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End-stage renal disease (ESRD) patients requiring renal replacement therapy, either by dialysis or transplantation, are at increased risk for developing cancer and at four- to five-fold increased risk of developing renal cancer in their native kidneys.1-3

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ESRD-associated renal cell carcinoma (RCC) and competing medical comorbidities, principally cardiovascular (CV), are a source of morbidity and mortality. New evidence also implicates chronic kidney disease (CKD) as placing patients at greater risk for developing cancer compared with the general population, and at a greater risk for developing RCC in particular.

Nephropathological changes are commonly observed in the non-neoplastic kidney at the time of nephrectomy for RCC, and correlate with a higher incidence of CKD in RCC patients than in the general population. It is unknown whether these changes are carcinogenic or if renal dysfunction increases circulating serum carcinogens or causes immune inhibition leading to RCC. 

An estimated 60,920 new cases and 13,120 deaths from RCC occurred in the U.S. in 2011. RCC is increasing at a rate of approximately 3% per year. Compared with 1971, this represents a fivefold increase in incidence and two-fold increase in mortality. Associated risk factors include hypertension, smoking, obesity, and diabetes, all of which can affect kidney function alone or in combination. Epidemiologic evidence suggests an increase in all stages of RCC.4,5 Approximately 30% to 40% of RCC patients will either present with or later develop metastatic disease.

The problem of kidney cancer

The widespread use of the modern abdominal imaging (CT, MRI, and ultrasound) over the last 20 years, usually ordered to evaluate nonspecific abdominal and musculoskeletal complaints or during unrelated cancer care, has changed the profile of the typical RCC patient from one with a massive, symptomatic tumor at presentation to one with a small, asymptomatic, renal mass (<4 cm) incidentally discovered in 70% of the cases.6 A documented increase in incidence in African Americans without an increase in RCC-specific mortality has raised the possibility that RCC may be less aggressive in this population.7

RCC-specific survival rates have not significantly improved over the last 15 years. The aggressive treatment of smaller tumors appears insufficient to offset increasingly virulent tumors presenting as localized or metastatic disease.8 A survival rate of 90% or greater, depending on the tumor histology, is expected for small tumors whether partial nephrectomy (PN) or radical nephrectomy (RN) is performed.9,10

Renal cortical tumors are members of a complex family with unique histopathology, cytogenetics, familial and hereditary syndromes, and variable metastatic potentials. Approximately 20% of surgically resected renal masses are benign lesions (i.e., angiomyolipoma, oncocytoma, metanephric adenoma, or hemorrhagic cyst), 25% are indolent tumors (papillary, chromophobe carcinoma) with limited metastatic potential, and 54% are the potentially malignant conventional clear-cell carcinoma that accounts for 90% of the metastatic 
renal tumors.11,12