Effects of dual blockade of renin-angiotensin system in type 2 diabetes mellitus patients with diabetic nephropathy.
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.


METHODS
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.


CONCLUSIONS
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.
Krairittichai
Udom
U
Department of Medicine, Rajavithi Hospital, Institute of Undergraduate Medical Education, Department of Medical Services in Affiliation with Rangsit University, Bangkok, Thailand. krairit@yahoo.com
Chaisuvannarat
Viranya
V
D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology* / Q000627:therapeutic use; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D000959:Antihypertensive Agents / Q000008:administration & dosage; D001562:Benzimidazoles / Q000008:administration & dosage; D001565:Benzoates / Q000008:administration & dosage; D001794:Blood Pressure / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000150:complications; D003928:Diabetic Nephropathies / Q000150:complications / Q000188:drug therapy*; D018450:Disease Progression; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D004656:Enalapril / Q000008:administration & dosage; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011507:Proteinuria / Q000188:drug therapy; D012084:Renin-Angiotensin System / Q000187:drug effects*; D000077333:Telmisartan; D016896:Treatment Outcome
D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D001562:Benzimidazoles; D001565:Benzoates; D004656:Enalapril; D000077333:Telmisartan