Febuxostat and increased frequency of dialysis improved renal function and total body uric acid function in anuric hemodialysis patient presented with severe tophaceous gout.

The patient had no history of nephrolithiasis. The patient was allergic to allopurinol (rash) and was on colchicine 0.6 mg/day for gout, with gout flares 2-3 times a month. The patient remained on colchicine throughout the subsequent treatment regimens.

His initial uric acid level at HD unit was 10.8 mg/dL (642 umol/L). Hand X-rays demonstrated osteopenia, erosions and several lytic lesions in the radial, ulnar, and carpal bones, and large soft tissue masses, all consistent with severe bilateral gout, with no evidence of calcium pyrophosphate deposition or other arthropathies.

He was initially treated with an increase of 30 minutes per treatment in dialysis time with TIW HD for 12 hours/week, with a weekly Kt/V of 3.6 (Kt/V is a measure of dialysis adequacy; weekly minimum standard is 3.6). His uric acid levels decreased to 5.4 mg/dL (321 umol/L). His dialysis regimen was changed to four times a week (still total 12 hours/week), but he continued to have gouty attacks, though less frequently. The patient was then referred to rheumatology department for treatment options. The rheumatologist commented on the unusual severity of the gouty arthropathy and recommended starting febuxostat 80 mg/day, using low dose prednisone 5–10 mg/d for flares, if necessary. His uric acid levels were decreased to below the lower limit of detection (<1.5 mg/dL [89 umol/L]) and remained there. After about three months, the patient noted that he had started to urinate again. A 24-hour urine for urea and creatinine clearance showed an average glomerular filtration rate (GFR) of 3 mL/min. The tophi were becoming smaller and softer, and he was able to move more easily, which is associated with this. Over the course of the next six months, the tophi continued to resolve. The patient was first able to get out of his wheelchair without assistance and then progressed over the next 6 months to being able to walk on his own. The incidence of gout flares decreased markedly to one every few months, treated only by increasing his colchicine dose to 0.6 mg twice a day for the duration of the flare. More than a year after starting febuxostat, the patient has a few small tophi on his hands and left wrist. Repeat 24- hour urine for urea and creatinine clearance at this time again demonstrated an average GFR of 3 mL/min.

This is the first reported case of increasing frequency of dialysis till now and the use of febuxostat to improve gouty arthritis and amazingly to demonstrate some return of residual renal function in a subject who had been on hemodialysis for at least two years. Some reports have suggested that the frequency of gouty arthritis is lower in subjects on HD compared to those with chronic kidney disease not yet on HD. There are only few reports of febuxostat use in hemodialysis patients, mostly documenting decreased serum uric acid levels, without necessarily decreasing gouty attacks. The role of uric acid inducing vascular inflammation and organ damage has been of interest for some time. Higher uric acid levels have been associated with increased cardiovascular and all-cause mortality in subjects with advanced CKD and those on peritoneal dialysis. Paradoxically, in the DOPPS trial, in countries where uric acid was commonly measured, higher uric acid levels were associated with lower mortality rates. The authors suggested that this was due to better nutritional status in those subjects. Inducing higher uric acid levels in rats has been shown to induce both systemic and glomerular hypertension and macrophage infiltration in the kidney, leading to accelerated renal functional decline.  Several recent trials in subjects with advanced CKD have shown changes in GFR; one in subjects with asymptomatic hyperuricemia demonstrating slowing of GFR decline and one demonstrating improvement in GFR after changing to febuxostat from allopurinol. Increasing the frequency of dialysis is known to improve weekly clearance of small water soluble non-protein-bound molecules like uric acid by ∼20–30%.

• Severe tophaceous gouty arthritis is uncommon in end stage renal disease
• Febuxostat can help lower uric acid levels in subjects with CKD and on HD
• Increasing dialysis frequency, rather than length of treatment, can also help lower uric acid levels
• Together these two treatments not only lower uric acid levels but also seem to improve total body uric acid burden and can maintain or perhaps improve residual renal function, perhaps by eliminating uric acid from the kidney tissue

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