Thiazide diuretics and the rate of disease progression in autosomal dominant polycystic kidney disease: an observational study

被引:7
作者
Kramers, Bart J. [1 ]
Koorevaar, Iris W. [1 ]
De Boer, Rudolf [2 ]
Hoorn, Ewout J. [3 ]
Pena, Michelle J. [4 ]
Gansevoort, Ron T. [1 ]
Meijer, Esther [1 ]
机构
[1] Univ Groningen, Univ Med Ctr Groningen, Dept Nephrol, Groningen, Netherlands
[2] Univ Groningen, Univ Med Ctr Groningen, Cardiol, Groningen, Netherlands
[3] Univ Med Ctr Rotterdam, Erasmus Med Ctr, Dept Internal Med, Div Nephrol & Transplantat, Rotterdam, Netherlands
[4] Univ Hosp Groningen, Univ Med Ctr Groningen, Dept Clin Pharm & Pharmacol, Groningen, Netherlands
关键词
ADPKD; diuretics; hypertension; polycystic kidney disease; thiazide diuretics; DIPAK; 1; TOLVAPTAN; VASOPRESSIN; LANREOTIDE; FUROSEMIDE; EXCRETION; EFFICACY; SODIUM;
D O I
10.1093/ndt/gfaa150
中图分类号
R3 [基础医学]; R4 [临床医学];
学科分类号
1001 ; 1002 ; 100602 ;
摘要
Background. 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. Methods. 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. Results. 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 -0.35mL/min/1.73m(2) per year [95% confidence interval (CI) -0.83 to -0.14], P=0.2} during 3.9years of follow-up (interquartile range 2.5-4.9). This did not change after adjustment for potential confounders [difference final model: 0.08mL/min/1.73m(2) 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]. Conclusions. 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.
引用
收藏
页码:1828 / 1836
页数:9
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