Hong Kong Journal of Nephrology
Volume 9, Issue 1 , Pages 31-35, April 2007

Combination Therapy of Angiotensin Converting Enzyme Inhibitor and Angiotensin AT1 Receptor Antagonist in Diabetic Nephropathy

Department of Medicine, Jichi Medical University Omiya Medical Center, Saitama, Japan

Article Outline

Background

The present study was undertaken to determine whether combination therapy of angiotensin converting enzyme inhibitor (ACEI) and angiotensin AT1 receptor antagonist (ARA) is a useful tool for reducing albuminuria in diabetic nephropathy.

Methods

Thirty-four subjects with diabetic nephropathy were enrolled in the present study. All the subjects had hypertension and urinary albumin index (UAI) < 1,000 mg/g creatinine. They were divided into three groups. Group 1 of 16 subjects was initially treated with imidapril (5–10 mg). Group 2 of eight subjects had losartan (50–100 mg) added to consecutive therapy with imidapril. Group 3 of 10 subjects had imidapril (5–10 mg) added to consecutive therapy with losartan. Blood pressure and UAI were determined before and 3 and 6 months after the start of the present study.

Results

Blood pressure was significantly decreased in Group 1 subjects. Blood pressure was also reduced in Groups 2 and 3, but its reduction was not significant. Imidapril significantly reduced UAI in Group 1, from 213.1 ± 46.6 to 111.6 ± 35.6 (p < 0.001) and 114.5 ± 35.4 mg/g creatinine (p < 0.01) 3 and 6 months after imidapril treatment, respectively. The addition of losartan further reduced UAI in Group 2, who had been treated with imidapril. UAI decreased from 328.8 ± 87.3 to 185.3 ± 51.4 (p < 0.05) and 244.8 ± 88.3 mg/g creatinine 3 and 6 months after the addition of losartan, respectively. In contrast, the addition of imidapril to losartan therapy did not alter UAI in Group 3.

Conclusion

These results indicate that the addition of ARA to consecutive therapy with ACEI augments a protective effect against the progression of diabetic nephropathy.

Key words:  albuminuria , angiotensin AT1 receptor antagonist , angiotensin converting enzyme inhibitor , combination therapy , diabetic nephropathy

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References 

  1. Parving HH , Andersen AR , Smidt UM , Svendsen PA . Early aggressive antihypertensive treatment reduces rate of decline in kidney function in diabetic nephropathy . Lancet . 1983;1:1175–1179
  2. The Diabetes Control and Complications Trial Research Group  . The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus . N Engl J Med . 1993;329:977–986
  3. UK Prospective Diabetes Study (UKPDS) Group  . Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33) . Lancet . 1998;352:837–853
  4. UK Prospective Diabetes Study (UKPDS) Group  . Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34) . Lancet . 1998;352:854–865
  5. Schrier RW , Estacio RO , Jeffers B . Appropriate blood pressure control in NIDDM (ABCD) trial . Diabetologia . 1996;39:1646–1654
  6. Carey RM , Wang ZQ , Siragy HM . Role of the angiotensin type 2 receptor in the regulation of blood pressure and renal function . Hypertension . 2000;35:155–163
  7. Zafari AM , Ushio-Fukai M , Akers M , Yin Q , Shah A , Harrison DG , et al.   Role of NADH/NADPH oxidase-derived H 2O2 in angiotensin II-induced vascular hypertrophy . Hypertension . 1998;32:488–495
  8. Hostetter TH . Mechanisms of diabetic nephropathy . Am J Kidney Dis . 1994;23:188–192
  9. Lewis EJ , Hunsicker LG , Bain RP , Rohde RD . The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy. The Collaborative Study Group . N Engl J Med . 1993;329:1456–1462
  10. Brenner BM, Cooper ME, de Zeeuw D, Keane WF, Mitch WE, Parving HH, et al  Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy . N Engl J Med . 2001;345:861–869
  11. Lewis EJ , Hunsicker LG , Clarke WR , Berl T , Pohl MA , Lewis JB , et al.   Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. The Collaborative Study Group . N Engl J Med . 2001;345:851–860
  12. Parving HH , Lehnert H , Brochner-Mortensen J , Gomis R , Andersen S , Arner P . Irbesartan in patients with type 2 diabetes and microalbuminuria study group. The effect of irbesartan on the development of diabetic nephropathy in patients with type 2 diabetes . N Engl J Med . 2001;345:870–878
  13. Palmer BF . Renal dysfunction complicating the treatment of hypertension . N Engl J Med . 2002;347:1256–1261
  14. Katayama S , Kikkawa R , Isogai S , Sasaki N , Matsuura N , Tajima N , et al.   Effect of captopril or imidapril on the progression of diabetic nephropathy in Japanese with type 1 diabetes mellitus: a randomized controlled study (JAPAN-IDDM) . Diabetes Res Clin Pract . 2002;55:113–121
  15. Liu YH, Yang XP, Sharov VG, Nass O, Sabbah HN, Peterson E, et al. Effects of angiotensin-converting enzyme inhibitors and angiotensin II type 1 receptor antagonists in rats with heart failure. Role of kinins and angiotensin II type 2 receptors . J Clin Invest . 1997;99:1926–1935
  16. Viberti G , Wheeldon NM . Microalbuminuria reduction with valsartan (MARVAL) study investigators. Microalbuminuria reduction with valsartan in patients with type 2 diabetes mellitus: a blood pressure-independent effect . Circulation . 2002;106:672–678
  17. Hebert LA , Falkenhain ME , Nahman NS , Cosio FG , O'Dorisio TM . Combination of ACE inhibitor and angiotensin II receptor antagonist therapy in diabetic nephropathy . Am J Nephrol . 1999;19:1–6
  18. Sterqiou GS , Skeva II , Baibas NM , Kalkana CB , Roussias LG , Mountokalakis TD . Does the antihypertensive response to angiotensin converting enzyme inhibition predict the anti-hypertensive response to angiotensin receptor antagonism? . Am J Hypertens . 2001;14:688–693
  19. Ruilope LM , Aldigier JC , Ponticelli C , Oddou-Stock P , Botteri F , Mann JF . Safety of the combination of valsartan and benazapril in patients with chronic renal disease. European Group for the Investigation of Valsartan in Chronic Renal Disease . J Hypertens . 2000;18:89–95
  20. Azizi M , Menard J . Combined blockade of the renin–angiotensin system with angiotensin-converting enzyme inhibitors and angiotensin II type 1 receptor antagonists . Circulation . 2004;109:2492–2499
  21. Leehey DJ , Singh AK , Alavi N , Singh R . Role of angiotensin II in diabetic nephropathy . Kidney Int . 2000;77:S93–S98
  22. Manley HJ . Role of angiotensin-converting-enzyme inhibition in patients with renal disease . Am J Health Syst Pharm . 2000;57:S12–S18
  23. Fujisawa T, Ikegami H, Ono M, Nishino M, Noso S, Kawabata Y, et al. Combination of half doses of angiotensin type 1 receptor antagonist and angiotensin-converting enzyme inhibitor in diabetic nephropathy . Am J Hypertens . 2005;18:13–17
  24. Song JH , Cha SH , Hong SB , Kim DH . Dual blockade of the renin– angiotensin system with angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers in chronic kidney disease . J Hypertens . 2006;24:S101–S106
  25. Matos JPS , de Lourdes Rodrigues M , Ismerim VL , Boasqueviscue EM , Genelhu V , Francischetti EA . Effects of dual blockade of the renin–angiotensin system in hypertensive type 2 diabetic patients with nephropathy . Clin Nephrol . 2005;64:180–189

PII: S1561-5413(07)60006-4

doi:10.1016/S1561-5413(07)60006-4

Hong Kong Journal of Nephrology
Volume 9, Issue 1 , Pages 31-35, April 2007

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