Gout is fully curable …

Gout is characterized by monosodium urate (MSU) crystal deposits in the joint that trigger an inflammatory response, producing episodes of intense pain and swelling [1]. The development of MSU crystal deposits is silent and potentially very prolonged; diagnosing gout before the first gout attack by screening for the crystals is currently difficult [2]. Nevertheless, MSU crystal formation is fully reversible and gout, therefore, is considered a curable disease [3].

Gout treatment and prevention strategies in patients with renal impairment must be approached carefully due to the complexity of renal impairment, and drug selection, dosage modification and the impact of the treatment on the existing renal impairment should be considered [4]. This article provides a summary of the treatment and management of gout in patients with renal impairment, as reviewed by Pascual et al. [4].

… and often co-exists with renal impairment

MSU crystal deposits form and persist with prolonged hyperuricaemia, which occurs most often from insufficient serum urate (SU) elimination [1]; as such, renal impairment contributes greatly to the development of gout [4]. However, hyperuricaemia may also contribute to renal impairment, with multiple studies showing a positive correlation between SU levels and the risk of kidney disease [4]; similarly, patients with gout have a greater risk of end-stage renal disease (ESRD) [5].

Gout treatment in patients with renal impairment, therefore, requires particular caution in terms of selecting the best treatment at the most appropriate dosage [4]. Creatinine clearance (CrCL) should be assessed beforehand in order to select the most appropriate drug and dosage [4].

Focus on lowering serum urate …

At the emergence of gout symptoms, treatment to eliminate MSU crystal deposits should be administered until all signs of gout are cleared and, if necessary, continued during treatment and prophylaxis for gout flares (Fig. 1) [4]. As MSU crystals dissolve completely at normal SU levels, the primary aim of gout treatment is to lower SU levels, typically with SU-lowering drugs (Table 1) [4]. Such treatment decreases the risk of gout flares, often without the need for additional prophylactic treatments [4].

Fig. 1
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Treating gout in patients with renal impairment, as suggested by Pascual et al. [4]

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Table 1 Gout treatment drugs to lower serum urate levels in patietns with impaired renal function, based on a review by Pascual et al. [4]
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SU levels should be reduced to < 0.30 mmol/L (< 5 mg/dL) in patients with severe gout [3]. Although MSU crystals dissolve faster when SU levels at low, lowering SU to < 0.18 mmol/L (< 3 mg/dL) for a period of years is advised against due to a possible increased risk of neurological disorders [3]. It is difficult to determine when MSU crystals have been fully dissolved, and ultrasounds may be useful in identifying any remaining deposits [4]. Once the deposits have been dissolved, SU levels should be maintained at < 0.36 mmol/L (< 6 mg/dL), the level at which new crystals cannot form [6].

… but start slow

In general, it is crucial to slowly ease into SU reduction therapy; gout flares are more likely (and at greater severity) if SU levels drop too sharply at the beginning of treatment [4]. Starting treatment with SU-lowering drugs at lower dosages (which can be gradually increased as appropriate) is particularly imperative for gout patients with renal impairment due to the potential for kidney-related adverse effects to occur (Table 1) [4].

Allopurinol and febuxostat are xanthine-oxidase inhibitors, and are the drugs most commonly used to treat hyperuricaemia (Table 1) [4]. If xanthine-oxidase inhibitor monotherapy is unable to adequately reduce SU levels, a uricosuric drug may be added to reduce MSU crystal formation and improve excretion of SU (Table 1) [4], especially in patients with severe gout and limited treatment options [7]. Uricosuric drugs may be less effective in lowering SU levels as renal impairment worsens [4]. Uricase and pegloticase (Table 1), are highly effective in reducing SU levels, but are associated with high immunogenicity [8]. Their use should be limited to the treatment of selected severe cases [4].

If necessary, haemodialysis is a highly effective in removing SU and may also clear tophi [4]. However, as sudden drops in SU may trigger gout attacks, post-dialysis SU levels should be examined before administering SU-lowering drugs, which should typically be administered at lower dosages in patients undergoing haemodialysis [4].

Address gout flares with caution

Untreated gout flares generally subside within 2 weeks [4]. Colchicine is an effective treatment for gout flares in patients with normal renal function, but its use has been discouraged in those with renal impairment (Table 2). Exposure to colchicine increases in patients with moderate to severe renal impairment [14], leading to a greater risk of colchicine-related toxicity [15]. Oral, parenteral and intra-articular corticosteroids seem to be a safe and effective alternative to colchicine in this population (Table 2), but their use in certain patients is contraindicated, not recommended or requires caution [4].

Table 2 Treatment and prevention of gout flares in individuals with renal impairment, based on a review by Pascual et al. [4]
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With interleukin (IL)-1 activation being the trigger for gout-related inflammation, the anti-IL-1 agents canakinumab and anakinra are also effective in gout patients with renal impairment (Table 2) [4]. For example, used on-demand to treat and prevent gout flares, subcutaneous canakinumab 150 mg was more effective than on-demand intramuscular triamcinolone acetonide 40 mg [16], and a single dose of canakinumab ≥ 50 mg was more effective than daily colchicine 0.5 mg as prophylaxis [17].

Importantly, despite the general effectiveness of NSAIDs in treatment gout flares and as prophylaxis, they should not be used to treat gout in patients with renal impairment [4].

Evidence suggests that prophylaxis should continue for > 6 months, although the optimal duration of prophylaxis not yet clear [4]. In more severe cases, such as frequently flaring severe gout, combination therapy with multiple drugs (e.g. colchicine + a corticosteroid) may be temporarily required [4].

Educate to improve treatment adherence

Patients should be thoroughly educated about gout and its treatment, and any misconceptions about the condition should be addressed [4]. Proper education may improve adherence to gout treatment. For example, in patients with gout who received individualized education, 90% were adherent to gout treatment after 5 years, with 85% of these taking their prescribed medication ≥ 6 days a week [22].

Take home messages

When managing gout in patients with renal impairment:

  • Consider the renal function of the patient, and select the best treatment at the most appropriate dosage.

  • Titrate allopurinol dosages to achieve target SU levels (outdated practice to base dosage on CrCL).

  • Avoid or use low dosages of colchicine.

  • Be aware that many uricosuric drugs are not widely available, and may be of limited effectiveness in this patient population.

  • Educate patients about gout and its treatment to improve treatment adherence.