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What types of adverse kidney events are associated with traditional chemotherapy agents?
Chemotherapeutic agents can cause kidney disease that fits the traditional grouping into pre-renal, intrarenal, and post-renal states.
However, most of these agents cause intrinsic kidney injury at various parts of the nephron, with a couple of notable exceptions.
For example, interleukin-2 (IL-2) is associated with capillary leak syndrome, which can cause intravascular volume depletion and prerenal azotemia.
Post-renal injury is rare with chemotherapy agents, but case reports have linked cyclophosphamide with bladder outlet obstruction from vesicular thrombi in the setting of hemorrhagic cystitis.
Intrinsic causes can be tubular, interstitial toxicities, but TMA and glomerular diseases have been reported as well.
Chemotherapeutic Agents Associated With Acute Kidney Injury and Other Forms of Kidney Injuries.
| CHEMOTHERAPEUTIC AGENT | MECHANISM OF INJURY | CLINICAL PRESENTATION | PROPHYLAXIS |
|---|---|---|---|
| Azacytidine | Proximal and distal tubular injury | Fanconi syndrome, and polyuria | None established. Self-limiting |
| Bisphosphonate (Pamidronate, Zoledronate) | Acute tubular injury, collapsing FSGS, MCD | AKI | Avoid use of zoledronate in patients with CrCl <35 mL/min. In those patients, reduced doses of pamidronate |
| Cisplatin | Toxic damage to renal tubule | AKI, magnesium wasting, diabetes insipidus, Fanconi syndrome | Volume expansion, magnesium replacement |
| Clofarabine | ATN, FSGS | Sudden onset AKI | None established |
| Cyclophosphamide | Increased ADH activity | Hyponatremia | None established. Self-limiting after discontinuation of drug |
| Gemcitabine (cell cycle-specific pyramidine antagonist) | TMA | HTN, TMA, proteinuria, and AKI ± Edema | None established |
| Ifosfamide | Proximal ± distal tubular injury | ATN (often subclinical); Type 2 RTA with Fanconi syndrome; severe electrolyte disarray; nephrogenic diabetes insipidus. | Moderate-severe nephrotoxicity generally occur with cumulative doses >100 g/m 2 Avoid concurrent use of cisplatin |
| Interferon (alpha, beta, or gamma) | Podocyte injury resulting in MCD or FSGS | Nephrotic syndrome, AKI | None established |
| Interleukin-2 | Kidney hypoperfusion due to capillary leak, kidney vasoconstriction | AKI, Hypotension, proteinuria, pyuria | None established |
| Methotrexate | Nonoliguric AKI | Tubular obstruction by precipitation of methotrexate and 7-hydroxymethotrexate | Volume expansion; urinary alkalization; leucovorin rescue; dose reduction for GFR 10–50 mL/min |
| Mitomycin C | AKI | TTP and HUS (associated with cumulative dose >60 mg | None established |
| Nitrosoureas | Glomerular sclerosis and tubulointerstitial nephritis | Insidious, often irreversible kidney injury | Volume expansion |
ADH , Antidiuretic hormone; AKI , acute kidney injury; ATN , acute tubular necrosis; CrCl , Creatinine Clearance; FSGS , focal segmental glomerulosclerosis; GFR , glomerular filtration rate; HTN , hypertension; HUS , hemolytic uremic syndrome; MCD , minimal change diseases; RTA , renal tubular acidosis; TMA , thrombotic microangiopathy; TTP , thrombotic thrombocytopenic purpura.
