The liver and the kidney: two critical organs influencing the atherothrombotic risk in metabolic syndrome

Abstract

The increased atherothrombotic risk in patients with metabolic syndrome (MetS) has been classically explained by the multiplicative effect of systemic concomitant pro-atherosclerotic factors. In particular, centripetal obesity, dyslipidaemia, glucose intolerance, hypertension (differently combined in the diagnosis of the disease) would be expected to act as classical cardiovascular risk conditions underlying accelerated atherogenesis. In order to better understand specific atherosclerotic pathophysiology in MetS, emerging evidence focused on the alterations in different organs that could serve as both pathophysiological targets and active players in the disease. Abnormalities in adipose tissue, heart and arteries have been widely investigated in a variety of basic research and clinical studies in MetS. In this narrative review, we focus on pathophysiological activities of the liver and kidney. Considering its key role in metabolism and production of soluble inflammatory mediators (such as C-reactive protein [CRP]), the liver in MetS has been shown to be altered both in its structure and function. In particular, a relevant amount of the fat accumulated within this organ has been shown to be associated with different degrees of inflammation and potential insulin resistance. In humans, non-alcoholic fatty liver disease (NAFLD) has been described as the hepatic manifestation of MetS. In an analogous manner, epidemiological evidence strongly suggested a "guilty" association between MetS and chronic kidney disease (CKD). Some biomarkers of hepatic (such as C-reactive protein, TNF-alpha or other cytokines) and renal diseases (such as uric acid) associated with MetS might be particularly useful to better manage and prevent the atherothrombotic risk

Metabolic syndrome, serum uric acid and renal risk in patients with T2D

“…On the contrary, higher insulin levels are known to reduce renal excretion of urate in both healthy and hypertensive subjects [30], providing a strong mechanism supporting the previously described link between the Mets and HU [31, 32] and confirmed in the present cohort where 74% of HU patients showed Mets (S1 Table). Interestingly, high SUA concentrations commonly precede the development of insulin resistance in experimental studies [33, 34] and frequently forerun the diagnosis of Mets in clinical reports [31, 35].…”

“…Interestingly, high SUA concentrations commonly precede the development of insulin resistance in experimental studies [33, 34] and frequently forerun the diagnosis of Mets in clinical reports [31, 35]. This has led several authors to suggest that hyperuricemia may be a risk factor and a new marker for Mets.…”

Sex-Specific Predictors of Metabolic Syndrome Independent of Its Components

“…These 2 substances, together with adiposity markers, have been reported to reflect fairly reliably HS. 13 Carbone et al 27 drew attention to recent research focusing on serum inflammatory surrogate biomarkers of HS as useful parameters for the association between HS and MetS. As they pointed out, prospective studies with clinical long-term follow-up were lacking.…”

Effect of Non-Alcoholic Fatty Liver Disease on Estimated Glomerular Filtration Rate Could Be Dependent on Age

“…These studies suggest that NAFLD may not only be associated with renal dysfunction, but also be actively involved in its pathogenesis. There may be several explanations on the effects of NAFLD on eGFR levels such as disturbed tumor necrosis factor system, imbalance of renin-angiotensin-aldosterone system, insulin resistance, and chronic inflammation [14,23,30,31]. However, underlying mechanisms between the association of NAFLD and renal dysfunction remains unclear.…”