Abstract: SA-PO387

The Effects of Sevelamer on Renal Klotho Expression and Serum Levels of Klotho, FGF23, and sTWEAK in Adenine Induced CKD Rats

Session Information

Category: Chronic Kidney Disease (Non-Dialysis)

  • 301 CKD: Risk Factors for Incidence and Progression

Author

  • Argani, Hassan, Modares Hospital, Tehran, Iran (the Islamic Republic of)
Background

Klotho down-regulation may be induced by specific cytokines such as tumour necrosis factor-α or TWEAK through the canonical activation of the inflammatory transcription factor nuclear factor kappa B (NFκB) and, specifically RelA. Klotho itself has antioxidant and anti-inflammatory properties and the canonical NFκB component RelA is one of its targets. Klotho is a key regulator of phosphate balance and phosphate play a role in ageing. Recent studies demonstrate soluble tumor necrosis factor (TNF) weak inducer of apoptosis (sTWEAK) levels follow declining of renal function, as a marker of cardiovascular events in nondialyzed chronic kidney disease patients were reduced, On the other hand high FGF23and low Klotho were reported in CKD patients. Over last few years, several studies have noted a direct correlation of inflammatory markers such as Tumor Necrosis Factor-α (TNF) with circulating FGF23 in patients with CKD.
The present study is aim at evaluating the sevelamer (phosphate binder) effect in renal Klotho expression and Serum levels of FGF23, s TWEAK, Klotho in rat model of adenine induced renal failure.

Methods

Adenine 3mg/kg was used to induce CKD in 60 male wistar rats. These divided into 6 groups based on the dose administration of sevelamer for 4 weeks.
Group 1 (n = 10) control group was given 0% adenine, 0% Sev, Group2 (n = 10) 0% Sev in Aenine group, Adeine contol group, Group 3(n = 10) 1% Sev in Aenine group, Group 4(n = 10) 2% Sev in Aenine group, Group 5 (n = 10) 3% Sev in Aenine group and group 6 (n = 10) 2% Sev in the normal diet.
Serum stweak, Klotho levels were measured by enzyme-linked immunosorbent assay. Real-time polymerase chain reaction and Western blotting were used to evaluate Renal Klotho expression in each group.

Results

Induced renal failure was induced by adenin, FGF23 levels could be manipulated through the control of serum phosphorus levels by sevelamer treatment. Treatment with sevelamer controlled sTWEAK and KLotho downregulated in CKD rats. Sevelamer treatment also improved reduced renal expression and serum levels of Klotho and deteriorated renal function and could alleviate adenine -induced renal histological changes.

Conclusion

Treatment with sevelamer might lead to ameliorat renal Klotho and downregulation sTWEAK in CKD and suppressed FGF23 increases through the control of serum phosphorus levels in CKD patients.

Funding

  • Government Support - Non-U.S.