Gulab et al. [Citation1] reviewed the pathophysiological mechanisms that link hyperuricemia with cardiovascular disease (CVD) and chronic kidney disease (CKD), as well as the effects of urate lowering drugs on cardiorenal outcomes. Some additional comments may be of interest.
Nonalcoholic fatty liver disease (NAFLD) is also linked with hyperuricemia [Citation2,Citation3], CVD [Citation4,Citation5] and CKD [Citation6,Citation7]. Apart from NAFLD, other abnormal peri-and intra-organ fat (APIFat) deposits have been associated with cardiometabolic diseases [Citation8]. Among them, perirenal adipose tissue has been recognized as an independent risk factor for cardiorenal dysfunction, CKD and hyperuricemia [Citation9,Citation10].
Statins have been reported to slightly reduce serum uric acid (SUA) levels [Citation11], as well as to beneficially affect CVD, CKD and NAFLD [Citation12]. Furthermore, similar to sodium glucose cotransporter 2 (SGLT 2) inhibitors, other antidiabetic drugs may also influence (increase or decrease) SUA concentrations [Citation13].
Gulab et al. [Citation1] mentioned that SUA was a strong mediator of cardiorenal risk, as shown in the CANagliflozin cardioVascular Assessment Study (CANVAS). However, it should also be noted that changes in SUA were among the important mediators of empagliflozin-induced CVD death reduction in an exploratory analysis from the Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients Removing Excess Glucose (EMPA-REG OUTCOME) [Citation14]. Furthermore, elevated SUA levels have been associated with CVD mortality as reported in a meta-analysis of the National Health and Nutrition Examination Surveys (NHANES, 1999–2010) [Citation15].
Declaration of interest
N Katsiki has given talks, attended conferences and participated in trials sponsored by Amgen, Astra Zeneca, Bausch Health, Boehringer Ingelheim, Elpen, Mylan, MSD, Novo Nordisk, Sanofi and Servier. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
Additional information
Funding
References
- Gulab A, Torres R, Pelayo J, et al. Uric acid as a cardiorenal mediator: pathogenesis and mechanistic insights. Expert Rev Cardiovasc Ther. 2021;19(6):547–556.
- Katsiki N, Athyros VG, Karagiannis A, et al. Hyperuricaemia and non-alcoholic fatty liver disease (NAFLD): a relationship with implications for vascular risk? Curr Vasc Pharmacol. 2011;9(6):698–705.
- Wei F, Li J, Chen C, et al. Higher serum uric acid level predicts non-alcoholic fatty liver disease: a 4-year prospective cohort study. Front Endocrinol (Lausanne). 2020;11:179.
- Katsiki N, Mikhailidis DP, Mantzoros CS. Non-alcoholic fatty liver disease and dyslipidemia: an update. Metabolism. 2016;65(8):1109–1123.
- Katsiki N, Perez-Martinez P, Anagnostis P, et al. Is nonalcoholic fatty liver disease indeed the hepatic manifestation of metabolic syndrome? Curr Vasc Pharmacol. 2018;16(3):219–227.
- Heda R, Yazawa M, Shi M, et al. Non-alcoholic fatty liver and chronic kidney disease: retrospect, introspect, and prospect. World J Gastroenterol. 2021;27(17):1864–1882.
- Cojocariu C, Singeap AM, Girleanu I, et al. Nonalcoholic fatty liver disease-related chronic kidney disease. Can J Gastroenterol Hepatol. 2020;2020:6630296.
- Katsiki N, Mikhailidis DP. Abnormal peri-organ or intra-organ fat deposition and vascular risk. Angiology. 2018;69(10):841–842.
- D’Marco L, Puchades MJ, Panizo N, et al. Cardiorenal fat: a cardiovascular risk factor with implications in chronic kidney disease. Front Med (Lausanne). 2021;8:640814.
- D’Marco L, Salazar J, Cortez M, et al. Perirenal fat thickness is associated with metabolic risk factors in patients with chronic kidney disease. Kidney Res Clin Pract. 2019;38(3):365–372.
- Derosa G, Maffioli P, Ž R, et al. Impact of statin therapy on plasma uric acid concentrations: a systematic review and meta-analysis. Drugs. 2016;76(9):947–956.
- Katsiki N, Athyros VG, Karagiannis A, et al. The role of statins in the treatment of type 2 diabetes mellitus: an update. Curr Pharm Des. 2014;20(22):3665–3674.
- Katsiki N, Dimitriadis GD, Mikhailidis DP. Serum uric acid and diabetes: from pathophysiology to cardiovascular disease. Curr Pharm Des. 2021 Jan 4;27:1941–1951. Epub ahead of print.
- Inzucchi SE, Zinman B, Fitchett D, et al. How does empagliflozin reduce cardiovascular mortality? Insights from a mediation analysis of the EMPA-REG OUTCOME trial. Diabetes Care. 2018;41(2):356–363.
- Mazidi M, Katsiki N, Mikhailidis DP, et al.; Lipid and Blood Pressure Meta-Analysis Collaboration (LBPMC) Group. Associations of serum uric acid with total and cause-specific mortality: findings from individuals and pooling prospective studies. Atherosclerosis. 2020;296:49–58.