Diagnostic Performance of [68Ga]Ga-FAPI PET/CT for Differentiating Histologically Confirmed Kidney Fibrosis Severity in Advanced Chronic Kidney Disease.

Background: Interstitial fibrosis is a hallmark of chronic kidney disease (CKD) progression; however, its assessment currently relies on kidney biopsy, which is invasive and prone to sampling error. Fibroblast activation protein inhibitor (FAPI) positron emission tomography/computed tomography (PET/CT) targets activated fibroblasts and may enable non-invasive assessment of renal fibrosis. We investigated whether renal parenchymal [68Ga]Ga-FAPI uptake reflects histological fibrosis and evaluated its performance in highly fibrotic kidneys. Methods: In this prospective single-center study, 23 patients undergoing clinically indicated kidney biopsy underwent [68Ga]Ga-FAPI PET/CT imaging. Standardized uptake values (SUV) of the kidneys were matched to histological fibrosis assessments as the H-score (0-300), the fibrotic area (%) and intensity grade (0-III). Associations were calculated by Spearman rank correlation and diagnostic performance for advanced fibrosis was evaluated by ROC analysis with leave-one-out cross-validation. Results: SUVmean correlated with H-score (ρ = 0.71), fibrotic area (ρ = 0.79) and intensity grade (ρ = 0.74; all p < 0.001), whereas SUVmax (ρ = 0.17) and SUVpeak (ρ = 0.29) did not. For advanced fibrosis (intensity grade III), SUVmean discriminated with an AUC of 0.89 (95% CI 0.67-1.00). A Youden-derived cut-off of ≥2.83 yielded cross-validated sensitivity/specificity of 92%/82%. Conclusions: Renal parenchymal FAPI expression, represented by SUVmean, correlates with the histological severity of interstitial fibrosis, supporting [68Ga]Ga-FAPI PET/CT as a non-invasive tool to potentially monitor renal fibrosis over time. FAPI expression is closely linked to renal function, and subsequent larger studies are needed to validate these findings and the proposed exploratory cut-off value.