IMMUNOSUPPRESSION II
`
`Abstract# 456
`THE BENEFIT OF CHILD· TO-PARENT KIDNEY DONATION: AN
`ANALYSIS OF UNOS DATA. Eric P. Cohen, 1 John D. Rosendale,' Christine
`J. Haywood-Bong,2 Sundaram Hariharan. 1 / Division Of Nephro/ogy,
`Medical College of Wisconsin, Milwaukee, WI; 'United Network of Organ
`Sharing, Richmond, VA.
`Unwarranted nsk to the younger donor has been assumed by some nephrologists to
`preclude child-to-parent kidney donation. This has not been tested. We used UNOS
`data to analyze the benefit of child-to-parent (CTP) kidney donation in comparison
`to other living or cadavenc kidney donation. 56,873 pnmary kidney transplant• (tx)
`between 1988 and 1998 were analyzed. Kidney tx type> were child-to-parent (group
`I, n=3,797), other living donor (LO) (group II, n=8,284) and cadaveric donor (group
`III, n=44,792). Rec1p1ents were subd1v1ded by age: 41-50, 51-60, and 61 or older.
`Add1t10nal variables such as· center volumes, donor and recipient gender or race.
`HLA mismatch, CIT, PRA, diabetic status, prior dialysis, and use of anti-rejection
`treatment were used for Cox and logistic regression analyses. Graft and patient
`half-lives were calculated. General results are shown:< P ahgn= ju•ttfy>
`Group
`Grafr Half Life Patient Half Life
`(mo)
`(mo)
`149
`116"'
`127•
`20<
`112
`91
`
`"' P<O 01 vs Group Ill
`
`I ICTPJ
`II (other LO)
`Ill (cadaver)
`For all rtup1ents censored for death with a
`func t1omnR gra/r
`24 I,,..
`I (CfP)
`211 **
`II (other LD)
`160
`Ill (cadavcnc)
`Logistic regression for I year graft failure revealed lower graft failure rates with CTP
`compared to cadavenc tx (34%, P<0.05) and lower death rates (23%, P<0.05). Cox
`proportial hazard model for post-I year revealed similar lower graft failure (18%,
`P<0.05) and death rates (13%, P<0.05). A surfeit ofO mismatch tx in group II accounts
`for their advantage over group I. The I ID 3,000 mortahty nsk from kidney donatton
`translates to -65 years of lost life in the 3,797 CTP kidney donors of this study.
`Because of the 17 month average gain in patient survival (149-132 mo.), we estimate
`-5,500 patient-years of increased survival for the group of CTP versus cadavenc
`kidney tx ID this study. This projected gain was seen in all age groups, but was
`smaller ID diabetic recipients over age 60. We conclude that graft and pallent survival
`is prolonged by using CTP compared to cadavenc kidneys. CTP kidney tx i• well
`worth 1ts risk, will tend to enhance organ ;upply, and should be considered whenever
`possible.
`
`p = n~
`
`Abstract# 457
`LONG-TERM RESULTS IN KIDNEY TRANSPLANTATION
`FROM HLA-IDENTICAL LIVING DONORS: A SINGLE·
`CENTER EXPERIENCE. Hiroaki Shimmura, 1 Kazunari Tanabe,1
`Tadahiko Tokumoto, 1 Nobuo Ishikawa,' Shohei Fuchinoue.' Hiroshi
`Toma.' 1Department of Urology, Kidney Center, Tokyo Women's
`Medical University, Tokyo; 'Department of Surgery, Kidney Center,
`Tokyo Women's Medical University, Tokyo, Japan.
`Background: Due to the cont1Duing shortage of cadaveric donors ID Japan, 1iv1Dg
`kidney transplantation has been carried out. Since livmg kidney transplantat10n is
`usually performed between parent and child, HLA-identical donor livlDg kidney
`transplantation is uncommon. According to UNOS (United Network for Organ
`Shanng) data, I 0-year graft survival was approximately 10% higher in HLA-matched
`cadavenc kidney transplantation than in HLA-matched transplantation. However
`the long-term results of kidney transplantatton from HLA-identical hvlDg donors is
`still unclear. Therefore we compared the survival rate in HLA-idenucal and HLA(cid:173)
`nonidentical living kidney transplantation.
`Matenals and Methods: One thousand and seventy-nine rec1p1ents who underwent
`living kidney transplantation at our institution between February 1983, and December
`1999, were enrolled ID this study. They were subd1v1ded into an HLA-identical
`donor group (group I, n=96) and an HLA-nonidentical donor group (group 2.
`n=983). All patients were treated with cyclosporine- or tacrohmus-based
`1mmunosuppression, includ1Dg methylprednisolone and azathtoprine or m1zonbine
`Results: The mean rec1p1ent age was 38.1 years in group I and 31.9 years in group 2
`(not s1gmficant). The mean donor age was s1gmficantly lower ID group I than ID
`group 2 (44.3 years vs 53.5 years, respectively; p<0.001) Patient survival was not
`sigmficantly different between the two groups (94.4% and 89.8% m group I, 93.8%
`and 89.3% ID group 2 at 5 and IO years, respecttvely). There was a s1gmficant
`difference in graft survival between the two groups (87.5% and 74.8% in group I,
`75.7% and 57 .2% in group 2 at 5 and IO years, respectively, p = 0.0025). The
`1Dc1dence of acute rejection was 11.5% and 58.3% m groups I and 2, respectively (P
`= 0.001 ). Although a higher donor age was associated with poorer graft survival,
`after adjustment for donor age, graft survival was also higher ID group I than ID
`group 2 (P = 0.0195 by Cox regression analysis).
`Conclusions: Although the 1Dcidence of acute rejection was much lower ID HLA(cid:173)
`identtcal livmg kidney transplantation, the I 0-year graft survival was only 15%
`higher. Therefore 11 1s speculated that the outcome of long-term hving kidney
`transplantat10n would be affected more by a non-1mmunolog1cal factor than HLA(cid:173)
`matchmg.
`
`250
`
`Abstract# 458
`DECLINING INFLUENCE OF RACE ON THE OUTCOME OF
`LIVING DONOR RENAL TRANSPLANTATION. Stephen R.
`Smith, 1 David W. Butterly.' 1Department of Medicine, Division of
`Nephrology, Duke University Medical Center, Durham, NC.
`A racial disparity in graft survival for renal transplant recipients has been documented
`both for cadavenc and living donor transplants. In the present single center study we
`analyzed graft survival by race for recipients of living donor kidney transplants in
`three eras: 1985-1989, 1990-1994, and 1995-1998. Living donor transplants were
`selected for study to mimm1ze confoundmg factors related to donor kidney cond1tton
`and HLA match1Dg. There was an inten•ification of the immunosuppre;;ant regimen
`beginning ID 1996 such that all patients received cyclosponne or tacrolimus with
`mycophenolate mofetil and prednisone. There were 76 black rec1p1ents and 174 white
`recipients with no difference ID mean age, degree of HLA matching, or proport10n of
`rec1p1ents with diabetes as the cause of end-stage renal disease. Using all data from
`1985-1998, graft survival was numerically better for whites versus blacks for O, 1,
`and 2 haplotype matched transplants, adjusting for age, gender, diabetes, and era of
`the transplant. However, when analyzed by era of the transplant, there was a temporal
`trend for a progressive decrease in the racial dispanty in graft survival, such that no
`difference was apparent ID the most recent era.
`1985-19!19
`1990-1994
`'i yr
`N
`I yr
`N
`I yr
`graft ~urv graft mrv
`graft ~urv
`
`1995·1998
`N
`I yr
`graft ~urv
`
`'Y'
`graft surv
`
`'i yr
`grafl ~urv
`
`14 %%
`94%
`6!1%
`!17%
`22
`Black 20 8l'l
`l9'l
`79%
`42 q4%
`H2%
`5oli 94%
`78%
`White 77 92'l
`In confirmation of this effect, there was a s1gmficant race by era mteract1on (p<.04) on
`multivariable Cox proportional hazards analysis. The most recent data from the USRDS
`are consistent with this not10n. Of those hvlDg donor rec1p1ents s1Dce 1990 who lost
`their grafts, the cause of graft loss was death with a funct10n1Dg graft for 9/24 (38%)
`whites versus only I/I I (9%) blacks. Immunologic graft loss was more common in
`blacks 7/11 (64%) than whites 9/24 (38%). Almost one quarter of the graft losses in
`both groups since 1990 were directly attributable to the patient having self(cid:173)
`discontinued one or more of the 1mmunosuppressant agents.
`We conclude that improved immunosuppression and other factors have closed the
`outcome gap between blacks and whites receiving living donor kidney transplants.
`
`CONCURRENT SESSION 24:
`IMMUNOSUPPRESSION II
`
`Abstract# 459
`RAPAMYCIN INHIBITS TUMOR GROWTH AND METASTASIS
`IN MICE BY ANTIANGIOGENESIS. Philipp v. Breitenbuch, 1
`Markus Guba.' Edward K. Geissler,' Gudrun Koehl,' Stefan Farkas,1
`Carl Zuelke,' Malhi as Anthuber, 1 Karl-Walter Jauch,' Markus
`Steinbauer.' 1Surgery, University of Regenshurg, Regenshurg, Germany.
`Background: Immunosuppressive drugs are effective in reducing rejection in organ
`transplantation. However, cancer development and recurrence are om1Dous risk factors
`for these 1mmunocompromised patients. Here, we show that the new
`1mmunosuppress1ve drug rapamyclD (RAPA) may have a umque ab1hty to reduce the
`risk of cancer, while simultaneously providing effective immunosuppression.
`Methods: Balb/c mice were treated by daily i.p. injection of saline (control), RAPA
`( 1.5 mg/kg). or cyclosporine (IO mg/kg, CsA). The effect of RAPA and CsA on meta•tatic
`tumor growth was tested after intraportal 1Dject1on of syngenic CT-26 adenocarc1Doma
`cells, and is expressed as the% ofhver replaced by tumor(day 11 ). Also, the effect of
`RAPA and CsA on tumor growth and angiogenesis was evaluated in a dorsal skin(cid:173)
`fold chamber by mtrav1tal m1cro•copy (IVM). Besides direct tumor-vessel
`v1suahzauon, tumor size and vessel density were measured by IVM. Blood vascular
`endothehal growth factor (VEGF) levels were measured by ELISA. Results: RAPA
`IDhtbned, while C,A 't1mulated, liver metasta.is of CT-26 cells(% liver replacement:
`saline=l5±3, RAPA=l±I, and CsA=35±6; n=7). Histological analysis of livers
`showed small avascular meta,ta•es ID RAPA-treated mice, whereas, CsA induced the
`growth of large vascular tumor mas>es. Compared to control mice, growth of tumor
`implants in dorsal •kin-fold chambers on day 11 was reduced in RAPA-treated mice,
`and increased with CsA (tumor volume ID mm': saline=l58±32, RAPA=33±12, and
`CsA=207±80; n=7). Importantly, RAPA markedly 1Dhib1ted, and CsA induced, tumor
`angiogenes1s, as evidenced by lower and higher tumor-m1crovascular density,
`respectively (density in cm': saline=l 16±9, RAPA=35±6, and CsA=l79±14, n=7).
`All stated effects were statistically s1gmficant (P<0.05) and confirmed by direct
`IVM tumor v1suahzat1on. A possible mechanistic link to the antiangiogenic RAPA
`effect wa• found through the reduced serum VEGF levels m RAPA-treated tumor(cid:173)
`bearing mice (ID pg/ml: saltne=60±3, RAPA=32±2, and CsA=79±14; n=7).
`Conclusion· RAPA IDhibits, while C,A promote>. tumor growth and metastasis in
`mice. Furthermore, the antitumoral effect of RAPA could be ltnked to VEGF
`antagomsm. Therefore, treatment of transplant rejection with RAPA may have a
`di;tinct advantage over conventional C•A u•e when there is a relatively high risk for
`previous tumor recurrence or de nol'O cancer development.
`
`West-Ward Exhibit 1060
`Breitenbuch #459 2001
`Page 001
`
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