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Abstract: FR-PO661

Effect of Angiotensin Converting Enzyme (ACE) and Angiotensinogen (AGT) Gene Polymorphisms on the Anti-Proteinuric Efficacy of ACE Inhibitor Therapy in Patients with Type 2 Diabetes with Nephropathy

Session Information

Category: Diabetes

  • 502 Diabetes Mellitus and Obesity: Clinical

Authors

  • Kalra, Om Parkash, Pt. B.D. Sharma University of Health Sciences, Rohtak, Haryana, India
  • Aggarwal, Neerja, University College of Medical Sciences, Delhi, Delhi, India
  • Kare, Pawan Kumar, University College of Medical Sciences, Delhi, Delhi, India
  • Varshney, Parul, University College of Medical Sciences, Delhi, Delhi, India
  • Yadav, Anil Kumar, GTB Hospital and University College of Medical Sciences, Delhi, Delhi, India
  • Raizada, Alpana, University College of Medical Sciences, Delhi, Delhi, India
  • Tripathi, Ashok Kumar, University College of Medical Sciences, Delhi, Delhi, India
  • Banerjee, Basu Dev, University College of Medical Sciences and GTB Hospital, Delhi, Delhi, India
  • S, Madhu V, University College of Medical Sciences, Delhi, Delhi, India
Background

Diabetic nephropathy (DN) is the leading cause of chronic kidney disease worldwide and affects approximately 20-30% of diabetic patients. ACE inhibitor drugs are commonly prescribed for reno-protection; however, anti-proteinuric response is not uniformly observed in all patients. The aim of this study was to evaluate the role of genetic variants of ACE and AGT genes on the anti-proteinuric efficacy of ACE inhibitor therapy in patients with DN.

Methods

In the present study, 270 patients with Type 2 diabetes mellitus with nephropathy aged between 30 to 65 years and a duration of diabetes ≥5 years were enrolled and treated with ACE inhibitor (ramipril) and followed at regular intervals for 6 months for assessment of urinary albumin/creatinine ratio (ACR) and eGFR (MDRD). Patients were classified as responders when they had a decrease in urinary ACR ≥30% at the end of 6 month follow up. Genotyping of ACE I/D and AGT M235T polymorphisms were performed by using primer specific polymerase chain reaction and PCR-RFLP technique, respectively.

Results

An overall significant reduction in ACR 36.2% was observed in the whole group at the end of 6 months; however, macro-albuminuric patients (55%) showed better response to therapy as compared to micro-albuminuric patients (45%). Overall, 130 (48%) of patients with DN were found to be responders to ACEI. The frequency of ACE genotype II, ID and DD was found to be 31%, 53% and 16% respectively. The frequency of AGT genotype MM, MT and TT was found to be 25%, 53% and 22% respecively. A reduction in urinary ACR was found to be independent of genotypes of ACE I/D and AGT M235T polymorphisms although macro-albuminuric patients having TT genotype showed higher response (72%) although it was statistically not significant. eGFR decreased from the base line value of 73.65±24.71 ml per minute per 1.73 m2 to 68.90±24.44 ml per minute per 1.73 m2 at the end of 6 months (p<0.081).

Conclusion

ACE inhibitor therapy reduced urinary ACR by ≥ 30% in 48% of patients with diabetic nephropathy and macroalbuminuric patients exhibited better response. The anti-proteinuric response was found to be independent of ACE I/D and AGT M235T polymorphisms.

Funding

  • Government Support - Non-U.S.