Impact of combined losartan/hydrochlorothiazide on proteinuria in patients with
chronic kidney disease and hypertension.
Author(s): Fujisaki K(1), Tsuruya K(2), Nakano T(1), Taniguchi M(1), Higashi H(3), Katafuchi
R(4), Kanai H(5), Nakayama M(6), Hirakata H(7), Kitazono T(1); Impact of Combined
Losartan/Hydrochlorothiazide on Proteinuria in Patients with Chronic Kidney
Disease and Hypertension (ILOHA) Study Investigators.
Collaborators: Eriguchi M, Fujisaki A, Haruyama N, Hirakawa M, Hirano T, Hori K,
Ikeda H, Ikeda K, Inenaga T, Maeda H, Matsui R, Mitsuiki K, Mizumasa T, Nagae H,
Nagara T, Nagashima A, Nakagawa K, Onaka S, Suehiro T, Sugawara K, Takeda K,
Tanaka S, Tokumoto M, Toyonaga J, Toyonaga M, Tsuchimoto A, Tsuruta H, Yamada S,
Yanagida T, Yoshida H, Yoshida T, Yotsueda H, Watanabe K, Noda N, Noda T.
Affiliation(s): Author information:
(1)Department of Medicine and Clinical Science, Graduate School of Medical
Sciences, Kyushu University, Fukuoka, Japan. (2)1] Department of Medicine and
Clinical Science, Graduate School of Medical Sciences, Kyushu University,
Fukuoka, Japan [2] Department of Integrated Therapy for Chronic Kidney Disease,
Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
(3)Department of Nephrology, St Mary's Hospital, Kurume, Japan. (4)Kidney Unit,
National Fukuoka Higashi Medical Center, Koga, Japan. (5)Division of Nephrology,
Kokura Memorial Hospital, Kitakyushu, Japan. (6)Division of Nephrology and
Clinical Research Institute, Department of Internal Medicine, National Kyushu
Medical Center Hospital, Fukuoka, Japan. (7)Division of Nephrology and Dialysis
Center, Japanese Red Cross Fukuoka Hospital, Fukuoka, Japan.
Publication date & source: 2014, Hypertens Res. , 37(11):993-8
It is unknown whether the use of diuretics is optimal over other antihypertensive
agents in patients with chronic kidney disease (CKD) whose blood pressure remains
uncontrolled despite treatment with renin-angiotensin system (RAS) inhibitors. In
this study, we assessed the additive effects of hydrochlorothiazide (HCTZ) on
reducing proteinuria in CKD patients under treatment with losartan (LS). We
conducted a multicenter, open-labeled, randomized trial. One hundred and two CKD
patients with hypertension and overt proteinuria were recruited from nine centers
and randomly assigned to receive either LS (50 mg, n=51) or a combination of LS
(50 mg per day) and HCTZ (12.5 mg per day) (LS/HCTZ, n=51). The primary outcome
was a decrease in the urinary protein-to-creatinine ratio (UPCR). The target
blood pressure was <130/80 mm Hg, and antihypertensive agents (other than RAS
inhibitors and diuretics) were added if the target was not attained. Baseline
characteristics of the two groups were similar. After 12 months of treatment,
decreases in the UPCR were significantly greater in the LS/HCTZ group than in the
LS group. There were no significant differences in blood pressure or the
estimated glomerular filtration rate between the two groups. LS/HCTZ led to a
greater reduction in proteinuria than treatment with LS, even though blood
pressure in the LS group was similar to that in the LS/HCTZ group following the
administration of additive antihypertensive agents throughout the observation
period. This finding suggests that LS/HCTZ exerts renoprotective effects through
a mechanism independent of blood pressure reduction.
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