Nephrotoxicity of Cancer Treatment in Children

Roderick Skinner

Disclosures

Pediatr Health. 2010;4(5):519-538. 

In This Article

Abstract and Introduction

Abstract

Chronic renal impairment in children with cancer may be caused by the malignant process itself or result from adverse effects of treatment including cytotoxic drugs, radiotherapy, surgery or supportive treatment. Although severe renal chronic disease is uncommon, occurring in only 0.8% of long-term survivors of childhood cancer, 1.9% of all cases of established renal failure are due to malignancy and 0.8% to drug nephrotoxicity. The relative risk of severe renal chronic disease (compared with siblings) is 8.1, and that of renal failure or the need for dialysis is 8.9. The cytotoxic drugs most likely to cause important chronic nephrotoxicity are ifosfamide and cisplatin, both of which are used widely in many solid tumors and may cause chronic glomerular and/or renal tubular toxicity in 30–60% of treated children. Significant renal toxicity is less frequent with other chemotherapeutic drugs, but may result from treatment with carboplatin, methotrexate and nitrosoureas. Other cytotoxic drugs occasionally cause specific patterns of glomerular or tubular toxicity in children. Partial or unilateral nephrectomy leads to hypertrophy and hyperfiltration of the remaining renal tissue, and may result in microalbuminuria, hypertension and in rare cases, chronic renal impairment. Radiotherapy to a field including renal tissue may cause late onset chronic renal damage, manifest by hematuria, proteinuria, hypertension and anemia, sometimes progressing to chronic renal failure. Chronic nephrotoxicity is also common in survivors of hemopoietic stem cell transplantation, and is often multifactorial with contributions from prior chemotherapy, total body irradiation, immunosuppressive drugs and transplant complications, such as infection or hemorrhage. Patients at risk of renal damage should be monitored regularly with a defined surveillance protocol to enable timely management. General measures often employed to prevent or reduce nephrotoxicity include the use of intravenous hydration during drug administration and avoidance of known risk factors, such as high drug doses. Although numerous potentially nephroprotective drugs have been suggested and investigated, none have yet been introduced into clinical use in children due to the lack of proven efficacy. Improved understanding of the pathogenesis of nephrotoxicity is necessary to reduce the frequency and severity of this potentially serious complication of treatment in children with cancer.

Introduction

The increasing long-term survival rates of children with malignancy, now approximating 75% in the UK, imply that nearly one in 700 young adults is a survivor of a childhood malignancy.[1] Furthermore, over 26,000 individuals alive in the UK in 2000 were successfully treated for cancer as a child.[2] Data from the population-based West Midlands Regional Children's Tumor Registry in the UK and its regional long-term follow-up (LTFU) clinic indicate that approximately 60 and 30%, respectively, of long-term survivors have at least one or at least two chronic medical problems, defined by a need for continuing medical intervention or advice, or the presence of the likely future development of disability or dysfunction.[3,4] Furthermore, the Childhood Cancer Survivor Study (CCSS), a large North American cohort study, found that nearly 30% of survivors had a severe (grade 3) or life-threatening/disabling (grade 4) chronic condition.[5]

Nephrotoxicity may be defined as the ability of an agent (including drugs or other treatment modalities) to cause functional or structural kidney damage. This definition is intentionally very broad, incorporating a wide variety of agents (numerous drugs, other treatments or exogenous toxins), functional consequences (any combination of glomerular or tubular dysfunction as well as impairment of blood pressure control and/or renal endocrine function) and structural lesions (ranging from microscopic abnormalities, e.g., histological changes of glomerular and/or tubular damage, to gross morphological lesions, e.g., the small kidneys associated with nephron loss in chronic renal failure [CRF]). This article focuses on the nephrotoxicity of treatments used in children with cancer, especially cytotoxic drug-induced toxicity.

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