The Toxic-Ties Network

Renal hypoperfusion from capillary leak and cytokine storm — IL-2 and CAR-T cytokine release syndrome.

Renal electrolyte derangement — magnesium/potassium/calcium wasting (cisplatin, anti-EGFR antibodies) or retention (FGFR-inhibitor hyperphosphatemia, tumor-lysis hyperkalemia/hyperphosphatemia).

Direct death of tubular epithelial cells — the dose-limiting lesion of the platinums and zoledronate.

Damage to the filtration barrier — podocyte injury, FSGS and protein leak from VEGF and mTOR blockade.

Intratubular precipitation of drug or metabolite — high-dose methotrexate and tumor lysis crystals.

Endothelial injury with microvascular thrombi, hemolysis and thrombocytopenia — gemcitabine, mitomycin C, anti-VEGF.

Raised blood pressure — archetypally on-target loss of endothelial nitric oxide from VEGF-pathway blockade, studied as a pharmacodynamic marker of drug exposure. Other agents raise it too: vascular effects of BCR-ABL, BTK and RET inhibitors and of copanlisib; abiraterone's mineralocorticoid excess; androgen suppression or blockade.

The great mimic — a rise in creatinine from blocked tubular secretion (OCT2/MATE), NOT true injury. The GFR is intact; confirm with cystatin C before stopping effective therapy.

Immune-mediated inflammation of the renal interstitium — the signature kidney injury of checkpoint inhibitors.

Inappropriate water retention at the collecting duct — high-dose cyclophosphamide.

Bleeding inflammation of the bladder urothelium — classically acrolein injury from the oxazaphosphorines (prevented by mesna), but also reported as immune-related, intravesical-chemical, or radiation-recall injury.

Slow, cumulative tubulointerstitial scarring — fibrosis, tubular atrophy and glomerulosclerosis with no discrete acute phase. The nitrosourea (carmustine/lomustine) lesion and delayed radioligand (radiation) nephropathy; often irreversible and detected only as a creeping creatinine months to years later.

Global failure of proximal tubule reabsorption — glucosuria, phosphaturia and acidosis, classically from ifosfamide.

Drug-induced complex renal cysts — the distinctive ALK-inhibitor lesion, classically crizotinib. Usually asymptomatic, dose/duration-related, and they tend to regress when the drug is stopped.