Doxorubicin
Adriamycin · Anthracycline
Experimental podocyte model; clinical proteinuria rare.
GLOM
MildOpen →
Bisphosphonate
Pamidronate
Aredia · Pam
The first drug ever tied to collapsing FSGS — a podocyte, not tubular, toxin.
SevereBisphosphonate · approved 1991
Hypercalcemia of malignancyMyeloma bone disease
Signature kidney injury
Glomerular Injury / Proteinuria
Not well quantified; the histopathologic pattern comes from case series, notably at higher-than-approved doses.
Source: Markowitz et al., JASN 2001
Mechanism of kidney injury
Direct podocyte toxicity producing collapsing focal segmental glomerulosclerosis.
Clinical presentation
Nephrotic-range proteinuria, edema and progressive renal failure.
Onset
Subacute — weeks to months of therapy.
Reversibility
Often irreversible
Anticancer mechanism
Nitrogen-containing bisphosphonate inhibiting osteoclasts. Hypercalcemia of malignancy and myeloma bone disease.
Management
Discontinue; supportive nephrotic care.
Risk factors
- High dose
- Prolonged use
- Pre-existing CKD
Prevention
- Use approved doses
- Monitor urine protein and creatinine
- Hydration
Note · Pamidronate → podocyte/FSGS; zoledronate → tubule/ATN. A useful contrast pair.
Where it strikes
Nephron segments
Glomerulus
Filtration barrier (podocytes + endothelium)
Injury signatures
Glomerular Injury / Proteinuria
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
3 peer-reviewed references. Citation metadata via PubMed / NLM.
LandmarkCollapsing focal segmental glomerulosclerosis following treatment with high-dose pamidronate.Markowitz GS et al. · J Am Soc Nephrol 2001 · PMID 11373339Landmark series — first association of collapsing FSGS with a therapeutic agent.PMIDCollapsing glomerulopathy.Schwimmer JA et al. · Semin Nephrol 2003 · PMID 12704581Review of collapsing glomerulopathy and its pamidronate association.PMIDBisphosphonate nephrotoxicity.Perazella MA et al. · Kidney Int 2008 · PMID 18685574Details pamidronate collapsing FSGS versus zoledronate ATN.
Related agents
Other agents sharing the same signature kidney injury.