Kynurenine Induces Renal Fibrosis which May Contribute to Bone Loss in Aging

Abstract

Aging results in both bone loss and renal dysfunction, and the two conditions are interrelated. Low‐protein diets are recommended to increase longevity in the elderly but may occur at the expense of bone density. Tryptophan, an essential amino acid, is at greatest risk of depletion. Aging is marked by low tryptophan levels and higher levels of its oxidized metabolite, kynurenine (KYN). Feeding a low‐protein diet supplemented with KYN results in bone loss in younger mice; however, the renal effects of KYN have not been evaluated in this model. We hypothesized that KYN feeding induces bone loss and renal dysfunction through the fibroblast growth factor‐23 (FGF23)/α‐Klotho pathway involved in renal handling of calcium and phosphate and production of 1,25‐dihydroxyvitamin D. Male C57BL/6 mice (13 months old) were fed either a low‐protein (LP, 8%) or normal‐protein (NP, 18%) diet with or without KYN for 8 weeks. LP induced significant diuresis (2.16 ± 0.08 mL/day) that was attenuated with KYN (1.28 ± 0.10 mL/day). Glomerular filtration rate (GFR) was not different among the groups. Albuminuria was increased with age in the NP‐ or NP+KYN‐fed mice but not in the LP or LP+KYN groups. Tubulo‐interstitial fibrosis was present in LP‐ and LP+KYN‐fed mice and was not different from 24‐month‐old mice. Serum levels of FGF23 were elevated in LP‐fed mice but did not reach significance. Kidney protein levels of α‐Klotho declined with age. Our preliminary data suggest that KYN feeding may induce renal fibrosis that may contribute to bone loss, and FGF23/α‐Klotho may be involved. Further studies are needed to define a role for KYN in renal aging.Support or Funding InformationPO1 AG036675 and AG036675S1This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.