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)