Effects of Dual Blockade of Renin-Angiotensin System in Type 2 Diabetes Mellitus Patients with Diabetic Nephropathy
Udom Krairittichai MD*, Viranya Chaisuvannarat MD*
Affiliation : * Department of Medicine, Rajavithi Hospital, Institute of Undergraduate Medical Education, Department of Medical Services in Affiliation with Rangsit University, Bangkok, Thailand
Background : Angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARB)
have been shown to delay the progression to proteinuria and kidney failure in hypertensive type 2 diabetic
patients with diabetic nephropathy. Further synergistic effect may be obtained by combined therapy with both
ARB and ACE inhibitors.
Objective : To evaluate the effect of dual blockage of the renin-angiotensin system by adding maximal
recommended dose of ARB with maximal recommended dose of ACE inhibitors in type 2 diabetic patients with
diabetic nephropathy.
Material and Method: Type 2 diabetic patients with urine protein/creatinine (UPCr) > 0.5 gm/gm and
hypertension who received maximal recommended dose of ACE inhibitors (Enalapril 40 mg/day) over three
months were randomized to two groups. ARB group received adding maximal recommended dose of ARB
(Telmisartan 80 mg/day) and control group received previous ACE inhibitors only for 24 weeks.
Results : Eighty patients were enrolled. ARB group led to significantly reduced UPCr from baseline at week 8,
12, and 24 (2.65 + 1.81, 2.24 + 1.85, 2.24 + 1.88, and 1.98 + 1.73 gm/gm respectively, p < 0.05) but UPCr in
the control group was unchanged (1.97 + 1.56, 1.85 + 1.27, 1.97 + 1.11 and 1.96 + 1.42 gm/gm respectively,
p > 0.05). ARB group induced an additional reduction in proteinuria of 29.25% (95% CI 9.68-48.82)
compared with control group. By the end of the present study, glomerular filtration rate had fallen from 41.76
+ 12.16 to 37.84 + 13.59 ml/min/1.73 m2 in ARB group and 50.89 + 29.43 to 49.41 + 29.85 ml/min/1.73 m2 in
control group (p > 0.05). Serum potassium had changed from 4.51 + 0.48 to 4.58 + 0.13 mEq/L in ARB group
and 4.60 + 0.58 to 4.40 + 0.13 mEq/L in the control group (p > 0.05). No other serious adverse effects were
reported during treatment.
Conclusion : Adding maximal recommended dose of ARB with maximal recommended dose of ACE inhibitors
in type 2 diabetic patients can reduce proteinuria more than ACE inhibitors alone. This treatment is safe and
well tolerated.
Keywords : Angiotensin-converting enzyme inhibitors, Angiotensin II type 1 receptor blockers, Diabetes mellitus, Type 2, Diabetic nephropathies
