Analysis of the Sensitivity and Specificity of Histopathological Findings for Diagnosing Lupus Nephritis

Background: Since the introduction of the SLICC criteria in 2012, biopsy-proven lupus nephritis (LN) has been the only independent diagnostic criterion for systemic lupus erythematosus (SLE). This was reaffirmed by the EULAR/ACR in 2019, emphasizing the importance of renal biopsy in LN. However, the current classification lacks specific histopathological criteria for defining LN. This study describes the histological findings of patients with LN, compares them with those of other glomerular diseases, and evaluates their diagnostic accuracy in a large Latin American population.

Methods: This retrospective cohort included 731 kidney biopsies from two distinct academic centers. The patients were divided into two groups as follows: a LN group and a control group comprising patients with membranous nephropathy, IgA nephropathy, membranoproliferative glomerulonephritis, pauci-immune glomerulonephritis, and proliferative glomerulonephritis. Sensitivity and specificity analyses were conducted for various histopathological features.

Results: We identified the following five features strongly correlated with LN: mesangial proliferation, subendothelial deposits, C1q staining ≥1+, dominant IgG, and ≥4 positive immunofluorescence elements. Combined, these features yielded an area under the ROC curve of 0.94 (95% CI: 0.91-0.95). These results were validated in a diverse population. In membranous nephropathy, histological features such as mesangial deposits, C1q positivity, and ≥4 positive immunofluorescence elements effectively distinguished class V LN from non-lupus membranous nephropathy, with an area under the ROC curve of 0.85 (95% CI: 0.76-0.93).

Conclusions: The combination of mesangial proliferation, subendothelial deposits, C1q staining ≥1+, dominant IgG, and ≥4 positive immunofluorescence elements offer good accuracy for diagnosing renal involvement in SLE in a large Latin American population. In the absence of pathognomonic features, combined criteria are valuable diagnostic tools, particularly when other SLE criteria are lacking.