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

J Renin Angiotensin Aldosterone Syst. 2009 Mar;10(1):41-50. doi: 10.1177/1470320309102326.

Abstract

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 m(2) vs. 428.4+/-74.8 ml/min/1.73 m(2), 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.

Publication types

  • Clinical Trial

MeSH terms

  • Angiotensin-Converting Enzyme Inhibitors / pharmacology*
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use
  • Captopril / pharmacology
  • Captopril / therapeutic use
  • Diabetes Mellitus, Type 2 / drug therapy
  • Diabetes Mellitus, Type 2 / enzymology*
  • Diabetes Mellitus, Type 2 / genetics
  • Diabetes Mellitus, Type 2 / physiopathology*
  • Female
  • Genotype
  • Hemodynamics / drug effects*
  • Humans
  • Kidney / drug effects
  • Kidney / physiopathology*
  • Male
  • Middle Aged
  • Peptidyl-Dipeptidase A / metabolism
  • Polymorphism, Genetic*
  • Radioisotope Renography
  • Receptor, Angiotensin, Type 1 / genetics
  • Renin-Angiotensin System / drug effects
  • Renin-Angiotensin System / genetics*
  • Technetium Tc 99m Mertiatide

Substances

  • Angiotensin-Converting Enzyme Inhibitors
  • Receptor, Angiotensin, Type 1
  • Technetium Tc 99m Mertiatide
  • Captopril
  • Peptidyl-Dipeptidase A