Males With Childhood-Onset SLE Face Early, Severe Kidney Involvement

Males with childhood-onset systemic lupus erythematosus (cSLE) tend to have early and severe kidney involvement, but a new study found those factors do not appear to translate to a predisposition toward end-stage kidney disease (ESKD) in pediatric patients.

The findings help provide insights into a relatively rare category of patients with SLE. They were published in Pediatric Reports.

The authors explained that only about 1 in 20 patients with SLE experiences disease onset as a child, and about 1 in 10 patients with SLE is male. As a result, data concerning this patient population are limited.

“Male-specific data on childhood-onset SLE is sparse and, as with many large adult SLE studies, is embedded within much larger gender-inclusive cohorts,” they wrote.

Although a handful of studies have looked at kidney involvement among males with cSLE, the authors said the results have been conflicting at times with regard to whether these patients are at a higher risk of progression to ESKD. Yet, the authors said, a comparison of male and female patients suggests there is reason to wonder if males are at a higher risk.

“While it may be argued that male cSLE is not distinct from female cSLE, data from CMS and the Renal Data System would suggest that this hypothesis is not correct, as the ratio of females to males shifts from 1:5 in those with all forms of lupus nephritis (LN) to 1:4 in those who progress to ESKD,” they noted. “The mechanistic basis for this apparent accelerated risk of ESKD in males with cSLE remains to be defined.”

To better define that risk, the investigators created what they believe to be the largest single-center cohort of male children with diagnosed SLE. They used 33 years of data to identify 95 males and 545 females with cSLE. They compared organ involvement, auto-antibody production, hypocomplementemia, and kidney biopsy findings between the 2 groups and used a variety of indexes to assess patient outcomes.

The authors found that for males and females, the median age of cSLE onset was 14 years. Sixty-two percent of male patients and 57% of female patients developed LN. Among males, non-Hispanic Whites were most likely to develop nephritis (80%) and Asian males were least likely (50%). Thirty-three percent of patients had pure and mixed class V membranous nephritis.

However, the investigators noted an interesting pattern when it came to kidney disease severity. At a median of 24 months, 70% of patients had a complete kidney response to therapy; however, 46% of patients went on to experience a relapse.

“Despite this, at least prior to transitioning their medical care from pediatric to internal medicine hospitals/clinics, very few male patients with cSLE progressed to ESKD,” the authors wrote.

Regarding auto-antibody production, the authors found that patients with cSLE had similar high cumulative incidence of anticardiolipin (aCL) antibodies and a low frequency of anti-Ro antibodies, which they said are similar to findings in adult males. Anti–double-stranded DNA and antiphospholipid antibody incidences were similar in this study to the findings in previous gender-inclusive studies.

“The findings that the rates of aCL and lupus anticoagulant were higher in males with cSLE without LN were surprising,” they noted. “No difference has been reported in [adult] SLE populations with and without LN.”

The authors said the strengths of their study were its large cohort size, the racial and ethnic diversity of the study population, and the utilization of consensus child-specific outcome definitions. However, they added that their results had limitations, including the inability to analyze factors such as treatment patterns or adherence.

Reference

Wenderfer SE, Orjuela A, Bekheirnia MR, et al. Lupus nephritis, autoantibody production and kidney outcomes in males with childhood-onset systemic lupus erythematosus. Pediatr Rep. 2022;14(2):220-232. doi:10.3390/pediatric14020030