Abstract

Introduction: Chronic Kidney Disease (CKD) is a major risk factor for end-stage renal disease (ESRD) and premature death. It remains unclear if abnormal serum potassium is associated with CKD progression. We assessed the prospective relationship between serum potassium with both CKD progression and all-cause mortality among participants with CKD in the Chronic Renal Insufficiency Cohort (CRIC) Study. Methods: The CRIC study is a prospective cohort study of 3,939 participants with CKD from seven locations in the United States. Serum potassium was calculated as the cumulative mean from serum samples collected at baseline and annual follow-up visits prior to developing an event. Clinical cut points were used to group serum potassium: hypokalemia (<3.5 mmol/L), normokalemia (≥3.5 and ≤5.0 mmol/L), and hyperkalemia (>5.0 mmol/L). Kidney disease progression was defined as either incident end-stage renal disease or a 50% decline in estimated glomerular filtration rate (eGFR) from baseline. Cox proportional hazards models were used to examine the associations between serum potassium and CKD progression and all-cause mortality adjusting for baseline age, sex, race/ethnicity, education, clinic site, body mass index, cigarette smoking, alcohol drinking, physical activity, history of diabetes, hypercholesterolemia, and cardiovascular disease, use of angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers, use of diuretics, use of other antihypertensive medications, and eGFR. Results: CRIC patients had a mean age of 57.7 years, were 45.1% female, and 41.9% Non-Hispanic Black. The prevalence of hypokalemia and hyperkalemia was 2.5% and 7.3%, respectively. Over an average 6.5 and 11.0 years of follow-up for CKD progression and all-cause mortality, respectively, 1,784 CKD progression events and 1,621 deaths occurred. Hypokalemia had a hazard ratio (HR) of 1.65 [95% confidence interval (CI): 1.25-2.10; p=.0004] for CKD progression compared with normokalemia. Similarly, hyperkalemia had a HR of 1.76 (95% CI, 1.50-2.06, p<.0001) for CKD progression compared to normokalemia. The HR for all-cause mortality were 1.57 (95% CI, 1.13-2.18; p=.0066) for hypokalemia compared with normokalemia, and 1.43 (95% CI, 1.19-1.72, p=.0001) for hyperkalemia compared with normokalemia, after multivariable adjustment. Conclusions: Our study found that abnormally high and low serum potassium is associated with increased risk of CKD progression and all-cause mortality. These findings suggest that interventions that maintain serum potassium levels in the normal range may reduce the risk of CKD progression and premature death among patients with CKD.

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