PARTNERS WITH
Carboplatin
Platinum based Alkylating agents
MECHANISM OF ACTION
Binds to DNA and inhibits DNA replication leading to cell death/excreted in urine
MECHANISM OF KIDNEY INJURY
AIN (Acute interstitial nephritis), ATN (Acute tubular necrosis), TMA (thrombotic microangiopathy) (systemic/kidney limited), Water/electrolyte disturbances, CKD, has significant emetic potential leading to pre renal state like nausea, vomiting diarrhea
CLINICAL KIDNEY SYNDROME
AKI, Hematuria, Fanconi's Syndrome, Pre renal in setting of nausea, vomiting, diarrhea secondary to Carboplatin use
CARDIOVASCULAR ADVERSE EFFECTS
hypertension
LYTE ABNORMALITIES
Hypomagnesemia, Hypocalcemia, Non Nephrotic range proteinuria, Hyponatremia, Hypokalemia, Elevated BUN, Hypochloremia
RISK FACTORS
Pre existing kidney injury, prior cisplatin use, hypovolemia, older age, higher dose of chemo agent, concomitant nephrotoxic agents,
MITIGATION STRATEGIES
correct dosage of drug, volume expansion, correction of electrolytes abnormalities
SUGGESTIONS
Hold offending drug and rechallenge after AKI/proteinuria resolves, Volume expansion, Check UA with urine culture, Check urine analysis for cyrstals, WBC, RBC, etc, Check urine protein creatinine ratio, Check TMA work up (send haptoglobin, peripheral smear, LDH), dose adjustment as per eGFR
NOTES/COMMENTS
Carboplatin 0%; Platinum (from carboplatin): 15% to 40%
PHARMACOKINETICS
Molecular Weight
371.249 g/mol
Volume of Distribution
16 L
Plasma Protein Binding
Metabolism
intracellular deactivation, Minimally hepatic to aquated and hydroxylated compounds
Bioavailability
---
Half-life elimination
Carboplatin: 1 to 6 hours; Platinum: ≥ 5 days
Time to peak
2 to 4 hours
Excretion
Urine (60-80% as carboplatin within 24 hours; 3-5% as platinum within 1-4 days)
Dialyzable?
Partially. PD, 75% dose reduction. Dialysis 12-24 after Carboplatin administration
REF:
Uptodate
ADDIKD
ACKD part 2
https://pubmed.ncbi.nlm.nih.gov/10074593/#:~:text=Carboplatin%20is%20considered%20less%20nephrotoxic,than%20a%20liter%20per%20day
https://pubmed.ncbi.nlm.nih.gov/20118214/
PATHOLOGY SLIDES:
ENTRY UPDATES:
Tanazul Pariswala
United States
Sep 25, 2022