Plasma potassium regulation within a narrow range is vital for life. The risk for hyperkalemia increases when kidney function is impaired and with therapeutic interventions such as mineralocorticoid receptor antagonists (MRAs). The kidney maintains potassium homeostasis by matching potassium intake and excretion, in part through the action of aldosterone. A mechanistic mathematical model was developed and used to investigate the effect of renal impairment and MRAs on plasma potassium levels. The model describes renal potassium filtration, reabsorption, and secretion along the nephron; potassium-aldosterone regulatory feedbacks; whole body potassium balance; and the pharmacologic effects of MRAs. The model was calibrated by fitting (1) the plasma potassium and aldosterone response to potassium infusion in humans on high/low potassium diets, and (2) the acute potassium excretion response to spironolactone. The model was validated by predicting steady-state plasma potassium with sustained spironolactone treatment in hyperaldosteronism patients. The model was then used to demonstrate that (1) declining renal function alone has a small effect on plasma potassium for GFR > 30 ml/min, but an increasing effect as GFR approaches end stage renal disease (GFR ~ 15 ml/min) (2) the effect of increasing potassium intake has minimal effect at normal GFRs but increasing effect on plasma potassium as GFR declines, and 3) MRAs have a minor effect on plasma potassium when GFR is normal, but cause larger increases as GFR falls below 60 ml/min. This model provides a quantitative framework for investigating integrated impacts of diseases and therapies in this complex system.

窄范围内的血浆钾调节对生命至关重要。当肾功能受损并使用盐皮质激素受体拮抗剂 (MRA) 等治疗干预措施时，高钾血症的风险会增加。肾脏通过匹配钾的摄入和排泄来维持钾的稳态，部分是通过醛固酮的作用。建立了一个机械数学模型，并用于研究肾损伤和 MRA 对血浆钾水平的影响。该模型描述了沿肾单位的肾钾滤过、重吸收和分泌；钾醛固酮调节反馈；全身钾平衡；以及 MRA 的药理作用。该模型通过拟合 (1) 高/低钾饮食对人类钾输注的血浆钾和醛固酮反应进行校准，(2) 对螺内酯的急性排钾反应。该模型通过预测醛固酮增多症患者持续螺内酯治疗的稳态血浆钾来验证。然后使用该模型证明（1）单独的肾功能下降对 GFR > 30 ml/min 的血浆钾的影响很小，但随着 GFR 接近终末期肾病（GFR ~ 15 ml/min），影响增加（ 2) 增加钾摄入量对正常 GFR 的影响最小，但随着 GFR 下降，对血浆钾的影响增加；3) MRA 在 GFR 正常时对血浆钾的影响较小，但在 GFR 低于 60 ml 时导致更大的增加/分钟。该模型提供了一个定量框架，用于研究该复杂系统中疾病和疗法的综合影响。