Autosomal dominant polycystic kidney disease (ADPKD) is an inherited genetic disease that is estimated to affect around 1 in 400 – 1,000 people (NIDDK, NIH). Most people with ADPKD can be attributed to defects in either PKD1, or to lesser extent, PKD2 genes. Of interest, metabolites of the kynurenine pathway (KP) have been associated with the cause of chronic kidney disease (Grams et al., 2017).
Nguyen, Kleczko and colleagues studied the role of the KP underlying polycystic kidney disease (PKD) model, published in JCI insight. In this study, the authors investigated KP activation in a PKD mouse model (C57Bl/6J PKD1 RC/RC) over 3, 6 and 9 months. They showed increased IDO1 expression in both the animal model and ADPKD cell lines. To examine the effect of IDO1 on the disease progression, they demonstrate that both genetic loss and pharmacological inhibition (1-MT) of IDO function resulted in reduction of PKD severity and changes in the cystic immune microenvironment which promotes an anti-cystogenic composition. Interestingly, a recent study (Pires et al., 2022) showed dysregulated KP activation in autosomal recessive PKD although their study pinpointed TDO rather than IDO1. Collectively, these studies indicate the detrimental role of KP in PKD and presents novel therapeutic targets for PKD.