Clinical manifestations, prognosis, and treat-to-target assessment of pediatric lupus nephritis

Abstract

Background Pediatric lupus nephritis (pLN) is one of the most refractory secondary kidney diseases in childhood. The treat-to-target (T2T) strategy has become the standard treatment for systemic lupus erythematosus (SLE). This study reviewed clinical features, overall remission status, and factors affecting prognosis, to guide pLN management according to T2T strategy. Methods This single-center retrospective study studied 220 children diagnosed with LN from January 2012 to December 2018, with > 6-month follow-up data on 173 and complete data on 137 patients. Primary outcome was treatment failure (deterioration or no response) at the latest follow-up. Results The most common pLN manifestation was proteinuria (81.36%). Females presented more often with rash (P<0.001) and alopecia (P=0.026) than males. Class IV LN (33.33%) was the most common grade on kidney biopsy. Median follow-up was 27.20 months (IQR, 15.78–44.45 months). One-, 3-, and 5-year cumulative overall survival rates were 93.5%, 87.8%, and 86.5%, respectively. The 5-year cumulative kidney survival rate was 97.1%. Regarding initial therapy, efficacy of corticosteroids combined with immunosuppressive agents was significantly better than corticosteroids alone (P=0.010). Factors with P<0.05 in univariate analysis, including hypoalbuminemia, higher SCr at diagnosis, lower eGFR at diagnosis, anti-dsDNA positivity, heavy proteinuria, hypertension, nervous-system involvement, treatment non-compliance, and SLEDAI-2K score, were used for logistic regression analysis. Logistic regression analysis showed hypertension (OR=0.845, P=0.011), nervous-system involvement (OR=4.240, P=0.005), treatment non-compliance (OR=6.433, P=0.001), and lower estimated glomerular filtration rate at diagnosis (OR=1.020, P=0.021) affected prognosis. At end of follow-up, 34.31% achieved varying levels of remission, and 8.76% were in low disease activity state (LDAS). Conclusions pLN usually presented with proteinuria, and class IV LN was the dominant pathology. Hypertension, nervous-system involvement, treatment non-compliance, and lower eGFR at diagnosis were independent risk factors for poor prognosis of kidney outcomes. Compared with renal remission rate and cumulative overall survival rate, the proportion of targets achieved was not ideal, suggesting T2T strategy should be used to guide pLN management. Graphical abstract

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

“…Our study reports the longest follow-up data to date on cLN and shows that patient and kidney survival in cLN seemed to have improved in the present era, probably attributed to effective treatment of active disease, efficacious long-term maintenance immunosuppression, and increased awareness of medication adherence. The overall mortality (2%), though appearing relatively favorable compared with 6% to 9% in other pediatric cohorts, 8 , 9 was still 22 times higher than that in age-matched and sex-matched healthy children. Approximately 8% of patients with cLN developed advanced CKD and/or ESKD.…”

“… 6 Improvement in survivals have also plateaued in past decades, 5 and up to 9% and 14% of children with cLN died or developed ESKD during the course of illness, respectively. 7 , 8 , 9 CKD progression and ESKD, together with complications in various organs, are major challenges in the long-term management of patients who transitioned to adulthood. 7 …”

Endocapillary hypercellularity levels are associated with early complete remission in children with class IV lupus nephritis as the initial presentation of SLE

“…It occurs in 50-60% of patients with childhood-onset SLE [16]. Among the pathologically proven LN cases reported thus far, class IV is the most commonly seen LN in children [17][18][19][20][21][22][23]. As the most severe form of LN, class IV LN requires intensified immunosuppressive therapy [19], and currently few studies have specifically examined early treatment outcome and its influencing factors of class IV LN in children [19,24].…”

Identification of genomic determinants contributing to cytokine release in immunotherapies and human diseases

“…The anti-cytokine drugs, tocilizumab and siltuximab (anti-IL-6 receptor antibodies) have been widely used to minimize rates of life-threatening CRS in patients receiving CAR T-cell therapy and in patients with severe COVID-19 [13][14][15]. Corticosteroids such as methylprednisolone or dexamethasone, are also used to help mitigate inflammatory and immune responses by providing broad immunosuppression in individuals with autoimmune diseases and COVID-19 [16][17][18]. However, while the usage of tocilizumab may decrease CRS severity, it may increase the risk of neurotoxicity, another common toxicity during CAR T-cell therapy [19,20].…”