What Are the Key Arguments Against Uric Acid as a True Risk Factor for Hypertension?
On March 24, 1882, at a dinner held by the Berlin Physiological Society, Robert Koch presented evidence to prove that galloping consumption, or tuberculosis, was attributable to a bacteria. His evidence was based on identifying the organism from the lungs of infected patients, growing it in a cell culture dish, and then injecting the bacteria in rabbits where it replicated the disease with similar lung lesions containing the bacteria. This approach, which included observations in humans as well as animal models, became adopted as Koch’s postulates for proving the cause of disease.
In recent years, uric acid has been proposed to have a causal role in some forms of hypertension. Nevertheless, there are observations that have challenged this hypothesis. Here we discuss some of the arguments that weaken the uric acid story, and how they might be addressed.
Uric Acid as a Cause of Hypertension
Uric acid is produced during purine metabolism with the generation of oxidants (Figure 1). In humans uric acid is the final end product, whereas in most mammals uric acid is further degraded into 5-hydroxyisourate by uricase, eventually producing allantoin. Serum uric acid levels vary in humans, with the normal range being between 3 and 7 mg/dL in the blood. Serum uric acid levels are increased by diets high in purine-rich foods or fructose, or by conditions associated with high cell turnover. Reduced urinary excretion of uric acid also results in higher serum uric acid levels, such as occurs with reduced renal function, reduced renal blood flow, and insulin resistance.
Serum uric acid was originally linked with hypertension in the 1870s. For years, this association was attributed to the effect of renal vasoconstriction to reduce urinary excretion of uric acid. More recently, uric acid has been proposed to have a causal role in hypertension.1 Hyperuricemia would seem to fulfill …