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Kidney Week

Abstract: TH-PO860

Prevalence of Angiotensin Type II Receptor (ATTR) Gene Polymorphism in Patients with Type 2 Diabetes with Nephropathy in India and Its Effect on the Antiproteinuric Efficacy of ACE Inhibitor Therapy

Session Information

Category: Diabetic Kidney Disease

  • 601 Diabetic Kidney Disease: Basic

Authors

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

Involvement of renin angiotensin system has been implicated in the etiopathogenesis of diabetic nephropathy (DN). Angiotensin converting enzyme inhibitor (ACEI) drugs are commonly prescribed for reno-protection in patients with DN; however, response to ACEI therapy is not uniform in all patients. Aim of this study was to investigate the prevalence of ATTR A1166C gene polymorphism in North Indian patients with DN and its role on the anti-proteinuric efficacy of ACEI therapy.

Methods

In the present study, 270 patients having Type 2 diabetes mellitus for ≥ 5 years with nephropathy aged between 30 to 65 (mean 52.23±6.01) years were enrolled and treated with ACE inhibitor (ramipril) and subsequently followed at regular intervals for 2 years for assessment of urinary albumin/creatinine ratio (ACR) and estimated GFR. Patients were classified as responders if they had a decrease in urinary ACR by ≥50% at the end of 2 years follow up. Genotyping of ATTR A1166C gene polymorphism was performed by primer specific polymerase chain reaction and RFLP technique.

Results

Out of 270 patients, 231 completed the follow up of 24 months. 151(65%) patients with DN were found to be responders following ACE inhibitor therapy. Median urinary ACR values declined from the baseline value of 109.9 mg/g creatinine to 47.3 mg/g creatinine (p<0.001). At the end of 24 months, increase in serum creatinine above the baseline (0.28±0.3 v/s 0.61±0.2) (p=0.269) and decline in eGFR-MDRD (8.40±16.0 v/s 12.84±15.0 mL/min/1.73m2) (p=0.058) between responders and non-responders respectively were not significantly different. All subjects displayed wild type allele (A) of this polymorphism and showed no genotypic variation; hence polymorphism of ATTR A1166C gene does not appear to have any role on the variability of anti-proteinuric effect following ACEI therapy.

Conclusion

In patients with Type 2 diabetes mellitus with nephropathy, approximately two third patients were found to have significant anti-proteinuric response following ACEI therapy. ATTR A1166C gene polymorphism is extremely rare in Northern India and does not appear to play any role in influencing the variation in anti-proteinuric effect following ACEI therapy.

Funding

  • Government Support - Non-U.S.