6.2 (1.4) 5.0 (1.7) |
0.012 |
|
Pyuria
|
Present (n=10) Absent (n=78) |
9.7 (1.4) 9.0 (2.2) |
0.94 |
5.2 (1.4) 5.4 (1.8) |
0.74 |
|
Anti-dsDNA
|
Present (n=37) Absent (n=51) |
9.9 (0.9) 8.6 (2.5) |
0.088 |
5.6 (1.8) 5.2 (1.6) |
0.31 |
|
Low C3 or C4
|
Present (n=31) Absent (n=55) |
10.1 (1.0) 8.6 (2.4) |
0.059 |
5.6 (1.9) 5.3 (1.6) |
0.12
|
|
Urine Protein/Creatinine Ratio |
≥0.5 (n=64) <0.5 (n=22) |
9.6 (1.2) 8.0 (2.9) |
0.022 |
5.9 (1.6) 3.8 (1.0) |
<0.0001 |
|
Renal Failure
|
Ever (n=3) Never (n=85) |
7.8 (1.1) 9.2 (2.1) |
0.28 |
4.6 (1.2) 5.4 (1.7) |
0.12 |
|
Hydroxychloroquine
|
Yes (n=66) No (n=22) |
8.9 (2.3) 9.8 (1.2) |
0.22 |
5.4 (1.8) 5.5 (1.6) |
0.41 |
|
Diabetes mellitus
|
Present (n=9) Absent (n=79) |
9.9 (1.1) 9.0 (2.2) |
0.38 |
6.7 (1.3) 5.2 (1.7) |
0.096 |
|
Use of ACE/ARB inhibitor |
Yes (n=64) No (n=24) |
9.2 (2.1) 8.9 (2.3) |
0.36 |
5.5 (1.7) 5.1 (1.7) |
0.79 |
|
SLICC Renal Activity Score |
≥4 (n=51) <4 (n=29) |
9.8 (1.1) 8.4 (2.7) |
0.036 |
6.1 (1.6) 4.2 (1.3) |
<0.0001 |
*P-values are based on a mixed effects model to account for the fact that some patients contributed multiple observations.
Conclusion:
Both urine VCAM-1 and angiostatin had a strong association with multiple renal activity descriptors. However, in contrast to a previous murine study which showed angiostatin may improve kidney function, our study showed the reverse (Am J Physiol Renal Physiol 2009:F145-152). Further studies of urinary VCAM-1 and angiostatin with larger sample size, and long-term renal outcomes ARE justified.
Disclosure:
A. Kiani,
None;
H. Fang,
None;
T. Wu,
None;
C. Mohan,
None;
M. Petri,
None.
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