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Kidney Week

Abstract: SA-PO370

Phosphorus Is an Exacerbation Factor in the Progression of CKD Model by the Accumulation of Small Kidney Injury in Klotho Deficit Mice

Session Information

Category: Chronic Kidney Disease (Non-Dialysis)

  • 301 CKD: Risk Factors for Incidence and Progression

Authors

  • Tsuchiya, Ken, Tokyo Women's Medical University, Shinjuku-ku, Tokyo, Japan
  • Sugiura, Hidekazu, Saiseikai Kurihashi Hospital, Kuki, Japan
  • Hanafusa, Norio, Tokyo Women's Medical University, Shinjuku-ku, Tokyo, Japan
  • Nitta, Kosaku, Tokyo Women's Medical University, Shinjuku-ku, Japan
Background

It has been established that klotho protein is a key molecule in the axis of Ca/P metabolism in CKD-MBD, on the other hand, klotho is speculated to be implicated in the mechanism of preceding the CKD, in which klotho suppression is likely to be a result and a cause of CKD. Previously, we reported that repeated minor kidney injury results in more reduction of klotho and cause of CKD in klotho deficit mice. In this study with this model, we investigated several factors which may be involved in making worse or improving the progression of CKD.

Methods

Short time clamping of renal artery for 20 minutes was performed and repeated once a week for 3 weeks in the klotho gene heterozygous mice (kl(-/+)). Renal function, the score of tissue damage and altered expression factors were monitored with immunohistochemistry and RT-PCR for mRNA expression. Then, klotho expression was modified by erythropoietin treatment or diet therapy assuming clinical matter. Practically, 200 μ/kg BW of recombinant erythropoietin (ESA) was injected subcutaneously 3 times per week. Since phosphorus is an old and new aggravating factor for CKD which has been drawing attention, stepwise dose of phosphorus was fed in diet in whole experimental period for dietary modification.

Results

Repeated ischemia reduced the renal function and worsen tissue score in kl (-/+) mice than in wild type mice. These changes were attenuated by ESA treatment. Klotho mRNA slightly recovered and the expression of fibrotic factors were reduced. Phosphorus is an aggravating factor that stands out than the other factors. Klotho deficit mice treated with repeated minor kidney injury were more sensitive to high phosphorus (2%) loading than control, resulting in more severely reducing the expression of klotho and accelerating renal damage (ATN scores 2.4 folds vs. control).

Conclusion

Repetitions of mild kidney injury possibly initiate or accelerate CKD in reduced klotho expression. Phosphorus loading damaged the kidney much more in these kl(-/+) mice, which may suggest that phosphorus restriction (reflecting low protein diet) is likely to be meaningful for the attenuation of the progression of CKD, indicating the importance of re-estimating of the significance of low protein diet (namely, low phosphorus) in clinical practice.

Funding

  • Government Support - Non-U.S.