Hyperuricemia as a trigger of immune response in hypertension and chronic kidney disease

Claudio Ponticelli, Manuel Alfredo Podestà, Gabriella Moroni

Research output: Contribution to journalReview articlepeer-review


Accumulating evidence indicates that asymptomatic hyperuricemia is involved in the development of hypertension and chronic kidney disease. A 2-hit model has been proposed to explain the role of urate in hypertension. The first hit entails activation of the renin-angiotensin system and inhibition of nitric oxide synthesis, which promote endothelial dysfunction, proliferation of vascular smooth muscle cells, and sodium reabsorption, leading to a moderate but consistent increase in systemic blood pressure. The second hit involves the immune system. Uric acid released in response to hypertension-induced damage can be recognized as a danger molecule by pattern-recognition receptors, the sentinels of the innate immunity. Downstream signaling from these receptors leads to dendritic cell maturation and activation of resting T cells, but it can also trigger the inflammasome and induce the secretion of proinflammatory cytokines. This proinflammatory milieu concurs in expanding the extracellular fluid volume and in increasing vascular resistances, which further promote systemic hypertension. Through similar mechanisms, hyperuricemia may also cause vascular and tubulointerstitial lesions that favor the development and progression of chronic kidney disease. To counteract these actions, xanthine oxidase inhibitors and uricosuric agents have been advocated as logical candidates to decrease the serum levels of uric acid. However, despite a clear rationale for using hypouricemic drugs in patients with chronic kidney disease, there is currently a lack of robust evidence that lowering uric acid may slow the progression of renal disease.

Original languageEnglish
Pages (from-to)1149-1159
Number of pages11
JournalKidney International
Issue number5
Publication statusPublished - Nov 2020


  • chronic kidney disease
  • hypertension
  • immune system
  • metabolism
  • treatment
  • urate
  • uric acid

ASJC Scopus subject areas

  • Nephrology


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