The effects of candesartan on diabetes glomerulopathy: a double-blind, placebo-controlled trial


Our objective was to study the effects of candesartan on diabetic glomerulopathy in young normoalbuminuric and normotensive patients with type 1 diabetes in a double-blind, placebo-controlled trial. In 13 patients aged 24 years at baseline, we evaluated blood pressure, kidney biopsies and kidney function tests at baseline and after 5 years of treatment. Kidney biopsies were examined with light and electron microscopy, glomerular filtration rate and effective renal plasma flow determined with inulin and para-aminohippuric acid clearances. Two patients in the placebo group needed antihypertensive treatment because they developed microalbuminuria and/or hypertension, but no patient in the candesartan group did. A significant reduction in mesangial matrix volume and mesangial volume occurred in the candesartan group, although changes in morphological parameters were similar between groups. Office blood pressure was significantly lower in the candesartan group at follow-up than in the placebo group. Deterioration in morphological parameters observed in earlier studies of our patients did not become worse during treatment with candesartan or placebo. The effects of candesartan, with reduction in morphological parameters and lowering of blood pressure, might influence future treatment of glomerulopathy in type 1 diabetes patients.

This is a preview of subscription content, access via your institution.

Fig. 1


  1. 1.

    Asao K, Sarti C, Forsen T, Hyttinen V, Nishimura R, Matsushima M, Reunanen A, Tuomilehto J, Tajima N (2003) Long-term mortality in nationwide cohorts of childhood-onset type 1 diabetes in Japan and Finland. Diabetes Care 26:2037–2042

    Article  Google Scholar 

  2. 2.

    Skrivarhaug T, Bangstad HJ, Stene LC, Sandvik L, Hanssen KF, Joner G (2006) Long-term mortality in a nationwide cohort of childhood-onset type 1 diabetic patients in Norway. Diabetologia 49:298–305

    CAS  Article  Google Scholar 

  3. 3.

    Stadler M, Auinger M, Anderwald C, Kastenbauer T, Kramar R, Feinbock C, Irsigler K, Kronenberg F, Prager R (2006) Long-term mortality and incidence of renal dialysis and transplantation in type 1 diabetes mellitus. J Clin Endocrinol Metab 91:3814–3820

    CAS  Article  Google Scholar 

  4. 4.

    Mokdad AH, Ford ES, Bowman BA, Dietz WH, Vinicor F, Bales VS, Marks JS (2003) Prevalence of obesity, diabetes, and obesity-related health risk factors, 2001. JAMA 289:76–79

    Article  Google Scholar 

  5. 5.

    Wild S, Roglic G, Green A, Sicree R, King H (2004) Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. Diabetes Care 27:1047–1053

    Article  Google Scholar 

  6. 6.

    The DIAMOND Project Group (2006) Incidence and trends of childhood Type 1 diabetes worldwide 1990–1999. Diabet Med 23:857–866

    Article  Google Scholar 

  7. 7.

    Mathiesen ER, Hommel E, Giese J, Parving HH (1991) Efficacy of captopril in postponing nephropathy in normotensive insulin dependent diabetic patients with microalbuminuria. BMJ 303:81–87

    CAS  Article  Google Scholar 

  8. 8.

    Viberti G (1994) Prognostic significance of microalbuminuria. Am J Hypertens 7:69S–72S

    CAS  Article  Google Scholar 

  9. 9.

    Laverman GD, Navis G, Henning RH, de Jong PE, de Zeeuw D (2002) Dual renin-angiotensin system blockade at optimal doses for proteinuria. Kidney Int 62:1020–1025

    CAS  Article  Google Scholar 

  10. 10.

    Jacobsen P, Andersen S, Rossing K, Jensen BR, Parving HH (2003) Dual blockade of the renin-angiotensin system versus maximal recommended dose of ACE inhibition in diabetic nephropathy. Kidney Int 63:1874–1880

    CAS  Article  Google Scholar 

  11. 11.

    Perrin NE, Torbjornsdotter TB, Jaremko GA, Berg UB (2006) The course of diabetic glomerulopathy in patients with type I diabetes: a 6-year follow-up with serial biopsies. Kidney Int 69:699–705

    CAS  Article  Google Scholar 

  12. 12.

    Berg UB, Torbjornsdotter TB, Jaremko G, Thalme B (1998) Kidney morphological changes in relation to long-term renal function and metabolic control in adolescents with IDDM. Diabetologia 41:1047–1056

    CAS  Article  Google Scholar 

  13. 13.

    Hoelzel W, Weykamp C, Jeppsson JO, Miedema K, Barr JR, Goodall I, Hoshino T, John WG, Kobold U, Little R, Mosca A, Mauri P, Paroni R, Susanto F, Takei I, Thienpont L, Umemoto M, Wiedmeyer HM (2004) IFCC reference system for measurement of hemoglobin A1c in human blood and the national standardization schemes in the United States, Japan, and Sweden: a method-comparison study. Clin Chem 50:166–174

    CAS  Article  Google Scholar 

  14. 14.

    The Diabetes Control and Complications Trial Research Group (1993) 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 329:977–986

    Article  Google Scholar 

  15. 15.

    Perrin NE, Torbjornsdotter TB, Jaremko GA, Berg UB (2004) Follow-up of kidney biopsies in normoalbuminuric patients with type 1 diabetes. Pediatr Nephrol 19:1004–1013

    Google Scholar 

  16. 16.

    Andersen S, Tarnow L, Rossing P, Hansen BV, Parving HH (2000) Renoprotective effects of angiotensin II receptor blockade in type 1 diabetic patients with diabetic nephropathy. Kidney Int 57:601–606

    CAS  Article  Google Scholar 

  17. 17.

    Mogensen CE, Neldam S, Tikkanen I, Oren S, Viskoper R, Watts RW, Cooper ME (2000) Randomised controlled trial of dual blockade of renin-angiotensin system in patients with hypertension, microalbuminuria, and non-insulin dependent diabetes: the candesartan and lisinopril microalbuminuria (CALM) study. BMJ 321:1440–1444

    CAS  Article  Google Scholar 

  18. 18.

    Taal MW, Brenner BM (2000) Renoprotective benefits of RAS inhibition: from ACEI to angiotensin II antagonists. Kidney Int 57:1803–1817

    CAS  Article  Google Scholar 

  19. 19.

    The European Study for the Prevention of Renal Disease in Type 1 Diabetes (ESPRIT) (2001) Effect of 3 years of antihypertensive therapy on renal structure in type 1 diabetic patients with albuminuria. Diabetes 50:843–850

    Article  Google Scholar 

  20. 20.

    Rudberg S, Osterby R, Bangstad HJ, Dahlquist G, Persson B (1999) Effect of angiotensin converting enzyme inhibitor or beta blocker on glomerular structural changes in young microalbuminuric patients with Type I (insulin-dependent) diabetes mellitus. Diabetologia 42:589–595

    CAS  Article  Google Scholar 

  21. 21.

    Bangstad HJ, Osterby R, Dahl-Jorgensen K, Berg KJ, Hartmann A, Nyberg G, Frahm Bjorn S, Hanssen KF (1993) Early glomerulopathy is present in young, type 1 (insulin-dependent) diabetic patients with microalbuminuria. Diabetologia 36:523–529

    CAS  Article  Google Scholar 

  22. 22.

    Rudberg S, Osterby R, Dahlquist G, Nyberg G, Persson B (1997) Predictors of renal morphological changes in the early stage of microalbuminuria in adolescents with IDDM. Diabetes Care 20:265–271

    CAS  Article  Google Scholar 

  23. 23.

    Bangstad HJ, Osterby R, Rudberg S, Hartmann A, Brabrand K, Hanssen KF (2002) Kidney function and glomerulopathy over 8 years in young patients with Type I (insulin-dependent) diabetes mellitus and microalbuminuria. Diabetologia 45:253–261

    CAS  Article  Google Scholar 

  24. 24.

    Laffel LM, McGill JB, Gans DJ (1995) The beneficial effect of angiotensin-converting enzyme inhibition with captopril on diabetic nephropathy in normotensive IDDM patients with microalbuminuria. North American Microalbuminuria Study Group. Am J Med 99:497–504

    CAS  Article  Google Scholar 

  25. 25.

    Ahmad J, Shafique S, Abidi SM, Parwez I (2003) Effect of 5-year enalapril therapy on progression of microalbuminuria and glomerular structural changes in type 1 diabetic subjects. Diabetes Res Clin Pract 60:131–138

    CAS  Article  Google Scholar 

  26. 26.

    Drummond K, Levy-Marchal C, Laborde K, Kindermans C, Wright C, Dechaux M, Czernichow P (1989) Enalapril does not alter renal function in normotensive, normoalbuminuric, hyperfiltering type 1 (insulin-dependent) diabetic children. Diabetologia 32:255–260

    CAS  Article  Google Scholar 

  27. 27.

    Mathiesen ER, Borch-Johnsen K, Jensen DV, Deckert T (1989) Improved survival in patients with diabetic nephropathy. Diabetologia 32:884–886

    CAS  Article  Google Scholar 

  28. 28.

    Brenner BM, Cooper ME, de Zeeuw D, Keane WF, Mitch WE, Parving HH, Remuzzi G, Snapinn SM, Zhang Z, Shahinfar S (2001) Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med 345:861–869

    CAS  Article  Google Scholar 

  29. 29.

    Tutuncu NB, Gurlek A, Gedik O (2001) Efficacy of ACE inhibitors and ATII receptor blockers in patients with microalbuminuria: a prospective study. Acta Diabetol 38:157–161

    CAS  Article  Google Scholar 

  30. 30.

    Strippoli GF, Bonifati C, Craig M, Navaneethan SD, Craig JC (2006) Angiotensin converting enzyme inhibitors and angiotensin II receptor antagonists for preventing the progression of diabetic kidney disease. Cochrane Database Syst Rev:CD006257

  31. 31.

    Parving HH, Hommel E, Jensen BR, Hansen HP (2001) Long-term beneficial effect of ACE inhibition on diabetic nephropathy in normotensive type 1 diabetic patients. Kidney Int 60:228–234

    CAS  Article  Google Scholar 

  32. 32.

    Walker JD, Close CF, Jones SL, Rafftery M, Keen H, Viberti GC, Osterby R (1992) Glomerular structure in type-1(insulin-dependent) diabetic patients with normo- and microalbuminuria. Kidney Int 41:741–748

    CAS  Article  Google Scholar 

  33. 33.

    Fioretto P, Steffes MW, Mauer M (1994) Glomerular structure in nonproteinuric IDDM patients with various levels of albuminuria. Diabetes 43:1358–1364

    CAS  Article  Google Scholar 

  34. 34.

    Bergstrom J, Alvestrand A, Bucht H, Gutierrez A (1986) Progression of chronic renal failure in man is retarded with more frequent clinical follow-ups and better blood pressure control. Clin Nephrol 25:1–6

    CAS  PubMed  Google Scholar 

  35. 35.

    Dobrilla G, Scarpignato C (1994) Placebo and placebo effect: their impact on the evaluation of drug response in patients. Dig Dis 12:368–377

    CAS  Article  Google Scholar 

  36. 36.

    Musial F, Klosterhalfen S, Enck P (2007) Placebo responses in patients with gastrointestinal disorders. World J Gastroenterol 13:3425–3429

    Article  Google Scholar 

Download references


We thank Astra Zeneca Company, Gothenburg, Sweden, for drug supply and funding the biopsy analyses. Financial support was provided through the regional agreement on medical training and research (ALF) between Stockholm County Council and the Karolinska Institutet, as well as the Foundation of Frimurare Barnhuset in Stockholm and Department of Pediatrics, CLINTEC, Karolinska Institutet for research grants (NP). This study was also supported by a grant from the Swedish Medical Research Council (no. 6864).

Author information



Corresponding author

Correspondence to Nina E. S. S. Perrin.

Additional information

Clinical Trials Government Identifier: NTC00328302 Name of registry: Diabetes Type 1, Treatment Study Atacand/Placebo after Kidney biopsy

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Perrin, N.E.S.S., Jaremko, G.A. & Berg, U.B. The effects of candesartan on diabetes glomerulopathy: a double-blind, placebo-controlled trial. Pediatr Nephrol 23, 947–954 (2008).

Download citation


  • Blood pressure
  • Kidney biopsy
  • Kidney function test
  • Microalbuminuria
  • Normoalbuminuria
  • Type 1 diabetes