Uric acid (UA) is the end product of purine metabolism in humans due to the loss of uricase activity by various mutations of its gene during the Miocene epoch, which led to humans having higher UA levels than other mammals. Furthermore, 90% of UA filtered by the kidneys is reabsorbed, instead of being excreted. These facts suggest that evolution and physiology have not treated UA as a harmful waste product, but as something beneficial that has to be kept. This has led various researchers to think about the possible evolutionary advantages of the loss of uricase and the subsequent increase in UA levels. It has been argued that due to the powerful antioxidant activity of UA, the evolutionary benefit could be the increased life expectancy of hominids. For other authors, the loss of uricase and the increase in UA could be a mechanism to maintain blood pressure in times of very low salt ingestion. The oldest hypothesis associates the increase in UA with higher intelligence in humans. Finally, UA has protective effects against several neurodegenerative diseases, suggesting it could have interesting actions on neuronal development and function. These hypotheses are discussed from an evolutionary perspective and their clinical significance. UA has some obvious harmful effects, and some, not so well-known, beneficial effects as an antioxidant and neuroprotector.

High uric acid (UA) levels can cause gout, urolithiasis and acute and chronic nephropathy, all of which are due to the deposit of urate crystals. There is also increasing evidence of relationships of hyperuricemia with other important disorders, including hypertension, chronic renal disease, metabolic syndrome and cardiovascular disease, as well as an increased mortality, although a causal relationship between these conditions has not been clearly established. On the other hand, low UA levels are not known to cause any disorder or disease. However, in the last few years a higher prevalence and progression of some neurological diseases have been associated with a low UA, and it is possible that they may predispose to some other disorders, mainly due to the decrease in its antioxidant activity. In this article, the known negative effects of UA are reviewed, as well as the much less-known possible positive actions, and their therapeutic implications.

The adverse effects of anti-tumour necrosis factor alpha (TNFα) drugs include an increase in the risk of infections, congestive heart failure, lupus-like syndrome, and the onset or worsening of various demyelinating diseases such as, multiple sclerosis, optic neuritis, and Guillain-Barrè syndrome (GBS), among others. We describe the case of a patient who developed GBS while she was on treatment with adalimumab. A 50-year-old woman with rheumatoid arthritis (RA) was admitted to the hospital due to progressive severe bilateral symmetric weakness of the legs, which quickly extended to the upper limbs and to the respiratory muscles. Adalimumab was started 13 months before. GBS was diagnosed and the anti-TNFα therapy discontinued. The serological test for Campylobacter jejuni was positive. She required invasive mechanical ventilatory support for 9 months. Twelve months later, the patient was using a wheelchair following a rehabilitation programme, and at 24 months she was walking a few steps with assistive devices. The relevant literature on the relationship between GBS and anti-TNFα is reviewed. Twenty three cases of GBS occurring during anti-TNFα therapy have been reported so far in the literature. In several cases, there was no clear temporal association, more than half had a possible previous infection, and in two cases the drug was reintroduced without recurrence of GBS. Our case, which is best explained by C. jejuni infection, as well as some of the cases described are probably not a direct result of anti-TNFα treatment, but an accidental coincidence. We also discuss the potential therapeutic options after anti-TNFα discontinuation.

Several evolutionary changes have led to uric acid levels being much higher in humans than in other mammals. Uric acid is the end product of purine metabolism in hominoids, including humans, due to the genetic loss of uricase activity during the Miocene epoch, and this is the main cause of the increased uric acid in hominoids. Additional factors that have contributed to increased levels of uric acid are the high renal tubular reabsorption of uric acid and the previous loss of the ability to synthesise vitamin C in hominoids. Several hypotheses have been proposed on the evolutionary advantage of increased serum uric acid levels in hominoids, although the biological reasons for this increase remain unclear. The large current increase in uric acid levels in humans in developed countries is mainly influenced by dietary factors and lifestyle changes. Key Concepts: Uric acid (UA) is the end product of purine metabolism in humans due to the loss of uricase activity by various mutations of its gene during the Miocene epoch. Loss of uricase activity led to humans having higher UA levels than other mammals. The high renal tubular reabsorption of UA and the previous loss of the ability to synthesise vitamin C may have also contributed to increased levels of UA in humans. The biological reason for the loss of uricase activity and increased levels of UA in humans and certain primates is unknown. UA is one of the most important antioxidants in human biological fluids. UA probably has neuroprotective activity. The current large increase in UA levels in humans in developed countries is mainly influenced by eating habits and lifestyle changes. Hyperuricaemia can cause gout and uric lithiasis, and is associated with hypertension, metabolic syndrome, renal disease and cardiovascular disease.

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