Rheumatology 2017;56:679–688

RHEUMATOLOGY doi:10.1093/rheumatology/kew293
Advance Access publication 3 August 2016

Review
Drug-induced hyperuricaemia and gout
C. Ben Salem1, Raoudha Slim1, Neila Fathallah1 and Houssem Hmouda2

Abstract
Hyperuricaemia is a common clinical condition that can be defined as a serum uric acid level >6.8 mg/dl

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(404 mmol/l). Gout, a recognized complication of hyperuricaemia, is the most common inflammatory arth-
ritis in adults. Drug-induced hyperuricaemia and gout present an emergent and increasingly prevalent
problem in clinical practice. Diuretics are one of the most important causes of secondary hyperuricaemia.
Drugs raise serum uric acid level by an increase of uric acid reabsorption and/or decrease in uric acid
secretion. Several drugs may also increase uric acid production. In this review, drugs leading to hyper-
uricaemia are summarized with regard to their mechanism of action and clinical significance. Increased
awareness of drugs that can induce hyperuricaemia and gout, and monitoring and prevention are key

R EV I E W
elements for reducing the morbidity related to drug-induced hyperuricaemia and gout.
Key words: hyperuricaemia, gout, drug-induced, uric acid, diuretics, organic anion transporters, prevention,
management

Rheumatology key messages

. Drug-induced-hyperuricaemia and gout present an emergent and increasingly prevalent problem in clinical
practice.
. Drugs raise serum uric acid level by increasing uric acid reabsorption and/or decreasing uric acid secretion in
gout.
. Adequate hydration and routine uric acid level monitoring should be encouraged for drugs known to induce
hyperuricaemia.

Introduction (Table 1). Several drugs may also increase uric acid
production.
Hyperuricaemia, the biochemical precursor to gout, is
Drug-induced hyperuricaemia and gout present an
usually defined as a serum uric acid level >6.8 mg/dl
emergent and increasingly prevalent problem in clinical
(404 mmol/l). Gout is the most common inflammatory arth-
practice. Although, the exact incidence and prevalence
ritis in adults, affecting an estimated 2.5% of the popula-
of drug-induced hyperuricaemia are unknown, Paulus et
tion in the UK and 3.9% in North America [1].
al. [4] noted that drugs were a major factor in the devel-
Hyperuricaemia may be present at up to 20% in some
opment of an elevated serum uric acid concentration in up
populations. It is an independent risk factor for all-cause
to 20% of the hyperuricaemic subjects in one hospital
cardiovascular and ischaemic stroke mortality [2].
study.
Elevated serum uric acid is also one of the best independ-
In this review, we shed light on the potential drugs caus-
ent predictors of diabetes, obesity and hypertension [3].
ing hyperuricaemia and gout, the mechanisms underlying
In addition to alcohol and purine-rich foods, drugs also
iatrogenic hyperuricaemia, and pertinent issues for the
play an important role in the pathogenesis of hyperuricae-
optimal management of drug-induced hyperuricaemia.
mia. They raise serum uric acid level by an increase of uric
Data were identified from MEDLINE and SCOPUS from
acid reabsorption and/or decrease in uric acid secretion
January 1960 to December 2015, and from Reactions
Weekly from 1992 to December 2015, regardless of the
language. We used the keywords hyperuricaemia and
1
Department of Pharmacovigilance, Faculty of Medicine of Sousse and gout with the subheading drug-induced, drug-interaction.
2
Medical Intensive Care Unit, Sahloul University Hospital, Sousse, Certain drugs were directly inserted as keywords, such as
Tunisia
diuretics, calcineurin inhibitors, pyrazinamide and cyto-
Submitted 29 December 2015; revised version accepted 29 June 2016
toxic drugs. Searches also included the terms blood and
Correspondence to: Chaker Ben Salem, Department of
Pharmacovigilance, Faculty of Medicine of Sousse, Avenue Mohamed uric acid. If there were relevant articles in many languages
Karoui, 4002 Sousse, Tunisia. E-mail: [email protected] that described the same topic, only English articles were

! The Author 2016. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: [email protected]
C. Ben Salem et al.

TABLE 1 Common drugs leading to hyperuricaemia

Drug Suggested mechanism

Anti-tubercular drugs Increased uric acid reabsorption (pyrazinamide)

Decreased uric acid secretion (pyrazinamide)
Reduction in the fractional excretion of uric acid (ethambutol)
Aspirin (low dose) Increased uric acid reabsorption
Decreased uric acid secretion
Cytotoxic chemotherapy Massive disruption of tumour cells
Diuretics Increased uric acid reabsorption in the proximal tubules
Increased uric acid secretion
Volume contraction
Immunosuppressant agents Increased uric acid reabsorption in the proximal tubules (ciclosporin)

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Decreased glomerular filtration rate secondary to afferent
arteriolar vasoconstriction (ciclosporin)
Reduced urate excretion (tacrolimus)
Inhibition of the synthesis of guanine nucleotide (mizoribine)
Fructose Increased nucleotide turnover and nucleotide synthesis
Increased uric acid tubular reabsorption
Lactate infusion Increased uric acid reabsorption
Nicotinic acid Increased uric acid reabsorption
Decreased uric acid secretion
Increased uric acid synthesis
Testosterone Increased uric acid reabsorption
Xylitol Increased purine degradation
Increased production of lactate

analysed. In this review, we focus only on drug-induced Loop diuretics and thiazide diuretics interact with renal
hyperuricaemia and gout. Alcohol and herbal remedies urate transporters. Like diuretics, many other drugs indu-
are excluded from this review. cing hyperuricaemia and gout may also interfere with
these renal urate transporters (Fig. 1). Loop diuretics
Causative drugs and thiazide diuretics inhibited basolateral organic anion
transporters OAT1 and OAT3, involved in the active
Diuretics uptake of plasma uric acid as a first step in its tubular
Diuretics are one of the most important causes of second- secretion in renal proximal tubules. Diuretics enter the
ary hyperuricaemia. The use of loop diuretics, thiazide di- proximal tubular cell from the blood side via OAT1 and
uretics and thiazide-like diuretics was associated with an OAT3 transporters and may be considered as competitive
increased risk of incident gout [5, 6]. The clinical features substrates of uric acid [13].
of diuretic-induced gout do not differ from other causes of Hydrochlorothiazide also increases significantly the uric
gout. The increase in serum uric acid concentration acid uptake via organic anion transporter OAT4 [14]. The
caused by diuretics may be noted within a few days exchange of diuretics for uric acid may lead to increased
after the initiation of treatment. It seems to be dose de- serum uric acid concentrations. Certain genetic variants in
pendent and persist during prolonged administration SLC22A11, which encodes OAT4, may lead to an
[7, 8]. The elevation in serum uric acid caused by diuretics increased transport capacity of OAT4, and the intake of
varies from 6 to 21% from corresponding baseline values diuretics may lead to an additional activation of the trans-
[9]. Uric acid level usually returned to the baseline a few porter, resulting in the highest incidence of gout in indi-
months after stopping diuretics. viduals [15]. However, this finding was not confirmed in a
Diuretics have different effects on the renal handling of recent study [16].
uric acid, and therefore the occurrence of gout. Gout Loop diuretics and thiazide diuretics may also increase
seems to be more strongly related to loop diuretics than serum uric acid levels by inhibiting the human voltage-
thiazides [10, 11]. Only a few studies have evaluated dif- driven drug efflux transporter NPT4 [13]. The latter is
ferences between diuretic subclasses or differences be- located at the apical side of renal proximal tubules and
tween individual diuretic agents. A recent study has induces uric acid secretion.
directly compared gout risk between two thiazides, Furosemide and hydrochlorothiazide were also
chlorthalidone and hydrochlorothiazide [12]. In this identified as substrates of human multidrug resistance-
study, patients taking chlorthalidone for hypertension associated protein 4 (MRP4). They inhibited MRP4-
have a similar risk of developing new-onset gout to pa- mediated uric acid transport, which might lead to hyper-
tients prescribed similar doses of hydrochlorothiazide. uricaemia [17].

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 Drug-induced hyperuricaemia and gout

FIG. 1 Interference of drug leading to hyperuricaemia with renal urate transporters

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The dotted arrows indicate drug interference. GLUT9: glucose transporter 9; I: inhibition; MRP4: multi-drug resistance-
associated protein 4; NPT: human sodium-dependent phosphate transporter; OAT: organic anion transporter;
S: stimulation; SMCT: Na+-dependent anion cotransporter; T: trans-stimulation; URAT1: urate/anion exchanger;
Adenosine triphosphate (ATP)-dependent unidirectional efflux transporter.

Moreover, diuretics produce sufficient salt and water hyperlactacidaemia sufficient to suppress tubular excre-
loss to lead to volume contraction, which stimulates uric tion of uric acid [19].
acid reabsorption. Indeed, intravenous saline in a dose For the sodium channel blockers amiloride and triam-
sufficient to prevent volume depletion prevents the hyper- terene, data are contradictory. Chronic use of triamterene
uricaemia induced by acute administration of intravenous was shown to induce hyperuricaemia without clinical evi-
furosemide and ethacrynic acid [18]. Volume contraction dence of gout in several studies, whereas no effect was
induced by thiazides leads to increased H+ secretion in the noted in other studies [20]. Amiloride has been shown not
proximal tubule via the apically located NHE3. to alter the uric acid level.
Consequently, cell pH increases, which in turn drives Like triamterene, studies of spironolactone have shown
urate uptake via OAT4 as a result of increased urate/ conflicting results on serum uric acid levels. Previous data
OH– exchange [7]. reported that spironolactone does not alter or tends to
Other factors may also contribute to the reduce the serum uric acid levels [21]. However, a
hyperuricaemic effect of diuretics. Furosemide induces recent study showed that low dose spironolactone

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C. Ben Salem et al.

increases serum uric acid levels in patients with chronic Ciclosporin, a calcineurin inhibitor, is considered the
kidney disease [22]. Roos et al. [23] investigated the effect most important risk factor for the development of gout in
of spironolactone on uric acid handling by the kidney in a transplant recipients [36]. In the pre-ciclosporin era,
small study. They found that spironolactone causes a de- hyperuricaemia was found in 25% of renal transplant
crease in uric acid renal clearance, probably mediated by patients, but the prevalence increased to over 80% after
the induced volume depletion and plasma renin activity the use of ciclosporin became widespread [37].
elevation, as with other diuretics, and, probably, inhibits Ciclosporin therapy may lead to an accelerated form of
endogenous uric acid production to approximately the gout, even with tophi occurring over a relatively short time
same degree as the clearance is decreased, so that period and in unusual locations including soft tissues,
serum uric acid concentration does not change. intraspinal sites and sacroiliac joints [38, 39]. Gouty arth-
ritis develops in 4–10% of all ciclosporin-treated patients
Anti-tubercular drugs [40]. The mean time from transplantation to the first epi-
Pyrazinamide, an anti-mycobacterial drug, not only in- sode of gout was a few months. Compared with patients

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duces hyperuricaemia, but may also lead to acute gouty who had hyperuricaemia without gout, those with epi-
attacks. It is a strong urate retention agent, causing a sodes of gout induced by ciclosporin were mostly men,
>80% reduction in renal clearance of uric acid at a were taking diuretics, and had more advanced renal dys-
300 mg therapeutic daily dose [24]. function [41]. Ciclosporin may induce an increase of prox-
Pyrazinecarboxylic acid or pyrazinoate (PZA), an active imal uric acid reabsorption, especially in the presence of
metabolite of pyrazinamide, increases serum uric acid volume depletion associated with diuretic use, and a de-
based on its trans-stimulatory effect on URAT1, which is crease in glomerular filtration rate secondary to afferent
a member of the organic anion transporter (OAT) family, arteriolar vasoconstriction [42, 43]. Experimental studies
causing the reabsorption of urate from the luminal side demonstrated that ciclosporin enhanced urate uptake via
into tubular cells [25]. Patients with renal hypouricaemia the human organic anion transporter OAT10, which may
and loss-of-function mutations in the gene for URAT1 lack be responsible for ciclosporin-induced hyperuricaemia
a full response to pyrazinamide, providing genetic con- [28].
firmation of the linkage between PZA and urate reabsorp- Tacrolimus, another calcineurin inhibitor, may also
tion [26]. cause hyperuricaemia in patients with renal transplant-
In addition, pyrazinamide inhibits OAT2 a protein ex- ation [44]. Hyperuricaemia rate of patients taking tacroli-
pressed at the basolateral membrane of human proximal mus was significantly lower than it was for those patients
tubule cells and implicated in the secretory urate transport taking ciclosporin [45]. However, there are also studies
[27]. OAT2 is a potential target of the anti-uricosuric effect that show no difference between the two drugs with
of pyrazinamide, as well as URAT1. regard to the occurrence of hyperuricaemia [46].
PZA interferes also with OAT10, an organic anion/dicar- Hyperuricaemia was also a common adverse event with
boxylate exchanger transporter. OAT10-mediated urate mizoribine, a potent immunosuppressant widely used in
uptake was elevated by an exchange with PZA [28]. Asia [47]. It mostly occurred within a few weeks and was
The incidence of hyperuricaemia in studies of patients usually transient. It may be due to the action of this drug,
undergoing combination therapy (isoniazide, rifampicin which inhibits the synthesis of guanine nucleotides [48].
and pyrazinamide) or therapy with pyrazinamide alone
varies widely from 43.4 to 86.3% [29, 30].
Ethambutol, another antitubercular drug, induces also a Nicotinic acid
significant increase in serum uric acid levels. This effect Nicotinic acid decreases urinary excretion of uric acid,
was observed mainly in the second, third and fourth week which may result in elevation of serum uric acid by
of ethambutol therapy [31]. However, an increase in the 14% and exacerbation of pre-existing gout [49]. It has
serum urate concentration was noted as early as 24 h after been reported to occasionally induce gout.
the administration of a single dose of ethambutol. Hyperuricaemia occurred in 41–78% of subjects receiving
Ethambutol therapy can not only lead to raised serum 3–6 g of nicotinic acid [49, 50]. Uric acid-raising effects of
uric acid but also precipitate gouty arthritis [32]. The with- nicotinic acid may also occur when the drug is given in
drawal of ethambutol led to a fall of serum uric acid levels therapeutic doses [51]. Nicotinic acid can increase urate
to normal. Re-introduction of the drug was followed by the reabsorption in the kidney, where nicotinate functions as a
reappearance of hyperuricaemia [33, 34]. The exact counter-ion for uric acid on URAT1 [25].
mechanism of ethambutol-induced hyperuricaemia has Nicotinate interferes also with the OAT10 transporter;
not been elucidated; however, a substantial reduction in OAT10-mediated urate uptake was elevated by an ex-
the fractional excretion of uric acid was noted in patients change with nicotinate [28]. OAT10 is a low affinity urate
treated with this drug [35]. transporter possibly involved in renal urate reabsorption,
like hOAT4. Its interactions with nicotinate may participate
Immunosuppressant agents in the pathogenesis of nicotinic acid-induced hyperuricae-
Hyperuricaemia and gout are common complications of mia. However, nicotinate may serve as a counter-ion for
organ transplantation, with a prevalence ranging from 5 to urate reabsorption in the proximal tubule only under thera-
84% for hyperuricaemia and 1.7 to 28% for gout [36]. peutic concentrations. Nicotinic acid may also inhibit

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 Drug-induced hyperuricaemia and gout

OAT2, which plays a role in renal uric acid uptake from as a rapid metabolism and a smaller effect on blood glu-
blood as a first step in tubular secretion [27]. cose concentration as compared with glucose infusions.
Changes in uric acid synthesis during nicotinic acid ad-
ministration have also been proposed as the explanation Fructose
of nicotinic acid-induced hyperuricaemia. Nicotinic acid Intravenous fructose administration or high fructose oral
and its amide derivative, nicotinamide, may increase the intake over several days is associated with increased uric
rate of purine biosynthesis de novo [20]. acid concentration. Fructose is strongly associated with
hyperuricaemia and an increased risk of gout in both gen-
Aspirin ders [57, 58].
The hyperuricaemic effect of fructose seems to be
In low dosages (60–300 mg once daily), aspirin reduces dose-related [59]. However, doses of fructose as low as
uric acid excretion, and may induce hyperuricaemia, 160 mg/kg body weight/h may also cause hyperuricaemia
whereas higher doses are uricosuric [52]. This paradoxical in critically ill patients [60]. Renal transplant recipients

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effect of salicylate can be explained by two modes of sa- treated with both calcineurin inhibitors (ciclosporin or
licylate interaction with the urate monocarboxylate ex- tacrolimus) are at similar risk of hyperuricaemia induced
changer (URAT1): acting as an exchange substrate to by fructose consumption [61].
facilitate urate reabsorption at low dose, and acting as Fructose increases intracellular and circulating uric acid
an inhibitor for urate reabsorption at high dose [53]. levels due to increased nucleotide turnover and nucleotide
Salicylate even at very low doses was able to inhibit synthesis (Fig. 2) [62]. Fructose may induce an increase of
MRP4-mediated urate transport [17]. In addition, salicyl- blood lactate concentration, which blocks urate excretion
ate may exert its hyperuricaemic effect through interacting and results in hyperuricaemia [63]. It may also increase the
with OAT1 and OAT3 (Fig. 1). In a recent large prospective risk of insulin resistance and subsequent hyperinsulinae-
case-crossover study, Zhang et al. [54] found that the use mia, decreasing uric acid excretion and further promoting
of low-dose aspirin (4325 mg/day) was associated with a hyperuricaemia [58]. It may, too, decrease urinary uric
higher risk of recurrent gout attacks. This association acid excretion, contributing to fructose-induced hyperur-
increased as the dose decreased. In this study the icaemia [59]. It facilitates the tubular reabsorption of urate,
effect of low-dose aspirin on recurrent gout attack was through glucose transporter 9 (GLUT9), a member of the
neutralized by concomitant use of allopurinol. GLUT family of hexose transporters.
Hypoalbuminaemia and concomitant treatment with di- Different alleles influence serum urate responses to
uretics enhanced the effects of aspirin on renal uric acid fructose. The SLC2A9 gene variant, which encodes
retention [52]. GLUT9, may influence the development of gout on expos-
ure to fructose particularly in European Caucasian popu-
Cytotoxic chemotherapy lations [64]. Furthermore, genetic variation in SLC17A1,
Cytotoxic drugs may induce tumour lysis syndrome (TLS). which encodes the human inorganic phosphate trans-
TLS, an oncological emergency, is characterized by mas- porter NPT1, an anion exchanger that secretes uric acid
sive disruption of tumour cells and dumping of intracellular into the urine, has also been associated with hyperuricae-
material into the blood causing hyperuricaemia and elec- mia and gout. In European people, variation in SLC17A1
trolyte abnormalities such as hyperkalaemia, hyperpho- influences serum urate and fractional excretion of uric
sphataemia, hypocalcaemia and metabolic acidosis. The acid throughout a fructose load [65].
release of cellular nucleic acids and purine nucleotides by Other non-glucose carbohydrates
these drugs induces uric acid production and may lead to
Glycerol consumption is also linked to an increase in
markedly increase serum uric acid levels with acute uric
serum urate concentration [66]. Glycerol stimulates uric
acid nephropathy in some cases. Hyperuricaemia induced
acid production, lowers cell ATP and increases glycerol
by cytotoxic drugs is the most serious type of drug-
3-phosphate [67]. Uric acid production correlates in-
induced hyperuricaemia. It usually develops 48–72 h
versely with ATP.
after cytotoxic therapy. TLS induces a higher mortality
Xylitol is a five-carbon sugar alcohol. It is used as a
rate, probably because of delayed presentation and
glucose substitute in total parenteral nutrition for diabetic
delayed recognition. In fact, if undiagnosed or diagnosed
patients. Infusion of xylitol leads to reduced gluconeogen-
too late, TLS can lead to death in 20–50% of cases [55].
esis, increased protein and muscle RNA content and
TLS is often associated with cytotoxic chemotherapy.
improved nitrogen balance [68]. It may increase the
However, it may also occur after treatment with dexa-
plasma concentrations of uric acid, hypoxanthine and
methasone, zoledronic acid, thalidomide and newer che-
xanthine by enhancing purine degradation. The increase
motherapeutic agents including bortezomib, rituximab
in purine degradation by xylitol may be due to the impair-
and ibrutinib [56].
ment of glycolysis in erythrocytes [69]. In addition, admin-
istration of large amounts of xylitol can produce lactic
Non-glucose carbohydrates acidosis [68].
The glucose substitutes used in total parenteral nutrition Sorbitol is converted to fructose when metabolized in
are fructose, glycerol, sorbitol and xylitol. The parenteral the liver and produces biochemical effects similar to those
infusion of these substrates has several advantages such of fructose on hepatic adenosine phosphate levels in

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C. Ben Salem et al.

FIG. 2 Non-glucose carbohydrate-induced hyperuricaemia

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": Increase; ADP: adenosine diphosphate; AMP: adenosine monophosphate; ATP: adenosine triphosphate; IMP: inosine
monophosphate.

humans, and can therefore increase uric acid production Lactate interacts with URAT1 [25]. This latter is an im-
[70]. Hyperuricaemia has been reported in a case of sorb- portant transporter of urate reabsorption in exchange for
itol overdose [71]. lactate at the apical membrane of the proximal tubules.
Therefore, lactate stimulates urate uptake, leading to
hyperuricaemia. In addition, lactate may also interfere
Lactate infusion with organ anion transporters OAT4 and OAT10 (Fig. 1).
Sodium lactate solution has many advantages and ap-
pears promising for resuscitation of critically ill patients Testosterone
[72]. However, high dose lactate infusion may induce Testosterone replacement therapy (TRT), used for pa-
hyperuricaemia by decreasing urinary excretion and the tients with female to male gender identity disorder, in-
fractional clearance of uric acid [73]. The infusion of lac- creases uric acid level in a dose-dependent manner. In
tate in healthy volunteers reduced the renal clearance of a recent study, the rates of serum uric acid increase
urate by 70–80%, resulting in an increase of 8–18% in after 3 months of TRT (intramuscular injection of testos-
serum urate [74]. terone enanthate) were 29 and 43.4% for a dosage of 125

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 Drug-induced hyperuricaemia and gout

TABLE 2 Miscellaneous drugs inducing hyperuricaemia and their suggested mechanism

Drug Suggested mechanism Reference

Acitretin Increased uric acid production [79]

Didanosine + ritonavir Unknown [80]
Filgrastim Increased myeloid turnover [81]
L-dopa Decreased uric acid excretion [82]
Omeprazole Unknown [83]
Peg-interferon + ribavirin Unknown [84]
Sildenafil Unknown [85]
Teriparatride Increased serum parathyroid hormone levels [86]
Ticagrelor Increased uric acid synthesis [87]
Decreased uric acid secretion

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Topiramate Inhibition of carbonic anhydrase isoenzymes [88]

and 250 mg every 2 weeks, respectively [75]. In addition, and the institution of appropriate anti-hyperuricaemic
the percentages of patients with onset of hyperuricaemia agents. Withdrawal of the offending drug should be
(serum uric acid level 57.0 mg/dl) at 3 months after the based on an assessment of the benefit–risk ratio. When
initiation of TRT in these two dosage groups were, re- alternative therapy is available, the offending drug may be
spectively, 5 and 14.8%. Testosterone-induced gout has replaced by a drug that does not cause hyperuricaemia.
also been reported [76]. However, in certain cases, the offending drug is neces-
Testosterone treatment leads to increased serum uric sary. For example, the use of low-dose aspirin for preven-
acid levels and reduced renal excretion of uric acid [77]. tion of cardiovascular disease should not be suspended
The induction of Smct1 (SLC5A8), an Na+-dependent for patients with gout. Close monitoring of serum uric acid
anion cotransporter that collaborates with urate trans- when an individual is taking low-dose aspirin may help to
porter-1 in proximal tubular reabsorption of urate, by tes- avoid the risk of gout attacks. However, allopurinol or
tosterone seems to be the mechanism of the underlying uricosuric agents may be necessary in some cases of as-
testosterone-induced hyperuricaemia in males [78]. The pirin-induced gout [54].
serum uric acid elevation may be also, at least partially, In hypertensive patients (controlled on one or two medi-
attributed to an increase in muscle mass during the early cations) with acute thiazide-induced gout, the reduction of
phase of TRT [75]. the dose of thiazide rather than its discontinuation is an
appropriate option because drug-induced hyperuricaemia
Miscellaneous agents is dose-related [8]. In hypertensive patients (controlled
In addition to the drugs listed above, many miscellaneous on three or more medications) thiazide continuation with
agents may induce hyperuricaemia and gout (Table 2) dose reduction or pharmacological anti-hyperuricaemic
[79–88]. therapy, that is, allopurinol, should be considered.
However, the withdrawal of thiazide is a reasonable
Prevention and management option if serum uric acid is > 6 mg/dl independently of
the status of hypertension control [8].
Although, there are no published guidelines on how to Treatment of ciclosporin-induced acute attacks may be
prevent drug-induced hyperuricaemia, patients receiving difficult since interactions with NSAIDs may lead to
drugs known to induce hyperuricaemia should be encour- enhanced renal toxicity. Colchicine, if prescribed in
aged to maintain adequate hydration and have their uric these acute attacks, should also be used cautiously and
acid levels routinely monitored. These patients should the dose reduced. Corticosteroids are an effective alter-
also be monitored for symptoms that might precede the native to colchicine. In patients who develop ciclosporin-
onset of gout. induced hyperuricaemia and gouty arthritis with tophi,
Approximately two out of three patients with drug- benzbromarone, a uricosuric agent, may be useful. It
induced hyperuricaemia will remain asymptomatic [24]. should be initiated at a low dose and gradually increased,
In drug-induced asymptomatic hyperuricaemia, especially and liver function should be monitored closely. Allopurinol
with diuretics, treatment to control serum uric acid levels is also a useful alternative in these patients. Interestingly,
is rarely required. However, gouty episodes in patients the normalization of uric acid levels by allopurinol or benz-
with a personal or family history of established gout may bromarone reduced the tubulointerstitial disease and ar-
be aggravated by diuretic therapy in hypertensive pa- teriolar hyalinosis induced by ciclosporin [89].
tients. When gout develops the decision to continue ther- Ciclosporin and tacrolimus withdrawal may be con-
apy needs to be individualized, and so too does a decision sidered for transplant patients with recurrent, severe
to initiate allopurinol or a uricosuric drug [7]. gout that cannot be managed safely or effectively [90].
In drug-induced symptomatic hyperuricaemia and gout, The cornerstone management of TLS is prevention.
management includes the identification of offending drugs Prevention strategies may also include hydration plus

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C. Ben Salem et al.

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Funding: No specific funding was received from any fund- Rheum Dis 2015;74:1394–8.
ing bodies in the public, commercial or not-for-profit sec-
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FG. Effect of hypouricaemic and hyperuricaemic drugs on
the renal urate efflux transporter, multidrug resistance
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conflicts of interest.
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