The published criteria for the proteinuria increase that constitutes a proteinuric flare in lupus glomerulonephritis (SLE GN) vary widely, likely because they are largely based on expert opinion. Ideally, the threshold for proteinuric flare should be set sufficiently high so that spontaneous variation in proteinuria does not likely explain the increase, but not so high that the patient is needlessly exposed to prolonged heavy proteinuria before a flare is declared and therapy is increased. Here we describe an evidence-based approach to setting the threshold for proteinuric flare based on quantifying the spontaneous variation in urine protein/creatinine (P/C) ratio of SLE GN patients who are not experiencing SLE flare.
SLE GN patients (N = 71) followed in the Ohio SLE Study (OSS) were tested at pre-specified bimonthly intervals within windows of ± 1 week, median follow-up > 44 mo, visit compliance > 90%. To assess spontaneous P/C ratio variation under no-flare conditions, we excluded P/C ratios measured within ± 4 month of renal flare.
For those with mean no-flare P/C ratios ≤ 0.5, the published flare thresholds are set well above the 99% confidence interval (CI) of the no-flare P/C ratios. The opposite is seen in those with patients whose mean no-flare P/C ratios ≥ 1.0.
Current thresholds for proteinuric flare appear to be set either too high or too low. A randomized trial would be needed to test whether re-setting the thresholds would result in faster remission, less therapy, and less chronic kidney disease.