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Kidney Week

Abstract: FR-PO366

Klotho Restrains RIG-1/NF-κB Signaling Activation and Monocyte Inflammatory Factor Release Under Uremic Conditions

Session Information

  • CKD: Mechanisms - II
    November 08, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
    Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

  • 2103 CKD (Non-Dialysis): Mechanisms

Author

  • He, Ting, Xinqiao Hospital, Chongqing, Chongqing, China
Background

Systemic inflammation is a main hallmark of chronic kidney disease (CKD). However, the mechanisms underlying the pathogenesis of CKD-associated systemic inflammation are unclear. Our study aimed to investigate the relationship between indoxyl sulphate (IS) and CKD-associated systemic inflammation, and the protective effect of Klotho against IS-induced systemic inflammation in CKD.

Methods

Serum Klotho was measured by ELISA. Heterozygous kl/kl (kl/+) mice or WT mice were treated with 5/6 renal damage and then injected with recombinant Klotho protein.

Results

It shows that in 286 CKD patients, the serum levels of inflammatory factors are positively related with IS, but negatively related with Klotho. Klotho can significantly inhibit IS-induced retinoic acid-inducible gene I (RIG-I) /NF-κB activation and the productions of IL-6 and TNF-α in cultured monocytes. In vivo, RIG-I/NF-κB activation is observed in monocytes in both CKD mice and patients. Notably, higher levels of IL-6 and TNF-α are detected in kl+/- mice with CKD. Klotho administration can evidently attenuate RIG-I/NF-κB activation in monocytes and systemic inflammation in CKD mice.

Conclusion

These results suggest that Klotho can suppress CKD-associated systemic inflammation through inhibiting IS-induced RIG-1/NF-κB activation and monocyte inflammatory factor release.

The basic information of 286 CKD patients
CKD stageCKD 2(n=36)CKD 3(n=51)CKD 4(n=55)CKD 5(n=144)P
Age, years39.86±11.949.88±13.8847.27±14.8946.29±14.18<0.05
Male gender, n(%)19(53)22(43)34(62)60(42)<0.001
eGFR(ml/min/1.73m2)71.16(67.41,82.22)42.79(36.04,53.27)19.71(16.99,25.22)8.14(6.39,10.45)<0.001
BMI(kg/m2)24.06±2.8924.50±3.5023.23±2.9922.34±3.43<0.001
ALB(g/L)41.50(34.43,45.28)39.00(35.30,42.40)40.40(35.30,43.80)38.85(36.40,42.08)>0.05
Uric acid(μmol/L)434.50±90.46429.24±94.02500.60±113.53539.04±123.22<0.001

Klotho inhibits IS-induced monocyte activation by restraining RIG-1/ NF-κB signaling