TITLE:
Intensive Antihypertensive Treatment with Angiotensin Receptor Blocker Combined with Hydrocholorthiazide Reduces Urinary Angiotensinogen in Patients with Type 2 Diabetes Mellitus
AUTHORS:
Satoru Kuriyama, Naoki Sugano, Kohki Takane, Akimitsu Kobayashi, Yasushi Otsuka, Tatsuo Hosoya
KEYWORDS:
Hypertension; Angiotensinogen; Proteinuria; Renin-Angiotensin System; ARB; Diabetic Nephropathy
JOURNAL NAME:
Open Journal of Nephrology,
Vol.3 No.2,
June
4,
2013
ABSTRACT: Purpose: Local activation of rennin-angiotensin system (RAS) is involved
in the progression of chronic kidney disease (CKD). One of the RAS components,
angiotensinogen (AGT) has been known to be a potential surrogate biomarker for the
renal RAS activity. Measuring the daily urinary excretion of AGT (U-AGT), the
present study addressed whether the intensive blood pressure (BP) lowering with
combined antihypertensive agents could improve such an abnormality in diabetic
CKD patients. Methods: Uncontrolled hypertensive
patients with type 2 diabetes with mild to moderate nephropathy previously receiving
angiotensin receptor blockers (ARB) in an optimal dose alone were recruited for
a better blood pressure (BP) control. Urinary specimens were subjected to a
quantitative measurement of a daily urinary protein (U-prot) and U-AGT. After
the baseline measurement, intensive antihypertensive therapy was attempted by
switching the ARB dose to a fixed combination formula of candesartan 8 mg plus hydrochlorthiazide (HCTZ)
6.25 mg and the patients were
followed up for 24 weeks. Comparison of parameters was then made between the
values at the baseline and the end of the study. Results: At baseline,
there was a significant positive correlation between U-AGT and U-prot, and
between U-AGT and serum creatinine (Cr) concentration. In addition, U-AGT was
inversely correlated with estimated glomerular filtration rate (e-GFR).
Switching the antihypertensive regime from ARB alone to the combined ARB/HCTZ
significantly reduced BP, U-AGT and U-prot. The magnitude of the reduction in
U-prot was positively correlated with that in U-AGT. A stepwise regression
analysis showed that HbA1c, e-GFR and the reduction in U-prot in response to
the intensive antihypertensive therapy were positively correlated with the
reduction in U-AGT. Conclusion: U-AGT is increased and positively correlated with U-prot in patients with type
2 diabetic nephropathy. Intensive antihypertensive treatment with ARB combined
with HCTZ reduces both U-AGT and U-prot, presumably via an amelioration of an
accelerated renal RAS activity. These data also suggest that U-AGT can be used
as a potential therapeutic surrogate biomarker for the activated renal RAS in
patients with diabetic nephropathy.