ACE Inhibition, Angiotensin II Receptor Blockade, and Diabetic Nephropathy

  • Norman K. Hollenberg


Only a large, rigorous randomized double-blind assessment of a therapeutic candidate compared to the appropriate alternative can prove therapeutic efficacy. One such trial assessed the effect of Captopril in patients with insulin-dependent diabetes mellitus (IDDM) who were at risk of nephropathy [1], with results that were sufficiently impressive that the use of Captopril quickly became a professional necessity supported by public policy. Moreover, multiple lines of evidence accumulated over a decade suggested that this useful feature of Captopril was a class action, extending to all ACE inhibitors. [2,3] In the case of the angiotensin II (Ang II) AT1 receptor blockers (AT1 antagonists), we are fortunate in having very early in the development of these agents two ongoing major, high quality trials in patients with NUDDM who are at risk of nephropathy — one involving Irbesartan, the other involving Losartan. Unfortunately, the outcome of these trials is unlikely to be available to us until the coming millennium, and this chapter is due well before!


Diabetic Nephropathy Plasma Renin Activity Renin Inhibitor High Salt Diet Renin System 
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  1. 1.
    Lewis EJ, Hunsicker LG, Bain RP, and Roh de RD: The effect of angiotensin converting enzyme inhibition on diabetic nephropathy. N Engl J Med 1993;329:1456–1462.PubMedCrossRefGoogle Scholar
  2. 2.
    Kasiske BL, Kalil RSN, Ma JZ, Liao M, and Keane WF: Effect of therapy on the kidney in patients with diabetes: A meta-regression analysis. Ann Intern Med 1993;118:129–138.PubMedCrossRefGoogle Scholar
  3. 3.
    Hollenberg NK and Raij L. Angiotensin-Converting enzyme inhibition and renal protection. An assessment of implications for therapy. Arch Intern Med 1993;153:2426–2435.PubMedCrossRefGoogle Scholar
  4. 4.
    Ichikawa I. Will Ang II Al be renoprotective in humans? Kidney Intern 1996;50:684–692.CrossRefGoogle Scholar
  5. 5.
    Hollenberg NK. ACE inhibitors, AT1 receptor blockers, and the kidney. E. Ritz (Ed) Nephrol Dial Transplant 1997;12:381–383.Google Scholar
  6. 6.
    Hollenberg NK and Fisher NK. Renal circulation and blockade of the renin-angiotensin system. Is angiotensin-converting enzyme inhibition the last word? Hypertension 1995;26:602–609.PubMedCrossRefGoogle Scholar
  7. 7.
    Roman RJ, Kaldunski ML, Scicli AG, and Carretero OA. Influence of kinins and angiotensin II on the regulation of papillary blood flow. Am J Physiol 1988;255:F690–F698.Google Scholar
  8. 8.
    Price D, DeOliveira J, Fisher N, and Hollenberg N. Contribution of Ang II to renal hemodynamics in healthy men: the renal vascular response to eprosartan, an Ang II antagonist. ASN Program Abstract # A1688 from 29th Annual Meeting in New Orleans, Nov. 3–6. J Am Soc Nephrol 1996,7:1587.Google Scholar
  9. 9.
    Price D, Porter L, DeOliveira J, Fisher N, Gordon M, Laffel L, Williams G, and Hollenberg N. The paradox of the low-renin state: hormonal and renal responses to an Ang II antagonist, Irbesartan, in diabetic nephropathy. ASN Program Abstract #A0591 from 29th Annual Meeting in New Orleans. J Am Soc Nephrology 1996;7:163.Google Scholar
  10. 10.
    Christlieb AR, Kaldany A, and D’Elia JA. Plasma renin activity and hypertension in diabetes mellitus. Diabetes 1976;25:969–974.PubMedCrossRefGoogle Scholar
  11. 11.
    Bjorck S. The renin-angiotensin system in diabetes mellitus: a physiological and therapeutic study. Scand JUrol Nephrol Suppl 1990;126:1–50.Google Scholar
  12. 12.
    Lush DJ, King JA, and Fray JCS. Pathophysiology of low renin syndromes: sites of renal renin secretory impairment and prorenin overexpression. Kid International 1993;43:983–999.CrossRefGoogle Scholar
  13. 13.
    Weidmann P, Ferrari P, and Shaw SG. Renin in Diabetes Mellitus. In: The Renin-Angiotensin System. In: JIS Robertson and MG Nicholls (Ed). Raven Press Ltd., New York, 1991. Chapter 75. pp. 75.1–75.26.Google Scholar
  14. 14.
    Rosenberg ME, Smith LJ, Correa-Rotter R, and Hostetter TH. The paradox of the renin-angiotensin system in chronic renal disease. Kid Internat 1994;45:403–410.CrossRefGoogle Scholar
  15. 15.
    Kikkawa R, Kitamura E, Fujiwara Y, Haneda M, and Shigeta Y. Biphasic alteration of renin-angiotensin-aldosterone system in streptozotocin-diabetic rats. Renal Physiol 1986;9:187–192.PubMedGoogle Scholar
  16. 16.
    Anderson S, Jung FF, and Ingelfinger JR. Renal renin-angiotensin system in diabetes: functional immunohistochemical, and molecular biological correlations. Am J Physiol 1993;265:F477–F486.Google Scholar
  17. 17.
    De’Ohveira JM, Price DA, Fisher NDL, Allan DR, McKnight JA, Williams GH, and Hollenberg NK. Autonomy of the renin system in type II diabetes mellitus: Dietary sodium and renal hemodynamic responses to ACE inhibition. Kidney International 1997;52:771–777.CrossRefGoogle Scholar
  18. 18.
    Miller JA, Floras JS, Zinman B, Skorecki KL, and Logan AG. Effect of hyperglycemia on arterial pressure, plasma renin activity and renal function in early diabetes. Clin Sci 1996;90:189–195.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 1998

Authors and Affiliations

  • Norman K. Hollenberg
    • 1
  1. 1.Departments of Mediane and RadiologyBrigham and Women’s HospitalBostonUSA

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