Izvorni znanstveni članak
https://doi.org/10.3325/cmj.2019.60.250
Dasatinib-induced nephrotic syndrome: a case of phenoconversion?
Inga Mandac Rogulj
orcid.org/0000-0001-5234-9464
; Department of Hematology Clinical Hospital Merkur, Zagreb, Croatia
Vid Matišić
; University of Zagreb School of Medicine, Zagreb, Croatia
Borna Arsov
; University of Zagreb School of Medicine, Zagreb, Croatia
Luka Boban
; University of Zagreb School of Medicine, Zagreb, Croatia
Alen Juginović
; 3School of Medicine, University of Split, Split, Croatia
Vilim Molnar
; University of Zagreb School of Medicine, Zagreb, Croatia
Dragan Primorac
; 3School of Medicine, University of Split, Split, Croatia
Sažetak
We present the case of a 33-year-old chronic myeloid leukemia
(CML) female patient, in whom the occurrence of
nephrotic syndrome, during the treatment with tyrosine
kinase activity inhibitors (TKIs), was potentially influenced
by transient phenoconversion. Seven years after the CML
diagnosis in 2004 and complete response, the patient experienced
pain in the mandible and extremities. After this,
imatinib was replaced by nilotinib, but generalized maculopapular
rash was presented and successfully treated with
antihistamines. The therapy was then discontinued due to
planned pregnancy, and the patient experienced a relapse
of CML with BCR-ABL/ABL1 transcripts of 18.9%. Dasatinib
was introduced, and CML was in remission. Two years later,
urine protein levels (6.19 g/L) and erythrocyte sedimentation
rate were elevated (ESR = 90 mm/3.6 ks). The patient
was diagnosed with nephrotic syndrome. With dasatinib
dose reduction, urine protein level returned to the reference
range. In order to determine the best genotype-guided
therapy, the patient underwent pharmacogenomic
testing, showing a homozygous CYP3A4 genotype *1/*1,
associated with extensive metabolizer (EM) enzyme phenotype,
typical for normal rates of drug metabolism for TKIs.
However, this was inconsistent with nephrotic syndrome
occurrence. A possible explanation would be CYP3A4 EM
genotype coding a poor metabolizer enzyme phenotype,
leading to the drug accumulation in the patient’s blood.
This transient phenoconversion can be explained by inflammation
with elevated ESR during nephrotic syndrome.
This case shows that a broader approach that recognizes
genetic, clinical, and epigenomic factors is required for a
quality decision on the personalized therapy regimen.
Ključne riječi
Hrčak ID:
240036
URI
Datum izdavanja:
15.6.2019.
Posjeta: 670 *