Cisplatin
Platinol · Platinum agent
Proximal tubular ATN + magnesium wasting; the archetype.
ATNLYTEPRE
SevereOpen →
Platinum agent
Carboplatin
Paraplatin · Carbo
Cisplatin's kidney-sparing cousin — dosed by GFR, limited by marrow not kidney.
MildSecond-generation platinum · approved 1989
OvarianLungGerm-cellHead & neck
Signature kidney injury
Acute Tubular Necrosis
Representative incidence5%
Clinically significant nephrotoxicity uncommon at standard doses; emerges mainly at high/myeloablative doses.
Source: Gupta et al., Adv Chronic Kidney Dis 2021
Toxicity fingerprint
Tap a signature to trace where it strikes the nephron.
0%incidence
SeverityMild
ReversibilityReversible
Evidence0 refs
Nephron map
Proximal TubuleBulk reabsorption + drug uptake (OCT2, OATs)
Distal Tubule / Collecting DuctFine-tuning of Na, K, Mg, acid & water
Acute Tubular Necrosis
Direct death of tubular epithelial cells — the dose-limiting lesion of the platinums and zoledronate.
Mechanism of kidney injury
Shares the proximal tubular uptake and injury pathway of cisplatin but with far lower reactivity, so tubular toxicity is modest except in high-dose stem-cell-transplant regimens.
Clinical presentation
Usually mild or asymptomatic GFR decline; electrolyte wasting much less frequent than cisplatin. Thrombocytopenia, not kidney injury, is dose-limiting.
Onset
Acute when it occurs (high-dose regimens).
Reversibility
Reversible
Anticancer mechanism
Same DNA-adduct mechanism as cisplatin but a more stable leaving group slows aquation. Dosed by the Calvert formula, AUC × (GFR + 25).
Management
Dose reduction, supportive care.
Risk factors
- High / myeloablative dosing
- Pre-existing CKD
- Prior cisplatin
Prevention
- GFR-based (Calvert) dosing
- Hydration
- Avoid concurrent nephrotoxins
Note · Preferred over cisplatin when renal sparing matters.
Where it strikes
Nephron segments
Proximal Tubule
Bulk reabsorption + drug uptake (OCT2, OATs)
Injury signatures
Acute Tubular NecrosisElectrolyte Wasting
Beyond the kidney
Class-level context for the major non-renal toxicities of platinum agents.
Neurologic
Neuropathy, encephalopathy, ICANS, PRES
- Peripheral neuropathy (esp. oxaliplatin) and ototoxicity (cisplatin)
Hematologic
Cytopenias, thrombosis, TMA
- Myelosuppression — thrombocytopenia prominent with carboplatin
Gastrointestinal
Diarrhea, colitis, mucositis, perforation
- Severe nausea and vomiting
Evidence
5 peer-reviewed references. Citation metadata via PubMed / NLM.
LandmarkCarboplatin dosage: prospective evaluation of a simple formula based on renal function.Calvert AH et al. · J Clin Oncol 1989 · PMID 2681557The landmark Calvert formula deriving dose from GFR to limit toxicity.PMIDCarboplatin pharmacokinetics in children: the development of a pediatric dosing formula.Newell DR et al. · J Clin Oncol 1993 · PMID 8246021Pediatric GFR-based dosing formula.PMIDComparative study of cisplatin and carboplatin on pharmacokinetics, nephrotoxicity and effect on renal nuclear DNA synthesis in rats.Yasumasu T et al. · Pharmacol Toxicol 1992 · PMID 1508841Explains carboplatin's lower nephrotoxicity via less renal platinum accumulation.PMIDConventional Chemotherapy Nephrotoxicity.Gupta S et al. · Adv Chronic Kidney Dis 2021 · PMID 35190107Authoritative onconephrology review of platinum incidence and dose modification.PMIDAnticancer drug-induced kidney disorders.Kintzel PE et al. · Drug Saf 2001 · PMID 11219485Review of dose-related platinum renal dysfunction and protective agents.
Related agents
Other agents sharing the same signature kidney injury.