医学
终末期肾病
内科学
糖尿病
代谢组学
肾脏疾病
内分泌学
2型糖尿病
泌尿系统
肾功能
胃肠病学
疾病
化学
色谱法
作者
Monika A. Niewczas,Tammy L. Sirich,Anna V. Mathew,Jan Skupień,Robert P. Mohney,James H. Warram,Adam M. Smiles,Xiaoping Huang,Walker Walker,Jaeman Byun,Edward D. Karoly,Elizabeth Kensicki,Gerard T. Berry,Joseph V. Bonventre,Subramaniam Pennathur,Timothy W. Meyer,Andrzej S. Królewski
摘要
Here we studied plasma metabolomic profiles as determinants of progression to end-stage renal disease (ESRD) in patients with type 2 diabetes (T2D). This nested case-control study evaluated 40 cases who progressed to ESRD during 8-12 years of follow-up and 40 controls who remained alive without ESRD from the Joslin Kidney Study cohort. Controls were matched with cases for baseline clinical characteristics, although controls had slightly higher eGFR and lower levels of urinary albumin excretion than cases. Plasma metabolites at baseline were measured by mass spectrometry-based global metabolomic profiling. Of the named metabolites in the library, 262 were detected in at least 80% of the study patients. The metabolomic platform recognized 78 metabolites previously reported to be elevated in ESRD (uremic solutes). Sixteen were already elevated in the baseline plasma of our cases years before ESRD developed. Other uremic solutes were either not different or not commonly detectable. Essential amino acids and their derivatives were significantly depleted in the cases, whereas certain amino acid-derived acylcarnitines were increased. All findings remained statistically significant after adjustment for differences between study groups in albumin excretion rate, eGFR, or HbA1c. Uremic solute differences were confirmed by quantitative measurements. Thus, abnormal plasma concentrations of putative uremic solutes and essential amino acids either contribute to progression to ESRD or are a manifestation of an early stage(s) of the disease process that leads to ESRD in T2D.
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