Background Data from the Euro-Lupus Nephritis Trial (ELNT) indicated that a proteinuria <0.8g/d at 12 months after randomization is the single best predictor of good long-term renal outcome (1).
Objectives The current analysis is aimed at testing the validity of this proteinuria cutoff level in another lupus nephritis (LN) patient population, taking advantage of the long-term MAINTAIN Nephritis Trial data set (2).
Methods The MAINTAIN Nephritis Trial is an European-based randomized trial performed in 105 LN patients comparing azathioprine and mycophenolate mofetil as maintenance therapy, after induction with low-dose Euro-Lupus intravenous cyclophosphamide. Renal relapse rate was similar in the two groups and early proteinuria decrease within the first year predicted long-term renal function (2). For this analysis, aimed at defining the best cutoff proteinuria level, we selected patients with at least 7 years of follow-up for whom proteinuria measurement was available at month 3 (n=81), 6 (n=80) or 12 (n=80). Good and poor long-term renal outcome was defined as serum creatinine ≤1mg/dl and >1mg/dl at last follow-up, respectively. Sensitivity and specificity were calculated for each proteinuria level, as predictor of good long-term renal outcome. Receiver Operating Characteristic (ROC) curves (area under the curve; AUC) were drawn and the best proteinuria cutoff value at each time point was determined based on Youden index. 95% confidence intervals (CI) were calculated.
Results The best proteinuria cutoff value (i. e. the point on the ROC curve furthest to the equality line, defined by Youden index) at month 3, 6 and 12 is indicated in the Table below, as well as their sensitivity and specificity (±95%CI) as predictor of good renal outcome. The AUCs (between 0.73 and 0.78) confirmed accuracy of the test. A proteinuria cutoff of 0.7g/day optimized sensitivity and specificity at month 12. Quite interestingly, this value is very close to the 0.8g/day at month 12 computed from the ELNT data (1).
Conclusions A 24-hour proteinuria cutoff level of 0.7 gram after 12 months of treatment best predicts long-term renal outcome in LN, confirming the ELNT data. We suggest that this target value be used as primary outcome in LN induction trials.
Dell'Ara M et al. Predictors of Long-Term Renal Outcome in Lupus Nephritis Trials: Lessons Learned from the Euro-Lupus Nephritis Cohort. Arthritis Rheumatol 2015; in press.
Tamirou F et al. Long-term follow-up of the MAINTAIN Nephritis Trial, comparing azathioprine and mycophenolate mofetil as maintenance therapy of lupus nephritis. Ann Rheum Dis 2015; in press.
Disclosure of Interest None declared