Wilms tumor or nephroblastoma is the most common renal malignancy of childhood (Miller 1995). It accounts for 6–7 % of all childhood cancers. The annual incidence rate is approximately 7–10 cases per million (Bernstein 1999). Most Wilms tumors are detected in the toddler and preschool age group with a median age of 3.5 years. Wilms tumor is uncommon in infants and rare in neonates. Less than 2 % of Wilms tumors are detected in neonates less than 3 months of age (CD 2004). Wilms tumor is typically identified due to a palpable abdominal mass or less commonly gross hematuria and abdominal pain.

The genetics of Wilms tumor continues to be extensively examined. The WT1 gene was the first gene identified in Wilms tumor. Currently, Wilms tumor can be associated with a genetic mutation of WT1 at 11p13 or a mutation of WT2 at 11p15. Most tumors result from a somatic mutation within tumor tissue but a small percentage result from germline mutations. Approximately 10 % of children with Wilms tumor have associated congenital syndromes. WT1 mutations are found in children with Denys-Drash syndrome (DDS), Frasier syndrome, and WAGR (Wilms tumor, aniridia, genital anomalies, mental retardation) syndrome (Muto 2002).

The current management of Wilms tumor is derived from cooperative group studies including the National Wilms Tumor Study Group (NWTSG) within the Children’s Oncology Group (COG), the International Society of Pediatric Oncology (SIOP), and the United Kingdom Children’s Cancer Study Group (UKCCSG). The 5-year overall survival rate for children with Wilms tumor is greater than 90 % (DM 2004). The goals of NTWS-5 included improving survival and understanding risk factors such as loss of heterozygosity at 11p14, 16p, 1p, age at diagnosis, precursor lesions such as nephroblastomatosis, bilateral disease, and the association with congenital anomalies. The objective of this risk stratification is to improve overall and disease-free survival while minimizing acute and long-term treatment associated morbidity.

Current Wilms tumor in the United States begins with radical nephrectomy for most children. This practice differs from the SIOP protocol that begins with neoadjuvant chemotherapy. The overall survival rates between these protocols are very similar (Metzger 2005). Treatment regimens are selected based on risk stratification and include biological, pathological, and clinical parameters. Multimodal therapy involves surgical extirpation, chemotherapy, and radiotherapy. Chemotherapeutic agents include vincristine, dactinomycin, and doxorubicin. Other therapeutic agents include cyclophosphamide and etoposide when necessary.

Given the significant improvements in survival, emphasis on evaluation of long-term treatment-related adverse events is increasingly important. Adverse events associated with Wilms tumor treatment can be associated with chemotoxicity, radiotoxicity, and surgical complications. Adverse events described in Wilms tumor survivors include tissue hypoplasia, secondary malignancies, nephrologic, endocrinologic, urologic, orthopedic, cardiovascular, and pulmonary events. Long-term nephrologic events include glomerular dysfunction, tubular dysfunction, and hypertension. Incontinence, hemorrhagic cystitis, and recurrent cystitis are documented long-term urologic events. Fertility concerns include elevated follicle stimulating hormone, elevated luteinizing hormone, oligospermia, and azoospermia. Twenty-five-year follow-up from the Childhood Cancer Survivor Study documented a 65.4 % incidence of chronic health conditions with 24 % reporting severe chronic conditions. Of the specific conditions evaluated, survivors reported higher rates of congestive heart failure, renal failure, and hypertension with hazard ratios of 23.6 (95 % CI 10.8–51.5), 50.7 (95 % CI 14.5–177.4), and 8.2 (95 % CI 0.4–10.5) respectively. Exposure to cardiac radiotherapy significantly increased the risk of congestive heart failure (Termuhlen 2011).

Children receiving doxorubicin as salvage therapy have a higher frequency of cardiac disease. Echographic evaluation of left ventricular function demonstrated increased end systolic wall stress suggestive of subclinical cardiac dysfunction in children exposed to doxorubicin versus children unexposed (Iarussi 2003). Evaluation of NTWS 1, 2, 3, 4 children demonstrated a 4.4 % cumulative frequency of congestive heart failure in children exposed to doxorubicin as initial therapy and a 17.4 % cumulative frequency in children treated with anthracyclines for relapse. The relative risk of congestive heart failure was also elevated in children receiving lung irradiation and left abdominal radiation. This risk is increased in children receiving both doxorubicin and cardiac radiotherapy (Green 2001; Termuhlen 2011).

Survivorship studies document that the majority of event-free survivors of unilateral Wilms tumor do not demonstrate severe renal dysfunction. Despite these data, renal disease does occur in certain populations of Wilms tumor survivors. A Cochrane review of six studies demonstrated a 0.5–18 % prevalence of chronic kidney disease in Wilms tumor survivors treated with unilateral nephrectomy (Knijnenburg 2013). Bilateral Wilms tumor presents a difficult challenge from an oncologic standpoint. Preoperative chemotherapy and nephron sparing surgery are often indicated for these children with partial nephrectomy as part of the operative armamentarium. This treatment shift has decreased the overall risk of renal failure from 16.4 % in NWTS-1-2 to 3.9 % in NWTS-4. Long-term follow-up does report significant morbidity with adults developing renal failure, requiring renal transplantation and developing secondary tumors (Aronson 2011). Bilateral nephrectomy is the most prevalent etiology for end-stage disease. Other etiologies include radiation nephritis, DDS, chemotherapy toxicity, and surgical complications (Ritchey 1996). Children with WAGR and other associated genitourinary anomalies are also at elevated risk for end-stage renal disease. Children with DDS have a greater than 50 % incidence of end-stage renal failure (Breslow 2005). Long-term effects include decreased glomerular filtration rate, microalbuminuria, and hypertension. Hypertension and prehypertension are commonly found in patients with Wilms tumor. A recent study sought to evaluate the blood pressure profile and cardiac diastolic function in adolescent survivors of unilateral Wilms in remission. Ambulatory blood pressure monitoring demonstrated a 20 % prevalence of hypertension. Specifically, daytime systolic blood pressure, nighttime systolic blood pressure, and nighttime diastolic pressure measurements were increased among Wilms tumor survivors compared to healthy matched controls (Elli 2013). Children who receive chemotherapy and radiotherapy are at highest risk for hypertension and renal insufficiency. This particular group of children is also at an elevated risk for growth hormone deficiency and cardiovascular disease (Geenen 2010).