Morphometric analysis and its application in lupus nephritis: a systematic review

Lupus nephritis (LN) is a severe manifestation of systemic lupus erythematosus (SLE), characterized by marked histological heterogeneity and high interobserver variability in the evaluation of renal biopsies. Digital morphometry has emerged as an objective and reproducible tool that enables precise quantification of tissuelesions, thereby enhancing diagnostic accuracy and prognostic assessment. To explore its application in LN, a systematic review was conducted following PRISMA guidelines, including observational studies in adults, children, and animal models with biopsy-proven LN in which digital morphometry was applied. Searches were performed inPubMed, Embase, Scopus, Web of Science, Cochrane, and Google Scholar. From 376 identified records, 46 studies fulfilled inclusion criteria. Among these, 30 analyzed the glomerularcompartment, 22 the tubulointerstitial, and the vascular. Both manual techniques and image analysis software such as ImageJ, ImagePro-Plus, and QuPath were used. In the glomerular compartment, parameters including cellularity, mesangial expansion, proliferation, and immune deposits were assessed. Tubulointerstitial studies measured fibrosis, tubular atrophy, and immune Infiltrates, while vascular analyses examined intimal thickening and complementactivation. Across compartments, morphometry consistently outperformed conventional visual evaluation, particularly in fibrosis quantification and prediction of renal prognosis. Overall, digital morphometry represents a valuable method for the comprehensive assessment of LN renal biopsies. Its application provides greater precision in characterizing renal damage and offers advantages interms of objectivity, reproducibility, and prognostic value. Standardization of morphometric approaches, together with integration into artificial intelligence-based tools, could optimize diagnostic accuracy and therapeutic strategies in LN.