Hyperuricemia; treatment indications beyond gout?

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What do you do when a patient with long standing CKD happens to have a uric acid level of 10mg/dl but has never had gout? Do you treat?
Hyperuricemia occurs when an imbalance exists between uric acid production, which is mainly due to purine metabolism, and uric acid excretion. Humans lack the enzyme uricase which is responsible for converting the less soluble uric acid to the more soluble allantoin. It is interesting to note that hyperuricemia only exists in higher animals. This article published in Hypertension hypothesized that a mutation in uricase (urate oxidase) in humans occurred during the Miocene era to give us survival advantage owing to hyperurecemia in maintaining blood pressure under low-salt dietary conditions.
In today’s developed salt-rich environment, hyperuricemia has been associated with increased morbidity in patients with hypertension and is associated with increased mortality in women and elderly persons. Hsu et al. found that patients on hemodialysis with the highest percentile of uric acid concentrations had an HR for mortality of 5.67 although the study only involved 146 haemodialysis patients.
Furthermore, there is some evidence that uric acid lowering therapy might retard progression of chronic kidney disease in a prospective study of 113 patients with CKD randomized to allopurinol or control.
In view of possible long term complications of hyperuricemia in general population as well as in CKD/ end stage renal failure, can uric acid lowering medications being used beyond its usual indications?
I think at this moment, treating hyperuricemia beyond the indication of treating gout and tumor lysis syndrome is still premature bearing in mind the possible disastrous side effect of allupurinol (Steven Johnson syndrome). However, new agents such as febuxostat and rasburicase might be used in future larger randomized trials to study the effects of these drugs in reversing or slowing the complications of hypertension and chronic kidney disease.
Heong Keong Goh, MBBS (Malaysia)


  1. Lets hope that these newer agents will prove safe/effective ("acceptable") in the CKD population.

    Relative risks:
    In terms of CV mortality, CKD is arguably far more "dangerous" than gout, yet is not sufficient threshold? Low ESRD compared to CKD is lack of *survival*, not lack of progression. It is to face up to this, in evaluating "risk/reward" questions.

    There are reasons to believe uric acid lowering will be a true "cardio-reno" protective strategy. Perhaps the current febuxostat trials will provide a suitable alternative.

    Regardless, if one thing has become clear, it is that actually *improving* cardio-renal outcomes will require multi-modal, and yes, "more aggressive" interventions, which (alas, fundamentally), cannot be done with zero risk.

  2. Interesting post and comments. Allopurinol was also shown to reduce SBP in hypertensive pts with high UA by a magnitude of 6-7mm Hg.

    Although, justifying its use is still extremely controversial.

    e.g. Given that there are only 287 reported cases of NSF (few in pts never received Gd based contrast) there are already guidelines to suggest not to use Gd. (well, there are over 3 million MRI done each year.)

    Thanks, keep up the good work

  3. However, overall allopurinol has a very good safety record, with adverse reaction (mostly skin rash) now on the order of perhaps 1-3%. When this occurs, practice is then switch to Febuxostat.

    Full blown, Stevens-Johnson syndrome occurs on the order of what, 300 cases per year in the US, out of how many MILLIONS of allopurinol prescriptions? Not just rare – very, VERY, VERY rare.

    Add to that evidence that allopurinol may simultaneously be cardioprotective (LVH regression, reductions of angina, significantly reduced hospitalizations in the Spanish study)

    Frightening, even "severe" side effects need to be balanced against their rarity. Aspirin and other NSAIDs kill over 16,000 people per year. Should we also be afraid to use these?

  4. Great post, there are so many issues that can cause trouble with the kidney, and the views on uric acid are interesting to say the least

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