Look for nephrotoxicity in adult survivors of childhood cancer

LAS VEGAS – Adult survivors of childhood cancer treated with high-dose cisplatin or high-dose ifosfamide are at markedly increased risk for chronic renal impairment, according to a large Dutch study with a median 18.3-year follow-up.

Long-term treatment-related nephrotoxicity was also seen in the adult survivors of childhood cancer who underwent unilateral nephrectomy combined with abdominal radiation therapy.

"This study is perhaps a warning to us when we’re seeing these adult survivors of childhood cancer in clinic, particularly if they have a history of ifosfamide or cisplatin use, to pay closer attention to the development of chronic kidney disease so they can be managed better in the future," Dr. Anushree C. Shirali said at a meeting sponsored by the National Kidney Foundation.

Drug-induced acute kidney injury is a common event during cancer therapy. Its mechanisms and treatments are well studied. In contrast, the long-term nephrotoxicity of the powerful therapies used in treating childhood cancers has received much less scrutiny. But it’s an increasingly relevant issue because childhood cancer survival rates have improved substantially. Indeed, as the Dutch investigators observed, today 1 in 570 young adults is a childhood cancer survivor (Clin. J. Am. Soc. Nephrol. 2013;8:922-9).

Dr. Shirali, a nephrologist at Yale University in New Haven, Conn., highlighted the Dutch study of 763 adult survivors of childhood cancer because of its unusually long and complete follow-up. The investigators included nearly 90% of all adult survivors treated at Erasmus University in Rotterdam, the Netherlands, during 1964-2005.

High-dose ifosfamide was associated with a 6.2-fold greater likelihood of an increased urinary beta₂-microglobulin/creatinine ratio indicative of persisting tubular dysfunction, compared with cancer survivors not receiving that therapy. High-dose cisplatin was associated with a 5.2-fold increased risk of albuminuria. The estimated glomerular filtration rate in adult survivors who had received high-dose ifosfamide was 88 mL/min per 1.73 m², significantly lower than the 98 mL/min per 1.73 m² in others. Similarly, patients who had received high-dose cisplatin had an average estimated glomerular filtration rate of 83 mL/min per 1.73 m², compared with 101 mL/min per 1.73 m² in survivors not treated with high-dose cisplatin.

In contrast to ifosfamide, its isomer cyclophosphamide was not associated with long-term nephrotoxicity; neither was carboplatin, a cisplatin analogue, or methotrexate. Although methotrexate is known to cause acute nephrotoxicity, this phenomenon appears to be completely reversible, since methotrexate-treated, long-term cancer survivors didn’t develop tubular or glomerular dysfunction.

This long-term study was supported by the Dutch Kidney Foundation. Dr. Shirali, who was not involved in the study, reported having no financial conflicts.

bjancin@frontlinemedcom.com

LAS VEGAS – Adult survivors of childhood cancer treated with high-dose cisplatin or high-dose ifosfamide are at markedly increased risk for chronic renal impairment, according to a large Dutch study with a median 18.3-year follow-up.

Long-term treatment-related nephrotoxicity was also seen in the adult survivors of childhood cancer who underwent unilateral nephrectomy combined with abdominal radiation therapy.

"This study is perhaps a warning to us when we’re seeing these adult survivors of childhood cancer in clinic, particularly if they have a history of ifosfamide or cisplatin use, to pay closer attention to the development of chronic kidney disease so they can be managed better in the future," Dr. Anushree C. Shirali said at a meeting sponsored by the National Kidney Foundation.

Drug-induced acute kidney injury is a common event during cancer therapy. Its mechanisms and treatments are well studied. In contrast, the long-term nephrotoxicity of the powerful therapies used in treating childhood cancers has received much less scrutiny. But it’s an increasingly relevant issue because childhood cancer survival rates have improved substantially. Indeed, as the Dutch investigators observed, today 1 in 570 young adults is a childhood cancer survivor (Clin. J. Am. Soc. Nephrol. 2013;8:922-9).

Dr. Shirali, a nephrologist at Yale University in New Haven, Conn., highlighted the Dutch study of 763 adult survivors of childhood cancer because of its unusually long and complete follow-up. The investigators included nearly 90% of all adult survivors treated at Erasmus University in Rotterdam, the Netherlands, during 1964-2005.

High-dose ifosfamide was associated with a 6.2-fold greater likelihood of an increased urinary beta₂-microglobulin/creatinine ratio indicative of persisting tubular dysfunction, compared with cancer survivors not receiving that therapy. High-dose cisplatin was associated with a 5.2-fold increased risk of albuminuria. The estimated glomerular filtration rate in adult survivors who had received high-dose ifosfamide was 88 mL/min per 1.73 m², significantly lower than the 98 mL/min per 1.73 m² in others. Similarly, patients who had received high-dose cisplatin had an average estimated glomerular filtration rate of 83 mL/min per 1.73 m², compared with 101 mL/min per 1.73 m² in survivors not treated with high-dose cisplatin.

In contrast to ifosfamide, its isomer cyclophosphamide was not associated with long-term nephrotoxicity; neither was carboplatin, a cisplatin analogue, or methotrexate. Although methotrexate is known to cause acute nephrotoxicity, this phenomenon appears to be completely reversible, since methotrexate-treated, long-term cancer survivors didn’t develop tubular or glomerular dysfunction.

This long-term study was supported by the Dutch Kidney Foundation. Dr. Shirali, who was not involved in the study, reported having no financial conflicts.

bjancin@frontlinemedcom.com

LAS VEGAS – Adult survivors of childhood cancer treated with high-dose cisplatin or high-dose ifosfamide are at markedly increased risk for chronic renal impairment, according to a large Dutch study with a median 18.3-year follow-up.

Long-term treatment-related nephrotoxicity was also seen in the adult survivors of childhood cancer who underwent unilateral nephrectomy combined with abdominal radiation therapy.

"This study is perhaps a warning to us when we’re seeing these adult survivors of childhood cancer in clinic, particularly if they have a history of ifosfamide or cisplatin use, to pay closer attention to the development of chronic kidney disease so they can be managed better in the future," Dr. Anushree C. Shirali said at a meeting sponsored by the National Kidney Foundation.

Drug-induced acute kidney injury is a common event during cancer therapy. Its mechanisms and treatments are well studied. In contrast, the long-term nephrotoxicity of the powerful therapies used in treating childhood cancers has received much less scrutiny. But it’s an increasingly relevant issue because childhood cancer survival rates have improved substantially. Indeed, as the Dutch investigators observed, today 1 in 570 young adults is a childhood cancer survivor (Clin. J. Am. Soc. Nephrol. 2013;8:922-9).

Dr. Shirali, a nephrologist at Yale University in New Haven, Conn., highlighted the Dutch study of 763 adult survivors of childhood cancer because of its unusually long and complete follow-up. The investigators included nearly 90% of all adult survivors treated at Erasmus University in Rotterdam, the Netherlands, during 1964-2005.

High-dose ifosfamide was associated with a 6.2-fold greater likelihood of an increased urinary beta₂-microglobulin/creatinine ratio indicative of persisting tubular dysfunction, compared with cancer survivors not receiving that therapy. High-dose cisplatin was associated with a 5.2-fold increased risk of albuminuria. The estimated glomerular filtration rate in adult survivors who had received high-dose ifosfamide was 88 mL/min per 1.73 m², significantly lower than the 98 mL/min per 1.73 m² in others. Similarly, patients who had received high-dose cisplatin had an average estimated glomerular filtration rate of 83 mL/min per 1.73 m², compared with 101 mL/min per 1.73 m² in survivors not treated with high-dose cisplatin.

In contrast to ifosfamide, its isomer cyclophosphamide was not associated with long-term nephrotoxicity; neither was carboplatin, a cisplatin analogue, or methotrexate. Although methotrexate is known to cause acute nephrotoxicity, this phenomenon appears to be completely reversible, since methotrexate-treated, long-term cancer survivors didn’t develop tubular or glomerular dysfunction.

This long-term study was supported by the Dutch Kidney Foundation. Dr. Shirali, who was not involved in the study, reported having no financial conflicts.

bjancin@frontlinemedcom.com