Hypokalemia, Its Contributing Factors and Renal Outcomes in Patients with Chronic Kidney Disease

BackgroundIn the chronic kidney disease (CKD) population, the impact of serum potassium (sK) on renal outcomes has been controversial. Moreover, the reasons for the potential prognostic value of hypokalemia have not been elucidated.Design, Participants & Measurements2500 participants with CKD stage 1–4 in the Integrated CKD care program Kaohsiung for delaying Dialysis (ICKD) prospective observational study were analyzed and followed up for 2.7 years. Generalized additive model was fitted to determine the cutpoints and the U-shape association between sK and end-stage renal disease (ESRD). sK was classified into five groups with the cutpoints of 3.5, 4, 4.5 and 5 mEq/L. Cox proportional hazard regression models predicting the outcomes were used.ResultsThe mean age was 62.4 years, mean sK level was 4.2±0.5 mEq/L and average eGFR was 40.6 ml/min per 1.73 m2. Female vs male, diuretic use vs. non-use, hypertension, higher eGFR, bicarbonate, CRP and hemoglobin levels significantly correlated with hypokalemia. In patients with lower sK, nephrotic range proteinuria, and hypoalbuminemia were more prevalent but the use of RAS (renin-angiotensin system) inhibitors was less frequent. Hypokalemia was significantly associated with ESRD with hazard ratios (HRs) of 1.82 (95% CI, 1.03–3.22) in sK 5 mEq/L conferred 1.6-fold (95% CI,1.09–2.34) increased risk of ESRD compared with sK = 4.5–5 mEq/L. Hypokalemia was also associated with rapid decline of renal function defined as eGFR slope below 20% of the distribution range.ConclusionIn conclusion, both hypokalemia and hyperkalemia are associated with increased risk of ESRD in CKD population. Hypokalemia is related to increased use of diuretics, decreased use of RAS blockade and malnutrition, all of which may impose additive deleterious effects on renal outcomes.

背景：在慢性肾脏病（chronic kidney disease, CKD）人群中，血清钾（serum potassium, sK）对肾脏结局的影响尚存争议。此外，低钾血症潜在预后价值的相关机制尚未阐明。
研究设计、受试者与测量指标：本研究针对「高雄延缓透析慢性肾脏病整合照护计划」（Integrated CKD care program Kaohsiung for delaying Dialysis, ICKD）前瞻性观察研究中的2500名1~4期慢性肾脏病受试者进行分析，随访时长为2.7年。采用广义可加模型确定血清钾的截断值，并明确其与终末期肾病（end-stage renal disease, ESRD）之间的U型关联。以3.5、4、4.5及5 mEq/L为截断值，将血清钾分为5组。采用Cox比例风险回归模型进行结局预测分析。
结果：受试者平均年龄为62.4岁，平均血清钾水平为4.2±0.5 mEq/L，平均估算肾小球滤过率（estimated glomerular filtration rate, eGFR）为40.6 ml/min/1.73 m²。女性相较于男性、使用利尿剂相较于未使用者、合并高血压、较高的eGFR、碳酸氢盐、C反应蛋白（C-reactive protein, CRP）及血红蛋白水平，均与低钾血症显著相关。在血清钾水平较低的受试者中，肾病范围蛋白尿与低白蛋白血症的患病率更高，但肾素-血管紧张素系统（renin-angiotensin system, RAS）抑制剂的使用频率更低。低钾血症与终末期肾病显著相关：血清钾＜3.5 mEq/L时，风险比（HR）为1.82（95%置信区间：1.03~3.22）；血清钾≥5 mEq/L时，相较于4.5~5 mEq/L组，终末期肾病风险升高1.6倍（95%置信区间：1.09~2.34）。此外，低钾血症还与肾功能快速下降相关，后者定义为eGFR斜率低于分布范围的20%。
结论：综上，慢性肾脏病人群中，低钾血症与高钾血症均与终末期肾病风险升高相关。低钾血症与利尿剂使用增加、肾素-血管紧张素系统阻滞剂使用减少及营养不良相关，上述因素可能对肾脏结局产生叠加有害影响。