Diabetics' ESRD Linked to Uremic Solutes

In a study, plasma metabolites were elevated years before development of ESRD with diabetes.
In a study, plasma metabolites were elevated years before development of ESRD with diabetes.

A recent study showed baseline plasma levels of 16 particular metabolites to be higher in patients with type 2 diabetes and end-stage renal disease (ESRD) than in type 2 diabetics who did not develop ESRD.

The nested case-control study compared 40 patients from the Joslin Kidney Study cohort who progressed to ESRD and 40 Joslin participants who remained alive without progressing to ESRD during 8-12 years of follow-up. Controls had slightly higher estimated glomerular filtration rates (eGFR) and lower levels of urinary albumin excretion than did cases. Mass spectrometry-based global metabolomic profiling was used to obtain baseline measurements of plasma metabolites.

Of 78 metabolites previously reported to be elevated in ESRD (uremic solutes), 16 were already elevated in the baseline plasma of the ESRD group years before ESRD developed, noted Monika A. Niewczas, MD, PhD, of Harvard Medical School in Boston, and colleagues in Kidney International. Although uremic solute molecules are known to accumulate in plasma in the presence of kidney failure, kidney function was normal in the vast majority of the study subjects at the time of sample collection.

Dr. Niewczas and her colleagues also found that essential amino acids and their derivatives were significantly depleted in persons with ESRD, 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 hemoglobin A1c. Quantitative measurements confirmed uremic solute differences.

“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 [type 2 diabetes],” the study authors concluded.

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