Captopril reduces the risk of nephropathy in IDDM patients with microalbuminuria

G. Boner, D. J. Van Dyk, M. H. Tan, J. Tan, A. Ekstrand, V. A. Koivisto, L. C. Groop, P. H. Groop, A. Lucas, R. Romero, I. Salinas, A. Sanmarti, F. Escobar, F. Escobar-Jimenez, M. M. Campos-Pastor, M. Mugoz, M. Gomez, R. Mangili, G. Pozza, D. SpottiK. Wurgler Hansen, J. Sandahl Christiansen, F. Klein, C. E. Mogensen, L. G. Van Doorn, P. F M J Spooren, J. K. Cruickshank, J. Jervell, P. N. Paus, D. J. Barnes, A. Collins, G. C. Viberti, G. Williams, G. A. Nelstrop, L. Amorosa, J. R. Anolik, S. L. Aronoff, B. Eubank, M. Bailie, L. Pelletier, T. Blevins, M. A. Charles, M. Perry, D. Clarke, D. Tomkey, D. Einhorn, D. Humphries, A. J. Garber, B. Haag, E. Williams, W. Hoy, M. Watkins, D. Kahkonen, D. Kruger, C. Kilo, L. Laffel, E. Golden, P. Lodewick, Lovinsky, J. Mason, S. Johnson, J. McGill, L. Schmidt, P. Orlander, K. Sorenson, Philip Raskin, D. Hellenbrand, S. Rosenblatt, S. Schwartz, J. Aufieri, J. P. Sheehan, M. Ulchaker, J. S. Skyler, R. Agramonte, J. Starr, D. Gagliastre, T. Taylor, K. Dawn, W. K. Ward, M. Rigdon

Research output: Contribution to journalArticle

190 Citations (Scopus)

Abstract

In insulin-dependent diabetes mellitus (IDDM), microalbuminuria predicts renal and cardiovascular disease. We report a combined analysis of 235 normotensive IDDM patients with microalbuminuria who participated in two 24-month double-blind, randomised, placebo-controlled trials to assess the effects of captopril 50 mg twice daily on the progression to overt clinical albuminuria. Of the 225 patients who were evaluable on an intent to treat basis, 25 of 114 placebo-treated patients (21.9%) and 8 of 111 captopril-treated patients (7.2%) progressed to persistent clinical albuminuria. The risk of progression over 24 months was significantly reduced by captopril (p = 0.004) with a risk reduction of 69.2% (95% confidence interval (CI): 31.7 to 86.1%). This degree of risk reduction remained at the same level (62.9% [16.1-83.6%], p = 0.017) after adjustment for differences in time-varying mean arterial blood pressure. Albumin excretion rate increased by an average of 14.2% [3.1-26.5%] per year in the placebo-treated group compared with a reduction of 9.6% [-18.6-0.4%] per year in the captopril-treated group (p = 0.002). The rate of fall of creatinine clearance tended to be faster in the placebo-treated group than in the captopril treated group (-6.4 [-10.2--2.5] vs -1.4 [-5.3-2.6] ml · min-1 · 1.73 m-2, p = 0.07). Baseline albumin excretion rate (p < 0.0001) and glycated haemoglobin (p = 0.03) were independent predictors of progression to clinical albuminuria and changes in mean arterial blood pressure (p = 0.02) and serum cholesterol level (p = 0.003) were significantly associated with percentage changes in albumin excretion rate. Captopril reduces the risk of progression to overt nephropathy in IDDM patients with microalbuminuria, an effect partly independent of its blood pressure-lowering effects.

Original languageEnglish (US)
Pages (from-to)587-593
Number of pages7
JournalDiabetologia
Volume39
Issue number5
DOIs
StatePublished - 1996

Fingerprint

Captopril
Type 1 Diabetes Mellitus
Albuminuria
Arterial Pressure
Placebos
Albumins
Risk Reduction Behavior
Glycosylated Hemoglobin A
Creatinine
Cardiovascular Diseases
Randomized Controlled Trials
Cholesterol
Confidence Intervals
Blood Pressure
Kidney
Serum

Keywords

  • angiotensin converting enzyme inhibition
  • diabetic nephropathy
  • insulin-dependent diabetes mellitus
  • microalbuminuria

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Boner, G., Van Dyk, D. J., Tan, M. H., Tan, J., Ekstrand, A., Koivisto, V. A., ... Rigdon, M. (1996). Captopril reduces the risk of nephropathy in IDDM patients with microalbuminuria. Diabetologia, 39(5), 587-593. https://doi.org/10.1007/s001250050482

Captopril reduces the risk of nephropathy in IDDM patients with microalbuminuria. / Boner, G.; Van Dyk, D. J.; Tan, M. H.; Tan, J.; Ekstrand, A.; Koivisto, V. A.; Groop, L. C.; Groop, P. H.; Lucas, A.; Romero, R.; Salinas, I.; Sanmarti, A.; Escobar, F.; Escobar-Jimenez, F.; Campos-Pastor, M. M.; Mugoz, M.; Gomez, M.; Mangili, R.; Pozza, G.; Spotti, D.; Hansen, K. Wurgler; Christiansen, J. Sandahl; Klein, F.; Mogensen, C. E.; Van Doorn, L. G.; Spooren, P. F M J; Cruickshank, J. K.; Jervell, J.; Paus, P. N.; Barnes, D. J.; Collins, A.; Viberti, G. C.; Williams, G.; Nelstrop, G. A.; Amorosa, L.; Anolik, J. R.; Aronoff, S. L.; Eubank, B.; Bailie, M.; Pelletier, L.; Blevins, T.; Charles, M. A.; Perry, M.; Clarke, D.; Tomkey, D.; Einhorn, D.; Humphries, D.; Garber, A. J.; Haag, B.; Williams, E.; Hoy, W.; Watkins, M.; Kahkonen, D.; Kruger, D.; Kilo, C.; Laffel, L.; Golden, E.; Lodewick, P.; Lovinsky; Mason, J.; Johnson, S.; McGill, J.; Schmidt, L.; Orlander, P.; Sorenson, K.; Raskin, Philip; Hellenbrand, D.; Rosenblatt, S.; Schwartz, S.; Aufieri, J.; Sheehan, J. P.; Ulchaker, M.; Skyler, J. S.; Agramonte, R.; Starr, J.; Gagliastre, D.; Taylor, T.; Dawn, K.; Ward, W. K.; Rigdon, M.

In: Diabetologia, Vol. 39, No. 5, 1996, p. 587-593.

Research output: Contribution to journalArticle

Boner, G, Van Dyk, DJ, Tan, MH, Tan, J, Ekstrand, A, Koivisto, VA, Groop, LC, Groop, PH, Lucas, A, Romero, R, Salinas, I, Sanmarti, A, Escobar, F, Escobar-Jimenez, F, Campos-Pastor, MM, Mugoz, M, Gomez, M, Mangili, R, Pozza, G, Spotti, D, Hansen, KW, Christiansen, JS, Klein, F, Mogensen, CE, Van Doorn, LG, Spooren, PFMJ, Cruickshank, JK, Jervell, J, Paus, PN, Barnes, DJ, Collins, A, Viberti, GC, Williams, G, Nelstrop, GA, Amorosa, L, Anolik, JR, Aronoff, SL, Eubank, B, Bailie, M, Pelletier, L, Blevins, T, Charles, MA, Perry, M, Clarke, D, Tomkey, D, Einhorn, D, Humphries, D, Garber, AJ, Haag, B, Williams, E, Hoy, W, Watkins, M, Kahkonen, D, Kruger, D, Kilo, C, Laffel, L, Golden, E, Lodewick, P, Lovinsky, Mason, J, Johnson, S, McGill, J, Schmidt, L, Orlander, P, Sorenson, K, Raskin, P, Hellenbrand, D, Rosenblatt, S, Schwartz, S, Aufieri, J, Sheehan, JP, Ulchaker, M, Skyler, JS, Agramonte, R, Starr, J, Gagliastre, D, Taylor, T, Dawn, K, Ward, WK & Rigdon, M 1996, 'Captopril reduces the risk of nephropathy in IDDM patients with microalbuminuria', Diabetologia, vol. 39, no. 5, pp. 587-593. https://doi.org/10.1007/s001250050482
Boner G, Van Dyk DJ, Tan MH, Tan J, Ekstrand A, Koivisto VA et al. Captopril reduces the risk of nephropathy in IDDM patients with microalbuminuria. Diabetologia. 1996;39(5):587-593. https://doi.org/10.1007/s001250050482
Boner, G. ; Van Dyk, D. J. ; Tan, M. H. ; Tan, J. ; Ekstrand, A. ; Koivisto, V. A. ; Groop, L. C. ; Groop, P. H. ; Lucas, A. ; Romero, R. ; Salinas, I. ; Sanmarti, A. ; Escobar, F. ; Escobar-Jimenez, F. ; Campos-Pastor, M. M. ; Mugoz, M. ; Gomez, M. ; Mangili, R. ; Pozza, G. ; Spotti, D. ; Hansen, K. Wurgler ; Christiansen, J. Sandahl ; Klein, F. ; Mogensen, C. E. ; Van Doorn, L. G. ; Spooren, P. F M J ; Cruickshank, J. K. ; Jervell, J. ; Paus, P. N. ; Barnes, D. J. ; Collins, A. ; Viberti, G. C. ; Williams, G. ; Nelstrop, G. A. ; Amorosa, L. ; Anolik, J. R. ; Aronoff, S. L. ; Eubank, B. ; Bailie, M. ; Pelletier, L. ; Blevins, T. ; Charles, M. A. ; Perry, M. ; Clarke, D. ; Tomkey, D. ; Einhorn, D. ; Humphries, D. ; Garber, A. J. ; Haag, B. ; Williams, E. ; Hoy, W. ; Watkins, M. ; Kahkonen, D. ; Kruger, D. ; Kilo, C. ; Laffel, L. ; Golden, E. ; Lodewick, P. ; Lovinsky ; Mason, J. ; Johnson, S. ; McGill, J. ; Schmidt, L. ; Orlander, P. ; Sorenson, K. ; Raskin, Philip ; Hellenbrand, D. ; Rosenblatt, S. ; Schwartz, S. ; Aufieri, J. ; Sheehan, J. P. ; Ulchaker, M. ; Skyler, J. S. ; Agramonte, R. ; Starr, J. ; Gagliastre, D. ; Taylor, T. ; Dawn, K. ; Ward, W. K. ; Rigdon, M. / Captopril reduces the risk of nephropathy in IDDM patients with microalbuminuria. In: Diabetologia. 1996 ; Vol. 39, No. 5. pp. 587-593.
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T1 - Captopril reduces the risk of nephropathy in IDDM patients with microalbuminuria

AU - Boner, G.

AU - Van Dyk, D. J.

AU - Tan, M. H.

AU - Tan, J.

AU - Ekstrand, A.

AU - Koivisto, V. A.

AU - Groop, L. C.

AU - Groop, P. H.

AU - Lucas, A.

AU - Romero, R.

AU - Salinas, I.

AU - Sanmarti, A.

AU - Escobar, F.

AU - Escobar-Jimenez, F.

AU - Campos-Pastor, M. M.

AU - Mugoz, M.

AU - Gomez, M.

AU - Mangili, R.

AU - Pozza, G.

AU - Spotti, D.

AU - Hansen, K. Wurgler

AU - Christiansen, J. Sandahl

AU - Klein, F.

AU - Mogensen, C. E.

AU - Van Doorn, L. G.

AU - Spooren, P. F M J

AU - Cruickshank, J. K.

AU - Jervell, J.

AU - Paus, P. N.

AU - Barnes, D. J.

AU - Collins, A.

AU - Viberti, G. C.

AU - Williams, G.

AU - Nelstrop, G. A.

AU - Amorosa, L.

AU - Anolik, J. R.

AU - Aronoff, S. L.

AU - Eubank, B.

AU - Bailie, M.

AU - Pelletier, L.

AU - Blevins, T.

AU - Charles, M. A.

AU - Perry, M.

AU - Clarke, D.

AU - Tomkey, D.

AU - Einhorn, D.

AU - Humphries, D.

AU - Garber, A. J.

AU - Haag, B.

AU - Williams, E.

AU - Hoy, W.

AU - Watkins, M.

AU - Kahkonen, D.

AU - Kruger, D.

AU - Kilo, C.

AU - Laffel, L.

AU - Golden, E.

AU - Lodewick, P.

AU - Lovinsky,

AU - Mason, J.

AU - Johnson, S.

AU - McGill, J.

AU - Schmidt, L.

AU - Orlander, P.

AU - Sorenson, K.

AU - Raskin, Philip

AU - Hellenbrand, D.

AU - Rosenblatt, S.

AU - Schwartz, S.

AU - Aufieri, J.

AU - Sheehan, J. P.

AU - Ulchaker, M.

AU - Skyler, J. S.

AU - Agramonte, R.

AU - Starr, J.

AU - Gagliastre, D.

AU - Taylor, T.

AU - Dawn, K.

AU - Ward, W. K.

AU - Rigdon, M.

PY - 1996

Y1 - 1996

N2 - In insulin-dependent diabetes mellitus (IDDM), microalbuminuria predicts renal and cardiovascular disease. We report a combined analysis of 235 normotensive IDDM patients with microalbuminuria who participated in two 24-month double-blind, randomised, placebo-controlled trials to assess the effects of captopril 50 mg twice daily on the progression to overt clinical albuminuria. Of the 225 patients who were evaluable on an intent to treat basis, 25 of 114 placebo-treated patients (21.9%) and 8 of 111 captopril-treated patients (7.2%) progressed to persistent clinical albuminuria. The risk of progression over 24 months was significantly reduced by captopril (p = 0.004) with a risk reduction of 69.2% (95% confidence interval (CI): 31.7 to 86.1%). This degree of risk reduction remained at the same level (62.9% [16.1-83.6%], p = 0.017) after adjustment for differences in time-varying mean arterial blood pressure. Albumin excretion rate increased by an average of 14.2% [3.1-26.5%] per year in the placebo-treated group compared with a reduction of 9.6% [-18.6-0.4%] per year in the captopril-treated group (p = 0.002). The rate of fall of creatinine clearance tended to be faster in the placebo-treated group than in the captopril treated group (-6.4 [-10.2--2.5] vs -1.4 [-5.3-2.6] ml · min-1 · 1.73 m-2, p = 0.07). Baseline albumin excretion rate (p < 0.0001) and glycated haemoglobin (p = 0.03) were independent predictors of progression to clinical albuminuria and changes in mean arterial blood pressure (p = 0.02) and serum cholesterol level (p = 0.003) were significantly associated with percentage changes in albumin excretion rate. Captopril reduces the risk of progression to overt nephropathy in IDDM patients with microalbuminuria, an effect partly independent of its blood pressure-lowering effects.

AB - In insulin-dependent diabetes mellitus (IDDM), microalbuminuria predicts renal and cardiovascular disease. We report a combined analysis of 235 normotensive IDDM patients with microalbuminuria who participated in two 24-month double-blind, randomised, placebo-controlled trials to assess the effects of captopril 50 mg twice daily on the progression to overt clinical albuminuria. Of the 225 patients who were evaluable on an intent to treat basis, 25 of 114 placebo-treated patients (21.9%) and 8 of 111 captopril-treated patients (7.2%) progressed to persistent clinical albuminuria. The risk of progression over 24 months was significantly reduced by captopril (p = 0.004) with a risk reduction of 69.2% (95% confidence interval (CI): 31.7 to 86.1%). This degree of risk reduction remained at the same level (62.9% [16.1-83.6%], p = 0.017) after adjustment for differences in time-varying mean arterial blood pressure. Albumin excretion rate increased by an average of 14.2% [3.1-26.5%] per year in the placebo-treated group compared with a reduction of 9.6% [-18.6-0.4%] per year in the captopril-treated group (p = 0.002). The rate of fall of creatinine clearance tended to be faster in the placebo-treated group than in the captopril treated group (-6.4 [-10.2--2.5] vs -1.4 [-5.3-2.6] ml · min-1 · 1.73 m-2, p = 0.07). Baseline albumin excretion rate (p < 0.0001) and glycated haemoglobin (p = 0.03) were independent predictors of progression to clinical albuminuria and changes in mean arterial blood pressure (p = 0.02) and serum cholesterol level (p = 0.003) were significantly associated with percentage changes in albumin excretion rate. Captopril reduces the risk of progression to overt nephropathy in IDDM patients with microalbuminuria, an effect partly independent of its blood pressure-lowering effects.

KW - angiotensin converting enzyme inhibition

KW - diabetic nephropathy

KW - insulin-dependent diabetes mellitus

KW - microalbuminuria

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