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    Light microscopy: Jones silver stain, proliferation of visceral epithelial cells and collapse of glomerulus known as collapsing focal segmental glomerulosclerosis (FSGS). Image credit: K.S. Vinay.

  • View in gallery

    Light microscopy: Hematoxylin & eosin stain; mesangiolysis and glomerular capillary thrombosis suggestive of TMA. Arrow shows fibrin thrombi. Image credit: K.S. Vinay.

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    Light microscopy: Hematoxylin & eosin stain; acute tubular injury. Image credit: V. Mahesha.

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    Silver methenamine stain showing normal glomerulus. Image credit: K.S. Vinay.

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    Light microscopy: Hematoxylin & eosin stain showing crescentic glomerulonephritis. Image credit: K.S. Vinay.

  • 1.

    Perazella MA, Markowitz GS. Bisphosphonate nephrotoxicity. Kidney Int 2008; 74:13851393. doi: 10.1038/ki.2008.356

  • 2.

    Izzedine H, et al. Thrombotic microangiopathy and anti-VEGF agents. Nephrol Dial Transplant 2007; 22:14811482. doi: 10.1093/ndt/gfl565

  • 3.

    Nissim I, et al. Ifosfamide-induced nephrotoxicity: Mechanism and prevention. Cancer Res 2006; 66:78247831. doi: 10.1158/0008-5472.CAN-06-1043

  • 4.

    Bertani T, et al. Steroids and adriamycin nephrosis. Appl Pathol 1984; 2:3238. PMID: 6525317; https://www.researchgate.net/publication/16671624_Steroids_and_Adriamycin_nephrosis

    • Search Google Scholar
    • Export Citation
  • 5.

    Fadel F, et al. Anti-CTLA4 antibody-induced lupus nephritis. N Engl J Med 2009; 361:211212. doi: 10.1056/NEJMc0904283

Do You Know Your Drug Toxicities? Test Your Knowledge

  • 1 Mythri Shankar, MD, is Assistant Professor, Nephrology, with the Institute of Nephrourology, Bangalore, India.
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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).

F1

Light microscopy: Jones silver stain, proliferation of visceral epithelial cells and collapse of glomerulus known as collapsing focal segmental glomerulosclerosis (FSGS). Image credit: K.S. Vinay.

Citation: Kidney News 14, 5

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).

F2

Light microscopy: Hematoxylin & eosin stain; mesangiolysis and glomerular capillary thrombosis suggestive of TMA. Arrow shows fibrin thrombi. Image credit: K.S. Vinay.

Citation: Kidney News 14, 5

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).

F3

Light microscopy: Hematoxylin & eosin stain; acute tubular injury. Image credit: V. Mahesha.

Citation: Kidney News 14, 5

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).

F4

Silver methenamine stain showing normal glomerulus. Image credit: K.S. Vinay.

Citation: Kidney News 14, 5

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).

F5

Light microscopy: Hematoxylin & eosin stain showing crescentic glomerulonephritis. Image credit: K.S. Vinay.

Citation: Kidney News 14, 5

References

  • 1.

    Perazella MA, Markowitz GS. Bisphosphonate nephrotoxicity. Kidney Int 2008; 74:13851393. doi: 10.1038/ki.2008.356

  • 2.

    Izzedine H, et al. Thrombotic microangiopathy and anti-VEGF agents. Nephrol Dial Transplant 2007; 22:14811482. doi: 10.1093/ndt/gfl565

  • 3.

    Nissim I, et al. Ifosfamide-induced nephrotoxicity: Mechanism and prevention. Cancer Res 2006; 66:78247831. doi: 10.1158/0008-5472.CAN-06-1043

  • 4.

    Bertani T, et al. Steroids and adriamycin nephrosis. Appl Pathol 1984; 2:3238. PMID: 6525317; https://www.researchgate.net/publication/16671624_Steroids_and_Adriamycin_nephrosis

    • Search Google Scholar
    • Export Citation
  • 5.

    Fadel F, et al. Anti-CTLA4 antibody-induced lupus nephritis. N Engl J Med 2009; 361:211212. doi: 10.1056/NEJMc0904283

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