Albuminuria Is More Closely Associated with Vascular Endothelial Function than eGFR in Type 2 Diabetes with Diabetic Kidney Disease

Abstract

Diabetic kidney disease (DKD), defined by decreased estimated glomerular filtration rate (eGFR) and/or existence of albuminuria, is an important issue for the prevention of cardiovascular disease (CVD) as well as end-stage renal disease. Recently, attention has been focused on the discordance between albuminuria and decreased eGFR in DKD in various clinical situations. However, clinical implication of albuminuria and/or eGFR on subclinical atherosclerosis does not fully remain clear as yet. The present study aims to investigate the association of albuminuria (ACR, mg/gCre) or decreased eGFR (mL/min/1.73m2) with endothelial dysfunction as an early surrogate marker of CVD in type 2 diabetic patients (T2D) with DKD. Six-hundred thirty-three patients (male, 363; median age 64 years, duration 10 years, HbA1c 8.4%) were enrolled. Flow-mediated dilatation (FMD, %) of brachial artery was measured by novel ultrasound equipment (UNEX EF®, Nagoya). All subjects were distributed in each stage of ACR or eGFR as follows; ACR, 425 (67.1%) subjects in A1 stage (<30), 101 (16.0%) in A2 (30-300), 107 (16.9%) in A3(>300); eGFR, 392 (61.9%) subjects in G1/2 stage (>60), 118 (18.6%) in G3a (45-60), 63 (10.0%) in G3b (30-45), 60 (9.5%) in G4/5 (<30). FMD was found to be significant lower in order of advanced stage of albuminuria or eGFR, respectively; 7.1±4.3 (A1), 6.3±3.5 (A2), 5.4±4.0 (A3), p =0.001; 7.3±4.2 (G1/2), 5.5±3.0 (G3a), 6.7±4.7 (G3b), 5.0±4.3 (G4/5), p <0.001. In multivariate analyses, only log-transformed ACR (β= -0.136, p=0.005) contributed to FMD independently even after adjustment for known classical risk factors such as age, BMI, HbA1c, and LDL-c, but eGFR did not. In conclusion, albuminuria is stronger independent determinant to endothelial function than eGFR in T2D patients with DKD. Our finding suggest that albuminuria may be more important than eGFR as a risk factor and/or potential therapeutic target for CVD in these high risk population. Disclosure Y. Kakutani: Speaker's Bureau; Self; Astellas Pharma US, Inc., Novo Nordisk Inc., Novartis Pharma K.K., Takeda Pharmaceuticals U.S.A., Inc. M. Emoto: Speaker's Bureau; Self; Eli Lilly and Company, Boehringer Ingelheim Pharmaceuticals, Inc., Sumitomo Dainippon Pharma Co., Ltd.. Research Support; Self; Astellas Pharma Inc, Ono Pharmaceutical Co., Ltd., Kissei Pharmaceutical Co., Ltd., Kowa Pharmaceutical Company Ltd., Taisho Toyama Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Corporation. Y. Yamazaki: None. K. Motoyama: None. T. Morioka: Consultant; Self; Ono Pharmaceutical Co., Ltd.. Research Support; Self; Novartis Pharma K.K., MSD K.K., Eli Lilly and Company, Sanofi K.K., Mitsubishi Tanabe Pharma Corporation. Speaker's Bureau; Self; Takeda Pharmaceuticals U.S.A., Inc., Novo Nordisk Inc., Kowa Pharmaceuticals America, Inc., Astellas Pharma US, Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Sumitomo Dainippon Pharma Co., Ltd. K. Mori: Speaker's Bureau; Self; Boehringer Ingelheim GmbH, Eli Lilly and Company, Mitsubishi Tanabe Pharma Corporation, MSD K.K., Sanofi, AstraZeneca, Daiichi Sankyo Company, Limited. S. Fukumoto: Speaker's Bureau; Self; Astellas Pharma US, Inc.. Research Support; Self; Chugai Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Corporation. Speaker's Bureau; Self; Novo Nordisk Inc., Sanofi K.K.. Research Support; Self; Takeda Pharmaceuticals U.S.A., Inc., Taisho Toyama Pharmaceutical Co., Ltd.. A. Shioi: None. T. Shoji: Speaker's Bureau; Self; Astellas Pharma Inc, Bayer Yakuhin Ltd. Research Support; Self; Bayer Yakuhin Ltd. Speaker's Bureau; Self; Kowa Pharamaceutical Co Ltd, Daiichi Sankyo Company, Limited, MSD K.K., Chugai Pharmaceutical Co., Ltd.. Research Support; Self; Chugai Pharmaceutical Co., Ltd.. Speaker's Bureau; Self; Kyowa Hakko Kirin Co., Ltd., Kissei Pharmaceutical Co., Ltd.. M. Inaba: None.