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.

Biomarkers Associated with Organ-Specific Involvement in Juvenile Systemic Lupus Erythematosus

“…There are multiple possible explanations for this. LN is the most common, severe organ manifestation in JSLE, occurring in up to half of children [ 6 ], whereas other organ involvement (especially CNS) is rarer, or poses less clinical challenges in terms of morbidity and mortality risk (e.g., arthritis and cutaneous manifestations), although significantly impacting patients’ quality of life. Furthermore, there is higher disease heterogenicity in NPSLE compared to LN, and the absence of a ‘gold-standard’ diagnostic test in NPSLE compared to the renal biopsy in LN impacts the ability to design good quality studies with large sample size.…”

“…The severity and clinical phenotype of SLE can vary considerably with an unpredictable disease course that is frequently relapsing and remitting in nature [ 3 ]. It is well recognised that JSLE is associated with a higher disease burden at diagnosis and a more aggressive clinical course when compared to adult-onset SLE, and thus it often associated with a poorer prognosis [ 1 , 2 , 3 , 5 , 6 ]. Major organ involvement occurs more frequently in JSLE compared to adult-onset SLE, and includes renal, neuropsychological, haematological, mucocutaneous, and cardiopulmonary manifestations, which in turn contributes to a significant increase in morbidity and mortality [ 3 , 7 ].…”

“…Major organ involvement occurs more frequently in JSLE compared to adult-onset SLE, and includes renal, neuropsychological, haematological, mucocutaneous, and cardiopulmonary manifestations, which in turn contributes to a significant increase in morbidity and mortality [ 3 , 7 ]. Lupus nephritis (LN) has increased prevalence in children with JSLE [ 6 ] compared to adult-onset SLE, and it is one of the main determining factors of poor prognosis [ 8 ], suggesting the need for better research focused on this patient population instead of extrapolating management strategies from adult-onset SLE.…”

Comprehensive Analysis of Clinical Trials Registration for Lupus Nephritis Therapy on ClinicalTrials.gov

“…LN is more likely to occur in children (35), and childhoodonset LN exhibits a more active disease course and worse long-term survival than adult-onset LN (36,37). However, recommendations for the management of childhood-onset LN published by American and European experts in pediatric SLE and LN are largely based on data extrapolated from studies in adults (38,39).…”

Clinical spectrum of systemic lupus erythematosus in children. Case report.

“…Se reconoce que el LES de inicio juvenil tiene un curso de la enfermedad más activo en comparación con la enfermedad de inicio en la edad adulta, como lo ocurrido en este caso. Los pacientes tienen una peor supervivencia a largo plazo (6) .…”