Journal Article

Uremic solutes and risk of end-stage renal disease in type 2 diabetes: metabolomic study

Niewczas, Monika A., Warram, James H., Karoly, Edward D., Bonventre, Joseph V., Mathew, Anna V., Byun, Jaeman, Sirich, Tammy L., Skupien, Jan, Meyer, Timothy W., Huang, Xiaoping, Pennathur, Subramaniam, Walker, Walker, Kensicki, Elizabeth M., Mohney, Robert P., Berry, Gerard T., Krolewski, Andrzej S., Smiles, Adam

2014

Overview

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.

• Publisher: Elsevier Inc,Elsevier Limited
• Subject: Aged / Amino Acids, Essential - blood / Biomarkers - blood / Boston / Case-Control Studies / Diabetes Mellitus, Type 2 - blood / Diabetes Mellitus, Type 2 - complications / Diabetes Mellitus, Type 2 - diagnosis / Diabetic Nephropathies - blood / Diabetic Nephropathies - diagnosis / Diabetic Nephropathies - etiology / Diabetic Nephropathies - physiopathology / diabetic nephropathy / Disease Progression / end-stage renal disease / Female / Glomerular Filtration Rate / Glycated Hemoglobin A - analysis / Humans / Kidney - physiopathology / Kidney Failure, Chronic - blood / Kidney Failure, Chronic - diagnosis / Kidney Failure, Chronic - etiology / Kidney Failure, Chronic - physiopathology / Male / Mass Spectrometry / metabolomic study / Metabolomics - methods / Middle Aged / Time Factors / Uremia - blood / Uremia - diagnosis / Uremia - etiology / Uremia - physiopathology / uremic toxins