Renal Interstitial Distribution of Full-Length IgG and Fab Fragments in Unilateral Ureteral Obstruction-Induced Fibrotic Kidneys

Renal fibrosis, a critical contributor to chronic kidney disease, is characterized by interstitial expansion and excessive extracellular matrix accumulation. Due to their specificity, monoclonal antibodies (mAbs) and their fragments are promising candidates for treating renal fibrosis, but their distribution characteristics in fibrotic kidneys, particularly within the renal interstitium, remain unclear. This study investigated the tissue distribution of full-length IgG and Fab fragments in a unilateral ureteral obstruction (UUO)-induced renal fibrosis mouse model. Full-length IgG and Fab fragments were intravenously administered in UUO-induced renal fibrosis model mice. The concentrations in each organ and plasma were quantified using enzyme-linked immunoassay. In addition, the localization within the renal interstitium was evaluated by multiple techniques, including intravital and ex vivo confocal imaging under near-living conditions and the observation of the tissue sections via an in vivo cryotechnique. Both full-length IgG and Fab fragments showed higher distribution in fibrotic kidneys than in other organs. Specifically, Fab fragments had excellent selective accumulation in the fibrotic kidneys, whereas full-length IgG had higher absolute distribution due to slower plasma elimination. Imaging assessments revealed that both had widespread localization within the interstitial spaces of the fibrotic kidneys. Due to their superior selectivity for fibrotic kidneys, Fab fragments can be used to target fibrotic lesions. Due to its prolonged distribution, full-length IgG may offer advantages in sustained therapeutic effects. This study provides foundational insights into the distribution of mAbs and their fragments in fibrotic kidneys and underscores the importance of further pharmacokinetic analyses to refine antibody-based therapies.