ASN's Mission

To create a world without kidney diseases, the ASN Alliance for Kidney Health elevates care by educating and informing, driving breakthroughs and innovation, and advocating for policies that create transformative changes in kidney medicine throughout the world.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005

email@asn-online.org

202-640-4660

The Latest on X

Kidney Week

Abstract: SA-PO1065

Sodium Restriction Is Associated with Decreased Kidney Function Through TonEBP Downregulation in Calcineurin Inhibitor (CNI)-Treated Kidney Transplant Recipients

Session Information

Category: Transplantation

  • 2102 Transplantation: Clinical

Authors

  • Sanada, Satoru, Japan Community Health Care Organization Sendai Hospital, Sendai, Miyagi, Japan
  • Katano, Saki, Japan Community Health Care Organization Sendai Hospital, Sendai, Miyagi, Japan
  • Sato, Mitsuhiro, Japan Community Health Care Organization Sendai Hospital, Sendai, Miyagi, Japan
Background

Tonicity responsive enhancer binding protein (TonEBP) protects kidney tubular cells against hypertonicity by adapting the osmolar gap across the membrane. Under hypertonic conditions, TonEBP shifts from the cytoplasm to the nucleus for the transactivation of tonicity responsive genes. Calcineurin inhibitors (CNI) are known to suppress TonEBP by hampering its nuclear translocation. We examined whether CNI induced nephrotoxicity in transplant recipients could be due to impaired TonEBP activity.

Methods

A total of 385 kidney transplant recipients at JCHO Sendai Hospital between 2000 to 2022 were enrolled. Data for these patients were extracted from medical records. TonEBP immunohistochemistry was performed by biopsy specimens from 144 patients. The decline of eGFR were described using Kaplan-Meier methods.

Results

By immunohistochemistry, TonEBP was predominantly located in the cytoplasm among CNI nephrotoxicity compared to nuclear-cytoplasmic staining in rejections, suggesting that TonEBP transactivation was restricted in CNI nephrotoxicity. Cytoplasmic TonEBP staining was observed regardless of acute or chronic CNI induced kidney injury. Next, we examined sodium intake, which is the primary TonEBP activator of the kidney. Patients diagnosed as CNI nephrotoxicity revealed significantly lower sodium chloride intake compared to rejections (7.5 vs 10.8g/day, p<0.05). A 10% decline of eGFR among transplant recipients without any history of rejection (nor pre/post renal injury events) was significantly faster in the low sodium intake group (<8g/day) compared to the higher intake group (≧8g/day) (Median follow up: 10 years, Log-Rank P=0.03).

Conclusion

1) TonEBP transactivation of renal tubular cells could be impaired in CNI nephrotoxicity and sodium restriction may exacerbate its activity, which could fail the TonEBP-mediated cell protection from the hypertonicity. 2) Sodium intake of kidney transplant recipients should be reevaluated from the view of preventing CNI nephrotoxicity.