A Pooled Analysis of Sex Differences in Lupus Nephritis

Lupus nephritis (LN) has been reported to be more severe and have worse outcomes in males than females. To determine if sex differences exist in disease severity at diagnosis or relapse, first treatment choice, response to initial treatment, and key kidney and patient outcomes, we performed a pooled analysis of data from 4 randomized controlled trials (RCTs) and 7 cohort studies of LN.

The study population included an international representation of 831 females and 122 males with LN with a median follow-up of 41.4 months. Baseline characteristics and outcomes (complete renal response [CRR], doubling of creatinine (Cr), dialysis, death, LN relapse, or composite outcomes) were compared between sexes using the entire data set. Cohort data were used to analyze treatment choice. Mixed model regression with studies as the random effects, controlled for age and race, was used to assess the effect size of sex on key clinical variables. Logistic regressions controlling for treatments and relevant baseline characteristics were used to evaluate outcomes.

We found no significant sex differences in age, race, systemic lupus erythematosus (SLE) or LN duration, C3, anti-double-stranded DNA, LN class distribution, or SLE Disease Activity Index (SLEDAI), although males had lower baseline estimated glomerular filtration rate (eGFR). Therapy choice, CRR, kidney, or patient outcomes were similar between sexes. Limitations to our study include the absence of detailed description of kidney histopathology, and incomplete outcomes data.

Apart from lower baseline eGFR, males and females with LN exhibit similar disease severity, treatment responses, kidney outcomes, and relapse-free survival in this large international analysis.