Abstract
Angiotensin converting enzyme inhibitors (ACE-Is) and angiotensin II receptor blockers (ARBs) are frequently used for the treatment for glomerulonephritis and diabetic nephropathy because of their albuminuria- or proteinuria-reducing effects. To many patients who are nonresponsive to monotherapy with these agents, combination therapy appears to be a good treatment option. In the present study, we examined the effects of the addition of an ARB (losartan) followed by titration upon addition and at 3 and 6 months (n=14) and the addition of an ACE-I followed by titration upon addition and at 3 and 6 months (n=20) to the drug regimen treatment protocol in type 2 diabetic patients with nephropathy for whom more than 3-month administration of an ACE-I or the combination of an ACE-I plus a conventional antihypertensive was ineffective to achieve a blood pressure (BP) of 130/80 mmHg and to reduce urinary albumin to <30 mg/day. During the 12-month treatment, addition of losartan or addition of an ACE-I to the treatment protocol reduced systolic blood pressure (SBP) by 10% and 12%, diastolic blood pressure (DBP) by 7% and 4%, and urinary albumin excretion by 38% and 20% of the baseline value, respectively. However, the effects on both BP and urinary albumin were not significantly different between the two therapies. In conclusion, addition of losartan or an ACE-I to an ongoing treatment with an ACE-I, or addition of an ACE-I to ongoing treatment with a conventional antihypertensive were equally effective at reducing the urinary albumin excretion and BP, and provided renal protection in patients with type-2 diabetic nephropathy.
Similar content being viewed by others
Article PDF
References
Remuzzi G, Ruggenenti P, Benigni A : Understanding the nature of renal disease progression. Kidney Int 1997; 51: 1–15.
Navi SG, de Zeeuw D : Titrating for antiproteinuric effect; the clue to renoprotection? J Hum Hypertens 1996; 10: 669–673.
William JD, Coles GA : Proteinuria—a direct cause of renal morbidity? Kidney Int 1994; 45: 443–450.
Peterson JC, Adler S, Burkart J, et al: Blood pressure control, proteinuria, and the progression of renal disease. Ann Intern Med 1995; 123: 754–762.
Lewis EJ, Hunsicker LG, Bain RP, Rhode RD : The effect of angiotensin-converting enzyme inhibition on diabetic nephropathy. N Eng J Med 1993; 329: 1456–1462.
Maschio G, Alberti D, Janin G, et al: Effect of the angiotensin converting enzyme inhibitor benazepril on the progression of chronic renal insufficiency. New Engl J Med 1996; 334: 939–945.
Ravid M, Lang R, Rachmani R, Lishner M : Long term renoprotective effect of angiotensin-converting enzyme inhibition in non–insulin-dependent diabetes mellitus. Arch Intern Med 1996; 334: 939–945.
Bretzel RG : Protecting thr residual renal function: which drugs of choice? Am J Hypertens 1997; 10: 159S–166S.
Russo D, Segal R, Balletta MM, et al: Additive antiproteinuric effect of converting enzyme inhibitor and losartan in normotensive patients with IgA nephropathy. Am J Kidney Dis 2001; 38: 18–25.
Russo D, Minutolo R, Pisani A, et al: Coadministration of losartan and enalapril exerts additive antiproteinuric effect in IgA nephropathy. Am J Kidney Dis 2001; 38: 18–25.
Mogensen CE, Neldam S, Tikkanen I, et al: Randomized controlled trial of dual blockade of renin-angiotensin system in patients with hypertension, microalbuminemia, and non-insulin dependent diabetes: the candesartan and lisinopril microalbuminemia (CALM) study. BMJ 2000; 321: 1440–1444.
Klag MJ, Whelton PK, Randall BL, et al: Blood pressure control on the progression of chronic renal disease. N Engl J Med 1994; 330: 877–884.
Hansson L, Zanchetti A, Carruthers SG, et al: Effects of intensive blood pressure lowering and low-dose aspirin in patients with hypertension: principal results of the hypertension optimal treatment (HOT) randomized trial. Lancet 1998; 351: 1755–1762.
Wang SL, Head J, Stevens L, Fuller JH, The World Health Organization Multinational Study Group: Excess mortality and its relation to hypertension and proteinuria in diabetic patients: the World Health Organization Multinational Study of Vascular Disease in Diabetes. Diabetes Care 1996; 19: 305–312.
Ruggenenti P, Remmuzzi G : Primary prevention of renal failure in diabetic patients: the Bergamo Nephrologic Diabetes Complication Trial. J Hypertens 1998; 16 ( Suppl): S95–S97.
Lewis EJ, Hunsicker LG, Clarke WR, et al: Renoprotective effect of the angiotensin receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. N Engl J Med 2001; 345: 851–860.
Brenner BM, Cooper ME, de Zeeuw D, et al: Effect of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med 2001; 345: 861–869.
Murayama S, Hirano T, Sakaue T, et al: Low-dose candesartan cilesitil prevents early kidney damage in type 2 diabetic patients with mildly elevated blood pressure. Hypertens Res 2003; 26: 453–458.
Iino Y, Hayashi M, Kawamura T, et al: Renoprotective effect of losartan in comparison to amlodipine in patients with chronic kidney disease and hypertension—a report of the Japanese losartan therapy intended for the global renal protection in hypertensive patients (JLIGHT) study. Hypertens Res 2004; 27: 21–30.
Mackinnon M, Shurraw S, Akbari A, Koll GA, Jaffey J, Clark HD : Combination therapy with an angiotensin receptor blocker and an ACE inhibitor in proteinuric renal disease: a systematic review of the efficacy and safety data. Am J Kidney Dis 2006; 48: 8–20 ( Review).
Fujisawa T, Ikegami H, Ohno M, 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.
Peterson JC, Adler S, Burkart JM, et al, The Modification of Diet in Renal Disease Study Group: Blood pressure control, proteinuria, and the progression of renal disease. Ann Intern Med 1995; 123: 754–762.
Hebert LA, Falkenhain M, Nohman N, Cosio FG, O'Dorisio TM : Combination ACE inhibitor and angiotensin II receptor antagonist in diabetic nephropathy. Am J Nephrol 1999; 19: 1–6.
Kuriyama S, Tomonari H, Abe A, Imasawa T, Hosoya T : Beneficial effect of combination therapy with an angiotensin II receptor antagonist and angiotensin converting enzyme inhibitor on overt proteinuria in a patient with type I diabetic nephropathy. Nephron 2000; 86: 529–530.
Horita Y, Tadokoro M, Taura K, et al: Low-dose combination therapy with temocapril and losartan reduces proteinuria in normatensive patients with immunoglobulin a nephropathy. Hypertens Res 2004; 27: 963–970.
Nakao N, Yoshimura A, Morita H, Takada M, Kayano T, Ideura T : Combination treatment of angiotensin-II receptor blocker and angiotensin-converting–enzyme inhibitor in non-diabetic renal disease (COOPERATE): a randomised controlled trial. Lancet 2003; 361: 117–124.
Rossing K, Jensen BR, Christensen PK, Parving HH : Dual blockade of the renin-angiotensin system in diabetic nephropathy: a randomized double-blind crossover study. Diabetes Care 2002; 25: 95–100.
Rossing K, Jacobsen P, Pietraszek L, Parving HH : Renoprotective effects of adding angiotensin II receptor blocker to maximal recommended doses of ACE inhibitor in diabetic nephropathy: a randomized double-blind crossover trial. Diabetes Care 2003; 26: 2268–2274.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Abe, H., Minatoguchi, S., Ohashi, H. et al. Renoprotective Effect of the Addition of Losartan to Ongoing Treatment with an Angiotensin Converting Enzyme Inhibitor in Type-2 Diabetic Patients with Nephropathy. Hypertens Res 30, 929–935 (2007). https://doi.org/10.1291/hypres.30.929
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1291/hypres.30.929
Keywords
This article is cited by
-
Combination Use of Angiotensin Converting Enzyme Inhibitors and Angiotensin Receptor Blockers in Diabetic Kidney Disease
Current Diabetes Reports (2013)