ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 663

Urinary Tumor-Necrosis Factor-like Weak Inducer of Apoptosis Is an Important Biomarker for Renal Lupus

Michelle Petri1, Daniel Goldman2, Linda Burkly3, Nicolas Wisniacki4, Chris Stebbins3 and Laurence S Magder5, 1Medicine (Rheumatology), Division of Rheumatology, Johns Hopkins University School of Medicine, MD, USA, Baltimore, MD, 2Rheumatology, Johns Hopkins University School of Medicine, Baltimore, MD, 3Biogen, Cambridge, MA, 4GlaxoSmithKline, London, United Kingdom, 5Epidemiology and Public health, University of Maryland School of Medicine, Baltimore, MD

Meeting: 2017 ACR/ARHP Annual Meeting

Date of first publication: September 18, 2017

Keywords: ,

Session Information

Date: Sunday, November 5, 2017

Title: Systemic Lupus Erythematosus – Clinical Aspects and Treatment Poster I: Biomarkers and Outcomes

Session Type: ACR Poster Session A

Session Time: 9:00AM-11:00AM

Background/Purpose: Tumor-necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) drives release of proinflammatory mediators from renal tubular and mesangial cells, and has been implicated in the pathogenesis of lupus nephritis, angiogenesis and fibrosis. We examined the utility of urinary levels of TWEAK (uTWEAK) as a biomarker for lupus nephritis activity in patients with systemic lupus erythematosus (SLE).

Methods: 296 SLE patients in a longitudinal cohort had urine collected at baseline and analyzed by an ELISA for TWEAK developed by Biogen. Urine TWEAK (uTWEAK) concentration was normalized by dividing by urine creatinine concentration. Patients were subsequently seen at regular intervals of three months. At every visit, assessment of disease activity was recorded using SELENA-SLEDAI, BILAG-2004 and the Physician’s Global Assessment (PGA). Standard of care laboratory tests were also performed at each visit.

Results: uTWEAK was associated with ethnicity (highest in Asians) and strongly associated with prednisone dose. Table 1 shows the relationship of uTWEAK with organ specific SLE activity. uTWEAK was only associated with renal activity. It was negatively associated with serum creatinine (r = -0.25, p < 0.00001). The association of uTWEAK with urine protein/cr was mainly seen after uTWEAK/creatinine ratio of approximately 0.12.

Table 1: Risk of specific types of SLE disease activity by urinary TWEAK levels at the same visit.

SLE Disease Activity

(SLEDAI descriptors)

Urinary TWEAK / Creatinine Ratio

P-value
(trend)

1st Quartile

(n=74)

2nd Quartile

(n=74)

3rd Quartile

(n=74)

4th Quartile

(n=74)

Renal

–Proteinuria > 500 mg

–Hematuria

–Pyuria

7 (9%)

5 (7%)

0 (0%)

2 (3%)

5 (7%)

5 (7%)

0 (0%)

0 (0%)

12 (16%)

10 (14%)

1 (1%)

3 (4%)

14 (19%)

13 (18%)

3 (4%)

1 (2%)

0.030

0.017

0.025

1.00

Skin

24 (32%)

23 (31%)

19 (26%)

21 (28%)

0.46

Hematologic

1 (1%)

3 (4%)

5 (7%)

3 (4%)

0.29

Musculoskeletal

1 (1%)

2 (3%)

3 (4%)

3 (4%)

0.29

Immunologic

22 (30%)

21 (28%)

22 (26%)

20 (27%)

0.77

uTWEAK at baseline was predictive of renal activity over the next year (Table 2).

Table 2: Risk of specific types of SLE disease activity in visits made in the next year by urinary TWEAK levels.

SLE Disease Activity

Urinary TWEAK / Creatinine Ratio

P-value1

1st Quartile

(n=240)

2nd Quartile

(n=224)

3rd Quartile

(n=228)

4th Quartile

(n=239)

Renal

–Proteinuria

–Hematuria

–Pyuria

11 (5%)

10 (4%)

1 (<1%)

2 (1%)

18(8%)

12 (6%)

1 (<1%))

9 (4%)

36 (16%)

36 (16%)

15 (7%)

5 (2%)

43 (18%)

40 (17%)

11 (5%)

9 (4%)

0.016

0.011

0.011

0.28

Skin

74 (31%)

69 (31%)

65 (29%)

51 (21%)

0.16

Hematologic

9 (4%)

10 (4%)

10 (4%)

10 (4%)

0.84

Musculoskeletal

8 (3%)

7 (3%)

3 (1%)

15 (6%)

0.35

Immunological

71 (30%

53 (24%)

72 (32%)

72 (30%)

0.80

1 Based on a test for trend, imputing scores of 0,1,2,3 for the consecutive quartiles, accounting for repeated measures on the same patient using GEE.

Conclusion: In a clinical trial, blocking TWEAK did not improve renal lupus. However, our results show that uTWEAK still has great utility as a lupus nephritis marker, as uTWEAK is only associated with renal activity and does not correlate with non-renal activity. In addition, it predicts renal activity over the next year.

Disclosure: M. Petri, Anthera Inc, 5,GlaxoSmithKline, 5,EMD Serono, 5,Eli Lilly and Company, 5,Bristol Meyer Squibb, 5,Amgen, 5,United Rheumatology, 5,Global Academy, 5,Exagen, 2; D. Goldman, None; L. Burkly, Biogen Idec, 3; N. Wisniacki, GlaxoSmithKline, 3; C. Stebbins, Biogen, 3; L. S. Magder, None.

To cite this abstract in AMA style:

Petri M, Goldman D, Burkly L, Wisniacki N, Stebbins C, Magder LS. Urinary Tumor-Necrosis Factor-like Weak Inducer of Apoptosis Is an Important Biomarker for Renal Lupus [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/urinary-tumor-necrosis-factor-like-weak-inducer-of-apoptosis-is-an-important-biomarker-for-renal-lupus/. Accessed .

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