Kidney outcomes for children with lupus nephritis

Abstract

Systemic lupus erythematosus is a rare lifelong multi-systemic autoimmune condition. Juvenile-onset SLE (JSLE) is recognized to have a more active disease course when compared with adult-onset disease and patients have a worse long-term survival. Kidney involvement occurs in over 50% of children and treatment decisions are guided by the histological classification. Several international groups have produced treatment protocols that rely on an intense period of immunosuppression to halt the acute kidney inflammatory process, followed by maintenance therapy with close observation for disease improvement and prompt evaluation of disease flares. A reduced glomerular filtration rate at presentation is predictive of later stage chronic kidney disease (CKD) in multivariate analysis. Kidney remission remains suboptimal with only 40-60% of patients achieving complete remission. Kidney flares are seen in over a third of patients. The rate of CKD 5 is reported to be up to 15% and the presence of lupus nephritis (LN) has an established link with an associated increase in mortality. In established kidney failure, transplantation seems to be the optimal kidney replacement modality for this group of patients, ideally after a period of disease quiescence. Modified outcome measures in clinical trials have demonstrated that biologic agents can be effective in this disease. Current biologic agents under investigation include obinutuzimab, belimumab, atacicept, anifrolumab, tocilizumab, eculizumab, dapirolizumab, and abatacept. Future research should focus on discovering early disease biomarkers, including surrogates for later cardiovascular disease, and evaluating biological agents as adjuncts to improve the rates of complete remission and subsequently influence the kidney outcome. The aim of this review article is to summarize the current kidney outcomes for this disease with a view to identifying key areas that may help to reduce the risk of long-term CKD.

Keywords: Childhood-onset SLE; Children; Lupus nephritis; Prognosis; SLE; Systemic lupus erythematosus.

Fig. 1

A proposed treatment protocol for the induction and maintenance management of histologically class III, IV, and V lupus nephritis in children as based on published recommendations [–18]. CR, complete response (UPCR < 50 mg/mmol, normal kidney function); PR, partial response (> 50% reduction in proteinuria, not nephrotic, normal kidney function). UPCR, urine protein:creatinine ratio; LN, lupus nephritis; DMARD, disease modifying anti-rheumatic drug; CR, complete response; PR, partial response; MMF mycophenolate mofetil; AZA, azathioprine; IV, intravenous; CNI, calcineurin inhibitor

Fig. 2

Using cohort data collected from children recruited to the UK JSLE Cohort Study [10], the incidence of chronic kidney disease (CKD) was 3.8% (15/399 children) after a median follow-up time of 6.6 years (range 0–21 years). The stages of CKD are shown demonstrating that the majority of children had CKD stage 2 (8/15; 53%, 8/399; 2% of entire cohort), followed by CKD 3 (5/15; 33%, 5/399; 1% of entire cohort), none had CKD 4 (0/15; 0%, 0/399; 0%) and 2 patients had CKD 5 (2/15; 13%, 2/399; 0.5% of entire cohort)