SCREENING FOR ACQUIRED CYSTIC DISEASE AND RENAL MALIGNANCY

5. Wong G, et al.: Cost-effectiveness of breast cancer screening in women on dialysis. Am J Kidney Dis 52:916929, 2008 6. LeBrun CL, et al.: Life expectancy benets of cancer screening in the end-stage renal disease population. Am J Kidney Dis 35:237243, 2000

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7. Cohen LM, et al.: Predicting six-month mortality for patients who are on maintenance hemodialysis. Clin J Am Soc Nephrol 5:7279, 2010

Should screening for acquired cystic disease and renal malignancy be undertaken in dialysis patients?
Acquired cystic kidney disease (ACKD) is a common and worrisome complication of end-stage renal disease (ESRD) and was rst described in 1977. Diagnostic criteria consist of the presence of four or more cysts in each kidney without a family history of cystic kidney disease. Patients with severe disease can have more than nine cysts in each kidney and cysts larger than 5 cm with little remaining non-cystic renal parenchyma. ACKD is usually asymptomatic but can be complicated by pain, spontaneous hemorrhage and renal cell carcinoma (RCC). Spontaneous hemorrhage, exacerbated by heparin use and platelet dysfunction, can be severe and cause sudden hypotension during hemodialysis (1). Prevalence of ACKD is primarily a function of time on dialysis; however up to 10% of patients with advanced CKD not yet on dialysis have ACKD. After 3 years on dialysis nearly half of ESRD patients have ACKD, and this number increases to 90-100% at 10 years (2). The etiology of ESRD does not seem to inuence the occurrence of ACKD, although there is slight preponderance in older men and there is no major racial difference (2,3). Dialysis duration is the only factor that affects the severity of ACKD. Age, dialysis adequacy, residual renal function does not appear to affect the severity of cystic disease (4). Although some report a lower risk in patients on peritoneal dialysis, this is not consistent across the literature (5). Renal cell carcinoma is a well-recognized complication of ACKD. The incidence of RCC in ESRD patients is 14% (6,7). It is predominantly unilateral but may be bilateral in 2530% of cases (8,9). Two major histological types have been described: clear cell and papillary type. Although papillary RCC is more common in ESRD patients than in the general population (30% versus 1015% respectively), clear cell is the most common type (5,9). Because of the increased risk of RCC in patients with ACKD, the overall prevalence of RCC is about 3035 fold higher in dialysis patients compared to general population.(5). RCC is accompanied by ACKD in about 7580% of the cases (7,8). Cysts >3 cm in diameter have a higher risk of malignancy (3). Duration on dialysis is again the most important risk factor for the development of malignancy
Seminars in DialysisVol 24, No 4 (JulyAugust) 2011 pp. 365366 DOI: 10.1111/j.1525-139X.2011.00908.x 2011 Wiley Periodicals, Inc.

Swathi Singanamala and Ursula C. Brewster

(8,10). The published mortality for patients undergoing radical nephrectomy for RCC without metastasis ranges from 0.5 to 6% and is up to 10% with metastatic disease (11). Screening for ACKD might make sense intellectually, but its cost effectiveness in the ESRD population, with its associated comorbidities, must be carefully considered. It is important to remember that the median age of patients starting dialysis is increasing and the USRDS data cites median 5 year survival of incident ESRD patient as only 38%. Decision analysis has been used to evaluate the benets of screening by performing either ultrasound (US) or computed tomography (CT) every 3 years and then annually in patients with ACKD in a recent study (12). Baseline analysis showed that both CT and US decrease the cancer deaths by half for those ESRD patients with a life expectancy of 25 years or more. Screening in these patients increased life expectancy by 1.6 years (12). However, a 25 year life expectancy is uncommon in the average dialysis unit. Another study used mathematical modeling to show a 35% reduction in risk of death, with survival benet of 3.3 years, from all causes after adjustment for age, duration of dialysis and other comorbid illnesses with a screening by CT or US (11). We cannot extrapolate these data to all patients, as most 64 year-old dialysis patients do not have 25-year life expectancy. Add to that, the 5 year survival of an ESRD patient with RCC stage 1 is 35%, which is similar to an ESRD patient without RCC. ESRD patients with RCC are more likely to die of cardiovascular disease rather than the RCC (2). The largest benecial effect in both the studies was seen in young patients who might be future transplant recipients. How about transplant patients? A recent review of 1000 transplant recipients followed for 28 years showed that ACKD is less common in transplant recipients compared to ESRD patients as a whole (23% versus 80%), but the prevalence of RCC was higher (19% versus 0.5%) in recipients with than without ACKD (13). The Bosniak scoring system (Table 1) categorizes cystic lesions, and is recommended as an excellent tool for risk stratication in patients. Most recommend yearly ultrasound screening after transplant for all irrespective of ACKD (13). Once ACKD develops, ultrasound should be done more frequently; every 6 months for

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Fissell and Robinson

Department of Medicine, Section of Nephrology, Yale University School of Medicine, New Haven, Connecticut Description Simple cyst Minimally complex Minimally complex needing follow up Indeterminate Clearly malignant Features Anechoic, imperceptable wall, round Single thin septation and thin Ca2+ Thin septation and thick Ca2+, hyper dense on computed tomography (CT) Thick or multiple septations, mural nodule, hyper dense on CT Solid mass with cystic spaces. Address correspondence to: Ursula C Brewster, Associate Professor of Medicine, Section of Nephrology, Yale University School of Medicine, BB122, 330 Cedar Street, PO Box 208029, New Haven, CT 06520-8029, Tel.: 2037854184, Fax: 2037857068, or e-mail: Ursula.brewster@yale.edu.

TABLE 1. Bosnaik staging system for cystic kidney disease Bosnaik stage 1 2 2F 3 4

References
1. Moore AE, et al.: Spontaneous retroperitoneal hemorrhage due to acquired cystic kidney disease. Hemodial Int 11(Suppl 3):S38S40, 2007 2. Matson MA, et al.: Acquired cystic kidney disease: occurrence, prevalence, and renal cancers. Medicine (Baltimore) 69:217226, 1990 3. Ishikawa I, et al.: Fifteen-year follow-up of acquired renal cystic diseasea gender difference. Nephron 75:315320, 1997 4. Weng CJ, et al.: Long-term online hemodialtration does not reduce the frequency and severity of acquired cystic kidney disease in hemodialysis patients. Ren Fail 31:555561, 2009 5. Truong LD, et al.: Renal neoplasm in acquired cystic kidney disease. Am J Kidney Dis 26:112, 1995 6. Filocamo MT, et al.: Renal cell carcinoma of native kidney after renal transplantation: clinical relevance of early detection. Transplant Proc 41:4197 4201, 2009 7. Kojima Y, et al.: Renal cell carcinoma in dialysis patients: a single center experience. Int J Urol 13:10451048, 2006 8. Gulanikar AC, et al.: Prospective pretransplant ultrasound screening in 206 patients for acquired renal cysts and renal cell carcinoma. Transplantation 66:16691672, 1998 9. Denton MD, et al.: Prevalence of renal cell carcinoma in patients with ESRD pre-transplantation: a pathologic analysis. Kidney Int 61:22012209, 2002 10. Doublet JD, et al.: Renal cell carcinoma of native kidneys: prospective study of 129 renal transplant patients. J Urol 158:4244, 1997 11. Ishikawa I, et al.: Renal cell carcinoma detected by screening shows better patient survival than that detected following symptoms in dialysis patients. Ther Apher Dial 8:468473, 2004 12. Sarasin FP, et al.: Screening for acquired cystic kidney disease: a decision analytic perspective. Kidney Int 48:207219, 1995 13. Schwarz A, et al.: Renal cell carcinoma in transplant recipients with acquired cystic kidney disease. Clin J Am Soc Nephrol 2:4, 2007 14. Narasimhan N, et al.: Clinical characteristics and diagnostic considerations in acquired renal cystic disease. Kidney Int 30:748752, 1986 15. Taylor AJ, et al.: Renal imaging in long-term dialysis patients: a comparison of CT and sonography. AJR Am J Roentgenol 153:765767, 1989

Bosniak 1 and 2, quarterly for 2F and 3. Nephrectomy should be considered anytime lesions are progressing. Although there are no strict guidelines, an arbitrary 2-year period after nephrectomy for RCC has been recommended to ensure non-recurrence to relist for transplant. The optimal imaging modality for screening is not clear as the data are mixed. CT scan is likely superior to ultrasound in detecting focal hyperplasia and small solid lesions <0.3 cm in small brotic kidneys of ESRD patients. Dynamic contrast CT scan is better than ultrasound with accuracy up to 100%, but this imaging modality comes with a contrast load, which may not be appropriate in CKD patients (14,15). In conclusion screening with either annual CT scan or ultrasound is benecial in young dialysis patients with signicantly better 510 year survival rates with the hope of detecting early RCC and offering surgical optionsparticularly if they are listed for renal transplant. In transplant recipients twice a year ultrasound screening for patients with Bosniak 1 and 2 scores and quarterly US or annual CT scan for Bosniak 2F and 3 scores is recommended.

Should high-dose oral diuretics be used to increase urine output in patients on chronic peritoneal and hemodialysis?
Diuretics are often discontinued upon initiation of renal replacement therapy (RRT) based on the assumption that dialysis treatments will be the primary clinical tool for managing uid in patients with end-stage renal disease (ESRD). There is also the impression among some

Rachel Fissell* and Bruce Robinson

Seminars in DialysisVol 24, No 4 (JulyAugust) 2011 pp. 366368 DOI: 10.1111/j.1525-139X.2011.00927.x 2011 Wiley Periodicals, Inc.

that diuretics will no longer be effective as a patients glomerular ltration rate (GFR) falls to levels requiring dialysis. We believe that these are misguided assumptions and further believe that there are many reasons to endorse the use of high-dose oral diuretics to increase urine output in patients on chronic peritoneal and hemodialysis. Oral diuretics can be used chronically to increase urine output in patients with ESRD on either peritoneal dialysis (PD) or hemodialysis (HD) if they have sufcient residual kidney function (RKF) to maintain a clinically