Carboplatin
Paraplatin · Platinum agent
Kidney-sparing; GFR-dosed by the Calvert formula.
ATNLYTE
MildOpen →
Platinum agent
Cisplatin
Platinol · Cis
The archetypal nephrotoxin — concentrated in the proximal tubule by its own transporters.
SevereFirst-generation platinum · approved 1978
TesticularOvarianBladderLungHead & neck
Signature kidney injury
Acute Tubular Necrosis
Representative incidence30%
AKI in ~20–35% per cycle (classic teaching: ~1 in 3). Hypomagnesemia in 40–100%.
Source: Tang et al., Nat Rev Nephrol 2022; Manohar et al., J Nephrol 2017
Toxicity fingerprint
Tap a signature to trace where it strikes the nephron.
0%incidence
SeveritySevere
ReversibilityPartially reversible
Evidence0 refs
Nephron map
Vasculature / Endothelium
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
Actively imported into proximal tubular cells via the OCT2 and Ctr1 transporters, then concentrated in the S3 segment, where it triggers mitochondrial injury, oxidative stress, DNA damage and a pro-inflammatory (TNF-α) cascade. Also vasoconstricts the afferent arteriole and induces a distal magnesium-wasting tubulopathy.
Clinical presentation
Non-oliguric AKI with creatinine peaking day 4–7, hypomagnesemia (with secondary hypocalcemia/hypokalemia, tetany), polyuria and granular casts.
Onset
Acute — creatinine peaks ~day 4–7; magnesium wasting can persist for months.
Reversibility
Partially reversible
Anticancer mechanism
Forms intra- and inter-strand DNA cross-links that block replication and transcription, driving apoptosis. Backbone of testicular, ovarian, bladder, lung and head & neck regimens.
Management
Hold or discontinue, IV fluids, aggressive Mg/K repletion, supportive AKI care, dialysis if severe.
Risk factors
- High / cumulative dose
- Volume depletion
- Concurrent nephrotoxins
- Older age
- Pre-existing CKD
Prevention
- Vigorous IV saline hydration
- Magnesium supplementation
- Dose capping / splitting
- Substitute carboplatin when feasible
- Amifostine (selected protocols)
Note · The 'one-third' AKI figure and 40–100% hypomagnesemia range are definition-, dose- and hydration-dependent.
Where it strikes
Nephron segments
Proximal Tubule
Bulk reabsorption + drug uptake (OCT2, OATs)
Distal Tubule / Collecting Duct
Fine-tuning of Na, K, Mg, acid & water
Vasculature / Endothelium
Glomerular & peritubular capillaries
Injury signatures
Acute Tubular NecrosisElectrolyte WastingPrerenal / Hemodynamic AKI
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
6 peer-reviewed references. Citation metadata via PubMed / NLM.
LandmarkCisplatin nephrotoxicity: new insights and therapeutic implications.Tang C et al. · Nat Rev Nephrol 2022 · PMID 36229672Authoritative recent review of DNA damage, mitochondrial injury, regulated necrosis and inflammation in AKI and CKD.LandmarkCisplatin nephrotoxicity: mechanisms and renoprotective strategies.Pabla N et al. · Kidney Int 2008 · PMID 18272962Landmark mechanism review on tubular cell-death signaling and renoprotection.PMIDCisplatin nephrotoxicity: a review of the literature.Manohar S et al. · J Nephrol 2017 · PMID 28382507Mayo Clinic review linking cytotoxicity to OCT2/Ctr1 uptake and electrolyte wasting.PMIDCisplatin and hypomagnesemia.Lajer H et al. · Cancer Treat Rev 1999 · PMID 10212589Review of renal magnesium wasting (up to 90%) and prevention.PMIDToxicity, risk factors and management of cisplatin-induced toxicity: A prospective study.Ben Ayed W et al. · J Oncol Pharm Pract 2020 · PMID 32046580Prospective study of incidence and risk factors.PMIDEarly detection of acute cisplatin nephrotoxicity: interest of urinary monitoring of proximal tubular biomarkers.Bunel V et al. · Clin Kidney J 2017 · PMID 28979774Tubular biomarkers rise hours before serum creatinine.
Related agents
Other agents sharing the same signature kidney injury.