Ask the Experts - Hyperuricemia with Gouty Arthritis and Tophi
Ask the Experts - Hyperuricemia with Gouty Arthritis and Tophi
How would you treat a patient with hyperuricemia (10.5 mg/dL); creatinine clearance of 52 mL/min; no history of alcohol abuse, liver disease, or toxin exposure; but each time his allopurinol dose is increased by 100 mg, his aspartate aminotransferase and alanine aminotransferase levels double. The patient has recurrent gouty arthritis with tophaceous deposits and erosive disease.
Joanna M. S. Davies, MD
Because the patient has tophaceous gout, uric acid-lowering therapy is indicated. However, the patient has mild renal insufficiency. Allopurinol has been prescribed appropriately. The uricosuric probenicid does not work well if the creatinine clearance is less than 60 mL/min. Although another uricosuric available only outside the United States, benzbromarone, can be effective with mild renal insufficiency, allopurinol is clearly a better choice as a primary treatment here.
In the setting of normal renal function and gout, uric acid-lowering therapy is generally optimized to decrease the serum uric acid level to 6 mg/dL or less. However, when treating gout patients with renal insufficiency, it is difficult, even with allopurinol, to achieve potent lowering of the serum uric acid and rapid shrinking of tophi because of impaired renal elimination of uric acid (the major route for urate disposal). Thus, with renal failure, it is generally best to choose an allopurinol dose appropriate for the creatinine clearance and to stick to that dose to avoid toxicities, some of which are allopurinol dose-related. For creatinine clearances of 60, 45, and 30 mL/min, I usually employ daily allopurinol doses of 200, 150, and 100 mg, respectively. Some other strategies can sometimes come into play for severe tophaceous gout. For example, losartan can have salutary uricosuric benefits in thiazide-induced and cyclosporine-induced hyperuricemia in the setting of mild renal insufficiency. Probenicid can occasionally be used successfully in combination with allopurinol in cases of mild renal insufficiency.
This patient has mild, reversible elevations of transaminases. Allopurinol use may cause abnormal liver function tests, most often manifesting as asymptomatic elevations of transaminases or alkaline phosphatase. Though significant allopurinol hepatotoxicity is rare, cases of serious and sometimes fatal allopurinol-associated liver disease do occur. Thus, I would continue to monitor the liver function tests (including serum albumin) closely in this patient. Because the transaminase elevations appear directly related to raising the allopurinol, I would not go above the lower allopurinol dose you are using.
How would you treat a patient with hyperuricemia (10.5 mg/dL); creatinine clearance of 52 mL/min; no history of alcohol abuse, liver disease, or toxin exposure; but each time his allopurinol dose is increased by 100 mg, his aspartate aminotransferase and alanine aminotransferase levels double. The patient has recurrent gouty arthritis with tophaceous deposits and erosive disease.
Joanna M. S. Davies, MD
Because the patient has tophaceous gout, uric acid-lowering therapy is indicated. However, the patient has mild renal insufficiency. Allopurinol has been prescribed appropriately. The uricosuric probenicid does not work well if the creatinine clearance is less than 60 mL/min. Although another uricosuric available only outside the United States, benzbromarone, can be effective with mild renal insufficiency, allopurinol is clearly a better choice as a primary treatment here.
In the setting of normal renal function and gout, uric acid-lowering therapy is generally optimized to decrease the serum uric acid level to 6 mg/dL or less. However, when treating gout patients with renal insufficiency, it is difficult, even with allopurinol, to achieve potent lowering of the serum uric acid and rapid shrinking of tophi because of impaired renal elimination of uric acid (the major route for urate disposal). Thus, with renal failure, it is generally best to choose an allopurinol dose appropriate for the creatinine clearance and to stick to that dose to avoid toxicities, some of which are allopurinol dose-related. For creatinine clearances of 60, 45, and 30 mL/min, I usually employ daily allopurinol doses of 200, 150, and 100 mg, respectively. Some other strategies can sometimes come into play for severe tophaceous gout. For example, losartan can have salutary uricosuric benefits in thiazide-induced and cyclosporine-induced hyperuricemia in the setting of mild renal insufficiency. Probenicid can occasionally be used successfully in combination with allopurinol in cases of mild renal insufficiency.
This patient has mild, reversible elevations of transaminases. Allopurinol use may cause abnormal liver function tests, most often manifesting as asymptomatic elevations of transaminases or alkaline phosphatase. Though significant allopurinol hepatotoxicity is rare, cases of serious and sometimes fatal allopurinol-associated liver disease do occur. Thus, I would continue to monitor the liver function tests (including serum albumin) closely in this patient. Because the transaminase elevations appear directly related to raising the allopurinol, I would not go above the lower allopurinol dose you are using.
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