Acquired Cystic Kidney Disease and Renal Cell Cancer after Transplantation: Time to Rethink Screening?

Acquired cystic kidney disease (ACKD) may have been first described more than a century ago (1). Its recognition as a disease of consequence in patients who undergo long-term maintenance hemodialysis was in the 1970s (2). In the ensuing three decades, repeated cross-sectional studies have corroborated early findings that this disease affects one third or more of long-term (≥3 yr) hemodialysis patients and that approximately 20% of those with ACKD will have renal cell carcinoma, representing a prevalence of approximately 5% (3). Age, male gender, and duration of dialysis are primary risk factors. It may occur less frequently in those who are on peritoneal dialysis and may regress after transplantation (4). Its pathogenesis is not understood but may relate to the activation of proto-oncogenes, which may also be responsible for the subsequent development of renal cell carcinoma (5).

Transplantation carries risk for cancer, more so as the years of exposure to the immunosuppressive agents accrue. Kidney transplant recipients in the United States have been shown to carry a 15-fold risk for kidney cancer (which would include non–renal cell cancers as well) in the first 3 yr after transplantation when compared with the general US population and a 39% higher risk for developing kidney cancer in those years in comparison with transplant candidates who are still on the waiting list (6).

Recommendation to screen patients with ESRD for ACKD and renal cell cancer has not been uniform because of their limited life expectancy (7). Screening kidney transplant candidates for ACKD and kidney cancer is recommended by the North American and European professional transplantation societies, but the guidelines as to who should be screened are vague. The guideline of the American Society of Transplantation recommends screening patients who are at high risk for renal cell carcinoma but does not define high risk (8). The guideline of the European Renal Association–European Dialysis and Transplant Association recommends screening of candidates who have been long-term dialysis patients but does not define long-term (9). It is not known whether these guidelines are followed in practice.

The two societies differ in their recommendation for screening after kidney transplantation. The American society guideline does not recommend screening (10). The European society guideline recommends screening but with the qualifier that it be done “when applicable,” which is not defined (11). Again, the adherence to this guideline in practice is unknown.

In this issue, Schwarz et al. (12) report their findings of ACKD and renal cell cancer in a cross-sectional study of a large population of kidney transplant recipients who were anywhere from having recently received a transplant to 33 yr after transplantation. The mean duration of dialysis was 4 to 5 yr, and the mean time since transplantation was 9 yr. Of 916 eligible patients, 561 (61%) participated and underwent ultrasound of the native kidneys. Of these, 129 (23%) were found to have ACKD, defined as more than three cysts in both kidneys. Eight (1.4%) patients had newly diagnosed renal cell cancer, seven of whom had ACKD. An additional 19 patients in the group studied had a history of formerly diagnosed renal cell cancer, 18 of whom had ACKD. Together, these 27 patients with renal cell cancer represented 4.8% of the 561 patients studied. The prevalence of renal cell cancer in those with ACKD was approximately 20% and >50% in those with complex cysts (Bosniak categories IIF, III, and IV) (13). These prevalences of renal cell cancer in a cohort of patients with ESRD and renal cell cancer in the presence of ACKD corroborate the findings of previous studies of both dialysis and transplant patients (3).

Schwarz et al. found that older age, male gender, a history of heart disease, larger kidneys, and greater kidney calcifications were associated with ACKD. There was no association with duration of dialysis, time since transplantation, or immunosuppressive regimen. Curiously, both duration of dialysis and time since transplantation were shorter in those with renal cell cancer. The type of renal cell cancer was clear cell carcinoma in 58% and papillary carcinoma in 42% (one patient had both types). All patients were asymptomatic at diagnosis, and only one was found to have a metastasis, a lung metastasis in a patient with clear cell carcinoma. All were treated successfully with surgical resection. The benign course in these patients was in distinct contrast to an earlier report from the same institution, wherein metastatic disease and mortality were more common (14). Their relatively benign course was thought to be related to earlier detection, small size of cancer at detection, the overrepresentation of papillary versus clear cell carcinoma in ACKD and lower proliferative activity in renal cell cancer associated with ACKD.

Schwarz et al. recommend a screening and management protocol in transplant recipients, incorporating the Bosniak renal cyst classification system (13):

1. All recipients: Yearly ultrasound screening of the native kidneys.

2. ACKD and Bosniak category I or II cysts (benign simple cysts): Twice yearly ultrasound screening, computed tomography scan if progression evident.

3. ACKD and Bosniak category IIF (F for follow-up) cysts (moderately complex cysts): Quarterly ultrasound screening and yearly computed tomography or magnetic resonance imaging scan, nephrectomy if progression evident even if not reaching category III or IV.

4. ACKD and Bosniak category III (“indeterminate” cystic masses) or IV (clearly malignant cystic masses): Nephrectomy.

Life expectancy after transplantation has improved with advances in the discipline over recent decades so that it is now well more than double that of a patient on dialysis regardless of age (15). In 2004, the expected remaining lifetime of a US transplant recipient 50 to 54 yr of age, which was the average age of the patients with renal cell cancer in the report by Schwarz et al., was 17 yr. Cancer may soon be the leading cause of death late after transplantation (16). Despite the low prevalence of renal cell cancer in ESRD, the relatively benign course of the affected patients in the report by Schwarz et al., and the possibility of lesser cancer risk with newer immunosuppressive regimens (17), it is time to rethink the published guidelines and consider screening all kidney transplant candidates and recipients for ACKD and renal cell cancer.

• Copyright © 2007 by the American Society of Nephrology