Hyperuricemia in Kidney Disease: A Major Risk Factor for Cardiovascular Events, Vascular Calcification, and Renal Damage

A. Ahsan Ejaz, Takahiko Nakagawa, Mehmet Kanbay, Masanari Kuwabara, Ada Kumar, Fernando E. Garcia Arroyo, Carlos Roncal-Jimenez, Fumihiko Sasai, Duk Hee Kang, Thomas Jensen, Ana Andres Hernando, Bernardo Rodriguez-Iturbe, Gabriela Garcia, Dean R. Tolan, Laura G. Sanchez-Lozada, Miguel A. Lanaspa, Richard J. Johnson

Research output: Contribution to journalReview articlepeer-review

12 Scopus citations

Abstract

Kidney disease, especially when it is associated with a reduction in estimated glomerular filtration rate, can be associated with an increase in serum urate (uric acid), suggesting that hyperuricemia in subjects with kidney disease may be a strictly secondary phenomenon. Mendelian randomization studies that evaluate genetic scores regulating serum urate also generally have not found evidence that serum urate is a causal risk factor in chronic kidney disease. Nevertheless, this is countered by a large number of epidemiologic, experimental, and clinical studies that have suggested a potentially important role for uric acid in kidney disease and cardiovascular disease. Here, we review the topic in detail. Overall, the studies strongly suggest that hyperuricemia does have an important pathogenic role that likely is driven by intracellular urate levels. An exception may be the role of extracellular uric acid in atherosclerosis and vascular calcification. One of the more striking findings on reviewing the literature is that the primary benefit of lowering serum urate in subjects with CKD is not by slowing the progression of renal disease, but rather by reducing the incidence of cardiovascular events and mortality. We recommend large-scale clinical trials to determine if there is a benefit in lowering serum urate in hyperuricemic subjects in acute and chronic kidney disease and in the reduction of cardiovascular morbidity and mortality in subjects with end-stage chronic kidney disease.

Original languageEnglish
Pages (from-to)574-585
Number of pages12
JournalSeminars in Nephrology
Volume40
Issue number6
DOIs
StatePublished - Nov 2020

Keywords

  • Hyperuricemia
  • acute kidney injury
  • allopurinol
  • cardiovascular mortality
  • chronic kidney disease

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