Departments of Nephrology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Nephrol Dial Transplant. 2021 Sep 27;36(10):1828-1836. doi: 10.1093/ndt/gfaa150.
In autosomal dominant polycystic kidney disease (ADPKD), hypertension is prevalent and cardiovascular events are the main cause of death. Thiazide diuretics are often prescribed as second-line antihypertensives, on top of renin-angiotensin-aldosterone system (RAAS) blockade. There is a concern, however, that diuretics may increase vasopressin concentration and RAAS activity, thereby worsening disease progression in ADPKD. We aimed to investigate the validity of these suggestions.
We analysed an observational cohort of 533 ADPKD patients. Plasma copeptin (surrogate for vasopressin), aldosterone and renin were measured by enzyme-linked immunosorbent assay and radioimmunoassay, respectively. Linear mixed models were used to assess the association of thiazide use with estimated glomerular filtration rate (eGFR) decline and Cox proportional hazards models for the association with the composite kidney endpoint of incident end-stage kidney disease, 40% eGFR decline or death.
A total of 23% of participants (n = 125) used thiazide diuretics at baseline. Compared with non-users, thiazide users were older, a larger proportion was male, they had lower eGFRs and similar blood pressure under more antihypertensives. Plasma copeptin was higher, but this difference disappeared after adjustment for age and sex. Both renin and aldosterone were higher in thiazide users. There was no difference between thiazide users and non-users in the rate of eGFR decline {difference -0.35 mL/min/1.73 m2 per year [95% confidence interval (CI) -0.83 to -0.14], P = 0.2} during 3.9 years of follow-up (interquartile range 2.5-4.9). This did not change after adjustment for potential confounders [difference final model: 0.08 mL/min/1.73 m2 per year [95% CI -0.46 to -0.62], P = 0.8). In the crude model, thiazide use was associated with a higher incidence of the composite kidney endpoint [hazard ratio (HR) 1.53 (95% CI 1.05-2.23), P = 0.03]. However, this association lost significance after adjustment for age and sex and remained unassociated after adjustment for additional confounders [final model: HR 0.80 (95% CI 0.50-1.29), P = 0.4].
These data do not show that thiazide diuretics have a detrimental effect on the rate of disease progression in ADPKD and suggest that these drugs can be prescribed as second-line antihypertensives.
在常染色体显性多囊肾病（ADPKD）中，高血压很常见，心血管事件是主要的死亡原因。噻嗪类利尿剂通常被开为二线降压药，以补充肾素-血管紧张素-醛固酮系统（RAAS）阻滞剂。然而，有人担心利尿剂可能会增加血管加压素浓度和 RAAS 活性，从而使 ADPKD 的疾病进展恶化。我们旨在研究这些建议的有效性。
我们分析了 533 名 ADPKD 患者的观察性队列。通过酶联免疫吸附试验和放射免疫测定法分别测量血浆 copeptin（血管加压素的替代物）、醛固酮和肾素。使用线性混合模型评估噻嗪类药物使用与估计肾小球滤过率（eGFR）下降的相关性，以及 Cox 比例风险模型与肾脏终点的复合相关性，包括终末期肾病、eGFR 下降 40%或死亡的发生。
共有 23%的参与者（n=125）在基线时使用噻嗪类利尿剂。与非使用者相比，噻嗪类使用者年龄较大，男性比例较高，eGFR 较低，在更多的降压药下血压相似。血浆 copeptin 较高，但在调整年龄和性别后，这种差异消失了。噻嗪类使用者的肾素和醛固酮均较高。在 3.9 年的随访期间（四分位距 2.5-4.9），噻嗪类使用者和非使用者的 eGFR 下降率没有差异{差异-0.35mL/min/1.73m2/年[95%置信区间（CI）-0.83 至-0.14]，P=0.2}。在调整潜在混杂因素后，这种差异仍然没有变化{最终模型差异：0.08mL/min/1.73m2/年[95%CI-0.46 至-0.62]，P=0.8}。在原始模型中，噻嗪类药物的使用与肾脏终点的发生率较高相关[风险比（HR）1.53（95%CI 1.05-2.23），P=0.03]。然而，在调整年龄和性别后，这种相关性失去了意义，在进一步调整其他混杂因素后，相关性仍然不显著[最终模型：HR 0.80（95%CI 0.50-1.29），P=0.4]。
这些数据并未显示噻嗪类利尿剂对 ADPKD 疾病进展速度有不良影响，并表明这些药物可以作为二线降压药开处方。
