NEPHROLOGY – REVIEW Allopurinol, uric acid, and oxidative stress in cardiorenal disease Markus Riegersperger • Adrian Covic • David Goldsmith Received: 6 December 2010 / Accepted: 16 February 2011 / Published online: 10 March 2011 Ó Springer Science+Business Media, B.V. 2011 Abstract In humans, the hepatic end product of purine metabolism is uric acid. Serum uric acid levels physiologically and gradually rise during human lifetime. Hyperuricemia also arises from excess dietary purine or ethanol intake, decreased renal excretion of uric acid, tumor lysis in lymphoma, leukemia or solid tumors, and sometimes pharmacotherapy. The defini- tion of hyperuricemia is currently arbitrary. Hyperuri- cemia is associated with chronic kidney disease, arterial hypertension, coronary artery and heart dis- ease, cerebrovascular disease and diabetes mellitus. Xanthine oxidase, a hepatic enzyme, catalyzes the production of uric acid, nitric oxide, and reactive oxygen species, which potentially damage deoxyribo- nucleic acid, ribonucleic acid and proteins, inactivate enzymes, oxidize amino acids and convert poly- unsaturated fatty acids to lipids. This is believed to contribute to atherosclerosis, endothelial dysfunction, renovascular hypertension, and cardiovascular dis- ease. Xanthine oxidase inhibition efficiently blocks uric acid generation, and this improves glomerular filtration rates, systemic blood pressure, and cerebro- cardiovascular outcomes. Here, data from animal, in vivo, retro- and prospective, and interventional studies are reported. Keywords Allopurinol Á Arterial hypertension Á Cardiovascular disease Á Chronic kidney disease Á Diabetes mellitus Á Heart disease Á Hyperuricemia Á Oxidative stress Á Uric acid Á Xanthine oxidase Background Uric acid and hyperuricemia In humans, the hepatic end product of purine metab- olism is uric acid. The kidneys eliminate two-thirds, and the gastrointestinal tract eliminates one-third of the uric acid load. Less than 5% of uric acid is filtered at the level of the glomerulus, and at least 95% is secreted by the kidney’s proximal tubules via trans- porters URAT1, OAT1, -2, and -3, -4, and -10, the multi-drug resistance proteins ABCC4 and ABCG2, and the glucose transporters GLUT 9a and b, and others. From first principles, therefore, a decrease in the glomerular filtration rate (GFR) leads to a decrease M. Riegersperger (&) Division of Nephrology and Dialysis, Department of Medicine III, Medical University Vienna, Wa ¨hringer Gu ¨rtel 18-20, A 1090 Vienna, Austria e-mail: markus.riegersperger@meduniwien.ac.at A. Covic Nephrology Department, Grigore T. Popa School of Medicine and Pharmacy, Parhon Hospital, Iasi, Romania D. Goldsmith Renal and Transplantation Department, Guy’s and St. Thomas 0 Hospital, London, UK 123 Int Urol Nephrol (2011) 43:441–449 DOI 10.1007/s11255-011-9929-6