Use of allopurinol in end-stage renal disease patients

E Montané1,3, AL Arellano1, A Barriocanal2,3, A López2, F García1, A Valderrama2, J Costa1,3. 1Hospital Universitari Germans Trias i Pujol, Department of Clinical Pharmacology (Barcelona), Spain, 2Fundaci ó Institut d\'Investigaci ó en Ci è ncies de la Salut Germans Trias i Pujol, Department of Clinical Pharmacology (Barcelona), Spain, 3Universitat Aut ò noma de Barcelona, Department of Pharmacology, Therapeutics and Toxicology (Barcelona), Spain

BACKGROUND

Hyperuricemia is associated with an increased risk for developing chronic kidney disease and accelerates renal deterioration. The efficacy evidence-based of allopurinol in treatment of hyperuricemia and in prevention of recurrent gout in end-stage renal disease patients is lacking. In these patients, doses of 300 mg on the dialysis day are recommended in the approved product information.

OBJECTIVE:

• To describe the patient’s characteristics of a cohort with end-stage renal disease.
• To assess the dosing regimen when treated with urate-lowering treatment (according to the approved product information recommendations).
• To identify patients with inappropriate use of allopurinol.

METHODS:

Observational, retrospective and unicentric study. Inclusion criteria: patients admitted in the hospital from 2009 to 2011 with end-stage renal disease (maintenance hemodialysis). Demographic, clinical, and laboratory data were collected. Inappropriate use of allopurinol include patients with previous history of hyperuricemia and/or gout, and a persistent or occasional elevated serum uric acid levels that receive allopurinol (insufficient doses) or not (not treated).

RESULTS:

A total of 229 patients met the inclusion criteria, mainly males (67%, 154); the mean (SD) age was 69 years (13.5), range 25-93 (70% were older than 65 years), and 24% (55/229 patients) had previous history of hyperuricemia and/or gout. Treatment with allopurinol was present in 22% (51/229) of the patients. Half of the patients with previous history of hyperuricemia and/or gout were treated with allopurinol (27/55, 49%). Two thirds of the patients (35/51, 69%) treated with allopurinol received concomitant drugs with potentially interactions; mainly diuretics, oral anticoagulants, angiotensin-converting enzyme inhibitors, and penicillin. The most frequently used allopurinol dosage was 100 mg/day (80%, 41/51 patients). Inappropriate use of allopurinol was detected in a third of the patients (20/55, 36%) with a previous history of hyperuricemia and/or gout, and a persistent or occasional elevated serum uric acid levels. All of these cases were insufficiently treated (10 patients should be treated with allopurinol and 10 needed higher doses).

CONCLUSIONS:

• One patient of four with end-stage renal disease had previous history of hyperuricemia and/or gout.
• One out of five patients received allopurinol; in all of them, the used allopurinol dosage was different from the recommended in the product information. Therefore, another non-evidence-based dosage (lower and daily) is widely accepted and used by nephrologists.
• Globally, inappropriate use of allopurinol (both insufficient doses and not treated) was observed in one third of the patients.
• Additional evidence-based efficacy research in this area is needed.