Relationship status remains unclear for uric acid, CKD, CVD
Current evidence is insufficient to identify the exact relationship between uric acid, chronic kidney disease (CKD), and cardiovascular disease (CVD), says a nephrologist.
Speaking at the Malaysian Society of Hypertension’s (MSH) 15th Annual Scientific Meeting, consultant nephrologist Dr Sunita Bavanandan said uric acid has been associated with hypertension, cardiovascular disease and kidney disease in large epidemiological and animal model studies. However, there are very few interventional studies and randomized controlled trials that focuses on the link between hyperuricaemia and cardiorenal disease.
Observational studies are inadequate to determine uric acid’s role in cardiovascular disease and CKD. It remains unclear if uric acid is a causal factor or part of the same causal pathway as CKD, said Sunita. Another possibility is that uric acid is merely a consequence of CKD. Hyperuricaemia is commonly associated with other cardiovascular and CKD risk factors, making it difficult to assess uric acid’s role as an independent pathogenic mediator, she said.
A recent systematic review and meta-analysis of observational cohort studies showed that hyperuricaemia is an independent predictor for incident CKD. [Eur Heart J 2011;32(6):712–720] Common risk factors for CKD are metabolic syndrome and obesity; both are strongly associated with hyperuricaemia. Moreover, CKD and hyperuricaemia often coexist because the kidneys are responsible for two-thirds of the daily excretion of uric acid. As such, the prevalence of hyperuricaemia increases in parallel to the decline in glomerular filtration rate (GFR), she explained. Hyperuricaemia is found in 40 to 60 percent of patients with CKD stage 1 to 3 and 70 percent of patients in CKD stage 4 and 5, Sunita continued.
The prevalence of hyperuricaemia is on the rise because of the increasing prevalence of overweight and obesity, and increasing consumption of sugar-sweetened beverages, purine-rich foods and alcohol, she said. Aging population, earlier screening and increased environmental exposure to organic pollutants, too add to the rise in the prevalence of hyperuricaemia. That is why hyperuricaemia has been labelled as a lifestyle-associated disease together with hypertension, diabetes and dyslipidaemia.
Allopurinol may have a therapeutic role in patients with hyperuricaemia and hypertension, kidney disease or coronary heart disease, but evidences from different trials are conflicting. [BMC Nephrol 2015;16:58, Nephrol Dial Transplant 2014;29(2):406–413] More research is necessary before the drug can be given routinely to these patient groups, she noted.
Among the issues that require consideration before prescribing allopurinol is that the drug can cause severe allergic reactions, said Sunita. In 2012, the Malaysian Adverse Drug Reactions Advisory Committee (MADRAC) noted 280 reports of adverse reactions related to the use of allopurinol from 2000 to 2012, 12 of which involved fatalities. [Available at: http://npra.moh.gov.my/images/Publications/Newsletter_MADRAC_Bulletin/Bulletin-MADRAC-2012August.pdf] Majority (80 percent) of the adverse reactions reported were skin reactions ranging from mild rash and itchiness to Steven Johnsons syndrome and Toxic Epidermal Necrolysis. Thus, allopurinol is not indicated for the treatment of asymptomatic hyperuricaemia, Sunita emphasized.