Lupus Nephritis Care Varies Widely in Children With SLE

The use of existing guidelines for pediatric treatment varies significantly among sites, a new study has found.

Children with systemic lupus erythematosus (SLE) who also receive a nephritis diagnosis tend to have worse short-term kidney outcomes if they are males and told they had SLE at an older age, according to a new report published in Arthritis Care & Research.

The study findingssuggest wide variation exists in the medications prescribed to treat pediatric lupus nephritis, with the authors explaining that lupus nephritis is a particularly devastating problem for patients with childhood-onset SLE (cSLE). Children with SLE who have lupus nephritis have higher rates of morbidity and mortality compared with adults.

“This is further complicated by an increased incidence of lupus nephritis in cSLE compared to adult-onset, with kidney disease as a leading cause of long-term damage in cSLE,” the authors wrote.

Moreover, they said, uncontrolled lupus nephritis can lead to significant burdens on patients, and there are significant disparities in health care delivery and outcomes among people of different demographic groups, insurance statuses, and geographic locations.

One way to improve these disparities would be to better standardize best practices for treatment. Yet, the investigators said this remains challenging because there are sparse contemporary real-world data that could be used as a base from which to build a care-improvement strategy.

To address that research gap, the investigators used data from the Childhood Arthritis Rheumatology Research Alliance Registry to identify North American children with cSLE and biopsy-proven lupus nephritis. They found 222 patients, 64% of whom had class III or IV nephritis at baseline. As with the general SLE population, most patients were female (83%) and not on private insurance (59%), instead using programs such as Medicaid or military insurance. Their mean age at diagnosis was 13.6 years.

Of the 106 patients with available data, 55% had abnormal kidney status at follow-up. The median follow-up time was 17 months. The investigators’ analysis showed that being male (odds ratio [OR], 3.88; 95% CI, 1.21-12.46) and older age at cSLE diagnosis (OR, 1.23; 95% CI, 1.01-1.49) were associated with a greater risk of abnormal kidney status at follow-up.

However, the investigators also said there were notable differences in the classification systems used on kidney biopsies. Only 46% of patients were classified using the 2003 International Society of Nephrology (ISN)/Renal Pathology Society (RPS) classification, meaning most rheumatology centers were not following the Single Hub and Access point for pediatric Rheumatology in Europe recommendations. The authors said ISN/RPS uptake levels may increase with the 2018 update of that classification system, which they said helped “clarify previous problematic definitions.”

They also noted surprising variations in therapeutic induction patterns and medication usage.

“Patients with class IV nephritis were more likely than class III to receive cyclophosphamide and rituximab (Rituxan) during induction,” they said. Usage of mycophenolate (CellCept), cyclophosphamide, and rituximab also varied significantly among rheumatology centers, they said.

In their conclusion, the investigators said more research is needed to better understand why recommendations uptake appears to be so low. They also said more clinical trials and comparative studies are warranted to ensure that recommendations truly reflect the best possible therapeutic strategies.

“Determining the key gaps in care that drive disparities in pediatric lupus nephritis is critical for the development of effective interventions to improve outcomes,” the authors said.

Smitherman EA, Chahine RA, Beukelman T, et al. Childhood‐onset lupus nephritis in the Childhood Arthritis and Rheumatology Research Alliance Registry: short‐term kidney status and variation in care. Arthritis Care & Res. Published online August 17, 2022. doi:10.1002/acr.25002

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