Renal relapse in childhood-onset lupus nephritis: When? Who’s at risk?

“Achieving CR appears to reduce the incidence of renal relapse, … [and] MMF is the preferred maintenance therapy for most Chinese children [with cLN],” the investigators highlighted. [Rheumatology (Oxford) 2023;doi:10.1093/rheumatology/kead447]

The investigators retrieved data from patients with biopsy-confirmed LN who presented to Hong Kong Children’s Hospital from 1 January 2001 to 31 December 2021, with a data retrieval cut-off date of 1 November 2022. The study cohort included 95 cLN patients (female, 83.2 percent; proliferative LN, 90.5 percent), all of whom were diagnosed before 18 years of age (mean, 13.6 years), treated with maintenance therapy, including MMF (55.8 percent) and azathioprine (30.5 percent), and followed up for >1 year (mean, 10.2 years). The total follow-up duration was 964.5 patient-years.

The study’s primary endpoint was relapse-free survival (RFS). Renal relapse was defined as urinary protein-to-creatinine ratio (UPCR) >1 mg/mg in patients with baseline proteinuria <0.5 mg/mg, or an increase of >1 mg/mg in UPCR in those with baseline proteinuria >0.5 mg/mg, and/or an increase in serum creatinine, supported by serological activity or histological evidence.

Secondary endpoints included remission at 6 months and 12 months after induction therapy, and complications. CR was defined as sustained UPCR <0.5 mg/mg in early morning urine, while partial remission (PR) was defined as >50 percent reduction in UPCR and UPCR <3 mg/mg. Both CR and PR required improved or stable kidney function (ie, <15 percent decline in estimated glomerular filtration rate [eGFR] vs baseline). Nonremission (NR) referred to not meeting CR or PR criteria.

Over the study period, 70 episodes of renal relapse occurred in 41 percent of patients (n=39), translating to a relapse rate of 0.07 episodes/patient-year. RFS rates were 68.3 percent at 5 years, 50.3 percent at 10 years, and 44.5 percent at 20 years, while mean time to first relapse was 5.2 years from cLN diagnosis.

In multivariate analysis, the risk of renal relapse increased in cLN patients diagnosed at ≤13.1 years of age (adjusted hazard ratio [aHR], 2.59; 95 percent confidence interval [CI], 1.27–5.29; p=0.009), those receiving azathioprine maintenance (aHR, 2.20; 95 percent CI, 1.01–4.79; p=0.047), and those not achieving CR at 12 months (PR: aHR, 3.90; 95 percent CI, 1.03–9.19; p=0.012) (NR: aHR, 3.08; 95 percent CI, 1.35–11.3; p=0.044).

Compared with relapse-free patients, those with renal relapse experienced worse renal outcomes, including renal impairment (ie, eGFR <90 mL/min/1.73 m² at the last follow-up; p=0.04), and stage 3–5 chronic kidney disease and end-stage renal disease (p<0.01). They also had higher rates of complications, such as osteopenia (p=0.04), infection (p=0.02) and hypertension (p<0.01).

“To prevent kidney injuries and treatment-related damage, cLN patients may receive low-dose maintenance therapy [eg, MMF] for 6–8 years. In those with sustained remission, cautious tapering [of maintenance therapy] can be considered,” the investigators suggested. “MMF-treated patients with frequent renal relapse may require evaluation of medication adherence and therapeutic drug monitoring.”

“Future research is warranted to explore the role of newer medications, including belimumab and voclosporin, in cLN patients at high risk of renal relapse,” the investigators added.