Cisplatin
Platinol · Platinum agent
Proximal tubular ATN + magnesium wasting; the archetype.
ATNLYTEPRE
SevereOpen →
Bisphosphonate
Zoledronic acid
Zometa · Zol
The tubule-toxic bisphosphonate — ATN driven by dose and infusion speed.
ModerateBisphosphonate · approved 2001
Hypercalcemia of malignancyBone metastasesMyeloma
Signature kidney injury
Acute Tubular Necrosis
Nephrotoxicity is the dose-limiting toxicity but largely avoidable; no precise population rate.
Source: Markowitz et al., Kidney Int 2003
Mechanism of kidney injury
Dose- and infusion-rate-dependent direct proximal tubular toxicity producing acute tubular necrosis.
Clinical presentation
AKI with a rising creatinine, often with partial recovery after withdrawal.
Onset
Acute — days to weeks after infusion(s).
Reversibility
Partially reversible
Anticancer mechanism
Nitrogen-containing bisphosphonate inhibiting osteoclast-mediated bone resorption. Hypercalcemia of malignancy, bone metastases and myeloma.
Management
Hold drug, hydration, supportive care.
Risk factors
- Rapid infusion
- High / frequent dosing
- Pre-existing CKD
- Volume depletion
Prevention
- Adequate hydration
- Slow infusion (≥15 min)
- Dose-adjust for CrCl
- Avoid if CrCl < 30–35
Note · The ATN pattern distinguishes it from pamidronate's collapsing FSGS.
Where it strikes
Nephron segments
Proximal Tubule
Bulk reabsorption + drug uptake (OCT2, OATs)
Injury signatures
Acute Tubular Necrosis
Beyond the kidney
Class-level context for the major non-renal toxicities of bisphosphonates.
Musculoskeletal
Myalgia, myositis, rhabdomyolysis, ONJ
- Osteonecrosis of the jaw, hypocalcemia, acute-phase reaction
Evidence
2 peer-reviewed references. Citation metadata via PubMed / NLM.
LandmarkToxic acute tubular necrosis following treatment with zoledronate (Zometa).Markowitz GS et al. · Kidney Int 2003 · PMID 12787420Landmark series establishing zoledronate as a cause of toxic ATN.PMIDBisphosphonate nephrotoxicity.Perazella MA et al. · Kidney Int 2008 · PMID 18685574Contrasts zoledronate ATN with pamidronate collapsing FSGS.