None listed
Conditions
Brief summary
Gout is very common in people with chronic kidney disease including individuals on dialysis. Gout is due to high concentrations of urate in the body and treatment is aimed at lowering urate by blocking it's formation using allopurinol. Oxypurinol, the active product of allopurinol, is normally removed by the kidneys and the dose of allopurinol is modified according to kidney function. However, we do not know how well oxypurinol is removed by peritoneal dialysis. This means that often the dose of allopurinol is insufficient to reduce the body’s urate concentration to prevent further episodes of gout. It is important to maintain the right concentration of oxypurinol to properly lower uric acid concentrations to prevent further gout. At present, there is no good data to help accurately prescribe the correct dose of allopurinol to safely reduce uric acid concentrations. We hypothesise that the majority of oxypurinol is eliminated by peritoneal dialysis and the current doses used are insufficient to optimally treat gout. Allopurinol is usually prescribed once a day, therefore we would like to carefully measure just how much oxypurinol is removed over a 24 hour period of peritoneal dialysis. By measuring the concentrations of oxypurinol in the blood, as well as in the dialysate and in the urine collected over the 24 hour period, we can accurately predict the amount being removed both by peritoneal dialysis and residual kidney function. At the same time we will measure the urate concentrations. To be effective in stopping gout urate concentrations need to be below 0.36umol/l. This will allow us to work out the correct dose to safely lower uric acid concentrations and prevent further attacks of gout.
Interventions
The study will observe the handling (pharmacokinetics) of oxypurinol (the active metabolite of allopurinol) in patients who are receiving peritoneal dialysis. The patients will have had a prior diagnosis of gout are already prescribed allopurinol therapy. The duration of the observation will be 24 hours.
The typical (nromal) daily PD schedule is to retain the dialysate for 4 hours before exchanging for fresh fluid. This is repeated by the subject 3 times during the day. The 4th exchange of the
The study will observe the handling (pharmacokinetics) of oxypurinol (the active metabolite of allopurinol) in patients who are receiving peritoneal dialysis. The patients will have had a prior diagnosis of gout are already prescribed allopurinol therapy. The duration of the observation will be 24 hours. The typical (nromal) daily PD schedule is to retain the dialysate for 4 hours before exchanging for fresh fluid. This is repeated by the subject 3 times during the day. The 4th exchange of the daily is retained overnight for 12 hours. Given this schedule, we will collect seven blood samples of 3 mL over a single day at the following times; • Immediately prior to the daily dose of allopurinol and the first dialysis bag exchange of the day (typically in the morning) • At the half-way point and at the end of the first dialysate dwell, just prior to draining and exchange (i.e. approximately 2 and 4 hours after the dose for a 4 hour dwell time) • At the half-way point and at the end of the second dialysate dwell, just prior to draining and exchange (i.e. approximately 6 and 8 hours for a 4 hour dwell time) • At the half-way point of the third dialysate dwell, just prior to draining and exchange (i.e. approximately 10 for a 4 hour dwell time) • At the end of the fourth dialysate dwell, just prior to draining and exchange (i.e. 24 hours for a 12 hour dwell time) Waste dialysate will be collected and the volume measured, with a correction for ultrafiltration. Oxypurinol and urate concentrations will be measured in the dialysate bag to determine the the excretion rate of both. For patients with residual renal function, 24 urine timed urine samples (0-4, 4–8, 8–24 hours - complete catch) will be collected to determine the renal clearances of oxypurinol, creatinine and urate.
Sponsors
Professor Robert Walker
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
A peritoneal dialysis patient with a prior diagnosis of gout receiving allopurinol therapy will be eligible for inclusion.
Exclusion criteria
Participants who are unable or unwilling to give written informed consent, who are taking concurrent losartan, probenecid, or benzbromarone, who are undergoing treatment for peritonitis, or who use an automated peritoneal dialysis set up will be excluded.
Outcome results
None listed