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Case History

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Image not available. A 57-year-old man presents with metastatic transitional cell cancer of the upper urinary tract causing solitary hydronephrosis and flank pain. He has a history of severe anxiety and is taking amitriptyline 200 mg once daily and ibuprofen 400 mg thrice daily. The patient's weight is 62kg. His urea and electrolytes are: Na+ 138 mmol/l; K+ 5.3 mmol/l; urea 4.0 mmol/l; creatinine 108 µmol/l; eGFR 61 ml/min/1.73 m2. His Eastern Cooperative Oncology Group (ECOG) performance status (PS) is 1 and he is keen to proceed with palliative chemotherapy.

What are the risk factors for chemotherapy-related renal toxicity?

Can we estimate renal function accurately?

Which chemotherapy drugs are commonly associated with renal toxicity?

What steps can be taken to prevent chemotherapy-related renal toxicity?

What are the long-term consequences?

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Background

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What are the risk factors for chemotherapy-related renal toxicity?

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Image not available. Toxicity from chemotherapy can cause both acute kidney injury (AKI) and chronic kidney disease (CKD). The diagnosis and management of AKI is discussed in Chapter 17. This chapter will focus on the recognition of the 'at-risk' patient and the adaptations required in their oncology management.

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Key risk factors for chemotherapy-related renal toxicity are:

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  • Age >75 yrs

  • Pre-existing chronic kidney disease (CKD) eGFR <60 ml/min/1.73 m2

  • Hypoalbuminaemia (alters drug handling)

  • Choice of chemotherapy

  • Hypovolaemia, e.g. vomiting, diuretics

  • Concomitant use of other nephrotoxins, e.g. NSAIDs, aminoglycosides, iodinated contrast

  • Urinary tract obstruction.

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Can we estimate renal function accurately?

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Many chemotherapy drugs are excreted by the kidneys via either glomerular filtration or tubular secretion. Where the drug and/or its active metabolites are excreted by the kidneys, an estimation of renal function is essential to ensure safe dosing of treatment. Unfortunately, serum creatinine is a poor biomarker of renal function in patients with cancer due to a reduced muscle mass (sarcopenia). Equations such as the Cockcroft-Gault formula, modification of diet in renal disease (MDRD) formula or Wright formula use serum creatinine to calculate renal function and therefore have the potential to overestimate the glomerular filtration rate (GFR) in patients with cancer. The gold standard investigation for renal function remains an isotope GFR and should be used to ensure safe treatment of those patients where estimated GFR is in doubt.

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Which chemotherapy drugs are commonly associated with renal toxicity?

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Many drugs used to treat malignant disease have the potential to cause renal toxicity and electrolyte disturbances. The drugs can exert their toxic effects either directly or indirectly, the latter as a consequence of sepsis or other severe toxicity such as mucositis or diarrhoea. The details of chemotherapy-related renal toxicity and mechanisms are outside the scope of this review but should be considered by the treating physician. However a brief review of common exemplar drugs can be found in Table 18.1.

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