Nephrology Section, Veterans Affairs San Diego Healthcare System, San Diego, California.
Division of Nephrology-Hypertension, University of California, San Diego, California.
J Am Soc Nephrol. 2022 Oct;33(10):1915-1926. doi: 10.1681/ASN.2022010117. Epub 2022 Aug 16.
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 m, 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.
肾脏管状分泌是清除许多常见降压药物和其他代谢物及毒素的重要机制。目前尚不清楚新型管状分泌指标是否与高血压治疗期间的不良事件（AE）有关。
在基线 eGFR<60ml/min/1.73m2 的 2089 名 SPRINT（收缩压干预试验）参与者中，我们通过平均十种新型内源性管状分泌指标的标准化点尿与血浆比值来创建分泌评分，其中尿与血浆比值越低反映管状分泌越差。多变量 Cox 比例风险模型用于评估分泌评分与特定严重 AE（低血压、晕厥、心动过缓、急性肾损伤、电解质异常和伤害性跌倒）复合风险之间的关系。SPRINT 的随访方案常规评估两种实验室监测 AE（高钾血症和低钾血症）。
总体而言，30%的参与者在中位数为 3.0 年的随访期间经历了至少一次 AE。在调整 eGFR 和白蛋白尿的多变量模型中，基线时较低（较差）的分泌评分与复合 AE 结局的风险增加相关（每降低 1-SD 分泌评分的风险比，1.16；95%置信区间，1.04 至 1.27）。在对单个 AE 的分析中，较低的分泌评分与 AKI、严重电解质异常和动态高钾血症的风险显著增加相关。关联在随机治疗分配组之间相似。
在 SPRINT 参与者中，CKD 患者管状分泌功能越差，AE 的风险越高，与 eGFR 和白蛋白尿无关。
