medwireNews: Male sex and older age may put people with childhood-onset systemic lupus erythematosus (cSLE) and nephritis at increased risk for abnormal short-term kidney status, US researchers report.
Writing in Arthritis Care and Research, Emily Smitherman (University of Alabama at Birmingham) and co-authors say their findings suggest that male patients and those who are older at diagnosis “may require closer monitoring especially considering the complexity of care for transition-age patients.”
The study included data for 222 patients with kidney biopsy-proven nephritis who were enrolled in the prospective Childhood Arthritis and Rheumatology Research Alliance Registry between 2017 and 2019.
The participants had a mean age of 13.6 years at cSLE diagnosis, 83% were female, and 64% had class III or IV proliferative nephritis on initial kidney biopsy.
At their most recent registry visit, a median of 17.3 months from initial kidney biopsy, 55% of 107 patients with available data had abnormal kidney status, defined as an estimated glomerular filtration rate below 90 mL/min per 1.73 m2, a urinary protein-to-creatinine ratio above 0.5 mg/mg, or a urinary protein dipstick score of 1+ or greater.
The researchers report that the proportion of male participants was significantly higher in the group with abnormal kidney status than in the normal kidney status group (36 vs 12%) and that individuals with abnormal kidney status were significantly older at diagnosis than those with normal kidney status (mean 14.6 vs 13.4 years). There was no significant difference between the two groups in terms of race/ethnicity, however.
After adjustment for potential confounders, the team found that male sex was associated with a significant 3.88-fold increased risk for abnormal kidney status, while each additional year of age at diagnosis was associated with a significant 1.23-fold increased risk.
Smitherman and colleagues also looked at treatment patterns across the cohort. They found that, during the induction period (30 days before and 60 days after initial kidney biopsy), mycophenolate was the most commonly used DMARD (40%), followed by cyclophosphamide (12%), cyclophosphamide plus rituximab (8%), rituximab (7%), hydroxychloroquine (7%), and other DMARDs (5%).
Cyclophosphamide use was more common in the 156 patients with proliferative (class III/IV or mixed class III+V or IV+V) nephritis than in the 29 with pure membranous (class V) disease, at 16% versus 3%, whereas the rate of “other DMARD” use was lower in the proliferative group than in the pure membranous group (1 vs 10%).
Among the patients with proliferative nephritis, cyclophosphamide use was significantly more common in class IV than class III disease (62 vs 9%) as was rituximab use (28 vs 13%). Conversely, patients with class IV nephritis were less likely than patients with class III nephritis to receive mycophenolate monotherapy (38% vs 91%).
Nearly all (97%) participants used hydroxychloroquine at some point during follow-up, while 84% were treated with mycophenolate. Other common treatments included cyclophosphamide and rituximab, used by 28% and 25% of participants, respectively, throughout the study.
However, the investigators note that they “observed more variation in treatment than would be expected” across the 15 rheumatology centers that had at least five patients enrolled in the registry.
For example, two centers reported only using mycophenolate, while another two only recorded cyclophosphamide and rituximab use for all patients.
Smitherman et al comment that they were unable to evaluate refractory disease – for which rituximab is recommended – but “rituximab use was high even within 60 days of kidney biopsy and there were distinct patterns of rituximab use between centers, suggesting provider preference is likely a strong predictor of rituximab use.”
They conclude: “Future studies to better understand the barriers to [treatment] recommendation uptake will help identify strategies to reduce this variation in care.
“Additionally, the generation of stronger evidence of best treatments for childhood-onset lupus nephritis through clinical trials and comparative effectiveness research is needed.”
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