The inflammatory state is a risk factor for cardiovascular disease and graft fibrosis in kidney transplantation

Claudio Ponticelli, Maria Rosaria Campise

Research output: Contribution to journalReview articlepeer-review

Abstract

Several factors, such as donor brain death, ischemia-reperfusion injury, rejection, infection, and chronic allograft dysfunction, may induce an inflammatory state in kidney transplantation. Furthermore, inflammatory cells, cytokines, growth factors, complement and coagulation cascade create an unbalanced interaction with innate and adaptive immunity, which are both heavily involved in atherogenesis. The crosstalk between inflammation and thrombosis may lead to a prothrombotic state and impaired fibrinolysis in kidney transplant recipients increasing the risk of cardiovascular disease. Inflammation is also associated with elevated levels of fibroblast growth factor 23 and low levels of Klotho, which contribute to major adverse cardiovascular events. Hyperuricemia, glucose intolerance, arterial hypertension, dyslipidemia, and physical inactivity may create a condition called metaflammation that concurs in atherogenesis. Another major consequence of the inflammatory state is the development of chronic hypoxia that through the mediation of interleukins 1 and 6, angiotensin II, and transforming growth factor beta can result in excessive accumulation of extracellular matrix, which can disrupt and replace functional parenchyma, leading to interstitial fibrosis and chronic allograft dysfunction. Lifestyle and regular physical activity may reduce inflammation. Several drugs have been proposed to control the graft inflammatory state, including low-dose aspirin, statins, renin–angiotensin inhibitors, xanthine–oxidase inhibitors, vitamin D supplements, and interleukin-6 blockade. However, no prospective controlled trial with these measures has been conducted in kidney transplantation.

Original languageEnglish
JournalKidney International
DOIs
Publication statusAccepted/In press - 2021

Keywords

  • cardiovascular disease
  • graft fibrosis
  • inflammatory cytokines
  • kidney transplantation
  • transplant inflammation

ASJC Scopus subject areas

  • Nephrology

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