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Abstract: SA-PO212

AKI Promotes Osteoid Formation Through Increased PTH Secretion in Rats

Session Information

Category: Bone and Mineral Metabolism

  • 401 Bone and Mineral Metabolism: Basic

Authors

  • Nakagawa, Yosuke, Tokai Daigaku Igakubu Jin Naibunpi Taisha Naika, Isehara, Kanagawa, Japan
  • Komaba, Hirotaka, Tokai Daigaku Igakubu Jin Naibunpi Taisha Naika, Isehara, Kanagawa, Japan
  • Hamano, Naoto, Tokai Daigaku Igakubu Jin Naibunpi Taisha Naika, Isehara, Kanagawa, Japan
  • Sawada, Kaichiro, Tokai Daigaku Igakubu Jin Naibunpi Taisha Naika, Isehara, Kanagawa, Japan
  • Wada, Takehiko, Tokai Daigaku Igakubu Jin Naibunpi Taisha Naika, Isehara, Kanagawa, Japan
  • Nakamura, Michio, Tokai Daigaku Igakubu Jin Naibunpi Taisha Naika, Isehara, Kanagawa, Japan
  • Fukagawa, Masafumi, Tokai Daigaku Igakubu Jin Naibunpi Taisha Naika, Isehara, Kanagawa, Japan
Background

Acute kidney injury (AKI) can induce alterations in mineral metabolism, but little is known about the longitudinal changes in bone morphology in the course of AKI and renal recovery. The purpose of this study was to determine the effect of AKI on mineral and bone metabolism and the underlying mechanism in a rat model of ischemia reperfusion injury (IRI).

Methods

Six-week-old male Sprague-Dawley rats were subjected to 35-min bilateral IRI or sham surgery. We evaluated the time course of changes in kidney function and mineral metabolism after surgery and assessed bone morphology at 3 days and 4 weeks by bone histomorphometry. We also repeated the experiment after performing parathyroidectomy followed by continuous infusion of 1-34PTH at a physiological dose.

Results

Rats with IRI exhibited acute hyperphosphatemia, decreased 1,25-dihydroxyvitamin D, and progressively increasing FGF23 and PTH levels, and demonstrated a striking increase in osteoid volume on day 3. During renal recovery, alterations in mineral metabolism and bone morphology normalized almost completely by week 4. To investigate the mechanism of the transient induction of osteoid formation after IRI, we performed qPCR of RNA isolated from femurs at 24 hours after surgery and found increased expression of secretory leukocyte protease inhibitor (SLPI), a downstream mediator of PTH-induced bone formation, suggesting a causal role of PTH in the osteoid formation after IRI. Supporting this possibility, we confirmed that parathyroidectomy prevented the induction of osteoid formation at 3 days after IRI.

Conclusion

AKI induces a transient, but marked increase of osteoid formation in association with alterations in mineral metabolism and increased PTH. The induction of osteoid formation after AKI can be attributed to the anabolic effect of PTH on bone.