Plasma potassium, diuretic use and risk of developing chronic kidney disease in a predominantly White population

Objective Both hypokalemia and hyperkalemia are associated with disease progression in patients with chronic kidney disease (CKD). It is unclear whether similar associations are present in the general population. Our aim was to examine the association of plasma potassium with risk of developing CKD and the role of diuretics in this association in a population-based cohort. Research design and methods We studied 5,130 subjects free of CKD at baseline of the Prevention of Renal and Vascular End-Stage Disease (PREVEND) study, a prospective, population-based cohort of Dutch men and women aged 28-75 years. Hypokalemia was defined as plasma potassium <3.5 mmol/L, and hyperkalemia as plasma potassium ≥5.0 mmol/L. Risk of CKD was defined as de novo development of eGFR <60 ml/min/1.73m² and/or albuminuria >30 mg/24h. Results Mean baseline plasma potassium was 4.4±0.3 mmol/L. The prevalences of hypokalemia and hyperkalemia were 0.5% and 3.8%, respectively; 3.0% of the subjects used diuretics. During a median follow-up of 10.3 years (interquartile range: 6.3-11.4 years), 753 subjects developed CKD. The potassium-CKD association was modified by diuretic use (P_interaction = 0.02). Both hypokalemia without (HR, 7.74, 95% CI, 3.43-17.48) or with diuretic use (HR, 4.32, 95% CI, 1.77-10.51) were associated with an increased CKD risk as compared to plasma potassium 4.0-4.4 mmol/L without diuretic use. Plasma potassium concentrations ≥3.5 mmol/L were associated with an increased CKD risk among subjects using diuretics (P_trend = 0.01) but not among subjects not using diuretics (P_trend = 0.74). Conclusion In this population-based cohort, hypokalemia was associated with an increased CKD risk, regardless of diuretic use. In the absence of hypokalemia, plasma potassium was not associated with an increased CKD risk, except among subjects using diuretics.