Yoshihide Ogawa*, Tomoharu Kobayashi, Akishima-city, Tokyo-to, Japan, Keimei Kojima, Rensuke Mannami, Makoto Mannami, Uwajima-city, Ehime-ken, Japan, Keiichi Kitajima, Kagoshima-city, Kagoshima-ken, Japan, Mitsuo Nishi, Marugame-city, Kagawa-ken, Japan, Naoki Mitsuhata,

Kure-city, Hiroshima-ken, Japan

Ex vivo Resection of Renal Cell Carcinoma and Restoration of the Kidney may Expand the

Supply of Available Organs for Renal Transplantation

• There are more than ten thousand dialysis patients waiting for kidney transplantation and the average waiting period for deceased kidney transplantation is 14 years and 10 months in Japan. • To expand the donor pool, Mannami already reported 8 cases of restored kidney transplantation using kidneys after resection of renal cell carcinoma (RCC) as well as Nicol 31 , Buel 14, Sener 3 cases and other single-case reports, making up more than 60 cases. • More than 80% of small renal tumors (4 cm or less) are nephectomized in Japan, estimating 2,000 kidneys as such discarded every year. • Nalesnik et al. recently performed the first step towards evaluating the risk of cancer transmission to optimize organ usage.• To address this issue and raise awareness, we performed a prospective open clinical trial that utilized these discarding kidneys by restoring nephrectomized kidneys to be transplanted into third-party recipients.

Introduction & Objectives

Materials & Methods• Our study of restored kidney transplantation between the third parties had an estimated enrollment of 5 patients with one year of follow-up and was approved by Tokushukai Joint Ethics Committee in July 2009 and registered in the U.S. ClinicalTrials.gov. • Donors were selected from among patients who had small renal cell carcinomas (<4 cm) and opted to undergo nephrectomy for small RCC after extensive discussion of other possible treatment modalities, including nephron-sparing procedures.• After nephrectomy, the tumor was removed from each resected kidney. • After careful pathological examination of the resection margin, the cut surface was sutured and repaired on the second table and the restored kidney was transplanted into an unrelated recipient. • The recipient was selected by a third-party selection committee based on the blood group match, high clinical evaluation score, and negative cross-match test.

Donor kidney tumor: RENAL Nephrometry Score

(Kutikiv and Uzzo. J Urol 182, 844, 2009)Case Histology Tumor size (cm)

RENAL Nephrometry score

1 51 y/o M

Clear cell 3.9 cm 5a Low complexity

2 57 y/o M

Clear cellG1>G2 INFα V-

3.5 cm 5a Low complexity

3 79 y/o M

Clear cellG2>G3=G1

2.0 cm 6p Low complexity

4 61 y/o M

Clear cellG2 INFα

3.5 cm 7p Moderate complexity

5 69 y/o M

Granular 3.8 cm 7p Moderate complexity

Donor renal functionDonor Serum

Cremg/dl atbaseline

eGFRml/min/1.73 m2

Affected kidney DTPA-GFR

Remaining kidney DTPA-GFR

Latestserum Cre

1 51 y/o M 0.84 76 30.32 42.60 1.25

2 57 y/o M 0.71 88 44.69 48.87 1.19

3 79 y/o M 1.35 39.9 27.84 25.97 3.44

4 61 y/o M 0.94 63.8 34.62 36.12 1.48

5 69 y/o M 0.94 61.6 22.80 23.90 1.40

Surgical Procedures: Nephrectomy, Irrigation with Via Span, Tumor Resection, Check Collecting System, Suture of Collecting System and Parenchyma, Approximation, and Restoration Completion ready for Transplantation

Case Age Sex

Warm ischemia

Cold ischemia

Donor Nx Restoration

Transplant

1 47 y/o

M

12 min 6 hr 2 min 5 hr 15min

10 min 1 hr 56 min

2 54 y/o

F

4 min 1 hr 42 min

3 hr 20 min 3 hr 12 min

3 62 y/o F3 min 3 hr 1 min 3 hr 43

min53 min 3 hr 39

minHx of Tx

4 66 y/o

M

4 min 3 hr 4 min 1 hr 52 min

33 min 2 hr 38 minHx of Tx

5 55 y/o

F

4 min 8 hr 22 min

2 hr 8 min 45 min 2 hr 25 min

Procedure times including nephrectomy, transport, reconstruction, and transplant

Recipients of 3rd-party restored kidney transplantation: Follow-up 15-23 months

Case

Age Sex

Latest immuno-suppression

Latest serum Cre mg/dL

Rejection episodes

Postop morbidity

1 47 y/o M MMF 1000 mgTAC 4 mgPSL 10mg

1.41Jan 1, 2009 Hypertension

2 54 y/o F MMF 500 mgTAC 5 mg 1.12

None Hypertension Anemia

3 62 y/o F MMF 500 mgTAC 2 mg 1.55

April 29, 2010

None

4 66 y/o M MMF 1500 mgTAC 3 mg

1.70July 25, 2010Aug 23, 2010

Post Tx nephrosisChr hypothyroid Anemia

555 y/o F MMF 1000

mgTAC 2 mg

1.94Sept 2, 2010Nov 30, 2010Jan 13, 2011March 27, 2011

D.M.

Treatment Trends for T1a RCC and Potential Donor Pool in Japan

• In Japan Tsutsumi estimated that 2,000 kidneys with small renal cell carcinomas are nephrectomized and discarded yearly, • Questionnaire survey was conducted by the JUA among teaching hospitals all over Japan in 2010. Based on the data, approximately 14,335 patients with RCC underwent surgery, accounting for 11,135 (77.7%) nephrectomized and 3,200 (22.3%) partial nephrectomized. • The prevalence of T1a and T1b RCC is not certain in Japan, but the numbers of T1 RCC, < 3 cm, and < 2 cm could be estimated to be respectively 7,540, 3,273, and 1,821, if the prevalence reported by Cooperberg be applied (J Urol, 2008).• Therefore, the estimation of 2,000 kidneys with small RCC by Tsutsumi appears reasonable or rather underestimated.

Conclusions• Selected candidates tolerate restored kidney transplant, and achieve good renal function without tumor recurrence.• The procedure seems to be acceptable for selected donors and is beneficial for patients on long-term dialysis andwaiting for a kidney. • Ex vivo resection of renal cell carcinoma and restoration of the kidney may expand the supply of available organs for renal transplantation in the future.• We should bridge the growing gap between the number of donor kidneys needed and the available supply by employing discarded kidneys with small RCC for renal transplantation.