Platinum Accumulation in the Kidney and Changes in Creatinine Clearance following Chemotherapy with Cisplatin in Humans

Abstract

To evaluate the effects of repeated administration of cisplatin on kidney platinum (Pt) accumulation and renal function, Pt content in the kidney was determined in 31 autopsy cases and changes in creatinine clearance (Co) were retrospectively assessed in 26 of 31 autopsy cases. There was no significant correlation between the cumulative dose of cisplatin and Pt content in the kidney. However, the kidney Pt level was correlated with the dose of cisplatin injected within a 7-month period prior to the patient’s death. We suggest that the dose of cisplatin injected during a relatively short period before a patient’s death affects Pt content in the kidney. Neither the total dose of cisplatin nor the Pt content in the kidney was significantly correlated with the decrease in Co-following chemotherapy with cisplatin.

Gamma Camera Imaging of Platinum in Tumours and Tissues of Patients after Administration of191Pt-Cisplatin

“…Furthermore, studies on tissues obtained from autopsies from patients who had received cisplatin ante-mortem demonstrated a high concentration of platinum in the liver. Both Stewart et al (21) and Uosumi et al (22) found a linear relationship between cumulative cisplatin dose and hepatic platinum concentration. Tothill et al (23) found the platinum concentration in the liver at autopsy to be much higher than that in any other organ, 2.0% of the dose administered following cisplatin administration at least two months before death.…”

“…This is consistent with our results of 0.4 -0.6% of the amount of platinum administered in the two kidneys together during the first day. When studying autopsy material from patients receiving cisplatin, Stewart et al (21) found no correlation between renal cortical platinum concentrations and total cumulative platinum dose, whereas Uozumi et al (22) found a correlation between the platinum concentration in the kidney and the total cumulative platinum injected within a 6-month period prior to death in their autopsy material. The excretion of platinum via the urine is in good agreement with other studies (9,(23)(24)(25)(26).…”

Alterations in Cisplatin Pharmacokinetics and Its Acute/Sub-chronic Kidney Injury over Multiple Cycles of Cisplatin Treatment in Rats

“…13,25) This dosage is approximately 2-fold larger than the clinical dosing (highest recommended dosage: 100 mg/m 2 ); moreover, the relationship between the total dose of CDDP and renal function remains to be clarified. 31) Thus, in our laboratory, the nephrotoxicity in multi-cycle CDDP at various dosage is now in progress with the aim to reflect actual clinical settings.…”

Melatonin reduces oxidative stress and restores mitochondrial function in the liver of rats exposed to chemotherapeutics

“…In the present study we investigated the effect of intraperitoneal administration of PVB on liver oxidative status and mitochondrial function. Several antitumor drugs, such as cisplatin, doxorubicin, mitomycin C, and bleomycin exhibit ROS dependent apoptotic cell death (Uozumi et al, ; Partibha et al, ; Yagmurca et al, ; El‐Sayyad et al, ). Jie et al () have shown that cisplatin produce apoptotic liver cells.…”

“…Chronic low doses of cisplatin exposure may induce hepatotoxicity due to drug accumulation in liver (Uozumi et al, ). One mechanism of cisplatin's antitumor action involves its binding to DNA, resulting in a cascade of events that culminate in cell death.…”