Underlying mechanisms of hyperuricemia-induced renal damage
https://doi.org/10.28996/2618-9801-2025-4-367-379
Abstract
Hyperuricemia (HU) is usually considered as a risk factor for gout, and, even being without arthritis, it can be associated with a large number of comorbid conditions, especially with kidney diseases. The results of representative studies and meta-analyses demonstrate the relationship between HU and development of progressive kidney diseases.
The traditionally discussed complex mechanisms of renal injury, induced by HU, include direct renal damage by monosodium urate (MSU) crystals, oxidative stress and endothelial dysfunction summarized in inflammatory response and resulted in glomerular and tubulointerstitial fibrosis. The key element, which triggers the inflammation, is activation of the cryopyrin inflammasome producing interleukin-1 at high level. Not only crystals although soluble UA could activate the inflammasome. Therefore, HU is to be considered as the autoinflammatory disease.
The data for the evolution of UA metabolism in animals and pathways of its intracellular formation suggest, that it is not the HU, but the intracellular hyperconcentration of uric acid (hyperuricocytosis) triggers "alarm signal" for the autoinflammatory reactions; morover, HU resulted from hyperuricocytosis is only a marker of already realized damage. Being on this position means to reconsider approaches to therapy focusing primarily on anti-inflammatory treatment (colchicine and/or interleukin-1 inhibitors) then urate-lowering strategy.
Further study of the molecular mechanisms of HU and associated inflammation is needed to prove the hypothesis given.
About the Authors
V. V. Rameev
Occupational Diseases and Rheumatology, Tareev Clinic of Internal Diseases, Sechenov First Moscow State Medical University (Sechenov University)
Russian Federation
Russian Federation
Vilen V Rameev
11/5, Rossolimo str., Moscow, 119435
M. V. Bogdanova
Occupational Diseases and Rheumatology, Tareev Clinic of Internal Diseases, Sechenov First Moscow State Medical University (Sechenov University)
Russian Federation
Russian Federation
Marina V Bogdanova
11/5, Rossolimo str., Moscow, 119435
L. V. Lysenko (Kozlovskaya)
Occupational Diseases and Rheumatology, Tareev Clinic of Internal Diseases, Sechenov First Moscow State Medical University (Sechenov University)
Russian Federation
Russian Federation
Lidia V. Lysenko (Kozlovskaya)
11/5, Rossolimo str., Moscow, 119435
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Rameev V.V., Bogdanova M.V., Lysenko (Kozlovskaya) L.V. Underlying mechanisms of hyperuricemia-induced renal damage. Nephrology and Dialysis. 2025;27(4):367-379. (In Russ.) https://doi.org/10.28996/2618-9801-2025-4-367-379
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