1. Collapsing glomerulopathy (CG)—high-dose pamidronate
Pamidronate has been found to be associated with CG in patients with multiple myeloma and breast cancer. In these patients, pamidronate is used in higher doses to prevent skeletal complications. It is hypothesized that pamidronate affects the glomerular epithelial cells (1).
2. Thrombotic microangiopathy (TMA)—bevacizumab; anti-vascular endothelial growth factor (anti-VEGF) agent
TMA can occur any time after the initiation of treatment with anti-VEGF agents. TMA is rarely systemic with positive hemolytic parameters. Usually, the presentation is kidney limited. Drug-induced TMA can be divided into immune-mediated (type 1) and non-immune-mediated (type 2) syndromes. Immune-mediated syndromes are idiosyncratic, dose independent, and antibody mediated. Non-immune-mediated syndromes usually occur when high doses of a drug are given for a long period of time or sometimes even with a single drug exposure. Anti-VEGF agents usually cause type 2 drug induced TMA. Some of the proposed mechanisms are direct endothelial injury, genetic predisposition, and increased platelet aggregation. The majority are reversible following discontinuation of the drug (2).
3. Severe acute tubular necrosis (ATN)—ifosfamide
Ifosfamide is a chemotherapeutic agent usually used to treat metastatic germ cell testicular cancer and some types of pediatric sarcoma. Direct tubular injury is the most common complication of ifosfamide use. In vitro studies have shown that chloroacetaldehyde—a metabolite of ifosfamide—causes direct tubular injury. Also, another metabolite—acrolein—can lead to hemorrhagic cystitis (3).
4. Minimal change disease (MCD) and diffuse podocytopathy—doxorubicin
Doxorubicin (anthracycline antibiotic) is used in combination with other chemotherapeutic drugs to treat different types of cancers that affect the bladder, kidneys, breast, ovaries, and so on. It is also used to treat certain types of lymphomas and leukemias. Doxorubin causes severe ultra-structural changes to the podocytes in mice models as well as in humans, causing diffuse podocyte foot process effacement and MCD. Doxorubicin is one of the secondary causes of MCD. Treatment is withdrawal of the drug. Data are limited for the role of steroids in drug-induced MCD (4).
5. Lupus-like glomerulonephritis—ipilimumab
Ipilimumab is a completely humanized monoclonal antibody that targets cytotoxic T lymphocyte antigen 4. It is the first immune checkpoint inhibitor to be approved for the treatment of metastatic melanoma. Few cases of ipilimumab causing lupus-like nephritis are reported. An immune phenomenon has been postulated to cause this type of kidney injury. Early recognition and treatment with steroids pave the way to recovery (5).
References
- 1.↑
Perazella MA, Markowitz GS. Bisphosphonate nephrotoxicity. Kidney Int 2008; 74:1385–1393. doi: 10.1038/ki.2008.356
- 2.↑
Izzedine H, et al. Thrombotic microangiopathy and anti-VEGF agents. Nephrol Dial Transplant 2007; 22:1481–1482. doi: 10.1093/ndt/gfl565
- 3.↑
Nissim I, et al. Ifosfamide-induced nephrotoxicity: Mechanism and prevention. Cancer Res 2006; 66:7824–7831. doi: 10.1158/0008-5472.CAN-06-1043
- 4.↑
Bertani T, et al. Steroids and adriamycin nephrosis. Appl Pathol 1984; 2:32–38. PMID: 6525317; https://www.researchgate.net/publication/16671624_Steroids_and_Adriamycin_nephrosis
- 5.↑
Fadel F, et al. Anti-CTLA4 antibody-induced lupus nephritis. N Engl J Med 2009; 361:211–212. doi: 10.1056/NEJMc0904283