Changes in lipid profiles of individuals with gout and hyperuricemia (HUA) lead to substantial effects on lipid metabolism, according to recent findings, and the most pronounced disruption in glycerophospholipids—in those aged 40 and below for both HUA and gout—can be rectified with urate-lowering treatment (ULT).¹

These findings resulted from a new study conducted to expand upon lipidomic research by using larger sample sizes and aiming at individuals with HUA and gout, seeking to assess early and late-onset and the impacts of ULT. The potential for ULT for non-gout conditions has been seen in prior research as well.²

This new research was led by Aleš Kvasnička, from the University Hospital Olomouc’s Laboratory for Inherited Metabolic Disorders and Palacký University Olomouc in the Czech Republic.

“Our study aimed to evaluate the differences between the plasma lipidome profile of patients with asymptomatic hyperuricemia and gout versus normouricemic controls,” Kvasnička and colleagues wrote. “Furthermore, we aim to characterize the changes in the lipidome between early and late asymptomatic hyperuricemia and gout (age ≤ vs. age > 40 years) and deepen our understanding of the molecular pathogenesis of gout, including the effect of ULT on plasma lipidome profiles.”

Background and Findings

Any modern predictions of the progression from HUA to gout are known to be impossible, and understanding the downstream results of ULT remains a difficult process to implement.

Kvasnička and colleagues sought to evaluate variations in plasma lipidome among those with asymptomatic HUA detected at or below 40 years, those who were over 40 years, people with goat and onset at or below 40 years, subjects over 40 years, and normouricemic healthy controls.

The investigators gathered plasma samples which had been provided from 94 asymptomatic subjects with HUA. They noted there were 77% with HUA ≤ 40 as well as 196 individuals with gout (59% with gout ≤ 40), and 53 healthy control participants.

The research team used a targeted lipidomic analysis to semi-quantify 608 lipids in the samples of plasma assessed in their work. Advanced visualizations as well as statistical analyses which were univariate and multivariate were implemented for the team’s assessment of their data.

Both subjects with HUA and those with gout ended up showing substantial shifts in their lipid profiles as the findings came out. These shifts noted by the research team were marked by a major rise in phosphatidylethanolamines and a notable diminishing of lysophosphatidylcholine plasmalogens/plasmanyls among the subjects’ samples.

Additionally, the investigators noted that the changes were more pronounced among those with HUA ≤ 40 and Gout ≤ 40 who were shown not to be receiving ULT. Through the team’s multivariate assessment of the data, it was shown to be possible for them to distinguish the HUA ≤ 40 and Gout ≤ 40 arms from the healthy control arm with a rate of accuracy exceeding 95%.

“Gout and hyperuricemia are associated with alterations in plasma lipid profiles (namely increased glycerophospholipids and TG and decreased LPC, LPC O-, and LPC P-),” they wrote. “These changes are significantly more pronounced in early-onset or early disease detection. This change cannot be explained based on the genetics of ABCG2 or by common features of metabolic syndrome, such as BMI.”

Further discussion on the use of a personalized approach for clinicians helping to manage HUA in clinical practice is viewed by the investigators as invaluable.

They additionally noted that variations in lipid concentrations as well as changes in biochemical pathways seen in HUA and gout patients may be linked to elevated uric acid levels. This, the team explained, shedded light on the molecular-level pathobiochemical mechanism of lipids in subjects’ progression from hyperuricemia to gout.

References

1. ^{Kvasnička, A., Friedecký, D., Brumarová, R. et al. Alterations in lipidome profiles distinguish early-onset hyperuricemia, gout, and the effect of urate-lowering treatment. Arthritis Res Ther 25, 234 (2023). https://doi.org/10.1186/s13075-023-03204-6.}
2. ^{Stamp L, Dalbeth N. Urate-lowering therapy for asymptomatic hyperuricaemia: A need for caution. Semin Arthritis Rheum. 2017;46:457–64.}