Predicting Endothelial Cell Injury from Urine Sodium-to-Potassium Ratio in Patients with CKD

Background: Chronic Kidney Disease (CKD) is a salt-sensitive state associated with endothelial cell dysfunction (ECD) and higher prevalence of hypertension than the general population. Increased dietary sodium (Na) intake and/or low potassium (K) intake is associated with higher blood pressure (BP). There is emerging evidence that increased Na intake induces ECD. We analysed data from a population-based cohort and evaluated associations between urinary Na/K ratio and markers for endothelial cell injury/activation. Methods: We conducted a cross-sectional study of CKD patients (estimated glomerular filtration rate <60 mL/min or urine albumin/creatinine [UACR]>30 mg/g) from the Dallas Heart Study (DHS). We conducted linear regression analyses with first morning spot urine Na/K as the primary predictor and intercellular adhesion molecule (ICAM), vascular cell adhesion molecule (VCAM) and s-endoglin as primary outcomes in separate models controlling for age, sex, race, diabetes, BMI, renal function, albuminuria, BP, serum magnesium (Mg), glucose, albumin, and cholesterol. Results: There were 240 participants with urine chemistry data. Mean age was 48.4 (9.3) years, with 54% women, 70% Black race, 65% with diabetes, and 27% on diuretics. Mean urine Na/K was 4.2 (3.0) and was similar between those taking vs. not taking diuretics (p=.7). Urine Na/K correlated with systolic BP (r=0.2, p=.002), Mg (r=-0.2, p=.001), ICAM (r=0.1, p=.03), VCAM (r=0.2, P=.002), and s-endoglin (r=-0.2, p=.006). In regression analyses, urine Na/K positively predicted ICAM and VCAM (β=45 and 159; p=.02 and .0007), but was negatively associated with log endoglin (β =-0.01, p=.002) when controlling for the above variables. Adding diuretics to our model did not change results. Conclusion: Our study suggests that elevated urine Na/K ratio is independently associated with endothelial injury/activation in a diverse CKD population. Further work is needed to identify if dietary Na restriction and/or K liberalization can minimize ECD, keeping in consideration the potential hyperkalemic risks in CKD patients. Multivariate regression analyses showing Standardized Regression coefficient and p value for each outcome - ICAM VCAM Endoglin urine Sodium potassium ratio 0.2(.02) 0.3(.007) -0.2(.002) ICAM-Intercellular adhesion molecule; VCAM- Vascular Cell adhesion molecule