Management and outcomes in children with lupus nephritis in the developing countries

Background: Lupus nephritis (LN) has variable prevalence, severity, and outcomes across the world. Objectives: This review compares the outcomes of childhood LN in low- and middle-income countries (LMICs) and high-income countries (HICs) and aims to summarize long-term outcomes of pediatric LN from LMICs. Data sources: A systematic literature search, conducted in PubMed, EMBASE, and Cochrane database in the last 30-years from January 1992, published in the English language, identified 113 studies including 52 from lower (n = 1336) and upper MICs (n = 3014). Study eligibility criteria: Cohort studies or randomized controlled trials, of patients ≤ 18 years of age (or where such data can be separately extracted), with > 10 patients with clinically or histologically diagnosed LN and outcomes reported beyond 12 months were included. Participants and interventions: Patients ≤ 18 years of age with clinically or histologically diagnosed LN; effect of an intervention was not measured. Study appraisal and synthesis methods: Two authors independently extracted data. We separately analyzed studies from developed countries (high income countries; HIC) and developing countries (LMICs). Middle-income countries were further classified as lower and upper MICs. Meta-analyses of data were performed by calculating a pooled estimate utilizing the random-effects model. Test for heterogeneity was applied using I statistics. Publication bias was assessed using funnel plots. Results: Kidney remission was similar across MICs and HICs with 1-year pooled complete remission rates of 59% (95% CI 51–67%); one third of patients had kidney flares. The pooled 5-year survival free of stage 5 chronic kidney disease (CKD5) was lower in MICs, especially in lower MICs compared to HICs (83% vs. 93%; P = 0.002). The pooled 5-year patient survival was significantly lower in MICs than HICs (85% vs. 94%; P < 0.001). In patients with class IV LN, the 5-and 10-year respective risk of CKD5 was 14% and 30% in MICs; corresponding risks in HICs were 8% and 17%. Long-term data from developing countries was limited. Sepsis (48.8%), kidney failure (14%), lupus activity (18.1%), and intracranial hemorrhage/infarct (5.4%) were chief causes of death; mortality due to complications of kidney failure was more common in lower MICs (25.6%) than HICs (6.4%). Limitations: The review is limited by heterogenous approach to diagnosis and management that has changed over the period spanning the review. World Bank classification based on income might not correlate with the standards of medical care. The overall quality of evidence is low since included studies were chiefly retrospective and single center. Conclusions and implications of key findings: Challenges in LMICs include limited access to pediatric nephrology care, dialysis, increased risk of infection-induced mortality, lack of frequent monitoring, and non-compliance due to cost of therapy. Attention to these issues might update the existing data and improve patient follow-up and outcomes. Systematic review registration number: PROSPERO 2022 number: CRD42022359002, available from: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022359002