Hyponatremia is Associated with Fluid Imbalance and Adverse Renal Outcome in Chronic Kidney Disease Patients Treated with Diuretics

Chronic kidney disease (CKD) is frequently complicated with hyponatremia, probably because of fluid overload or diuretic usage. Hyponatremia in CKD population is associated with increased mortality, but the effect on renal outcome was unknown. We investigated whether hyponatremia is associated with fluid status and is a prognostic indicator for adverse outcomes in a CKD cohort of 4,766 patients with 1,009 diuretic users. We found that diuretic users had worse clinical outcomes compared with diuretic non-users. Hyponatremia (serum sodium <135 mEq/L) was associated with excessive volume and volume depletion, measured as total body water by bioimpedance analysis, in diuretic users, but not in diuretic non-users. Furthermore, in Cox survival analysis, hyponatremia was associated with an increased risk for renal replacement therapy (hazard ratio, 1.45; 95% CI, 1.13-1.85, P < 0.05) in diuretic users, but not in diuretic non-users (P for interaction <0.05); restricted cubic spline model also showed a similar result. Hyponatremia was not associated with all-cause mortality or cardiovascular event whereas hypernatremia (serum sodium >141 mEq/L) was associated with an increased risk for all-cause mortality. Thus, hyponatremia is an indicator of fluid imbalance and also a prognostic factor for renal replacement therapy in CKD patients treated with diuretics.