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NDT Advance Access published online on March 5, 2004

Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfh163
© 2004 by European Renal Association - European Dialysis and Transplant Association
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Received August 28, 2003
Accepted January 16, 2004


Original Article

C-peptide and captopril are equally effective in lowering glomerular hyperfiltration in diabetic rats

Björn Samnegård 1*, Stefan H. Jacobson 2, Bo-Lennart Johansson 3, Karin Ekberg 3, Britta Isaksson 4, John Wahren 3, Mats Sjöquist 4

1 Department of Nephrology, Danderyd Hospital, Stockholm, Sweeden; Department of Cell Biology, Biomedicum, Uppsala University, Sweden
2 Department of Nephrology, Division of Clinical Physiology, Karolinska Hospital, Stockholm, Sweden
3 Department of Surgical, Sciences, Division of Clinical Physiology, Karolinska Hospital, Stockholm, Sweden
4 Department of Cell Biology, Biomedicum, Uppsala University, Sweden

* To whom correspondence should be addressed. E-mail: bjorn.samnegard{at}medks.ki.se.



  Abstract

Background. C-peptide has been shown to reduce glomerular hyperfiltration, glomerular hypertrophy and urinary albumin excretion in type 1 diabetes, but its effect has not been compared with that of an angiotensin-converting enzyme inhibitor (ACEI) in the early stage of renal involvement in diabetes.

Methods. Glomerular filtration rate (GFR) was measured in terms of inulin clearance and renal blood flow, using ultrasound technique, in four groups of streptozotocin-induced diabetic rats before and after a 60 min infusion of C-peptide (D-Cp), captopril (D-ACEI), C-peptide and captopril (D-Cp-ACEI) or placebo (D-placebo). In addition, a non-diabetic control group was studied before and after captopril infusion (C-ACEI).

Results. GFR was 37-51% higher in the diabetic groups than in the control animals. GFR decreased after treatment in the D-Cp, D-ACEI and D-Cp-ACEI groups, but did not change in the D-placebo group. Blood flow increased by 26-32% in the three groups receiving captopril and by 5% in the diabetic groups treated with C-peptide alone or placebo. The increase in blood flow in the three ACEI-treated groups was significantly greater than in the D-placebo group. Filtration fraction fell significantly in all groups, but only in the combined D-Cp-ACEI group did it fall significantly more than in the D-placebo group.

Conclusions. C-peptide and captopril lower diabetes-induced glomerular hyperfiltration to a similar extent, but the influence of captopril on blood flow is greater than that of C-peptide, suggesting different mechanisms of action. No statistically significant additive effects of C-peptide and captopril were shown in this acute infusion study.

Keywords: captopril, C-peptide, diabetic nephropathy, glomerular hyperfiltration, renal blood flow


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