Kidney tubular secretion is an essential mechanism for clearing many common antihypertensive drugs and other metabolites and toxins. It is unknown whether novel measures of tubular secretion are associated with adverse events (AEs) during hypertension treatment.

Among 2089 SPRINT (Systolic Blood Pressure Intervention Trial) participants with baseline eGFR <60 ml/min per 1.73 m², we created a summary secretion score by averaging across the standardized spot urine-to-plasma ratios of ten novel endogenous tubular secretion measures, with lower urine-to-plasma ratios reflecting worse tubular secretion. Multivariable Cox proportional hazards models were used to evaluate associations between the secretion score and risk of a composite of prespecified serious AEs (hypotension, syncope, bradycardia, AKI, electrolyte abnormalities, and injurious falls). The follow-up protocol for SPRINT routinely assessed two laboratory monitoring AEs (hyperkalemia and hypokalemia).

Overall, 30% of participants experienced at least one AE during a median follow-up of 3.0 years. In multivariable models adjusted for eGFR and albuminuria, lower (worse) secretion scores at baseline were associated with greater risk of the composite AE outcome (hazard ratio per 1-SD lower secretion score, 1.16; 95% confidence interval, 1.04 to 1.27). In analyses of the individual AEs, lower secretion score was associated with significantly greater risk of AKI, serious electrolyte abnormalities, and ambulatory hyperkalemia. Associations were similar across randomized treatment assignment groups.

Among SPRINT participants with CKD, worse tubular secretion was associated with greater risk of AEs, independent of eGFR and albuminuria.

肾小管分泌是清除许多常见抗高血压药物以及其他代谢物和毒素的重要机制。目前尚不清楚肾小管分泌的新测量方法是否与高血压治疗期间的不良事件（AE）相关。

^{在基线 eGFR <60 ml/min 每 1.73 m 2}的 2089 名 SPRINT（收缩压干预试验）参与者中，我们通过对 10 种新颖的内源性肾小管分泌测量的标准化现场尿液与血浆比率进行平均，创建了一个汇总分泌评分，尿液与血浆比率较低反映肾小管分泌较差。使用多变量 Cox 比例风险模型来评估分泌评分与预先指定的严重 AE（低血压、晕厥、心动过缓、AKI、电解质异常和伤害性跌倒）复合风险之间的关联。SPRINT 的后续方案定期评估两种实验室监测 AE（高钾血症和低钾血症）。

总体而言，30% 的参与者在中位随访 3.0 年期间经历了至少一种 AE。在针对 eGFR 和蛋白尿进行调整的多变量模型中，基线时较低（较差）的分泌评分与复合 AE 结果的较高风险相关（每 1-SD 较低分泌评分的风险比为 1.16；95% 置信区间为 1.04 至 1.27）。在对个别 AE 的分析中，较低的分泌评分与显着较高的 AKI、严重电解质异常和动态高钾血症风险相关。随机治疗分配组之间的关联相似。

在患有 CKD 的 SPRINT 参与者中，肾小管分泌较差与 AE 风险较高相关，与 eGFR 和蛋白尿无关。