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Angiotensin converting enzyme inhibition and chronic cyclosporine-induced renal dysfunction in type 1 diabetes
T P Hannedouche1, S Natov, C Boitard
1Département de Néphrologie, Hôpital Necker, Paris, France.
Aim:
This study was designed to evaluate whether the angiotensin converting enzyme inhibitor enalapril could prevent cyclosporine-induced renal dysfunction in diabetic patients treated with CsA in monotherapy.
Design:
Twenty-four recent onset insulin-dependent diabetic patients without prior renal involvement were randomized to receive a 3 month course of either cyclosporine (CsA) alone (7.5 mg/kg. b.i.d. in olive oil) or CsA+enalapril (20mg p.o. oad.).
End Points:
were mean arterial pressure, plasma creatinine, GFR, renal plasma flow, renal vascular resistance, sodium and lithium clearances measured before and after 3 months of treatment.
Results:
Baseline values were identical in both groups except for mean arterial pressure which was slightly higher in the subjects subsequently receiving CsA + enalapril. Three month treatment with CsA increased significantly mean arterial pressure and renal vascular resistance by 9 and 24% respectively, while decreasing significantly glomerular filtration rate and renal plasma flow by 17 and 14% respectively. Enalapril was able to prevent the decline in GFR and the increase in blood pressure induced by CsA. This effect was demonstrated despite a similar increase in renal vascular resistance suggesting a dissociation between changes in glomerular filtration rate and renal vascular resistance during angiotensin converting-enzyme inhibition.
Conclusion:
Chronic angiotensin converting-enzyme inhibition could afford some degree of protection against CsA-induced renal dysfunction. Whether these results can be extrapolated to transplant recipients in whom CsA is usually associated to treatment by glucocorticosteroids deserves further evaluation.
Insights
Enalapril, an angiotensin converting enzyme inhibitor, protected diabetic patients from cyclosporine-induced kidney dysfunction. This suggests ACE inhibition may prevent renal damage in patients treated with cyclosporine.
Area of Science:
- Nephrology
- Pharmacology
- Endocrinology
Background:
- Cyclosporine (CsA) is an immunosuppressant frequently used in organ transplantation.
- CsA can induce renal dysfunction, particularly in patients with diabetes mellitus.
- Diabetic patients are at increased risk for CsA-associated nephrotoxicity.
Purpose of the Study:
- To investigate the renoprotective effect of enalapril against CsA-induced nephrotoxicity in diabetic patients.
- To evaluate whether angiotensin converting enzyme (ACE) inhibition can prevent renal dysfunction caused by CsA monotherapy.
Main Methods:
- A randomized controlled trial involving 24 recent-onset insulin-dependent diabetic patients.
- Patients received either CsA alone or CsA plus enalapril for 3 months.
- Key renal function parameters including GFR, renal plasma flow, and blood pressure were measured.
Main Results:
- CsA monotherapy significantly increased mean arterial pressure and renal vascular resistance while decreasing GFR and renal plasma flow.
- Enalapril co-administration prevented the rise in blood pressure and the decline in GFR induced by CsA.
- These protective effects occurred despite similar increases in renal vascular resistance, indicating a dissociation between GFR and renal vascular resistance changes.
Conclusions:
- Chronic ACE inhibition with enalapril offers protection against CsA-induced renal dysfunction in diabetic patients.
- Further studies are needed to determine if these findings apply to transplant recipients on combined CsA and corticosteroid therapy.