Comparison of urinary parameters, biomarkers, and outcome of childhood systemic lupus erythematosus early onset-lupus nephritis

Abstract

Background: Urinary parameters, anti-dsDNA antibodies and complement tests were explored in patients with childhood-Systemic Lupus Erythematosus (cSLE) early-onset lupus nephritis (ELN) from a large multicenter cohort study. Methods: Clinical and laboratory features of cSLE cases with kidney involvement at presentation, were reviewed. Disease activity parameters including SLEDAI-2 K scores and major organ involvement at onset and follow up, with accrued damage scored by SLICC-DI, during last follow up, were compared with those without kidney involvement. Autoantibodies, renal function and complement tests were determined by standard methods. Subjects were grouped by presence or absence of ELN. Results: Out of the 846 subjects enrolled, mean age 11.6 (SD 3.6) years; 427 (50.5%) had ELN. There was no significant difference in the ELN proportion, according to onset age, but ELN frequency was significantly higher in non-Caucasians (p = 0.03). Hematuria, pyuria, urine casts, 24-h proteinuria and arterial hypertension at baseline, all had significant association with ELN outcome (p < 0.001). With a similar follow up time, there were significantly higher SLICC-DI damage scores during last follow up visit (p = 0.004) and also higher death rates (p < 0.0001) in those with ELN. Low C3 (chi-square test, p = 0.01), but not C3 levels associated significantly with ELN. High anti-dsDNA antibody levels were associated with ELN (p < 0.0001), but anti-Sm, anti-RNP, anti-Ro, anti-La antibodies were not associated. Low C4, C4 levels, low CH50 and CH50 values had no significant association. High erythrocyte sedimentation rate (ESR) was associated with the absence of ELN (p = 0.02). Conclusion: The frequency of ELN was 50%, resulting in higher morbidity and mortality compared to those without ELN. The urinary parameters, positive anti-dsDNA and low C3 are reliable for discriminating ELN.

Renal manifestations of paediatric systemic lupus erythematosus

“…These parameters were reinforced by a Brazilian study in 2020 that showed a significant correlation between these markers and the presence of lupus nephritis in children. This study also reported that high antidouble stranded DNA antibodies and low-C3 levels were significantly associated with lupus nephritis [10].…”

An Update on the Management of Childhood-Onset Systemic Lupus Erythematosus

“…Knowledge of cSLE prognosis factors is relevant to disease management since predictive factors of the long-term renal outcome at early stages of SLE are important to define clinically relevant targets of drug intervention [ 164 ]. Three laboratory or urinalysis tests have been used regularly in clinical practice as noninvasive predictors for cSLE renal involvement: kidney function (serum creatinine levels and measurement of glomerular filtration rate), urinary protein excretion, and glomerular hematuria [ 15 , 165 ].…”

“…The hallmark of cSLE is the wide spectrum of clinical and laboratory abnormalities, particularly with the production of multiple autoantibodies against histone, nonhistone, cytoplasm, and nuclear proteins, and a marked increase in proinflammatory cytokines [11,12,[14][15][16]. The clinical cSLE presentation spectrum is very diverse, varying from acute, severe, life-threatening disease to chronic condition with an intermittent or continuous course, and is rarely…”

Towards development of treat to target (T2T) in childhood-onset systemic lupus erythematosus: PReS-endorsed overarching principles and points-to-consider from an international task force

“…In cSLE, patients have a higher rate of both anti-dsDNA positivity and low C3 levels than in aSLE,6 47 particularly in adolescents at diagnosis (vs prepubertal and peripubertal patients) 48. Low C3 and high anti-ds-DNA antibody titres are associated with early onset LN 49. Low C3 levels are also associated with LN at disease onset, and a predictor of subsequent LN development 50.…”