Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.
Are the Current Thresholds for SLE Proteinuric Flare Set Too High? Determining the 99 Confidence Intervals for Spontaneous Variation in Urine Protein/Creatinine Ration in SLE GN Patients Who Are Clinically Stable (Not Flaring).
Ardoin1, Stacy P., Birmingham2, Dan J., Rovin2, Brad H., Hebert3, P., Yu2, C.-Y., Hebert2, Lee A.
Statement of Purpose:
Proteinuria is the most common manifestation of a moderate or severe flare of SLE glomerulonephritis (GN). However, there is no general consensus on the threshold for proteinuric flare and the proposed criteria are based largely on expert opinion. The criteria that have been proposed can be categorized as having low, medium or high thresholds, depending upon the minimum increase in proteinuria deemed necessary to constitute a proteinuric flare. This study provides an evidence-based approach to validate the magnitude of proteinuria increase that should constitute a proteinuric flare.
This work involved analysis of data collected as part of the Ohio SLE Study (OSS), a prospective observational study of 106 SLE patients with recurrently active disease, 72 of whom had moderate or severe renal disease. Patients were managed by pre-specified protocols. Median follow up was > 46 months with over 2400 visits. >90% of visits occurred bimonthly, within pre-specified windows of ± 1 week. The renal OSS patients provided 24 hour urine collections at 84% of OSS visits and random spot urine collections at remaining visits. At each visit it was determined, using pre-specified criteria (JASN 16: 467473, 2005), whether a renal or non-renal SLE flare had occurred at the previous OSS visit.
To assess spontaneous variation in protein/creatinine (P/C) ratio in patients with SLE under no-flare conditions, P/C ratios measured within 4 months of a renal flare were excluded. "P/C ratio datasets" were developed and required a minimum of 3 bimonthly consecutive urine collections spanning 4 months. At least 50% of the P/C ratios were required to be measured by 24 hour urine collection. The P/C ratio datasets were stratified into groups according to the mean P/C ratio of the dataset: group 1 (mean P/C ratio <0.15), group 2 (mean P/C ratio >=0.15 to <=0.38), group 3 (mean P/C ratio >0.38 to <=0.77), group 4 (mean P/C ratio >0.77 to <=1.54), group 5 (mean P/C ratio >1.54). For each group, 99% confidence intervals were developed.
Of 1168 urine collections in the OSS study, 895 met the above criteria. These were provided by 58 of the 72 SLE GN patients (mean age 34 ± 11 years, 91% female, 38% African American, 58% European American, 4% Other). Mean P/C ratio was 1.5 ± 2.4. 91% were taking prednisone and 88% an immunosuppressant. Confidence intervals (CI) for each group are displayed in Figure 1.
Most of the current thresholds for SLE GN proteinuric flare are set well above the 99% CI for spontaneous variation in P/C ratios under no-flare conditions. This suggests that SLE GN patients by be exposed to unnecessarily prolonged periods of increasing proteinuria before flare is declared and treated. This work is hypothesis generating and needs to be confirmed in a prospective randomized trial to determine whether lowering proteinuric flare threshold would benefit SLE patients.
Figure 1-3. Individial urine protein/creatinine (P/C) ratios measured under non-flare conditions for P/C ratio groups 1 to 5. These ratios are shown in relation to the currently published low (LCT), intermediate (ICT), and high threshold (HTC) criteria for proteinuria flare. The 99% CI for the given P/C ratio group is provided.
To cite this abstract, please use the following information:
Ardoin, Stacy P., Birmingham, Dan J., Rovin, Brad H., Hebert, P., Yu, C.-Y., Hebert, Lee A.; Are the Current Thresholds for SLE Proteinuric Flare Set Too High? Determining the 99 Confidence Intervals for Spontaneous Variation in Urine Protein/Creatinine Ration in SLE GN Patients Who Are Clinically Stable (Not Flaring). [abstract]. Arthritis Rheum 2010;62 Suppl 10 :1400