Abstract: The present disclosure provides compositions and methods for renal therapy. In various aspects, the present disclosure provides a composition comprising a knotted peptide, wherein upon administration to a subject the knotted peptide homes, targets, is directed to, accumulates in, migrates to, is retained by, and/or binds to renal tissue of the subject. In various aspects, the composition further comprises an active agent coupled to the knotted peptide. The composition, when administered to the subject, may induce protective preconditioning or acquired cytoresistance.