Background/Purpose: Lupus nephritis remains one of the most devastating SLE complications, occurring in over 50% of the patients.  It is important to identify clinical conditions that precede nephritis for the purposes of patient care and to identify preventive strategies.  Most previous studies of predictors of incident nephritis in SLE are cross-sectional or do not incorporate time-varying predictors. We leveraged a large clinical cohort which evaluated patients quarterly to identify fixed and time-varying predictors of lupus nephritis.

Methods: Since 2006, the urine protein/creatinine ratio was measured quarterly in patients in our SLE cohort.  This analysis was based on cohort follow-up after 2006 in patients who did not have a history of diabetes and who did not have a prior episode of sustained elevated proteinuria, nor a  history of nephritis, renal insufficiency, or failure.  Among these patients, we defined an incident case of proteinuria as two or more measures of urine protein/creatinine (or 24-hour protein measure) greater than 0.5 in two visits separated by more than 30 days and less than 180 days, among patients with no prior episodes of proteinuria.  We estimated rates of incident proteinuria in subgroups of patients defined by time-invariant and time-varying predictors. 

Results: Among 895 patients included in the analysis, 840(94%) were  female, and 518 (58%) were Caucasian, 304 (34%) African-American, with mean age of 42 at the start of follow-up. We observed 58 incident cases of proteinura over a span of 4669 person-years of cohort follow-up. The overall rate of incident proteinuria was 12.4 per 1000 person-years.  The Table shows the association between select predictors and the rate incident proteinuria.  The rate was significantly lower among those of older age, and significantly higher among those who were not Caucasian.  Among those with a history of low C3, the rate was 8 times higher, and highest among those with a recent measure of low C3.  The rate among those prescribed hydroxychloroquine was similar to those not prescribed hydroxychloroquine.  Among those taking medicine for hypertension, the rate among those prescribed ACE inhibitor or ARB was similar to the rate among those prescribed other treatments.   Table :  Rates of incident proteinuria by patient characteristics.

Conclusion: Older SLE patients who have not previously had renal involvement are at low risk for developing proteinuria.  There was not strong evidence that hydroxychloroquine or ACE inhibitor’s reduced the risk of proteinuria. The highest rates of incident proteinuria were among those with recent low complement.  These results suggest that those with declines in complement should be monitored closely for renal disease.