Kidney Week

Abstract: FR-PO1172

Plasma Potassium Negatively Correlates with Sodium-Chloride Cotransporter (NCC) Abundance and Phosphorylation in Urinary Extracellular Vesicles (uEVs) from Patients with CKD

Session Information

• CKD: Kidney Function and Extrarenal Complications
  October 25, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

• 2302 CKD (Non-Dialysis): Clinical, Outcomes, and Trials

Authors

• Wu, Aihua, Vanderbilt University Medical Center, Nashville, Tennessee, United States

Aihua Wu, PhD

• Welling, Paul A., Johns Hopkins Medicine, Baltimore, Maryland, United States

Paul A. Welling, MD

• Terker, Andrew S., Vanderbilt University Medical Center, Nashville, Tennessee, United States

Andrew S. Terker, MD, PhD, FASN

Group or Team Name

• Leudcq Network Potassium in Hypertension.

Background

Hypertension is a leading cause of CKD. Low potassium diet is often advised in moderate to severe CKD. Emerging data now suggest that higher dietary potassium may be beneficial in these patients, but the underlying mechanism is unclear. Using uEVs we recently demonstrated that dietary potassium interventions can regulate distal sodium and potassium handling via the “renal-K switch” mechanism (the WNKs-SPAK/OSR1-NCC pathway) in both healthy adults and those with primary aldosteronism (PA). The close relationship between blood pressure and CKD has led to the hypothesis that blood pressure-lowering effects of high potassium intake may also be reno-protective through the same mechanism. This study is to use uEVs to evaluate if plasma potassium negatively correlates with NCC and its phosphorylation in patients with CKD.

Methods

Morning blood and 2^nd morning urine were collected on a single occasion between 8-11 am from patients with CKD at all stages. Clinical and biochemical features were assessed by Pathology Queensland. uEVs were obtained by progressive ultracentrifugation and analysed by Western blot. Those taking SGLT2 inhibitors or K binders were excluded

Results

Analysis of 20 participants demonstrates plasma potassium negatively correlates with uEV abundance of NCC (R²=0.41, P=0.003) and its phosphorylation (R²=0.22, P=0.04). These correlations persisted even patients with a low level of uEV. (Figure 1).

Conclusion

Plasma potassium measurements showed a strong negative correlation with the abundance of NCC and its phosphorylation state in uEVs from 20 patients with CKD. If the “renal-K switch” mechanism in CKD functions in the same way as has previously been demonstrated in patients without CKD, then increasing dietary potassium may assist in natriuresis, providing a renoprotective effect via reductions in blood pressure.

Figure 1. Correlations of plasma K⁺ with uEV levels of NCC and pNCC.