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The treatment of CKD patients with NAC with the aim of improving renal function and preventing ESKD has been largely disappointing, with no evidence of reduction in proteinuria [100, 101]

However, the clinical advancement of oridonin faced limitations [24, 25], stemming not only from its unclear molecular mechanisms but also due to hydrophobicity and deficient targeting capabilities [26,27,28,29]

Recessive mutations in genes coding for enzymes of the kynurenine pathway namely kynureninase and 3-hydroxyanthranilic-acid 3,4-dioxygenase lead to combined vertebral, anal, cardiac, tracheo-esophageal, renal, and limb (VACTERL) congenital malformations (76)

The role of dipeptidyl peptidase IV in the cleavage of glucagon family peptides: in vivo metabolism of pituitary adenylate cyclase activating polypeptide-(1-38)

doi: 10.3389/fgene.2018.00579 130 de CalignonAFoxLMPitstickRCarlsonGABacskaiBJSpires-JonesTLet al