Histopathological Assessment of Precision‐Cut Kidney Slices: A Live Human Tissue‐Based Model of Renal Fibrosis

Chronic kidney disease (CKD) is characterized by a progressive decline of renal function. A major challenge in CKD drug development is the low success rate of drug candidates, with fewer than 10% of drugs entering Phase I clinical trials demonstrating clinical benefit. Traditional in vitro and in vivo models, while valuable, do not fully recapitulate human kidney complexity. To address this, we utilized human precision-cut kidney slices (PCKS), an ex vivo model that preserves human cellular diversity and organ architecture. Although this model lacks factors such as blood flow and osmotic gradients, it enables controlled induction of fibrosis through TGF-β treatment. To assess potential therapeutic interventions, we adapted a histopathological scoring system that was originally developed for human kidney biopsies. Our findings demonstrate that PCKS exhibit progressive fibrosis and tubular atrophy during culture up to 48 h, with TGF-β treatment further exacerbating these effects at the 48 h time-point. In contrast to PCKS from healthy patients, 48 h incubation of PCKS from CKD patients did not induce additional fibrosis or tubular atrophy. Thus, our scoring system provides a robust method for assessing fibrosis and tubular atrophy in human PCKS and may serve as a promising tool in preclinical drug screening.