Asymptomatic Hyperuricemia Promotes Recovery from Ischemic Organ Injury by Modulating the Phenotype of Macrophages

11Citations
Citations of this article
16Readers
Mendeley users who have this article in their library.

Abstract

Acute organ injury, such as acute kidney injury (AKI) and disease (AKD), are major causes of morbidity and mortality worldwide. Hyperuricemia (HU) is common in patients with impaired kidney function but the impact of asymptomatic HU on the different phases of AKI/AKD is incom-pletely understood. We hypothesized that asymptomatic HU would attenuate AKD because soluble, in contrast to crystalline, uric acid (sUA) can attenuate sterile inflammation. In vitro, 10 mg/dL sUA decreased reactive oxygen species and interleukin-6 production in macrophages, while enhancing fatty acid oxidation as compared with a physiological concentration of 5 mg/dL sUA or medium. In transgenic mice, asymptomatic HU of 7–10 mg/dL did not affect post-ischemic AKI/AKD but accelerated the recovery of kidney excretory function on day 14. Improved functional outcome was associated with better tubular integrity, less peritubular inflammation, and interstitial fibrosis. Mech-anistic studies suggested that HU shifted macrophage polarization towards an anti-inflammatory M2-like phenotype characterized by expression of anti-oxidative and metabolic genes as compared with post-ischemic AKI-chronic kidney disease transition in mice without HU. Our data imply that asymptomatic HU acts as anti-oxidant on macrophages and tubular epithelial cells, which endorses the recovery of kidney function and structure upon AKI.

References Powered by Scopus

STAR: Ultrafast universal RNA-seq aligner

29787Citations
N/AReaders
Get full text

Improving bioscience research reporting: The arrive guidelines for reporting animal research

5689Citations
N/AReaders
Get full text

Gout-associated uric acid crystals activate the NALP3 inflammasome

4373Citations
N/AReaders
Get full text

Cited by Powered by Scopus

Uric Acid and Chronic Kidney Disease: Still More to Do

64Citations
N/AReaders
Get full text

Hyperuricemia and its related diseases: mechanisms and advances in therapy

46Citations
N/AReaders
Get full text

Nrf2 Activation in Chronic Kidney Disease: Promises and Pitfalls

40Citations
N/AReaders
Get full text

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Cite

CITATION STYLE

APA

Gnemmi, V., Li, Q., Ma, Q., De Chiara, L., Carangelo, G., Li, C., … Steiger, S. (2022). Asymptomatic Hyperuricemia Promotes Recovery from Ischemic Organ Injury by Modulating the Phenotype of Macrophages. Cells, 11(4). https://doi.org/10.3390/cells11040626

Readers' Seniority

Tooltip

PhD / Post grad / Masters / Doc 4

67%

Professor / Associate Prof. 1

17%

Researcher 1

17%

Readers' Discipline

Tooltip

Medicine and Dentistry 3

50%

Biochemistry, Genetics and Molecular Bi... 2

33%

Chemistry 1

17%

Article Metrics

Tooltip
Mentions
News Mentions: 1

Save time finding and organizing research with Mendeley

Sign up for free