Certain clinical and serological markers — including younger age, psychosis, lymphopenia, elevated autoantibody count, and the presence of anti-double-stranded DNA (anti-dsDNA) antibodies — were predictive of future incident proteinuria in patients with systemic lupus erythematosus (SLE) who had no proteinuria at baseline, according to findings published in The Journal of Rheumatology.
Clinicians consider incident proteinuria a useful indicator of the onset of lupus nephritis, but studies detailing early risk factors for lupus nephritis are limited. The investigators were interested in determining which SLE-related manifestations at the time of classification might be associated with subsequent proteinuria and lupus nephritis.
Of 850 patients with SLE recruited for the retrospective longitudinal study, a total of 604 (90.7% women; median age, 34 years; median prodromal time, 1.8 years; median follow-up, 12 years) without proteinuria at diagnosis were enrolled. The primary outcome of proteinuria was defined as ≥2 elevated urine protein measurements (>0.5 g/d), which were obtained using a 24-hour urine sample. The total number of SLE-related positive autoantibodies was recorded for each participant along with other relevant demographic, clinical, and serologic information. Hazard ratios (HR) were calculated using regression analysis.
Of the 604 patients considered, 184 (30.5%) developed proteinuria after SLE classification, and 17 (2.8%) progressed to end-stage renal disease by the end of the study period. Upon univariate analysis, younger patients, especially patients between 21 and 40 years (HR, 3.18; 95% CI, 1.17-8.70; P =.023), and participants with a history of psychosis (HR, 1.94; 95% CI 1.03-3.06; P =.041) had an increased risk for incident proteinuria.
In addition, lymphopenia (HR, 1.45; 95% CI, 1.04-1.96; P =.029), positive anti-dsDNA (HR, 1.36; 95% CI, 1.00-1.83; P =.047), and high autoantibody count (HR, 1.25; 95% CI, 1.06-1.46; P =.008) were all correlated with increased risk for proteinuria. Compared with participants with ≤1 positive autoantibody at diagnosis, patients with ≥4 autoantibodies were more than twice as likely to develop incident proteinuria during follow-up (HR, 2.15; 95% CI, 1.09-4.21; P =.026). Multivariate analyses accounting for the total number of autoantibodies and anti-dsDNA positivity continued to yield statistically significant results for all categories.
Study strengths included the large cohort size, comprehensive clinical data, and the extended follow-up period, which allowed investigators to perform survival analyses. Study limitations included the use of proteinuria to indicate lupus nephritis rather than renal biopsy and histological examination, the lack of adjustment for fluctuations in laboratory variables over time, and the risk of confounding by indication.
Patients with non-renal SLE at baseline were at the higher risk for subsequent incident proteinuria if they had one or more of the described risk factors, which may prove useful as biomarkers for clinicians assessing newly diagnosed patients with SLE. The authors noted that lymphopenia might be prognostically significant with regard to the development of incident proteinuria and lupus nephritis.
Tanha N, Hansen RB, Nielsen CT, Faurschou M, Jacobsen S. Clinical and serological associations with the development of incident proteinuria in Danish patients with systemic lupus erythematosus [published online April 15, 2018]. J Rheumatol. doi:10.3899/jrheum.170933