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TOPLINE:

A prospective study showed that serum levels of eleven acylcarnitines were associated with the rate of decline in estimated glomerular filtration rate (eGFR) among patients with type 2 diabetes (T2D). Furthermore, combining six of these molecules into a score improved clinical risk prediction models for kidney function decline.

METHODOLOGY:

• Although several metabolites have been found to affect the risk for kidney function decline in T2D, the role of circulating acylcarnitines — whose accumulation is considered a potential mechanism in kidney disease — has not been fully explored.
• Researchers conducted a prospective study to examine the association between baseline levels of 40 serum acylcarnitines and the decline in eGFR (mL/min/1.73 m²) in patients with T2D.
• They investigated two cohorts of patients with T2D: a discovery cohort of 575 patients (mean age, 60.9 years; 47.8% female; median follow-up duration, 9 years) from the Gargano Mortality Study, and a validation set of 252 patients (mean age, 57.8 years; 33.7% female; median follow-up duration, 10 years) from the Joslin Kidney Study (JKS).
• Serum levels of acylcarnitines (14 short-chain, 11 medium-chain, and 15 long-chain acylcarnitines) at baseline were measured using targeted metabolomics.
• Significant associations were validated internally using repeated threefold cross-validation and externally in the JKS cohort; the study also examined whether the identified acylcarnitines improved prediction of kidney function loss provided by established clinical models.

TAKEAWAY:

• Serum levels of 11 of the 40 measured acylcarnitines were independently associated with accelerated decline in eGFR in patients with T2D (beta estimates ranging from -0.30 to 0.26; P = 9.4E-8 to 1.0E-3); all 11 metabolites were internally validated. Hydroxyvalerylcarnitine, propenoylcarnitine, and tiglylcarnitine (all short-chain acylcarnitines) showed the strongest associations, and hexenoylcarnitine and dodecanedioylcarnitine were inversely associated with eGFR decline.
• Of the four acylcarnitines available for external validation in the JKS cohort, tiglylcarnitine and methylglutarylcarnitine were validated as predictors of eGFR decline (beta, -0.38; P = 2.0E-2 and beta, -0.50; P = 2.0E-3, respectively).
• A multimarker score comprising six acylcarnitines (methylglutarylcarnitine, hydroxyvalerylcarnitine, hexenoylcarnitine, decadienylcarnitine, dodecanedioylcarnitine, and tetradecadienylcarnitine) improved the performance of established clinical models in identifying individuals at a higher risk for rapid eGFR decline.

IN PRACTICE:

“We identified several serum acylcarnitines related to the decline of kidney function in patients with type 2 diabetes and suggest that they can be used to improve our ability to predict individuals most at risk,” the authors of the study wrote.

SOURCE:

The study was led by Vincenzo Trischitta, Fondazione Casa Sollievo della Sofferenza IRCCS, San Giovanni Rotondo, Italy. It was published online in BMJ Open Diabetes Research & Care.

LIMITATIONS:

External validation was only partial because many metabolites associated with the discovery sample were not available in the JKS dataset. The predictive performance of the six-metabolite score could not be validated externally. Additionally, the lack of dietary data prevented the assessment of the effects of diet on acylcarnitine levels and kidney function decline.

DISCLOSURES:

The study received financial support from the Ministero dell’Istruzione dell’Università, Ministero dell’Università, Ministero della Salute, and other sources. The authors declared having no competing interests.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.