Renal insufficiency is associated with an increased risk of papillary renal cell carcinoma histology.

Purpose: End-stage renal disease (ESRD) and acquired renal cystic disease associated with dialysis are known risk factors of papillary renal cell carcinoma (pRCC); however, it is not known whether renal insufficiency alone is a risk factor for pRCC. Our aim was to test whether renal insufficiency is associated with an increased preponderance of pRCC.

Methods: Retrospective review of institutional database to identify all patients who underwent extirpative renal surgery for renal cell carcinoma (RCC) with complete records from 1992 to 2012. We excluded those patients with preoperative ESRD as defined by GFR < 15 mL/min/1.73 m(2). The dependent variable was histologic RCC subtype. Independent variables included demographic data, comorbidities, and renal functional data. Multivariate analysis by binary logistic regression was used to determine factors that independently were associated with pRCC development.

Results: A total of 1,226 patients met inclusion criteria, of which 15 % were pRCC. There was a positive association between likelihood of pRCC histology of RCC and increasing preoperative chronic kidney disease (CKD) stage (p = 0.021). Multivariate regression analysis indicated that male gender, race, and declining renal function categorized both by GFR and CKD stage were independently associated with a higher likelihood of pRCC histology as compared to other RCC histology.

Conclusions: Within a large cohort of patients with a diagnosis of RCC, declining renal function was independently associated with an increased likelihood of pRCC histology. This finding and the available molecular evidence indicating protein expression similarity between pRCC and resident stem cells, which appear to be upregulated with kidney damage, suggest a possible causal relationship between renal injury and pRCC.