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Impact of renin-angiotensin system polymorphisms on renal haemodynamic responsiveness to acute angiotensin-converting enzyme inhibition in type 2 diabetes mellitus

Department of Nuclear Medicine, Faculty of Medicine, Hacettepe University, Ankara, Turkey

Selcuk Dagdelen

Division of Endocrinology and Metabolism, Department of Internal Medicine, Faculty of Medicine, Hacettepe University, Ankara, Turkey

Mehmet Alikasifoglu

Division of Medical Genetics, Department of Paediatrics, Faculty of Medicine, Hacettepe University, Ankara, Turkey

Tomris Erbas

Division of Endocrinology and Metabolism, Department of Internal Medicine, Faculty of Medicine, Hacettepe University, Ankara, Turkey,

Mutlu Hayran

Epidemiologist, Research Office, Faculty of Medicine, Hacettepe University, Ankara, Turkey

Belkis Erbas

Department of Nuclear Medicine, Faculty of Medicine, Hacettepe University, Ankara, Turkey, berbas{at}hacettepe.edu.tr

Introduction.The aim of this study was to document the impact of renin-angiotensin system (RAS) polymorphisms on renal haemodynamics and renal hormones in type 2 diabetes mellitus. Materials and methods. Fifty-nine adult patients were studied. Renal haemodynamics were evaluated using 99mTc-MAG3 clearance (MAG3 _Cle) using Bubeck's method and captopril renogram. RAS hormones and angiotensin-converting enzyme (ACE) levels were measured before and after captopril.ACE, angiotensin II type 1 receptor and angiotensinogen gene polymorphisms were analysed. Results. Post-captopril MAG3_Cle values were significantly lower in patients with microalbuminuria compared to nonproteinuric patients. Statistically significant negative correlation was found between clearance percentage change values and HbA_1c levels (r: —0.42, p=0.009). MAG3_Cle was relatively lower following captopril administration in DD patients, while a relative increment was observed in I allele carriers (p=0.02).TheAC-CC group had significantly higher mean post-captopril clearance value compared to the AA genotype (480.9±56.1 ml/min/1.73 m² vs. 428.4±74.8 ml/min/1.73 m², p=0.022). Conclusions. Our data indicate that the heterogeneity of patients' response to ACE inhibition is, at least partly, genetically determined, and the genetic polymorphisms in RAS might predict the acute responsiveness to ACE inhibitors.

Key Words: captopril renogram • diabetes mellitus • polymorphisms • renin-angiotensin-aldosterone system • 99mTc-MAG3 clearance

Journal of Renin-Angiotensin-Aldosterone System, Vol. 10, No. 1, 41-50 (2009)
DOI: 10.1177/1470320309102326


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