| Renoprotective effects of losartan in diabetic nephropathy: interaction with ACE insertion/deletion genotype? | |
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MedLine Citation:
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PMID: 12081578 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Steen Andersen; Lise Tarnow; Francois Cambien; Peter Rossing; Tina R Juhl; Jaap Deinum; Hans-Henrik Parving |
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Publication Detail:
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Type: Clinical Trial; Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Kidney international Volume: 62 ISSN: 0085-2538 ISO Abbreviation: Kidney Int. Publication Date: 2002 Jul |
Date Detail:
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Created Date: 2002-06-25 Completed Date: 2002-12-10 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0323470 Medline TA: Kidney Int Country: United States |
Other Details:
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Languages: eng Pagination: 192-8 Citation Subset: IM |
Affiliation:
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Steno Diabetes Center, Niels Steensensvej 2, 2820 Gentofte, Copenhagen, Denmark. stan@dadlnet.dk |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adult Antihypertensive Agents / therapeutic use* Blood Pressure / drug effects Diabetic Nephropathies / drug therapy*, enzymology, genetics Double-Blind Method Female Genotype Hemoglobin A, Glycosylated / analysis Humans Kidney / drug effects* Losartan / therapeutic use* Male Middle Aged Peptidyl-Dipeptidase A / blood, genetics* Prospective Studies Receptors, Angiotensin / antagonists & inhibitors* Sodium / metabolism |
| Chemical | |
Reg. No./Substance:
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0/Antihypertensive Agents; 0/Hemoglobin A, Glycosylated; 0/Receptors, Angiotensin; 114798-26-4/Losartan; 7440-23-5/Sodium; EC 3.4.15.1/Peptidyl-Dipeptidase A |
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