Approximately one-third of all patients treated with cisplatin develop renal dysfunction after a single dosage of cisplatin. Germline genetic polymorphisms may cause variations in cisplatin pharmacokinetics and in the ability of epithelial kidney cells to take up cisplatin and repair cisplatin-induced Deoxyribonucleic Acid (DNA) damage. Knowledge concerning which genotypes are associated with cisplatin-induced nephrotoxicity may help to identify at-risk patients and initiate strategies, such as using lower or fractionated cisplatin doses or avoiding cisplatin altogether, to prevent Acute Kidney Injury (AKI).
Approximately one-third of all patients treated with cisplatin develop renal dysfunction after a single dosage of cisplatin. Germline genetic polymorphisms may cause variations in cisplatin pharmacokinetics and in the ability of epithelial kidney cells to take up cisplatin and repair cisplatin-induced DNA damage. Knowledge concerning which genotypes are associated with cisplatin-induced nephrotoxicity may help to identify at-risk patients and initiate strategies, such as using lower or fractionated cisplatin doses or avoiding cisplatin altogether, to prevent AKI. Patient written informed consent will be taken prior to study conductance 1. Full laboratory evaluation before and after cisplatin administration including: (Complete Blood Count) CBC, liver and renal functions. glomerular filtration rate (GFR), and estimated glomerular filtration rate (eGFR) Serum electrolytes. Marker of nephrotoxicity: Cystatin C. 2. Sample Collection and single nucleotide polymorphism (SNP) Genotyping: Venous blood (2 mL) will be collected from each subject into tubes containing 50 mmol of Ethylenediamine tetraacetic acid (EDTA) per liter and genomic DNA will be isolated with the GeneJET Whole Blood Genomic DNA purification Mini kit, according to manufacturer's instructions. Polymorphisms will be assessed using the TaqMan based real-time polymerase chain reaction (PCR) assay. This study aims to assess the influence of single nucleotide polymorphisms in the DNA repair gene Excision Repair Cross Complementation group 1 (ERCC1) and Cisplatin uptake transporter gene Organic Cation Transporter 2 (OCT2) on cisplatin-induced nephrotoxicity by assessment of the following: 1. Occurrence of nephrotoxicity. 2. Degree of renal impairment. 3. Changes in traditional and novel protein biomarkers for AKI.
Study Type
OBSERVATIONAL
Enrollment
89
ERCC1 is a rate-limiting enzyme in the nucleotide excision repair pathway that is known to repair cisplatin-induced DNA damage. Polymorphisms in ERCC1 are known to affect response to cisplatin treatment. A mechanism explaining the effect of the ERCC1 polymorphism on the kidney may be that the homozygous carriers of this rs3212986 allele might have a greater capacity to repair cisplatin-induced DNA damage in their kidney epithelia, and thus would be more resistant to cisplatin-induced nephrotoxicity
OCT2 is expressed on the basolateral membrane of Proximal Tubular Epithelial Cell (PTEC) and plays a central role in cisplatin uptake into tubular cells. Genetic variants in the cisplatin uptake transporter OCT2 showed association with the preservation of kidney function. Patients with the CT genotype in OCT2 polymorphism rs596881 exhibited positive changes in eGFR compared to individuals with the wild type CC genotype
Faculty of medicine, Ain Shams University
Cairo, Egypt
Serum Creatinine
available in patient profile
Time frame: Change from baseline at the end of cycle 1 (each cycle is 28 days)
Serum Creatinine
available in patient profile
Time frame: Change from baseline at the end of cycle 2 (each cycle is 28 days)
cystatin c
measured by Human cystatin C ELISA kit
Time frame: Change from baseline at the end of cycle 2 (each cycle is 28 days)
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