Risk factors of infection-associated mortality in children with lupus nephritis in under-resourced areas

Treatment of lupus nephritis class III, IV and V with immunosuppressive therapy increases patient survival but poses a risk of infection-related mortality. This study was conducted to evaluate risk factors for fatal infection in children with lupus nephritis in under-resourced areas.

Medical records of patients, who were admitted to a tertiary-care university-based hospital from January 2002 to July 2018 with the diagnosis of systemic lupus erythematosus, were reviewed. Only patients aged less than 18 years with lupus nephritis and documented infection were included in the study. The primary outcome was infection-associated mortality. The logistic regression model was used to identify independent variables associated with fatal infection. Predicted probabilities of infection-related mortality adjusted for factors significant in multivariate analysis were calculated using marginal effects at representative values.

Infection-related deaths occurred in 27 of 179 patients (15.1%). Hospital-acquired infections occurred in 72 of 375 episodes of hospital admissions (19.2%) and 13 hospital-acquired infections (18.1%) resulted in fatal infection. Invasive fungal infections were the leading cause of death (44.4%) and pulmonary infections were the predominant site (55.5%). Haemoglobin levels and glomerular filtration rates were significantly lower in deceased versus surviving patients. Percentages of patients with hospital-acquired infections, invasive fungal infections and pulmonary infections were significantly higher in deceased than surviving patients. Urine protein, the neutrophil-to-lymphocyte ratio, cumulative methylprednisolone dose and daily prednisolone dose were significantly higher in deceased than surviving patients. In multivariate analysis, a neutrophil-to-lymphocyte ratio more than 20, invasive fungal infections and high daily prednisolone dose were independently predictive of fatal infection with adjusted odds ratio of 3.02 (95% confidence interval 1.02-8.97, p = 0.04), 15.08 (95% confidence interval 4.72-48.24, p < 0.001) and 1.03 (95% confidence interval 1.01-1.06, p = 0.04), respectively. A high daily prednisolone dose intensified the impact of invasive fungal infections and high neutrophil-to-lymphocyte ratio on predicted probability of infection-associated mortality.

Prevention of invasive fungal infections and minimization of daily prednisolone should be emphasized in routine clinical practice of children with lupus nephritis in under-resourced areas to achieve better survival. Children with lupus nephritis and a high neutrophil-to-lymphocyte ratio should be under cautious surveillance for infection.