Long-Term Outcomes of Children and Adolescents With Biopsy-Proven Childhood-Onset Lupus Nephritis

Abstract

Introduction: Long-term data pertaining to childhood-onset lupus nephritis (cLN) remain extremely scarce.

Methods: We conducted a retrospective cohort study of biopsy-proven cLN with onset age <18 years diagnosed from 2001 to 2020 to ascertain the long-term patient and kidney survival rates, and the incidence of advanced chronic kidney disease (CKD) (estimated glomerular filtration rate [eGFR] <60 ml/min per 1.73 m²).

Results: A total of 92 subjects (78 female; age 13.7 ± 3.3 years; all Chinese) were included, with follow-up duration of 10.3 years (interquartile range, 5.8-15.9). Of these, 83 children (90%) had proliferative lupus nephritis (LN) (Class III/IV ± V). Mycophenolate was used for induction in 36%, whereas 34% received cyclophosphamide (CYC); 55% received mycophenolate as maintenance immunosuppression. The rates of complete remission (CR) and partial remission (PR) at 6 months and 12 months, respectively, were 65% and 20% and 78% and 8%. Two patients died (mortality rate 2.1/1000 patient-years), with a standardized mortality ratio of 22.3. Three patients (3.2%) developed end-stage kidney disease (ESKD), and advanced CKD occurred in 5 patients (5.4%). Survival rates without advanced CKD, ESKD, or death were 96.7%, 94.2%, 92.7%, 83.2% and 83.2% at 1 year, 5 years, 10 years, 15 years, and 20 years, respectively. Multivariate analysis revealed that severe kidney failure necessitating dialysis at presentation (adjusted hazard ratio 37.7, 95% confidence interval [CI] 4.0-355.6, P = 0.002), nonresponse (NR) after 12 months of treatment (adjusted hazard ratio 11.2, 95% CI 2.3-54.9, P = 0.003), and multiple nephritis flares (adjusted hazard ratio 2.6, 95% CI 1.1-6.2, P = 0.03) were predictive of advanced CKD, ESKD, or death. Other adverse outcomes included infections (2.9 episodes/100 patient-years), osteopenia (32%), hypertension (17%), short stature (14%), and avascular necrosis (7%).

Conclusion: The long-term outcomes of cLN appeared to have improved in the present era with effective immunosuppression, cautious drug tapering, and assurance of medication adherence. There is still an unacceptably high prevalence of adverse outcomes.

Keywords: childhood-onset; chronic kidney disease; dialysis; lupus nephritis; mortality; systemic lupus erythematosus.

Graphical abstract

Figure 1

(a) Kaplan-Meier plot of patient and renal survivals in 92 patients with childhood-onset lupus nephritis. (b) Kaplan-Meier plot of the composite outcome including advanced chronic kidney disease (stage 3–5), ESKD, and deaths in 92 patients with childhood-onset lupus nephritis. CKD, chronic kidney disease; ESKD, end-stage kidney disease.

Figure 2

Kaplan-Meier plot of the composite outcome including advanced chronic kidney disease (stage 3–5), ESKD, and deaths in 92 patients by (a) need of acute dialysis at presentation, (b) number of renal relapse, and (c) medication adherence.

Figure 3

Kaplan-Meier plot of the composite outcome including advanced chronic kidney disease (stage 3–5), ESKD, and deaths in 92 patients by (a) remission status at 12-month posttreatment, (b) remission status at 6-month posttreatment, and (c) proteinuria >1 mg/mg at 12-month posttreatment.