Clin Exp Dermatol 2024; 49:1052–1055
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Advance access publication date: 15 April 2024 Concise Report
A report on the safety of acitretin use in patients with
renal failure on haemodialysis
Paul Jaehoon Shim ,1,2 Jessica Leigh Quintos,3 Khushnood Faraz, 2 Isabelle Taylor Smith,3
Amy Jiayue Petty, 2 Matthew Bottomley,4,5 Lee Emerson Wheless3,6 and Melodi Javid Whitley 2
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1Department of Medicine, University of Arizona College of Medicine, Phoenix, AZ, USA
2 Department of Dermatology, Duke University School of Medicine, Durham, NC, USA
3 Department of Dermatology, Vanderbilt School of Medicine, Nashville, TN, USA
4 CAMS Oxford Institute, University of Oxford, Oxford, UK
5 Oxford Kidney and Transplant Unit, Churchill Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, UK
6 Tennessee Valley Healthcare System VA Medical Center, Nashville, TN, USA
P.J.S and J.L.Q. contributed equally. L.E.W. and M.J.W. are co-senior authors.
Correspondence: Melodi Javid Whitley. Email: [Link]@[Link]
Abstract
Acitretin, commonly used for severe psoriasis and keratinocyte carcinoma chemoprevention in high-risk patients, is contraindicated in patients
with end-stage renal disease (ESRD) on haemodialysis (HD). However, these patients often lack medication choices and in certain clinical sce-
narios the benefits of acitretin may outweigh the potential risks. We identified 24 patients with ESRD on HD undergoing acitretin treatment
from the Duke and Vanderbilt University Medical Centers. While adverse effects were common, they were not a frequent cause of treatment
discontinuation among patients. We also found no association between acitretin treatment and hospital admissions or mortality. Lastly, we found
statistically significant increases in alkaline phosphatase (ALP; P = 0.03) and total bilirubin (P < 0.001) when patients were receiving acitretin and
HD compared with baseline. However, there was no dose dependency or temporal association with acitretin or HD initiation. Based on these
preliminary findings, we find that acitretin may safely be used in patients receiving HD, with close monitoring of ALP and bilirubin.
Acitretin is a hepatically metabolized second-generation reti- Explorer query platform and the Vanderbilt University
noid that acts by binding to intracellular retinoid receptors Medical Center Synthetic Derivative database, using the
to modulate gene transcription in order to induce cellular respective International Classification of Diseases codes
differentiation, proliferation and keratinization. It is used for (Table S1; see Supporting Information). Manual chart
severe chronic psoriasis and chemoprevention of keratino- review was performed to identify our final cohort (Figure
cyte carcinomas (KCs) in solid organ transplant recipients. 1). Data collected included patient demographics, acitre-
Acitretin has been shown to be effective in managing pus- tin dosage and duration, acitretin indications, adverse
tular, erythrodermic and plaque-type psoriasis,1 as well as effects experienced while taking acitretin, acitretin dis-
in reducing the incidence of both actinic disease and KCs in continuations, hospital admissions and mortality while
transplant patients.2 It is generally contraindicated in patients using acitretin or within 6 months of discontinuation.
with end-stage renal disease (ESRD) on haemodialysis (HD), Additionally, baseline minimum laboratory values were
based on a single study, which showed that acitretin was collected 3–6 months prior to starting either acitretin or
not dialysed and that plasma blood concentrations of acitre- HD, and maximum laboratory values were collected while
tin were 53% lower than in healthy individuals. 3 However, patients were receiving both acitretin and HD. To deter-
there are certain clinical scenarios in which the benefits of mine whether there were statistically significant increases
acitretin use may outweigh the potential risks in patients in laboratory values, a Wilcoxon signed rank test was per-
with ESRD. Currently, no studies have investigated whether formed using Prism (GraphPad, La Jolla, CA, USA). We
patients with renal failure on HD can safely tolerate acitretin. identified 24 patients with ESRD who were taking acitre-
Therefore, our aim was to report the safety outcomes of tin while on HD (Table 1). We were able to group these
this patient population by conducting a retrospective chart patients into 2 categories: 11 patients who were receiving
review of patients with renal failure on HD receiving acitretin acitretin treatment and then started HD, and 13 patients
treatment at several tertiary care centres. who were on HD and then started acitretin treatment.
Interestingly, the median [interquartile range (IQR)] age
of patients in the latter group [66 years (IQR 59–68)] was
Report greater than that of patients in the former [57 years (IQR
51–63)]. The most common overall indications for acitretin
Patients with ESRD on HD while taking acitretin were included KC chemoprevention and psoriasis, while cuta-
identified on the Duke Enterprise Data Unified Content neous T-cell lymphoma, pompholyx and pityriasis rubra
Accepted: 14 March 2024
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Acitretin safety in renal failure and haemodialysis, P.J. Shim et al. 1053
Table 1 Study cohort data related to demographics, acitretin
indications, adverse effects, discontinuations, hospital admission and
mortality
Acitretin → HD HD → acitretin
(n = 11) (n = 13)
Race
White 8 (73) 12 (92)
Black 3 (27) 1 (8)
Sex
Male 10 (91) 11 (85)
Female 1 (9) 2 (15)
Age at HD initiation, years; 57 (51–63) 51 (44–54)
median (IQR)
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Age at acitretin initiation, 54 (52–59) 66 (59–68)
years; median (IQR)
Acitretin indications
Psoriasis 5 (45) 2 (15)
Chemoprevention 5 (45) 9 (69)
Other 1 (9) 2 (15)
Acitretin adverse effectsa 0 (0) 6 (46)
Hypertension 0 (0) 1 (8)
Headaches 0 (0) 2 (15)
Vision changes 0 (0) 0 (0)
Bone growths 0 (0) 1 (8)
Avascular necrosis 0 (0) 1 (8)
Other 0 (0) 4 (31)
Acitretin discontinuations 6 (55) 9 (69)
Due to adverse effects 0 (0) 2 (15)
Hospital admissions
While on acitretin 5 (45) 6 (46)
Related to acitretin 0 (0) 0 (0)
Mortality 4 (36) 3 (23)
While on acitretin 2 (18) 1 (8)
Within 6 months of 2 (18) 2 (15)
discontinuing acitretin
Mortality related to acitretin 0 (0) 0 (0)
Data are presented as n (%) unless otherwise stated. HD, haemodialy-
sis. aSome patients experienced more than one adverse effect.
Figure 1 Flow diagram of identification, screening, eligibility
and inclusion of patients with end-stage renal disease (ESRD) on
haemodialysis (HD) receiving acitretin therapy at Duke University
Medical Center and Vanderbilt University Medical Center. discontinuing acitretin related to chronic graft failure, sep-
sis, myocardial infarction and unknown causes. However,
no hospital admissions or mortalities could be attributed to
pilaris were also found. Dosing schedules included 10 mg acitretin.
daily, 25 mg daily and 25 mg every other day. In general, for each of the laboratories we investigated,
Patients received acitretin treatment for a total of 763 the clinically significant end of the range was only reached
patient months with a mean (SD) of 31.8 (31.9) months per with elevated values. Thus, we compared patients’ baseline
patient. Six patients developed adverse effects attributable minimum laboratory values 3–6 months prior to beginning
to acitretin, as documented in their health records, includ- acitretin or HD treatment with their maximum laboratory
ing headache, hypertension (systolic blood pressure > 140 values while on acitretin and HD. With regard to hepatic
mmHg), bone growths, avascular necrosis, hypertriglyc- function and lipid values, there were statistically signifi-
eridaemia (triglycerides > 300 mg dL–1), lower-extremity cant differences between baseline and maximum values
oedema, pruritis and cheilitis. All six of these patients had of alkaline phosphatase (ALP; P = 0.03) and total bilirubin
begun acitretin treatment after having been on HD. While 15 (P < 0.001; Figure 2). However, we did not find any tempo-
patients discontinued acitretin, only 2 discontinued owing to ral associations of laboratory value increases in relation to
adverse effects of acitretin. Indications for discontinuation beginning acitretin or HD treatment. Specifically, maximum
included drug cost, hospitalizations, hospice placement and ALP values were seen 13, 21 and 41 months after acitretin
disease improvement. No dose dependency was observed initiation and maximum total bilirubin values were seen 5
with adverse effects. Eleven patients were admitted to and 145 months after acitretin initiation. Statin treatment
hospital while receiving acitretin, related to adrenal insuf- was discontinued in one patient with elevated triglyceride
ficiency, hypovolaemia, transplant complications, hyper- levels; however, the levels resolved to baseline after restart-
volaemia, infection, pulmonary oedema and scheduled ing the statin.
surgeries. Additionally, there were three mortalities among To our knowledge, we report the first cohort study describ-
patients taking acitretin related to respiratory failure and ing acitretin use in patients with ESRD on HD, a high-risk
unknown causes, and four mortalities within 6 months after cohort who often lack alternative treatment modalities. We
1054 Acitretin safety in renal failure and haemodialysis, P.J. Shim et al.
Downloaded from [Link] by Harvard Library user on 27 August 2024
Figure 2 Comparison of aspartate aminotransferase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), total bilirubin, triglycerides,
low-density lipoprotein (LDL), high-density lipoprotein (HDL) and cholesterol values taken at baseline vs. maximum values during treatment with
acitretin. Data points in red represent patients with baseline laboratory values 3–6 months prior to starting acitretin who later began haemodialysis
(HD). Data points in blue represent patients with baseline laboratory values 3–6 months prior to starting HD who later began acitretin. Patients
without both baseline and maximum laboratory values were excluded. Grey regions indicate the normal range of values. Laboratory values were not
differentiated between fasting and nonfasting. ns, nonsignificant. Adjusted *P < 0.03; **P < 0.002.
identified 24 patients and found that few patients discontin- have shown that there was no deterioration in renal function
ued the medication due to adverse effects, and no admis- while taking acitretin.5,6 Our findings suggest that acitretin
sions or mortalities were related to acitretin. Additionally, may safely be used in patients receiving HD, and acitretin
there was no dose dependency regarding adverse effects. may be safely continued in those initiating HD. However,
Adverse effects were seen only among those already ALP and total bilirubin levels should be carefully monitored
on HD when acitretin was started, although this might and interpreted based on the particular clinical context.
be related to the HD itself, as patients in this group had However, given the limited cohort size, we cannot exclude
started HD, on average, 15 years before starting acitretin the possibility of adverse effects on laboratory results and
treatment. The overall mortality in our cohort was 29%, therefore recommend that these patients be monitored in
which is similar to that commonly observed in patients on line with recommendations, similar to the general popula-
HD (30%),4 suggesting that our cohort was representative tion. To further validate the safety of acitretin in this patient
of patients on HD. population, larger trials are required.
Although there was a statistically significant difference
between baseline and maximum values of ALP (P = 0.03)
and total bilirubin (P < 0.001), our methods tended to over- Learning points
estimate the difference between the minimum and maxi-
mum values and thus may not represent the true impact • Acitretin may safely be used in patients with end-stage
of starting either acitretin or HD treatment. Furthermore, renal disease receiving haemodialysis (HD).
the increase in bilirubin observed was not clinically signif- • Acitretin use in this patient population has not been
icant and was not an indication to discontinue treatment. shown to have any association with rates of hospital
Despite recommendations to monitor lipids during acitre- admission or mortality.
tin therapy, we found no significant changes. This is an • Adverse effects may be more common in patients who
important consideration in patients on HD, who exhibit a start acitretin after having been on HD.
markedly increased risk of cardiovascular complications. • Close monitoring of alkaline phosphatase and total biliru-
Furthermore, previous studies evaluating acitretin use as bin levels with clinical observation should be performed
KC chemoprevention in renal transplant patients not on HD in this patient population.
Acitretin safety in renal failure and haemodialysis, P.J. Shim et al. 1055
Funding sources Supporting Information
L.E.W. is supported by the US Department of Veterans Additional Supporting Information may be found in the
Affairs Clinical Sciences R&D Service (IK2 CX002452). The online version of this article at the publisher’s website.
views expressed in this article are those of the authors
and do not necessarily reflect the position or policy of the
Department of Veterans Affairs or the United States gov-
ernment. M.B. is supported by the Chinese Academy of References
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