Assessing kidney outcomes in childhood-onset lupus nephritis: role of National Institutes of Health-modified histological indices.

backgroundChildhood-onset lupus nephritis (cLN) is an aggressive disease. Although histological class has historically guided its treatment, its prognostic value remains limited. Although the National Institutes of Health (NIH)-modified activity index (AI) and chronicity index (CI) incorporate glomerular and tubulointerstitial changes and may provide better prognostic insight, their utility in cLN is not well established. PURPOSE: Here we aimed to assess the utility of the NIH-modified-modified AI and CI for predicting kidney outcomes and identify histopathological features and treatment-related factors associated with the development of kidney function impairment in cLN.

methodsWe retrospectively analyzed 60 children with biopsy-proven proliferative lupus nephritis. Their baseline clinical and histological features, treatments, and outcomes were assessed. The association between AI and CI scores, along with individual histological components, and kidney function impairment, defined as an estimated glomerular filtration rate < 90 mL/min/1.73 m² sustained for ≥3 months, was evaluated.

resultsOver a median follow-up of 55.5 months, 30% of patients developed kidney function impairment. AI scores and glomerular lesions did not differ significantly between patients with and without kidney function impairment. However, the CI scores were significantly higher in patients who developed kidney function impairment, with tubular atrophy and interstitial fibrosis being the most predictive components. On a multivariate analysis, tubular atrophy was an independent predictor of kidney function impairment (hazard ratio [HR], 17.74; 95% confidence interval [CI], 1.94-162.5; P=0.01). Use of mycophenolate mofetil (MMF) as maintenance therapy was associated with a reduced risk of kidney function impairment (HR, 0.09; 95% CI, 0.02-0.47; P=0.003).

conclusionChronic tubulointerstitial changes, particularly tubular atrophy, are a stronger predictor of longterm kidney function than glomerular findings or AI scores. These findings highlight the prognostic value of NIH-modified CI and the importance of MMF in maintenance therapy. The early identification of chronic lesions on biopsy may guide therapeutic decisions aimed at preserving kidney function and improving long-term outcomes in patients with cLN.