Session Information
Date: Wednesday, November 16, 2016
Title: Vasculitis IV: Diagnosis and Assessment of Disease Activity
Session Type: ACR Concurrent Abstract Session
Session Time: 9:00AM-10:30AM
Background/Purpose: The significance of persistent hematuria or proteinuria in patients with ANCA-associated vasculitis (AAV) who are in clinical remission is still unclear. This study examined the utility of urinalysis in predicting renal relapse in AAV.
Methods: Participants enrolled in the Wegener’s Granulomatosis Etanercept Trial (WGET) and the Rituximab in ANCA-Associated Vasculitis (RAVE) trial who had active glomerulonephritis due to AAV, positive ANCA, and achieved remission by month 6 were included. Exposures included persistent hematuria (or proteinuria) for the first 6 months from enrollment after onset of active renal disease and cumulative hematuria (or proteinuria) as a time-varying covariate. Renal relapse was defined as new or worsening RBC casts and/or rise in serum creatinine according to the Birmingham Vasculitis Activity Score for Wegener’s Granulomatosis (BVAS/WG). In RAVE only, the relationship between worsening levels of hematuria and renal relapse was evaluated. Competing risk regression was used to examine renal relapse (with non-renal relapse and end-stage renal disease as competing events); results were expressed as subdistribution hazard ratios (sHR). All models adjusted for study, ANCA type, baseline serum creatinine, and pulmonary involvement.
Results: There were 149 patients included: 42% had persistent hematuria and 43% had persistent proteinuria beyond 6 months (Table 1). There was a significantly higher risk of relapse among patients with persistent hematuria beyond 6 months (sHR 3.99 [95% CI 1.20, 13.25], p = 0.02) (Figure 1) as well as with each additional month of cumulative hematuria (sHR per month 1.07 [95% CI 1.02, 1.13], p = 0.01) (Table 2). Persistent proteinuria was not associated with renal relapse (p = 0.53). Evaluation of changes in level of hematuria showed that an increase in hematuria level over the prior 6 months was associated with renal relapse (sHR 4.90 [95% CI 1.81, 13.27], p < 0.01) and larger changes in hematuria conferred greater risk.
Conclusion: Persistent hematuria and increasing hematuria, but not proteinuria, are associated with renal relapse among patients with AAV and recent renal disease. These findings suggest that the urinalysis may be a useful tool in predicting renal relapse in AAV.
Table 1. Characteristics of Study Population at Enrollment
|
|
All (N = 149) |
Persistent hematuria beyond 6 months |
P-value |
|
|
Yes (N = 63) |
No (N = 86) |
|||
| Age at baseline, years |
55 (44, 66) |
54 (43, 68) |
55 (44, 63) |
0.67 |
| Female, % |
41% |
56% |
30% |
< 0.01 |
| Achieved menopause (if female), % |
62% |
51% |
77% |
0.04 |
| ANCA type by ELISA, % |
|
|
|
0.45 |
| Anti-PR3 |
68% |
65% |
71% |
|
| Anti-MPO |
32% |
35% |
29% |
|
| Newly-diagnosed at enrollment, % |
59% |
57% |
60% |
0.68 |
| Prior kidney involvement, % |
98% |
100% |
94% |
0.05 |
| BVAS/WG at baseline |
7 (5, 10) |
8 (6, 10) |
7 (4, 9) |
< 0.01 |
| VDI at baseline |
0 (0, 1) |
0 (0, 1) |
0 (0, 1) |
0.70 |
| Serum creatinine at baseline, mg/dL |
1.4 (1.1,2.3) |
1.8 (1.1, 2.6) |
1.3 (1, 2.2) |
0.07 |
| Renal disease at baseline, % |
|
|
|
|
| Hematuria |
100% |
100% |
100% |
— |
| Proteinuria |
74% |
86% |
66% |
0.01 |
| Red blood cell casts* |
56% |
62% |
52% |
0.24 |
| Rise in serum creatinine* |
50% |
63% |
41% |
< 0.01 |
| Duration of persistent hematuria, months |
6 (3, 12) |
17 (11, 26) |
3 (2, 4) |
< 0.01 |
| Persistent proteinuria ≥ 6 months, % |
43% |
60% |
31% |
< 0.01 |
| Pulmonary involvement at baseline, % Alveolar hemorrhage at baseline |
60% 26% |
54% 30% |
65% 23% |
0.17 0.44 |
| Induction therapy, % Cyclophosphamide Rituximab |
66% 34% |
54% 46% |
76% 24% |
< 0.01 |
Values expressed as median (interquartile range) or percentage. *Based on BVAS/WG items.
AAV, ANCA-associated vasculitis. BVAS/WG, Birmingham Vasculitis Activity Score for Wegener’s Granulomatosis. CI, confidence interval. ELISA, enzyme-linked immunosorbent assay. GPA, granulomatosis with polyangiitis. MPA, microscopic polyangiitis. PR3, proteinase-3. MPO, myeloperoxidase. VDI, Vasculitis Damage Index
Table 2. Risk of Renal Relapse in ANCA-Associated Vasculitis after Multivariate Adjustment for Duration of Hematuria and Proteinuria
| Variable |
sHR (95% CI) |
P-value |
| Cumulative duration of hematuria (per month) |
1.07 (1.02, 1.13) |
0.01 |
| Cumulative duration of proteinuria (per month) |
1.04 (0.99, 1.08) |
0.10 |
| ANCA (PR3 vs MPO) |
0.77 (0.30, 1.92) |
0.57 |
| Baseline pulmonary involvement |
2.84 (0.34, 23.98) |
0.34 |
| Baseline Creatinine (per 1 mg/dL) |
0.94 (0.48, 1.83) |
0.85 |
| Study (RAVE vs WGET) |
0.30 (0.06, 1.64) |
0.17 |
Cumulative duration of hematuria and proteinuria were analyzed as time-varying covariates. Hematuria-by-proteinuria interaction was not significant (p for interaction = 0.11).
sHR, subdistribution hazard ratio. CI, confidence interval.
PR3, proteinase-3. MPO, myeloperoxidase.
WGET, Wegener’s Granulomatosis Etanercept Trial.
RAVE, Rituximab in ANCA-associated Vasculitis trial. 
To cite this abstract in AMA style:
Rhee RL, Davis JC, Ding L, Fervenza F, Hoffman GS, Kallenberg CGM, Langford CA, McCune WJ, Monach PA, Seo P, Spiera RF, St.Clair EW, Specks U, Stone JH, Merkel PA. The Utility of Urinalysis in Determining the Risk of Renal Relapse in ANCA-Associated Vasculitis [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/the-utility-of-urinalysis-in-determining-the-risk-of-renal-relapse-in-anca-associated-vasculitis/. Accessed .« Back to 2016 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/the-utility-of-urinalysis-in-determining-the-risk-of-renal-relapse-in-anca-associated-vasculitis/