PMID- 29522788
OWN - NLM
STAT- MEDLINE
DCOM- 20190212
LR  - 20190215
IS  - 1872-8227 (Electronic)
IS  - 0168-8227 (Linking)
VI  - 147
DP  - 2019 Jan
TI  - Urinary afamin levels are associated with the progression of diabetic 
      nephropathy.
PG  - 37-46
LID - S0168-8227(17)31788-6 [pii]
LID - 10.1016/j.diabres.2018.02.034 [doi]
AB  - AIMS: In this study, we applied quantitative proteomic analysis to identify 
      urinary proteins associated with diabetic nephropathy (DN). METHODS: 
      Two-dimensional image-converted analysis of liquid chromatography and mass 
      spectrometry detected the proteins differentially excreted between 
      normoalbuminuric and macroalbuminuric patients with type 2 diabetes mellitus 
      (T2DM) (n = 6 each). Urinary levels of excreted proteins were measured by 
      multiple reaction monitoring (MRM) analysis using an independent sample set 
      (n = 77). Urinary afamin levels were measured by ELISA in T2DM and DN patients 
      enrolled in this cohort study (n = 203). RESULTS: One-hundred-four proteins 
      displayed significant alterations in excretion. Nine of these candidates were 
      validated by MRM analysis. Among them, the levels of afamin, CD44 antigen, and 
      lysosome-associated membrane glycoprotein 2, which have not previously been 
      implicated in DN, were significantly associated with both the urinary albumin to 
      creatinine ratio (ACR) and eGFR. We further measured afamin levels in urine 
      collected from T2DM patients who did not yet have significant kidney disease 
      (ACR < 300 mg/g or eGFR change rate </= 3.3%/year). The urinary afamin to 
      creatinine ratio (Afa/Cre) was significantly higher in patients who progressed to 
      a more severe DN stage or had early renal decline than in patients who did not. 
      CONCLUSIONS: Afa/Cre was significantly increased in T2DM patients who 
      subsequently developed DN. Afa/Cre may be useful to predict patients with T2DM at 
      high risk of nephropathy before the development of macroalbuminuria or reduced 
      kidney function, although further validation studies in a larger population are 
      needed.
CI  - Copyright (c) 2018 Elsevier B.V. All rights reserved.
FAU - Kaburagi, Yasushi
AU  - Kaburagi Y
AD  - Department of Diabetic Complications, Diabetes Research Center, Research 
      Institute, National Center for Global Health and Medicine, Tokyo, Japan.
FAU - Takahashi, Eri
AU  - Takahashi E
AD  - Department of Diabetic Complications, Diabetes Research Center, Research 
      Institute, National Center for Global Health and Medicine, Tokyo, Japan.
FAU - Kajio, Hiroshi
AU  - Kajio H
AD  - Department of Diabetes, Endocrinology, and Metabolism, Center Hospital, National 
      Center for Global Health and Medicine, Tokyo, Japan.
FAU - Yamashita, Shigeo
AU  - Yamashita S
AD  - Division of Diabetes and Endocrinology, Department of Internal Medicine, Tokyo 
      Yamate Medical Center, Japan Community Health Care Organization, Tokyo, Japan.
FAU - Yamamoto-Honda, Ritsuko
AU  - Yamamoto-Honda R
AD  - Health Management Center and Department of Endocrinology and Metabolism, 
      Toranomon Hospital, Tokyo, Japan.
FAU - Shiga, Tomoko
AU  - Shiga T
AD  - Department of Complete Medical Checkup, Center Hospital, National Center for 
      Global Health and Medicine, Tokyo, Japan.
FAU - Okumura, Akinori
AU  - Okumura A
AD  - Department of Diabetic Complications, Diabetes Research Center, Research 
      Institute, National Center for Global Health and Medicine, Tokyo, Japan.
FAU - Goto, Atsushi
AU  - Goto A
AD  - Division of Epidemiology, Center for Public Health Sciences, National Cancer 
      Center, Tokyo, Japan.
FAU - Fukazawa, Yuka
AU  - Fukazawa Y
AD  - Department of Diabetes and Endocrinology, JR Tokyo General Hospital, Tokyo, 
      Japan.
FAU - Seki, Naoto
AU  - Seki N
AD  - Department of Clinical Research, National Hospital Organization Chiba-East 
      Hospital, Chiba, Japan.
FAU - Tobe, Kazuyuki
AU  - Tobe K
AD  - First Department of Internal Medicine, Graduate School of Medicine and 
      Pharmaceutical Sciences, University of Toyama, Toyama, Japan.
FAU - Matsumoto, Michihiro
AU  - Matsumoto M
AD  - Department of Molecular Metabolic Regulation, Diabetes Research Center, Research 
      Institute, National Center for Global Health and Medicine, Tokyo, Japan.
FAU - Noda, Mitsuhiko
AU  - Noda M
AD  - Department of Endocrinology and Diabetes, Saitama Medical University, Saitama, 
      Japan.
FAU - Unoki-Kubota, Hiroyuki
AU  - Unoki-Kubota H
AD  - Department of Diabetic Complications, Diabetes Research Center, Research 
      Institute, National Center for Global Health and Medicine, Tokyo, Japan. 
      Electronic address: hkubota@ri.ncgm.go.jp.
LA  - eng
PT  - Journal Article
DEP - 20180306
PL  - Ireland
TA  - Diabetes Res Clin Pract
JT  - Diabetes research and clinical practice
JID - 8508335
RN  - 0 (AFM protein, human)
RN  - 0 (Carrier Proteins)
RN  - 0 (Glycoproteins)
RN  - ZIF514RVZR (Serum Albumin, Human)
SB  - IM
MH  - Carrier Proteins/*urine
MH  - Cohort Studies
MH  - Diabetes Mellitus, Type 2/*diagnosis/pathology/urine
MH  - Diabetic Nephropathies/*diagnosis/pathology/urine
MH  - Disease Progression
MH  - Female
MH  - Glycoproteins/*urine
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Proteomics/*methods
MH  - Serum Albumin, Human/*urine
OTO - NOTNLM
OT  - 2DICAL
OT  - Afamin
OT  - Diabetic nephropathy
OT  - MRM
EDAT- 2018/03/10 06:00
MHDA- 2019/02/13 06:00
CRDT- 2018/03/10 06:00
PHST- 2017/11/10 00:00 [received]
PHST- 2018/01/17 00:00 [revised]
PHST- 2018/02/23 00:00 [accepted]
PHST- 2018/03/10 06:00 [pubmed]
PHST- 2019/02/13 06:00 [medline]
PHST- 2018/03/10 06:00 [entrez]
AID - S0168-8227(17)31788-6 [pii]
AID - 10.1016/j.diabres.2018.02.034 [doi]
PST - ppublish
SO  - Diabetes Res Clin Pract. 2019 Jan;147:37-46. doi: 10.1016/j.diabres.2018.02.034. 
      Epub 2018 Mar 6.