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Renoprotective effects of losartan in diabetic nephropathy: interaction with ACE insertion/deletion genotype?
- Source :
- Kidney International, 62, 192-198. Elsevier Inc., Kidney International. Supplement, 62, 1, pp. 192-8, Kidney International. Supplement, 62, 192-8
- Publication Year :
- 2002
-
Abstract
- Renoprotective effects of losartan in diabetic nephropathy: Interaction with ACE insertion/deletion genotype?BackgroundThe 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.MethodsFifty-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.ResultsAt 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).ConclusionOur 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.
- Subjects :
- Adult
Male
medicine.medical_specialty
Hypertension and Circulation
hypertension
Genotype
type 1 diabetes
Renal function
Angiotensin II receptor antagonist
Blood Pressure
Peptidyl-Dipeptidase A
Kidney
albuminuria
Losartan
Nephropathy
polymorphism
renoprotection
Diabetic nephropathy
Angiotensin Receptor Antagonists
Hypertensie en circulatie
SDG 3 - Good Health and Well-being
Double-Blind Method
Internal medicine
Diabetes mellitus
medicine
Humans
Diabetic Nephropathies
Prospective Studies
Antihypertensive Agents
Glycated Hemoglobin
business.industry
Sodium
Middle Aged
medicine.disease
Angiotensin II
Endocrinology
angiotensin II receptor antagonism
Nephrology
Albuminuria
Female
medicine.symptom
business
medicine.drug
Subjects
Details
- ISSN :
- 00852538 and 21571724
- Volume :
- 62
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Kidney international
- Accession number :
- edsair.doi.dedup.....27c94d7c15ccefecd2ae738d69eb5f15