Document Detail

Renoprotective effects of losartan in diabetic nephropathy: interaction with ACE insertion/deletion genotype?
MedLine Citation:
PMID:  12081578     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: The beneficial short- and long-term renoprotective effects of angiotensin I-converting enzyme (ACE) inhibition are lower in albuminuric diabetic patients homozygous for the deletion compared to the insertion polymorphism of the ACE gene. In an attempt to overcome this interaction, we evaluated the short-term renoprotective effect in diabetic nephropathy of the angiotensin II receptor antagonist losartan in patients homozygous for the insertion or the deletion allele. METHODS: Fifty-four hypertensive type 1 diabetic patients with diabetic nephropathy homozygous for the insertion (I; N = 26) or the deletion (D; N = 28) allele of the ACE/ID polymorphism were included. After four weeks of washout, the patients received losartan 50 mg daily followed by 100 mg in two treatment periods each lasting two months. Patients and investigators were blinded to ACE genotypes. At baseline and in the end of the treatment periods, 24-hour blood pressure, albuminuria and glomerular filtration rate values were determined. RESULTS: At baseline, blood pressure, albuminuria and glomerular filtration rate (GFR) values were similar in the two genotype groups [II vs. DD, 1134 (238 to 5302) vs. 1451 (227 to 8129) mg/24 h, median (range); 156/82 (17/9) vs. 153/80 (17/11) mm Hg, mean (SD); and 86 (22) vs. 88 (24) mL/min/1.73 m2, respectively]. Both doses of losartan significantly lowered blood pressure, albuminuria, and GFR (P < 0.05 vs. baseline). Losartan 100 mg was more effective than 50 mg in reducing albuminuria, 51% (95% CI; 40 to 61) versus 33% (23 to 42), respectively (P < 0.01). No differences in the impact of losartan between the II and DD groups were observed: Losartan 100 mg lowered systolic/diastolic blood pressure by 12/6 and 10/4 mm Hg, whereas albuminuria decreased by 55% (35 to 68) and 46% (28 to 61), in the II and DD groups, respectively (P = NS). CONCLUSION: Our data suggest that losartan offers similar short-term renoprotective and blood pressure lowering effects in albuminuric hypertensive type 1 diabetic patients with the ACE II and DD genotypes. However, the long-term renoprotective effects remain to be evaluated.
Steen Andersen; Lise Tarnow; Francois Cambien; Peter Rossing; Tina R Juhl; Jaap Deinum; Hans-Henrik Parving
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Publication Detail:
Type:  Clinical Trial; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Kidney international     Volume:  62     ISSN:  0085-2538     ISO Abbreviation:  Kidney Int.     Publication Date:  2002 Jul 
Date Detail:
Created Date:  2002-06-25     Completed Date:  2002-12-10     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0323470     Medline TA:  Kidney Int     Country:  United States    
Other Details:
Languages:  eng     Pagination:  192-8     Citation Subset:  IM    
Steno Diabetes Center, Niels Steensensvej 2, 2820 Gentofte, Copenhagen, Denmark.
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MeSH Terms
Antihypertensive Agents / therapeutic use*
Blood Pressure / drug effects
Diabetic Nephropathies / drug therapy*,  enzymology,  genetics
Double-Blind Method
Hemoglobin A, Glycosylated / analysis
Kidney / drug effects*
Losartan / therapeutic use*
Middle Aged
Peptidyl-Dipeptidase A / blood,  genetics*
Prospective Studies
Receptors, Angiotensin / antagonists & inhibitors*
Sodium / metabolism
Reg. No./Substance:
0/Antihypertensive Agents; 0/Hemoglobin A, Glycosylated; 0/Receptors, Angiotensin; 114798-26-4/Losartan; 7440-23-5/Sodium; EC A

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