External validation of a nomogram for predicting tubulointerstitial lesions in IgA nephropathy: a cross-regional study in China

• Cross-regional validation of IgAN tubulointerstitial lesion prediction nomogram in China. • eGFRcr and eGFRcr-cys perform equally, supporting use in low-resource settings. • High-altitude IgAN subgroup shows improved nomogram predictive performance. A diagnostic nomogram for predicting tubulointerstitial lesions (T1/2) in IgA Nephropathy (IgAN), developed in Guangzhou (GZ) using estimated Glomerular Filtration Rate (eGFR) and Urinary Protein Excretion (UPE), demonstrated high accuracy (AUC = 0.92) but lacked external validation. The authors externally validated the nomogram in an independent cohort from Kunming (KM, n = 387; median altitude: 1,891 m), including a high-altitude subgroup (> 2,000 m, n = 155). Model performance was evaluated using Receiver Operating Characteristic (ROC) curves, calibration plots, and Decision Curve Analysis (DCA). Both creatinine-based eGFR (eGFRcr) and Creatinine-Cystatin C-based eGFR (eGFRcr-cys), each combined with UPE, were assessed. The nomogram achieved nearly identical AUCs of 0.80 in the overall KM cohort for both eGFRcr-UPE (95% CI: 0.75–0.85) and eGFRcr-cys-UPE (95% CI: 0.74–0.85), demonstrating strong generalizability across eGFR formulas. In the high-altitude subgroup, performance significantly improved (AUC = 0.89; 95% CI: 0.83–0.95) for both models. External validation demonstrates that the nomogram combining eGFR and UPE is feasible for non-invasive prediction of T1/2 lesions, with comparable performance between eGFRcr and eGFRcr-cys. The improved accuracy observed at high altitude suggests altitude-related influences that merit further study. Prospective studies are needed to determine its prognostic value for clinical outcomes such as CKD progression and treatment response.