Factors Associated with Hyperkalemia in Chronic Kidney Disease: Insights from a Cohort with Measured Glomerular Filtration Rate.

INTRODUCTION: Hyperkalemia is a life-threatening disorder in chronic kidney disease (CKD), yet the contribution of key factors including age, sex, body mass index and proteinuria remain controversial. We aimed to identify factors associated with chronic hyperkalemia in a large cohort of patients with gold-standard measured glomerular filtration rate (GFR) and standardized plasma potassium measurements. METHODS: This cross-sectional study of 5046 adults with non-dialysis CKD referred for kidney workup, including radio-isotopic measured GFR, defined hyperkalemia as a plasma potassium concentration ≥5.0 mmol/L or the use of potassium binders. We analyzed demographic, clinical, pharmacological and biochemical risk factors for hyperkalemia using logistic regression models. RESULTS: Mean measured GFR was 59±26 mL/min/1.73 m2, mean age was 52±15 years, 42% were women, 22% of sub-Saharan African ancestry, 25% had diabetes, and 36% were kidney transplant recipients. The prevalence of hyperkalemia was 6.4% and increased with declining measured GFR, from 1% in CKD stages 1-2 to 8% in CKD stage 3 and 21% in stages 4-5. In the multivariable model, measured GFR remained strongly associated with hyperkalemia (OR 1.65 [1.51-1.81] per 10 mL/min/1.73m² decrease), an effect amplified in renin-angiotensin-aldosterone system inhibitor (RAASi) users (1.82 [1.61-2.07]) (p for interaction 0.036). Other independently associated factors were diabetes (OR 1.67 [1.38-2.17]), RAASi and calcineurin inhibitors (OR 2.30 [1.72-3.11] and 1.39 [1.06-1.83] respectively), higher urinary albumin-to-creatinine ratio and lower venous bicarbonate level, whereas female sex (OR 0.71 [0.55-0.92]), sub-Saharan African ancestry (HR 0.68 [0.48-0.94]), and loop-diuretics (OR 0.71 [0.51-0.98]) were protective, and age and body mass index showed no independent association. CONCLUSION: In this large cohort, across the entire range of gold-standard measured GFR, hyperkalemia is driven primarily by reduced kidney function, diabetes, and RAASi, whereas protective factors were female sex, sub-Saharan African ancestry, and loop diuretic therapy. These robust findings, based on unbiased GFR assessment, identify key contributors for individualized prevention of hyperkalemia in CKD.