An approach to validating criteria for proteinuric flare in systemic lupus erythematosus glomerulonephritis

Published criteria on the degree of proteinuria increase that defines a proteinuric flare in systemic lupus erythematosus (SLE) with glomerulonephritis (GN) vary widely, likely because they are not evidence based, but are largely based on expert opinion. Ideally, the threshold for proteinuric flare should be set sufficiently high that spontaneous variation in proteinuria does not likely explain the increase, but not so high that the patient needlessly experiences prolonged severe proteinuria before a flare is declared and therapy is increased. The present study was undertaken to develop an evidence-based approach to setting the threshold for proteinuric flare, based on quantifying the spontaneous variation in the urine protein:creatinine ratio in SLE GN patients who are not experiencing SLE flare.

SLE GN patients (n = 71) in the Ohio SLE Study were tested at prespecified bimonthly intervals within windows of ±1 week. The median duration of followup was >44 months, and the rate of visit compliance was >90%. To assess spontaneous variation in the protein:creatinine ratio under no-flare conditions, we excluded protein:creatinine ratios measured within 4 months before or after renal flare.

Our findings showed that in the group of SLE GN patients with a mean no-flare protein:creatinine ratio of ≤0.5, the published flare thresholds are set well above the 99% confidence interval of the no-flare protein:creatinine ratio. The opposite was seen in the group with a mean no-flare protein:creatinine ratio of ≥1.0.

Current thresholds for defining proteinuric flare appear to be set either too high or too low. A randomized trial would be needed to test whether resetting the thresholds would result in faster remission, reduction in therapy, and decrease in the frequency of chronic kidney disease.