Risk of Renal Cell Carcinoma Among Kidney Transplant Recipients in the United States

Abstract

Renal cell carcinoma (RCC) is a common malignancy following kidney transplantation. We describe RCC risk and examine RCC risk factors among US kidney recipients (1987-2010). The Transplant Cancer Match Study links the US transplant registry with 15 cancer registries. Standardized incidence ratios (SIRs) were used to compare RCC risk (overall and for clear cell [ccRCC] and papillary subtypes) to the general population. Associations with risk factors were assessed using Cox models. We identified 683 RCCs among 116,208 kidney recipients. RCC risk was substantially elevated compared with the general population (SIR 5.68, 95%CI 5.27-6.13), especially for papillary RCC (SIR 13.3 vs. 3.98 for ccRCC). Among kidney recipients, RCC risk was significantly elevated for blacks compared to whites (hazard ratio [HR] 1.50) and lower in females than males (HR 0.56). RCC risk increased with prolonged dialysis preceding transplantation (p-trend<0.0001). Risk was variably associated for RCC subtypes with some medical conditions that were indications for transplantation: ccRCC risk was reduced with polycystic kidney disease (HR 0.54), and papillary RCC was increased with hypertensive nephrosclerosis (HR 2.02) and vascular diseases (HR 1.86). In conclusion, kidney recipients experience substantially elevated risk of RCC, especially for papillary RCC, and multiple factors contribute to these cancers.

Differences in Clinical and Pathological Features of Renal Cell Carcinoma Between Japanese Patients After Kidney Transplantation and Those on Hemodialysis

“…In the USA, Karami and colleagues analyzed data from The Transplant Cancer Match Study and showed a substantially elevated RCC risk among transplant patients, compared with the general population (SIR =5.68, 95% confidence interval: 5.27-6.13), especially for papillary RCC (SIR =13.3 vs. 3.98 for clear cell RCC). In addition, the clear cell RCC risk was reduced among patients with polycystic kidney disease (HR 0.54) in their study (19). In the present study, although the frequency of papillary RCC tended to be higher among patients who underwent transplantation than among hemodialysis patients (31% vs. 21%), this difference was not statistically significant (P = 0.3452).…”

Urologic malignancies in kidney transplantation

“…Compared with the general population, kidney transplant recipients have a 5‐ to 7‐fold increased risk of renal cancers, with RCC accounting for 4.6% of post–renal transplantation malignancies . Ninety percent of RCCs develop in the native kidneys as opposed to the allograft .…”

“…The posttransplantation group had higher incidence of Kaposi sarcoma, lymphomas, and skin cancers but lower incidences of thyroid and renal cancers . In addition, the rarity of RCC in the allograft compared with native kidneys suggests that an intrinsic factor within the native kidneys may be contributing to the higher incidence . In fact, autosomal dominant polycystic kidney disease (ADPKD) has been described as a risk factor for RCC development, with these patients having a 2 to 3 times higher risk of RCC compared with the general ESRD population; in contrast, among patients transplanted for ESRD secondary to ADPKD, the risk of RCC is lower than that among patients transplanted for other disease etiologies .…”

“…Risk factors for development of RCC posttransplantation include male sex (hazard ratio [HR] 1.79), increasing age (60+ years; HR 6.59), African descent (HR 1.50), and longer time on dialysis (3+ years; HR 2.23) . With regard to disease etiology, patients transplanted for ESRD secondary to glomerular diseases (HR 1.24), hypertensive nephrosclerosis (HR 1.55), and vascular disease (HR 1.53) appear to have the greatest associated risk; in contrast, patients with ESRD secondary to diabetes (HR 0.77) or ADPKD (HR 0.81) have a lower risk of RCC.…”

“…With regard to disease etiology, patients transplanted for ESRD secondary to glomerular diseases (HR 1.24), hypertensive nephrosclerosis (HR 1.55), and vascular disease (HR 1.53) appear to have the greatest associated risk; in contrast, patients with ESRD secondary to diabetes (HR 0.77) or ADPKD (HR 0.81) have a lower risk of RCC. Interestingly, patients undergoing repeat transplantation (unadjusted incidence rate ratio [IRR] 1.61) have an increased risk for RCC, as well as patients receiving kidney transplants from older, male donors (HR 1.16) . The incidence of ACKD in both patients with ESRD and kidney transplant recipients who go on to develop RCC has been reported to be greater than 80%.…”