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

Bart J. Kramers, Iris W. Koorevaar, Rudolf De Boer, Ewout J. Hoorn, Michelle J. Pena, Ron T. Gansevoort, Esther Meijer

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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 ¼ 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 fdifference
0.35 mL/min/1.73 m2 per year [95% confidence interval (CI)
0.83 to –0.14], P ¼ 0.2g 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 ¼ 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 ¼ 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 ¼ 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.
Original languageEnglish
Pages (from-to)1828-1836
Number of pages9
JournalNephrology Dialysis Transplantation
Issue number10
Publication statusPublished - 5 Nov 2020

Bibliographical note

The DIPAK Consortium is sponsored by grants from the Dutch Kidney Foundation (grants CP10.12 and CP15.01) and Dutch government (LSHM15018). Besides the above grants, the authors received unrestricted grants from Ipsen (manufacturer of a somatostatin analogue for ADPKD) and Otsuka Pharmaceuticals (manufacturer of a vasopressin V2 receptor antagonist) to make the DIPAK 1 trial and DIPAK observational study possible. This study was sponsored by the Dutch Kidney Foundation (18OKG04).


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