Session Information
Date: Sunday, November 13, 2016
Title: Systemic Lupus Erythematosus – Clinical Aspects and Treatment I: Nephritis
Session Type: ACR Concurrent Abstract Session
Session Time: 2:30PM-4:00PM
Background/Purpose: Alternatively activated (M2) macrophages are the major macrophage subtype infiltrating the glomeruli in lupus nephritis (LN). CD163 is a marker of M2 macrophages. In urine, soluble CD163 (sCD163), which is the shed form of CD163, may reflect the activation of M2 macrophages in kidney. Thus, it may serve as a biomarker for identification and assessment of treatment response in patients with LN.
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 SLEDAI and renal SLEDAI (rSLEDAI). Patients in AN group were treated according to the ACR guidelines and followed up every 3 months for 1 year. Urine and plasma samples were collected at baseline for all and every 3 months in AN group. Urine samples from 25 healthy subjects (HC) and 20 patients of rheumatoid arthritis (RA) served as controls. Plasma sCD163 (pCD163) and urinary sCD163 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 analysis.
Results: A total of 122 SLE patients (females 114) were enrolled. At baseline, normalized urinary sCD163 (uCD163) was significantly higher in AN group as compared to ANR, ID, HC and RA (p-value <0.001 for all). uCD163 showed good correlation with protein:creatinine ratio (r=0.55; p-value <0.001), rSLEDAI (r=0.47, p-value <0.001) and SLEDAI (r=0.3, p-value <0.001) but not with pCD163 levels (r=0.23). uCD163 but not pCD163 could differentiate between AN and ANR groups (Table 1) and on ROC analysis, uCD163 (AUC=0.76) performed better than pCD163, C3, C4 and anti-ds DNA antibodies. In the longitudinal study, with reduction in disease activity, uCD163 also decreased significantly at all follow-up visits as compared to baseline (p-value <0.001) (Table 2). pCD163 also decreased significantly but had an erratic and irregular trend. uCD163 and not pCD163 showed a rise before conventional markers in 4 patients who relapsed within 1 year of follow-up.
Conclusion: uCD163 is a potential biomarker of LN disease activity. Among patients with active SLE, it helps differentiate between patients with and without LN. It shows modest correlation with renal disease activity and has a potential to predict relapse of LN.
Table1: Baseline characteristics of SLE patients in the three categories
| Active Nephritis (AN) | Active Non-Renal (ANR) | Inactive Disease (ID) | |
| Number | 57 | 23 | 42 |
| F:M | 55:2 | 18:5 | 41:1 |
| Median age (yrs) | 27 (12 – 50) | 29 (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) | 47.1 (<16.9 – 156) | 48.6 (17.3 – 139) | 113.5 (34.2 – 194) |
| C4 (mg/dl) | 7.6 (<5.6 – 56) | 9.4 (<5.6 – 26) | 22.1 (6 – 45) |
| Anti-ds DNA (IU/ml) | 200 (24 – >300) | 185 (<6.25 – >300) | 59.95 (<6.25 – 200) |
| UPr/UCr ratio | 3.37 (0.3 – 20.25) | 0.38 (0.03 – 1.46) | 0.09 (0 – 10.69) |
| Serum Creatinine (mg/dl) | 0.9 (0.4 – 3.87) | 0.82 (0.6 – 1.25) | 0.8 (0.4 – 1.3) |
| Plasma sCD163 (ng/ml) | 2837.1 (701.3 – 7433.2) | 2759 (619.8 – 9931) | 1503.6 (564.5 – 3142.8)*** |
| UCD163/UCr (x 100 pg/mg) | 127 (0 – 1435) | 3.82 (0 – 179)*** | 10.34 (0 – 1923)*** |
p-value ***= <0.001 as compared to AN group Table 2. Change in different disease activity parameters, plasma and normalized urinary sCD163 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 – 8) | 0 (0 – 8) |
| SLEDAI | 18 (6 – 28) | 2 (0 – 14) | 2 (0 – 6) | 2 (0 – 10) | 2 (0 – 15) |
| C3 (mg/dl) | 47.1 (<16.9 – 156) | 85.9 (7 – 161) | 93.9 (47.1 – 174) | 89.7 (33.4 – 168) | 103 (35 – 165) |
| C4 (mg/dl) | 7.6 (<5.6 – 56) | 17.4 (<5.6 – 73.7) | 19.6 (<5.6 – 61.1) | 20.1 (<5.6 – 76.5) | 19.6 (<5.6 – 79) |
| Anti-ds DNA (IU) | 200 (24 – >300) | 60.4 (6.1 – >300) | 54.6 (<6.25 – 300) | 67.45 (<6.5 – 300) | 53.4 (<6.5 – 300) |
| UPr/UCr ratio | 3.37 (0.3 – 20.25) | 0.35 (0 – 13.55) | 0.4 (0 – 8.69) | 0.3 (0 – 6.98) | 0.25 (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) |
| Plasma SCD163 (ng/ml) | 2837.1 (701.3 – 7433.2) | 1409.5 (393.7 – 4162.1)*** | 1071.6 (246.6 – 2753.8) *** | 1307.7 (555.9 – 3580)*** | 1141.7 (398 – 4124)*** |
| USCD163/UCr (x 100 pg/mg) | 127 (0 – 1435) | 19.7 (0 – 534.9)*** | 12.7 (0 – 580.5)*** | 11.9 (0 – 113)*** | 7.2 (0 – 378)*** |
p-value ***= <0.001 as compared to baseline values
To cite this abstract in AMA style:
Gupta R, Yadav A, Aggarwal A. Urinary Soluble CD163, an M2 Macrophage Marker, Reflects the Renal Disease Activity in Lupus Nephritis: A Cross Sectional and Longitudinal Assessment [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/urinary-soluble-cd163-an-m2-macrophage-marker-reflects-the-renal-disease-activity-in-lupus-nephritis-a-cross-sectional-and-longitudinal-assessment/. Accessed .« Back to 2016 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/urinary-soluble-cd163-an-m2-macrophage-marker-reflects-the-renal-disease-activity-in-lupus-nephritis-a-cross-sectional-and-longitudinal-assessment/