Addition of hydrochlorothiazide to angiotensin receptor blocker therapy can achieve a lower sodium balance with no acceleration of intrarenal renin angiotensin system in patients with chronic kidney disease.
OBJECTIVE
Angiotensin receptor blockers (ARBs) produce a lower sodium (Na) balance, and the natriuretic effect is enhanced under Na deprivation, despite falls in blood pressure (BP) and glomerular filtration rate (GFR).


METHODS
The effect of additional hydrochlorothiazide (HCTZ; 12.5 mg/day) to ARB treatment (valsartan; 80 mg/day) on glomerulotubular Na balance was evaluated in 23 patients with chronic kidney disease.


RESULTS
Add-on HCTZ decreased GFR, tubular Na load, and tubular Na reabsorption (t(Na)), although 24-hour urinary Na excretion (U(Na)V) remained constant. Daily urinary angiotensinogen excretion (U(AGT)V, 152±10→82±17 μg/g Cre) reduced (p=0.02). Changes in tubular Na load (r(2)=0.26) and t(Na) (r(2)=0.25) correlated with baseline 24-hour U(AGT)V. Changes in filtered Na load correlated with changes in nighttime systolic BP (r(2)=0.17), but not with changes in daytime systolic BP. The change in the t(Na) to filtered Na load ratio was influenced by the change in daytime U(Na)V (β=-0.67, F=16.8), rather than the change in nighttime U(Na)V.


CONCLUSIONS
Lower Na balance was produced by add-on HCTZ to ARB treatment without an increase of intra-renal renin-angiotensin system activity, leading to restoration of nocturnal hypertension. A further study is needed to demonstrate that the reduction of U(AGT)V by additional diuretics to ARBs prevents the progression of nephropathy or cardiovascular events.
Department of Cardio-Renal Medicine and Hypertension, Nagoya City University Graduate School of Medical Sciences, Japan.
Daisuke
D
Fuwa
Department of Cardio-Renal Medicine and Hypertension, Nagoya City University Graduate School of Medical Sciences, Japan m-fukuda@med.nagoya-cu.ac.jp.
Michio
M
Fukuda
Department of Cardio-Renal Medicine and Hypertension, Nagoya City University Graduate School of Medical Sciences, Japan.
Yoshiaki
Y
Ogiyama
Department of Cardio-Renal Medicine and Hypertension, Nagoya City University Graduate School of Medical Sciences, Japan.
Ryo
R
Sato
Department of Cardio-Renal Medicine and Hypertension, Nagoya City University Graduate School of Medical Sciences, Japan.
Masashi
M
Mizuno
Department of Cardio-Renal Medicine and Hypertension, Nagoya City University Graduate School of Medical Sciences, Japan.
Toshiyuki
T
Miura
Department of Biochemistry, Nagoya City University Graduate School of Medical Sciences, Japan.
Sumiko
S
Abe-Dohmae
Department of Biochemistry, Nagoya City University Graduate School of Medical Sciences, Japan.
Makoto
M
Michikawa
International University of Health and Welfare, Japan.
Hiroyuki
H
Kobori
Department of Cardio-Renal Medicine and Hypertension, Nagoya City University Graduate School of Medical Sciences, Japan.
Nobuyuki
N
Ohte
D000419:Albuminuria / Q000150:complications; D057911:Angiotensin Receptor Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D004359:Drug Therapy, Combination; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006852:Hydrochlorothiazide / Q000494:pharmacology / Q000627:therapeutic use*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D007678:Kidney Glomerulus / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D007684:Kidney Tubules / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D051436:Renal Insufficiency, Chronic / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D012084:Renin-Angiotensin System / Q000187:drug effects*; D012964:Sodium / Q000378:metabolism* / Q000652:urine
D057911:Angiotensin Receptor Antagonists; D006852:Hydrochlorothiazide; D012964:Sodium
Angiotensin receptor blocker; angiotensinogen; chronic kidney disease; hydrochlorothiazide; sodium