Article published in The Townsend Letter, June 2021
The views expressed in this article are not The Townsend Letter’s, they are those of the author. This article is not intended to be viewed as medical advice. Please check with your health care provider before starting to take any herbal supplements.
A high level of uric acid is an often-unrecognized contributor to many disease states. While the uremic wastes creatinine and BUN are measured on a basic metabolic panel, a blood test for serum uric acid (urate) is usually not run unless the patient complains of gout symptoms. Gout is the most well-known consequence of high uric acid, but only one of many conditions impacted by uric acid.
There may be a classical presentation of gout in the big toe or tophi with uric acid crystals forming nodules in various places. Gout may occur in the context of kidney weakness but is also seen in patients with normal creatinine and BUN. If other renal indicators are normal, diet and lifestyle factors are to blame.
Conversely low uric acid can also be problematic. Depending on the conditions, uric acid can be both pro-inflammatory and anti-inflammatory. Too much or too little uric acid can be detrimental depending on the patient’s health status.
Processing of Uric Acid
Uric acid is produced in the liver cells by the major catabolic pathway of purine degradation. Uric acid is not metabolized in the liver but is excreted by the kidneys and intestinal tract. The enzyme directly responsible for the formation of uric acid is xanthine oxidase (XO), and many medications for uric acid target this enzyme. Other published approaches to lowering production of uric acid include the inhibition of purine nucleoside phosphorylase (PNP), just upstream from XO.1
Hyperuricemia induces the expression of hepatic inflammatory molecules by activating the pro-inflammatory NF-κB signaling cascade. It is also associated with higher levels of hsCRP, fibrinogen, complement C3, ferritin, and ESR. However, uric acid can also act as an antioxidant and free radical scavenger depending on the microenvironment.1
The pro-oxidant effects of uric acid mostly relate to its copper reducing, as Cu(+) can initiate lipid peroxidation. Uric acid also increases alpha-tocopherol consumption. The presence of nitric oxide, however, completely inhibited the pro-oxidant activity of uric acid.2
A variety of factors can make one more susceptible to hyperuricemia.
Chronic kidney disease
Heavy meat diet
Hyperparathyroidism (even in the absence of renal disease)6
Tumor lysis syndrome seen in cancer and chemotherapy, as there is a rapid release of the cell’s contents.7
Serum uric acid is the most direct way to check the patient’s status. In human blood plasma, the reference range of uric acid is from 3.6 to 8.3 mg/dL. There may be a more acidic urinary pH as the kidneys are passing uric acid or a higher urinary pH if the uric acid is crystalizing into stones.7
Uric Acid and Kidney Health
It is often hard to separate cause and effect. High uric acid can result from kidney weakness, but uric acid itself can contribute to kidney damage.
Hypertension: Uric acid increases salt sensitivity and xanthine oxidase-related oxidative stress causes endothelial dysfunction and renal vasoconstriction.8
Nephrotic syndrome: Increased xanthine oxidase activity and uric acid are associated with an increase in the pro-inflammatory compounds toll like receptor 4 (TLR4) and fibronectin. Expression of these compounds is part of a maladaptive immune response associated with proteinuria. Use of allopurinol was seen to reduce proteinuria.9
Loss of filtration: High uric acid can be a causative factor in the progression of chronic kidney disease, altering tubular epithelial cells, endothelial cells, and vascular smooth muscle cells, leading to a pro-inflammatory, profibrotic state.10
Uric acid kidney stones: After oxalate stones, uric acid stones are the second most prevalent type. Some kidney stones are mixed in composition. As oxalates are only found in plants and uric acid is associated with a heavy meat intake, knowing the patient’s eating habits is helpful in determining a course of action.