Session Information
Date: Monday, November 9, 2015
Title: Systemic Lupus Erythematosus - Clinical Aspects and Treatment III: Biomarkers
Session Type: ACR Concurrent Abstract Session
Session Time: 2:30PM-4:00PM
Background/Purpose:
Urinary biomarkers may help in identification, treatment and assessment of response to therapy in patients with lupus nephritis (LN). Osteoprotegerin (OPG) is produced by the kidney and may reflect the renal disease activity better than conventional markers. The data on its utility is sparse.
Methods:
Patients with SLE with active nephritis (AN), active disease without nephritis (active non-renal; ANR) and inactive disease (ID) were enrolled. Disease activity was assessed using renal SLEDAI (rSLEDAI) and SLEDAI. Patients with active nephritis were treated according to the ACR guidelines and followed up every 3 months for 1 year. Urine and serum samples were collected at baseline for all and every 3 months in patients of AN group. Urine samples from 24 healthy subjects (HC) and 20 patients each of rheumatoid arthritis (RA) and diabetic nephropathy (DM) served as controls. Serum (sOPG) and urinary OPG were measured using ELISA and urinary values were normalized for creatinine excretion. Variables are expressed as median (range) and non-parametric tests were used for statistical analysis.
Results:
A total of 121 SLE patients (females 113) were enrolled. At baseline, normalized urinary OPG (uOPG) was significantly higher in AN group as compared to ANR, ID, HC and DM (p-value <0.001 for all) but it was not different from RA. At baseline, uOPG correlated modestly with rSLEDAI (r=0.4, p-value <0.001) and SLEDAI (r=0.317, p-value <0.001) but not with sOPG levels. uOPG but not sOPG could differentiate between AN and ANR groups (Table 1).
Table 1. Baseline characteristics of SLE patients in the three categories
|
|
Active Nephritis (AN) |
Active Non-Renal (ANR) |
Inactive Disease (ID) |
|
Number |
58 |
24 |
39 |
|
F:M |
56:2 |
19:5 |
38:1 |
|
Median age (yrs) |
27 (12 – 50) |
28.5 (15 – 50) |
28 (14 – 48) |
|
rSLEDAI |
8 (4 – 16) |
0 (0) |
0 (0) |
|
SLEDAI |
18 (6 – 28) |
10 (5 – 20) |
2 (0 – 4) |
|
C3 (mg/dl) |
48.5 (<16.9 – 125) |
66.7 (17.3 – 163) |
117 (34.2 – 194) |
|
C4 (mg/dl) |
7.8 (<5.6 – 55.7) |
11.05 (<5.6 – 32.2) |
24.15 (5.6 – 44.7) |
|
Anti-ds DNA (IU/ml) |
200 (24.7 – >300) |
186.3 (<6.25 – >300) |
51.35 (<6.25 – 200) |
|
UPr/UCr ratio |
3.3.7 (0.3 – 20.25) |
0.37 (0.01 – 1.46) |
0.11 (0 – 10.69) |
|
Serum Creatinine (mg/dl) |
0.9 (0.4 – 3.87) |
0.82 (0.4 – 1.4) |
0.8 (0.4 – 1.3) |
|
Serum OPG (pg/ml) |
1492.86 (624.09 – 4137.88) |
1280.33 (116.16 – 2048.13) |
1213.28 (368.37 – 1899.83)** |
|
UOPG/UCr (x 100 pg/mg) |
12.29 (0 – 85.77) |
2.36 (0 – 147.13)*** |
4.63 (0.07 – 42.53)*** |
p-value **= <0.01 and ***= <0.001 as compared to AN group
In the longitudinal study, uOPG decreased significantly at 3 and 6 months visits as compared to baseline (p-value <0.001) along with reduction in disease activity (Table 2). It showed an insignificant rise at 9 and 12 months. sOPG trends did not correlate with disease activity.
uOPG and not sOPG showed a rise before conventional markers in 2 patients who relapsed at 11 and 12 months respectively. Similarly, in 2 patients who developed chronic kidney disease, uOPG values remained persistently high throughout whereas sOPG did not.
Table 2. Change in different disease activity parameters, serum and normalized urinary OPG in the active nephritis group with treatment over 1 year
|
|
Baseline |
3 months |
6 months |
9 months |
12 months |
|
rSLEDAI |
8 (4 – 16) |
0 (0 – 12) |
0 (0 – 4) |
0 (0 – 4) |
0 (0 – 8) |
|
SLEDAI |
18 (6 – 28) |
2 (0 – 14) |
2 (0 – 6) |
2 (0 – 6) |
2 (0 – 15) |
|
C3 (mg/dl) |
48.5 (16.9 – 125) |
81.3 (7 – 161) |
91.6 (47.1 – 174) |
88.7 (33.4 – 168) |
99.1 (35 – 165) |
|
C4 (mg/dl) |
7.8 (<5.6 – 55.7) |
17.6 (<5.6 – 73.7) |
19.6 (<5.6 – 61.1) |
20.1 (<5.6 – 76.5) |
19.2 (<5.6 – 58.4) |
|
Anti-ds DNA (IU) |
200 (24.7 – >300) |
74.2 (8.4 – >300) |
53.75 (<6.25 – 300) |
72 (<6.5 – 300) |
63.8 (<6.5 – 300) |
|
UPr/UCr ratio |
3.3.7 (0.3 – 20.25) |
0.35 (0 – 13.55) |
0.62 (0 – 3.98) |
0.22 (0 – 6.98) |
0.24 (0 – 6.25) |
|
Serum Creatinine (mg/dl) |
0.9 (0.4 – 3.87) |
0.77 (0 – 4.12) |
0.8 (056 – 1.7) |
0.79 (0.4 – 1.3) |
0.81 (0.4 – 1.3) |
|
Serum OPG (pg/ml) |
1492.86 (624.09 – 4137.88) |
981.94 (591.57 – 1627.59)*** |
1219.74 (453.42 – 1916.27)** |
826.79 (270.7 – 1872.65)*** |
1151.02 (0 – 1578.99)*** |
|
UOPG/UCr (x 100 pg/mg) |
12.29 (0 – 85.77) |
4.66 (0.3 – 48.74)** |
1.04 (0 – 15.98)*** |
3.25 (0 – 40.25)*** |
5.55 (0.06 – 67.71)*** |
p-value **= <0.01 and ***= <0.001 as compared to baseline values
Conclusion:
uOPG is derived from kidneys and among patients with active SLE, it helps differentiate between patients with and without LN. It shows modest correlation with disease activity and has a potential to predict poor response to therapy and relapse of LN.
To cite this abstract in AMA style:
Gupta R, Aggarwal A, sinha S, Rajasekhar L, Yadav A, Gaur P, Misra R, Negi V. Urinary Osteoprotegerin As Biomarker of Lupus Nephritis Disease Activity: Cross Sectional and Longitudinal Study [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/urinary-osteoprotegerin-as-biomarker-of-lupus-nephritis-disease-activity-cross-sectional-and-longitudinal-study/. Accessed .« Back to 2015 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/urinary-osteoprotegerin-as-biomarker-of-lupus-nephritis-disease-activity-cross-sectional-and-longitudinal-study/