Junya Teranishi1, Ryohei Yamamoto1, Yasuyuki Nagasawa1, Tatsuya Shoji2, Hirotsugu Iwatani1, Noriyuki Okada3, Toshiki Moriyama4, Atsushi Yamauchi5, Yoshiharu Tsubakihara6, Enyu Imai1, Hiromi Rakugi1, Yoshitaka Isaka7. 1. Department of Geriatric Medicine and Nephrology, Osaka University Graduate School of Medicine, Japan. 2. Department of Kidney Disease and Hypertension, Osaka General Medical Center, Japan. 3. Clinical Laboratory Medicine, Osaka General Medical Center, Japan. 4. Health Care Center, Osaka University, Japan. 5. Division of Nephrology, Department of Internal Medicine, Osaka Rosai Hospital, Japan. 6. Department of Kidney Disease and Hypertension, Osaka General Medical Center, Japan Department of Comprehensive Kidney Disease Research, Osaka University Graduate School of Medicine, Japan. 7. Department of Geriatric Medicine and Nephrology, Osaka University Graduate School of Medicine, Japan isaka@kid.med.osaka-u.ac.jp.
Abstract
INTRODUCTION: Little is known about genetic predictors that modify the renoprotective effect of renin-angiotensin system (RAS) blockade in IgA nephropathy (IgAN). MATERIALS AND METHODS: The present multicenter retrospective observational study examined effect modification between RAS blockade and three RAS-related gene polymorphisms in 237 IgAN patients, including ACE I/D (rs1799752), AT1R A1166C (rs5186) and AGT T704C (rs699). RESULTS: During 9.9 ± 4.2 years of observation, 63 patients progressed to a 50% increase in serum creatinine level. Only ACE I/D predicted the outcome (ACE DD vs ID/II, hazard ratio 1.86 (95% confidence interval 1.03, 3.33)) and modified the renoprotective effect of RAS blockade (p for interaction between ACE DD and RAS blockade = 0.087). RAS blockade suppressed progression in ACE DD patients but not in ID/II patients (ACE ID/II with RAS blockade as a reference; ID/II without RAS blockade 1.45 (0.72, 2.92); DD without RAS blockade 3.06 (1.39, 6.73); DD with RAS blockade 1.51 (0.54, 4.19)), which was ascertained in a model with the outcome of slope of estimated glomerular filtration rate (p = 0.045 for interaction). CONCLUSION: ACE I/D predicted the IgAN progression and the renoprotective effect of RAS blockade in IgAN patients whereas neither AT1R A1166C nor AGT T704C did.
INTRODUCTION: Little is known about genetic predictors that modify the renoprotective effect of renin-angiotensin system (RAS) blockade in IgA nephropathy (IgAN). MATERIALS AND METHODS: The present multicenter retrospective observational study examined effect modification between RAS blockade and three RAS-related gene polymorphisms in 237 IgANpatients, including ACE I/D (rs1799752), AT1R A1166C (rs5186) and AGT T704C (rs699). RESULTS: During 9.9 ± 4.2 years of observation, 63 patients progressed to a 50% increase in serum creatinine level. Only ACE I/D predicted the outcome (ACE DD vs ID/II, hazard ratio 1.86 (95% confidence interval 1.03, 3.33)) and modified the renoprotective effect of RAS blockade (p for interaction between ACE DD and RAS blockade = 0.087). RAS blockade suppressed progression in ACE DD patients but not in ID/II patients (ACE ID/II with RAS blockade as a reference; ID/II without RAS blockade 1.45 (0.72, 2.92); DD without RAS blockade 3.06 (1.39, 6.73); DD with RAS blockade 1.51 (0.54, 4.19)), which was ascertained in a model with the outcome of slope of estimated glomerular filtration rate (p = 0.045 for interaction). CONCLUSION:ACE I/D predicted the IgAN progression and the renoprotective effect of RAS blockade in IgANpatients whereas neither AT1R A1166C nor AGT T704C did.