TY - JOUR
T1 - Usefulness of urinary tubule injury markers for predicting progression of renal dysfunction in patients with type 2 diabetes and albuminuria
T2 - The Fukuoka Diabetes Registry
AU - Ide, Hitoshi
AU - Iwase, Masanori
AU - Ohkuma, Toshiaki
AU - Fujii, Hiroki
AU - Komorita, Yuji
AU - Oku, Yutaro
AU - Higashi, Taiki
AU - Yoshinari, Masahito
AU - Nakamura, Udai
AU - Kitazono, Takanari
N1 - Funding Information:
The authors thank Drs. Dongchon Kang, Shinako Ogata-Kaizu, Yoichiro Hirakawa, Tamaki Jodai-Kitamura, Ai Murao-Kimura (Kyushu University), Satoshi Sasaki (University of Tokyo), Nobuhiro Sasaki (Fukuoka Red Cross Hospital), Kiyohide Nunoi, Yuichi Sato (St. Mary's Hospital), Daisuke Gotoh (Kyushu Central Hospital), Sakae Nohara (Fukuoka Higashi Medical Center), Masae Minami (Clinic Minami Masae), Miya Wada (Wada Miya Naika Clinic), Yoshifumi Yokomizo (Yokomizo Naika Clinic), Masanori Kikuchi, Yohei Kikuchi (Kikuchi Naika Clinic), Riku Nomiyama (Suzuki Naika Clinic), Shin Nakamura (Nakamura Naika Clinic), Kenji Tashiro (Oshima Eye Hospital), Mototaka Yoshinari (Yoshinari Naika Clinic), Kojiro Ichikawa (Fukutsu Naika Clinic), and Yutaka Kiyohara (Hisayama Research Institute for Lifestyle Diseases). The authors also thank Chiho Ohba and Yoko Nishioka as the clinical research coordinators and Tomoko Matake (Hisayama Research Institute for Lifestyle Diseases). This work was supported by The Japan Society for the Promotion of Science KAKENHI from the Ministry of Education, Culture, Sports, Science and Technology of Japan (23249037 and 23659353 to M.I. 16K00861 to H.F. 19K24229 and 21K11700 to T.O. and 20K19663 to Y.K.), Junior Scientist Development Grant of the Japan Diabetes Society (to Y.K. and T.O.), a grant from the Clinical Research Promotion Foundation (to Y.K.), and a grant for young researchers from the Japan Association for Diabetes Education and Care (to T.O.). The Kyushu University Institutional Review Board (approval number 290). All participants provided their written informed consent to take part. The authors declare that no potential conflicts of interest relevant to this article exist. H.I. and M.I. was responsible for the study concept and design, and drafted the manuscript. M.I. H.I, H.F. and Y.K. conducted the analysis. T.O. Y.O. T.H. M.Y. U.N. and T.K. interpreted the data and contributed to the discussion. All authors participated in critically revising the manuscript and approved the final version. M.I. is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for integrity of the data and accuracy of the data analysis.
Funding Information:
This work was supported by The Japan Society for the Promotion of Science KAKENHI from the Ministry of Education, Culture, Sports, Science and Technology of Japan ( 23249037 and 23659353 to M.I., 16K00861 to H.F., 19K24229 and 21K11700 to T.O., and 20K19663 to Y.K.), Junior Scientist Development Grant of the Japan Diabetes Society (to Y.K. and T.O.), a grant from the Clinical Research Promotion Foundation (to Y.K.), and a grant for young researchers from the Japan Association for Diabetes Education and Care (to T.O.).
Publisher Copyright:
© 2022 Elsevier B.V.
PY - 2022/4
Y1 - 2022/4
N2 - Aims: We prospectively investigated the association of urinary tubule injury markers with estimated glomerular filtration rate (eGFR) decline in Japanese patients with type 2 diabetes. Methods: Urinary kidney injury molecule 1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), liver-type fatty-acid-binding protein (L-FABP), and urinary albumin-to creatinine ratio (UACR) were measured in 2,685 participants with type 2 diabetes. Renal outcomes were ≥ 30% decline in eGFR from the baseline and annual eGFR decline for 5 years. Results: In normoalbuminuric participants, no tubular markers were associated with ≥ 30% decline in eGFR or annual eGFR changes. In those with UACR ≥ 30 mg/gCr, hazard ratios for ≥ 30% eGFR decline were 1.37 (95% confident interval (CI) 1.07–1.75) for urinary KIM-1 (>1.5 µg/gCr), 1.46 (95% CI 1.13–1.66) for urinary NGAL (>16.4 µg/gCr), and 1.26 (95% CI 0.94–1.66) for urinary L-FABP (>12.5 µg/gCr), 2.61 (95% CI 1.64–4.17) for the combination of 3 tubular markers above the cutoff after multivariable adjustments including UACR and eGFR. Conclusions: The current study demonstrated that urinary tubule injury markers and their combination were significant predictors for the future eGFR decline in those with type 2 diabetes and albuminuria independently of UACR and eGFR. Urinary tubular markers may be useful to identify high-risk patients with albuminuria.
AB - Aims: We prospectively investigated the association of urinary tubule injury markers with estimated glomerular filtration rate (eGFR) decline in Japanese patients with type 2 diabetes. Methods: Urinary kidney injury molecule 1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), liver-type fatty-acid-binding protein (L-FABP), and urinary albumin-to creatinine ratio (UACR) were measured in 2,685 participants with type 2 diabetes. Renal outcomes were ≥ 30% decline in eGFR from the baseline and annual eGFR decline for 5 years. Results: In normoalbuminuric participants, no tubular markers were associated with ≥ 30% decline in eGFR or annual eGFR changes. In those with UACR ≥ 30 mg/gCr, hazard ratios for ≥ 30% eGFR decline were 1.37 (95% confident interval (CI) 1.07–1.75) for urinary KIM-1 (>1.5 µg/gCr), 1.46 (95% CI 1.13–1.66) for urinary NGAL (>16.4 µg/gCr), and 1.26 (95% CI 0.94–1.66) for urinary L-FABP (>12.5 µg/gCr), 2.61 (95% CI 1.64–4.17) for the combination of 3 tubular markers above the cutoff after multivariable adjustments including UACR and eGFR. Conclusions: The current study demonstrated that urinary tubule injury markers and their combination were significant predictors for the future eGFR decline in those with type 2 diabetes and albuminuria independently of UACR and eGFR. Urinary tubular markers may be useful to identify high-risk patients with albuminuria.
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U2 - 10.1016/j.diabres.2022.109840
DO - 10.1016/j.diabres.2022.109840
M3 - Article
C2 - 35331809
AN - SCOPUS:85126887281
SN - 0168-8227
VL - 186
JO - Diabetes Research and Clinical Practice
JF - Diabetes Research and Clinical Practice
M1 - 109840
ER -
