Kidney Week

Abstract: TH-PO0047

Role of Kir4.2 in Controlling Renal Blood Pressure, Electrolyte Homeostasis, and Acid-Base Balance in Salt-Sensitive Hypertension

Session Information

• Fluid, Electrolyte, and Acid-Base Disorders: Basic Research
  October 22, 2026 | Location: Exhibit Hall A, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Fluid, Electrolytes, and Acid-Base Disorders

• 1101 Fluid, Electrolyte, and Acid-Base Disorders: Basic

Authors

• Xu, Biyang, University of South Florida, Tampa, Florida, United States

Biyang Xu, PhD

• Lowe, Melissa, University of South Florida, Tampa, Florida, United States

Melissa Lowe

• Levchenko, Vladislav, University of South Florida, Tampa, Florida, United States

Vladislav Levchenko

• Geurts, Aron M., Medical College of Wisconsin, Milwaukee, Wisconsin, United States

Aron M. Geurts, PhD

• Staruschenko, Alexander, University of South Florida, Tampa, Florida, United States

Alexander Staruschenko, PhD, FASN

Background

The inwardly rectifying potassium channel K_ir4.2, encoded by the Kcnj15 gene, is essential for various physiological functions. In the kidney, K_ir4.2 has been linked to acid-base balance and kidney injury. However, its role in salt-sensitive (SS) hypertension remains largely unknown. Here, we aimed to investigate the role of K_ir4.2 in controlling blood pressure, electrolyte homeostasis, and acid-base balance in SS hypertension.

Methods

Kcnj15 knockout (SS^Kcnj15-/-) rats based on the Dhal SS rat background were generated using CRISPR/Cas9 technology. For baseline measurements, male and female SS^Kcnj15-/- rats and the wild-type littermates (SS^WT) were maintained on a normal salt (NS, 0.4% NaCl) diet for 12 weeks. For blood pressure evaluation, all rats were first fed an NS diet for 8-9 weeks and then challenged with a high salt (HS, 4% NaCl) diet for 3 weeks, with continuous blood pressure measurements. At the end of the experiments, blood pH and HCO₃^-, urine pH and ammonium excretion, and blood electrolytes were measured.

Results

Results indicated that under the NS diet, both male and female SS^Kcnj15-/- rats exhibited significantly lower total body weight but a significantly higher heart-to-body weight ratio compared to SS^WT rats. Significantly lower blood pH, HCO₃^-, and urine pH were also observed in SS^Kcnj15-/- rats compared to SS^WT rats in both genders, while urinary ammonium excretion remained similar. Both male and female SS^Kcnj15-/- rats displayed significantly lower blood K⁺ but significantly higher blood Cl^- and creatinine compared to SS^WT rats. Interestingly, compared to the SS^WT rats, male SS^Kcnj15-/- rats exhibited a blunted increase in blood pressure after 3 weeks on the HS diet (last day blood pressure 139 ± 2 vs 115 ± 1 mmHg, SS^WT vs SS^Kcnj15-/-). The blood pH, HCO₃^-, K⁺, and urine pH of male SS^Kcnj15-/- rats remained significantly lower than those of the SS^WT rats after the HS diet.

Conclusion

In summary, our results demonstrated that the lack of K_ir4.2 altered acid-base and electrolyte homeostasis under both NS and HS diets, and impaired blood pressure elevation under the HS diet, suggesting the essential role of K_ir4.2 in acid-base balance, electrolyte homeostasis, and blood pressure control in SS hypertension. Future studies will continue to evaluate the phenotype of female SS^Kcnj15-/- rats under the HS diet and the underlying mechanisms.

Funding

• NIDDK Support