Tomohito Gohda1, Yuji Nishizaki2, Maki Murakoshi3, Shuko Nojiri2, Naotake Yanagisawa2, Terumi Shibata3, Mami Yamashita4, Kanako Tanaka5, Yoshinori Yamashita6, Yusuke Suzuki7, Nozomu Kamei8. 1. Department of Nephrology, Juntendo University Faculty of Medicine, 2-1-1, Hongo, Bunkyo-ku, Tokyo 113-8421, Japan. Electronic address: goda@juntendo.ac.jp. 2. Juntendo University, Medical Technology Innovation Center, 2-1-1, Hongo, Bunkyo-ku, Tokyo 113-8421, Japan. 3. Department of Nephrology, Juntendo University Faculty of Medicine, 2-1-1, Hongo, Bunkyo-ku, Tokyo 113-8421, Japan. 4. Department of Endocrinology and Diabetology, National Hospital Organization, Kure Medical Center and Chugoku Cancer Center, 3-1, Aoyama-cho, Kure-city, Hiroshima 737-0023, Japan; Department of Endocrinology, Infectious Disease Control and Prevention, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3, Kasumi-cho, Minami-ku, Hiroshima 734-8551, Japan. 5. Department of Endocrinology and Diabetology, National Hospital Organization, Kure Medical Center and Chugoku Cancer Center, 3-1, Aoyama-cho, Kure-city, Hiroshima 737-0023, Japan. 6. Institute for Clinical Research, National Hospital Organization, Kure Medical Center and Chugoku Cancer Center, 3-1, Aoyama-cho, Kure-city, Hiroshima 737-0023, Japan. 7. Department of Nephrology, Juntendo University Faculty of Medicine, 2-1-1, Hongo, Bunkyo-ku, Tokyo 113-8421, Japan. Electronic address: yusuke@juntendo.ac.jp. 8. Department of Endocrinology and Diabetology, National Hospital Organization, Kure Medical Center and Chugoku Cancer Center, 3-1, Aoyama-cho, Kure-city, Hiroshima 737-0023, Japan; Department of Endocrinology and Metabolism, Hiroshima Red Cross Hospital and Atomic-bomb Survivors Hospital, 1-9-6, Senda-machi, Naka-ku, Hiroshima 730-8619, Japan.
Abstract
AIMS: A portion of patients with diabetes mellitus follow the progression of a non-albuminuria-based pathway; i.e., normoalbuminuric diabetic kidney disease (NA-DKD). However, the risk factors which determine NA-DKD are not yet fully understood. This cross-sectional study was therefore aimed to investigate the association between various biomarker levels and estimated glomerular filtration rate (eGFR) in patients with type 2 diabetes mellitus and normoalbuminuria (T2D-NA). METHODS: We measured cardiovascular disease (CVD) [serum osteoprotegerin (OPG), plasma brain natriuretic peptide (BNP), cardio-ankle vascular index (CAVI)], tubular damage [urinary L-type fatty acid binding protein (L-FABP)], and inflammatory [serum tumornecrosis factor (TNF) α and its receptors (TNFRs)] biomarkers in 314 patients with T2D-NA. RESULTS: The biomarkers of CVD and inflammation showed a significant negative correlation with eGFR. In a logistic multivariate model, none of the biomarkers, except TNFα and TNFRs, were associated with reduced renal function (eGFR < 60 mL/min/1.73 m2) after adjustment for possible biological and clinical covariates. However, the association observed in TNFα was lost after adjusting for TNFR and other covariates. CONCLUSIONS: In patients with T2D-NA, elevated levels of circulating TNFRs, but not of TNFα, were strongly associated with reduced renal function, independently of all relevant covariates.
AIMS: A portion of patients with diabetes mellitus follow the progression of a non-albuminuria-based pathway; i.e., normoalbuminuric diabetic kidney disease (NA-DKD). However, the risk factors which determine NA-DKD are not yet fully understood. This cross-sectional study was therefore aimed to investigate the association between various biomarker levels and estimated glomerular filtration rate (eGFR) in patients with type 2 diabetes mellitus and normoalbuminuria (T2D-NA). METHODS: We measured cardiovascular disease (CVD) [serum osteoprotegerin (OPG), plasma brain natriuretic peptide (BNP), cardio-ankle vascular index (CAVI)], tubular damage [urinary L-type fatty acid binding protein (L-FABP)], and inflammatory [serum tumornecrosis factor (TNF) α and its receptors (TNFRs)] biomarkers in 314 patients with T2D-NA. RESULTS: The biomarkers of CVD and inflammation showed a significant negative correlation with eGFR. In a logistic multivariate model, none of the biomarkers, except TNFα and TNFRs, were associated with reduced renal function (eGFR < 60 mL/min/1.73 m2) after adjustment for possible biological and clinical covariates. However, the association observed in TNFα was lost after adjusting for TNFR and other covariates. CONCLUSIONS: In patients with T2D-NA, elevated levels of circulating TNFRs, but not of TNFα, were strongly associated with reduced renal function, independently of all relevant covariates.
Authors: Simke W Waijer; Taha Sen; Clare Arnott; Bruce Neal; Jos G W Kosterink; Kenneth W Mahaffey; Chirag R Parikh; Dick de Zeeuw; Vlado Perkovic; Brendon L Neuen; Steven G Coca; Michael K Hansen; Ron T Gansevoort; Hiddo J L Heerspink Journal: Clin J Am Soc Nephrol Date: 2021-12-07 Impact factor: 8.237
Authors: Monika A Niewczas; Meda E Pavkov; Jan Skupien; Adam Smiles; Zaipul I Md Dom; Jonathan M Wilson; Jihwan Park; Viji Nair; Andrew Schlafly; Pierre-Jean Saulnier; Eiichiro Satake; Christopher A Simeone; Hetal Shah; Chengxiang Qiu; Helen C Looker; Paolo Fiorina; Carl F Ware; Jennifer K Sun; Alessandro Doria; Matthias Kretzler; Katalin Susztak; Kevin L Duffin; Robert G Nelson; Andrzej S Krolewski Journal: Nat Med Date: 2019-04-22 Impact factor: 53.440