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This case represents a 75 years old Caucasian man with end stage renal disease from long-standing hypertension, anuric on hemodialysis since 2012, and with severe tophaceous gout for three decades. He moved to California to be with his family in 2013. On arrival at hemodialysis hospital, he was wheelchair bound and unable to stand without assistance and had extremely limited mobility of his elbows, wrists, knees, and ankles due to gouty tophi, in some places >3× 3 cm, and soft tissue swelling. The fingers of both hands were almost completely immobilized.
The most likely
diagnosis of this presentation is
Allopurinol and colchicine have been the standard treatment
for gout for decades, but have significant side effects, often cannot be
tolerated by many patients with gout, and need to be dose adjusted in renal
failure. A recently approved medication, febuxostat, selectively inhibits
xanthine oxidase, an enzyme responsible for the conversion of hypoxanthine to
xanthine to uric acid. This decreases the uric acid production and blood uric
acid levels. Very few side effects for febuxostat have been noted in subjects
with advanced chronic kidney disease (CKD) at varying doses1. Uric
acid has a molecular weight of 168 daltons and is water soluble and more than
95% unbound in the circulation. The clearance of uric acid is 70–80% with both
low flux and high flux hemodialyzers. Three-times-a-week (TIW) hemodialysis
(HD) is the standard in many western countries. Short daily hemodialysis has
been shown to remove more solute (such as uric acid) than TIW hemodialysis.
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%.
Case Reports in Nephrology : 2016 :9106935 :(3)
Febuxostat and Increased Dialysis as a Treatment for Severe Tophaceous Gout in a Hemodialysis Patient
Lynda Ann Frassetto, Suzanne Gibson
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