Kidney Week

Abstract: SA-PO372

Tubular Matrix Gla Protein Expression Increases Progressively with CKD

Session Information

• CKD: Risk Factors for Incidence and Progression - III
  November 04, 2017 | Location: Hall H, Morial Convention Center
  Abstract Time: 10:00 AM - 10:00 AM

Category: Chronic Kidney Disease (Non-Dialysis)

• 301 CKD: Risk Factors for Incidence and Progression

Authors

• Miyata, Kana N., LA Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, California, United States

Kana N. Miyata,

• Zhang, Pei, LA Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, California, United States

Pei Zhang,

• Dai, Tiane, LA Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, California, United States

Tiane Dai,

• Nast, Cynthia C., Cedars-Sinai Medical Center, Los Angeles, California, United States

Cynthia C. Nast,

• Dukkipati, Ramanath B., LA Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, California, United States

Ramanath B. Dukkipati,

• La page, Janine A., LA Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, California, United States

Janine A. La page,

• Troost, Jonathan P., University of Michigan, Ann Arbor, Michigan, United States

Jonathan P. Troost,

• Schurgers, Leon J., Maastricht University, Maastricht, Netherlands

Leon J. Schurgers,

• Adler, Sharon G., LA Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, California, United States

Sharon G. Adler,

Background

Experimental data indicate that renal tubule dedifferentiation may contribute to CKD progression. A vitamin K–dependent protein, Matrix Gla Protein (MGP), is a potent in vivo inhibitor of arterial calcification. Little is known about de novo MGP expression and function in kidney.

Methods

We performed 5/6 nephrectomy (Nx) in rats, sacrificed them at 2 days, 2 weeks, and 4 weeks, and measured gene expression by microarray. Altered expression was noted for many proteins involved in vascular calcification. We focused on MGP and localized carboxylated MGP (cMGP) in kidneys from patients with CKD. Then, we analyzed the association between eGFR at biopsy and the MGP transcript levels of patients in the Nephrotic Syndrome Study Network (NEPTUNE) cohort.

Results

Renal MGP expression was significantly increased in 5/6Nx rats: 2.16-fold (2 days, p=0.002), 3.27-fold (2 weeks, p=0.0002), and 3.31-fold (4 weeks, p=0.0002). There was a trend for patients with advanced CKD (n=8) to have greater tubulointerstitial (TI) cMGP staining vs controls (NS). In NEPTUNE samples, there was an inverse relationship between eGFR and the TI MGP transcript. The TI MGP transcript correlated positively with interstitial fibrosis (r=0.47, p<0.01) and tubular atrophy (r=0.45, p<0.01), even after adjustment for eGFR, and was significantly higher in kidneys with acute tubular injury(p<0.01).

Conclusion

Our experiments demonstrate increased TI MGP expression in CKD in experimental animals and patients. TI MGP transcript levels increased progressively with CKD progression and was associated with interstitial fibrosis, tubular atrophy, and acute tubular injury. In published microarrays, TI MGP expression is also increased in patients with diabetic kidney disease and in ageing rats. Additional studies are needed to determine if the de novo expression of MGP represents tubular dedifferentiation or an adaptation to injury.

Funding

• Other NIH Support