2272 RHABDOMYOLYSIS WITH ACUTE RENAL FAILURE IN DECEASED DONORS IS NOT A CONTRAINDICATION FOR KIDNEY...

2
Source of Funding: Department of Defense 2270 POSTTRANSPLANT DIABETES MELLITUS IN ADULT RENAL TRANSPLANT RECIPIENTS: INCIDENCE, CLINICAL CHARACTERISTICS, TACROLIMUS PHARMACOKINETICS, AND RELATED GENOMIC POLYMORPHISMS Kazuyuki Numakura*, Shigeru Satoh, Norihiko Tsuchiya, Mitsuru Saito, Shinya Maita, Takashi Obara, Takamitsu Inoue, Shintaro Narita, Yohei Horikawa, Hideaki Kagaya, Masatomo Miura, Tomonori Habuchi, Akita, Japan INTRODUCTION AND OBJECTIVES: The present study inves- tigated the incidence of posttransplant diabetes mellitus (PTDM) and calculated the risk of developing PTDM under a tacrolimus (TAC) and mycophenolate mofetil (MMF)-based immunosuppression based on clinical characteristics, risk factors, TAC-pharmacokinetics (PK), and genomic polymorphisms related to TAC-PK, cytokines and diabetes mellitus (DM). METHODS: One hundred twenty-three non-diabetic adult renal allograft recipients (male 72, female 51) transplanted between January 2001 and October 2009 were studied. Patients with continuous high plasma glucose levels, over 6.5mg/dl of hemoglobin A1c, or requiring insulin and/or oral anti-diabetic agents for more than 3 months 1-year after transplantation were diagnosed as having PTDM. Fifty genomic polymorphisms were assessed. RESULTS: After transplantation, 19 recipients (15.4%) devel- oped PTDM. Older age (p0.030) and high body mass index (BMI) (p0.038) at the time of transplantation were associated with the development of PTDM. There was no relationship between the devel- opment of PTDM and other clinical parameters, TAC-PK or its related genomic polymorphisms. The frequencies of PTDM were significantly higher in patients with the adiponectin T45G TT genotype than in those with the G allele (p 0.038). On multivariate analysis, older age (50 years old), high BMI (24) and adiponectin T45G TT genotype were risk factors for the development of PTDM. CONCLUSIONS: The incidence of PTDM in our cohort was 15.4%. Older age and high BMI were clinical risk factors for PTDM. The adiponectin T45G TT genotype may influence the occurrence of PTDM, but TAC-PK and related genes did not. These findings might contribute to elucidating the mechanism of PTDM and predict a patient’s risk for developing PTDM. Source of Funding: None 2271 DOES PRESERVED RENAL VOLUME PREDICT 1-YEAR DONOR RENAL FUNCTION FOLLOWING LIVING DONOR NEPHRECTOMY? Rachid Yakoubi*, Riccardo Autorino, Ahmad Kassab, Humberto K. Laydner, Shahab Hillyer, Robert J. Stein, Georges-Pascal Haber, Jihad H. Kaouk, Cleveland, OH INTRODUCTION AND OBJECTIVES: Living donor nephrec- tomy represents a well-known risk factor for decreased renal function. Kidney volume was found as a good predector or renal fuction for recipient, but few studies assessed the role of kidney volume in donor. The aim of this study was to evaluate whether preserved renal volume predicts donor renal function at 1-year following living donor nephrectomy. METHODS: Data of patients who underwent laparoscopic living donor nephrectomy at our Institution between October 2006 and Sep- tember 2010 were retrospectively reviewed. Kidney volume was esti- mated by CT scan using an automated segmentation algorithm. For each donor, the following variables were evaluated, kidney volume adjusted to donor body surface area (BSA), proportion of preserved kidney volume, eGFR before surgery and at 1 year. Comparison was made between donors with eGFR at 1 year 60 ml/min/1.73m2, and those how developed an eGFR of less than 60 ml/min/1.73m2. Multiple linear regression was fitted to study predictors of the eGFR at 1 year. Varaible included in the model were age, gender, BSA, side, preoper- ative eGFR and preserved kidney volume. RESULTS: One year renal function was available in 140 pa- tients. The median age was 40 years and the median preoperative preserved kidney volume was 160.5 cc/1.73m2 (IQR 143.7 - 177.9). The median eGFR was 92.4 (IQR 81.9 - 01.2) and 61.2 ml/min/1.73m2 (IQR 53.4 - 68.7) respectively at baseline and at 1 year. Patients with an eGFR 60ml/min/1.73m2 at 1 year follow-up were older (44 vs 38 p0.002), had small preserved kidney volume (155.4 vs 166.2 cc/ 1.73m2, p0.002) and low pre-donation eGFR (83 vs 97.4 ml/min/ 1.73m2, p 0.001). No significant difference was found between the two groups in terms of absolute change in eGFR at 1 year (-30.8 vs -29.8 ml/min/1.73m2). Age (p0.01), gender (p0.04), preserved kid- ney volume (p0.04) and preoperative eGFR (p0.001) were inde- pendent predictors of renal function at 1 year follow-up. A preserved Volume 160 cc/1.73m2 was an independent predictor of eGFR at 1 year. However, the ratio of preserved kidney was not statistically related to the renal function (p0.68). CONCLUSIONS: Remaining kidney volume, as preoperatively assessed by CT scan, represents an independent predictor of the donor renal function at 1 year following living donor nephrectomy. In order to maximize preservation of donor renal function, the kidney volume/BSA should be included in the criteria when deciding for living kidney donation. Source of Funding: None 2272 RHABDOMYOLYSIS WITH ACUTE RENAL FAILURE IN DECEASED DONORS IS NOT A CONTRAINDICATION FOR KIDNEY DONATION Rajinikanth Ayyathurai*, Shivam Joshi, Obi Ekwenna, Junichiro Sageshima, Linda Chen, George Burke III, Gaetano Ciancio, Miami, FL INTRODUCTION AND OBJECTIVES: The continuing shortage of kidneys available for transplantation requires major effort to expand the donor pool. Grafts from deceased donors (DD) with rhabdomyolysis could increase the number of available kidneys, but it is unknown whether patients who receive these kidneys will have good long term graft function. METHODS: Three potential donors had rhabdomyolysis with acute renal failure (ARF) as evidenced by the presence of urine hemoglobin, levels of plasma creatinine phosphokinase (CK) five times more than normal and elevated serum creatinine. Two donors required dialysis. All DD kidneys received machine perfusion (MP) preservation e916 THE JOURNAL OF UROLOGY Vol. 187, No. 4S, Supplement, Wednesday, May 23, 2012

Transcript of 2272 RHABDOMYOLYSIS WITH ACUTE RENAL FAILURE IN DECEASED DONORS IS NOT A CONTRAINDICATION FOR KIDNEY...

Source of Funding: Department of Defense

2270POSTTRANSPLANT DIABETES MELLITUS IN ADULT RENALTRANSPLANT RECIPIENTS: INCIDENCE, CLINICALCHARACTERISTICS, TACROLIMUS PHARMACOKINETICS, ANDRELATED GENOMIC POLYMORPHISMS

Kazuyuki Numakura*, Shigeru Satoh, Norihiko Tsuchiya,Mitsuru Saito, Shinya Maita, Takashi Obara, Takamitsu Inoue,Shintaro Narita, Yohei Horikawa, Hideaki Kagaya, Masatomo Miura,Tomonori Habuchi, Akita, Japan

INTRODUCTION AND OBJECTIVES: The present study inves-tigated the incidence of posttransplant diabetes mellitus (PTDM) andcalculated the risk of developing PTDM under a tacrolimus (TAC) andmycophenolate mofetil (MMF)-based immunosuppression based onclinical characteristics, risk factors, TAC-pharmacokinetics (PK), andgenomic polymorphisms related to TAC-PK, cytokines and diabetesmellitus (DM).

METHODS: One hundred twenty-three non-diabetic adult renalallograft recipients (male 72, female 51) transplanted between January2001 and October 2009 were studied. Patients with continuous highplasma glucose levels, over 6.5mg/dl of hemoglobin A1c, or requiringinsulin and/or oral anti-diabetic agents for more than 3 months 1-yearafter transplantation were diagnosed as having PTDM. Fifty genomicpolymorphisms were assessed.

RESULTS: After transplantation, 19 recipients (15.4%) devel-oped PTDM. Older age (p�0.030) and high body mass index (BMI)(p�0.038) at the time of transplantation were associated with thedevelopment of PTDM. There was no relationship between the devel-opment of PTDM and other clinical parameters, TAC-PK or its relatedgenomic polymorphisms. The frequencies of PTDM were significantlyhigher in patients with the adiponectin T45G TT genotype than in thosewith the G allele (p� 0.038). On multivariate analysis, older age (�50years old), high BMI (�24) and adiponectin T45G TT genotype wererisk factors for the development of PTDM.

CONCLUSIONS: The incidence of PTDM in our cohort was15.4%. Older age and high BMI were clinical risk factors for PTDM. Theadiponectin T45G TT genotype may influence the occurrence of PTDM,but TAC-PK and related genes did not. These findings might contributeto elucidating the mechanism of PTDM and predict a patient’s risk fordeveloping PTDM.

Source of Funding: None

2271DOES PRESERVED RENAL VOLUME PREDICT 1-YEAR DONORRENAL FUNCTION FOLLOWING LIVING DONORNEPHRECTOMY?

Rachid Yakoubi*, Riccardo Autorino, Ahmad Kassab,Humberto K. Laydner, Shahab Hillyer, Robert J. Stein,Georges-Pascal Haber, Jihad H. Kaouk, Cleveland, OH

INTRODUCTION AND OBJECTIVES: Living donor nephrec-tomy represents a well-known risk factor for decreased renal function.Kidney volume was found as a good predector or renal fuction forrecipient, but few studies assessed the role of kidney volume in donor. Theaim of this study was to evaluate whether preserved renal volume predictsdonor renal function at 1-year following living donor nephrectomy.

METHODS: Data of patients who underwent laparoscopic livingdonor nephrectomy at our Institution between October 2006 and Sep-tember 2010 were retrospectively reviewed. Kidney volume was esti-mated by CT scan using an automated segmentation algorithm. Foreach donor, the following variables were evaluated, kidney volumeadjusted to donor body surface area (BSA), proportion of preservedkidney volume, eGFR before surgery and at 1 year. Comparison wasmade between donors with eGFR at 1 year �60 ml/min/1.73m2, andthose how developed an eGFR of less than 60 ml/min/1.73m2. Multiplelinear regression was fitted to study predictors of the eGFR at 1 year.Varaible included in the model were age, gender, BSA, side, preoper-ative eGFR and preserved kidney volume.

RESULTS: One year renal function was available in 140 pa-tients. The median age was 40 years and the median preoperativepreserved kidney volume was 160.5 cc/1.73m2 (IQR 143.7 - 177.9).The median eGFR was 92.4 (IQR 81.9 - 01.2) and 61.2 ml/min/1.73m2(IQR 53.4 - 68.7) respectively at baseline and at 1 year. Patients withan eGFR � 60ml/min/1.73m2 at 1 year follow-up were older (44 vs 38p�0.002), had small preserved kidney volume (155.4 vs 166.2 cc/1.73m2, p�0.002) and low pre-donation eGFR (83 vs 97.4 ml/min/1.73m2, p� 0.001). No significant difference was found between thetwo groups in terms of absolute change in eGFR at 1 year (-30.8 vs-29.8 ml/min/1.73m2). Age (p�0.01), gender (p�0.04), preserved kid-ney volume (p�0.04) and preoperative eGFR (p�0.001) were inde-pendent predictors of renal function at 1 year follow-up. A preservedVolume � 160 cc/1.73m2 was an independent predictor of eGFR at 1year. However, the ratio of preserved kidney was not statisticallyrelated to the renal function (p�0.68).

CONCLUSIONS: Remaining kidney volume, as preoperativelyassessed by CT scan, represents an independent predictor of thedonor renal function at 1 year following living donor nephrectomy. Inorder to maximize preservation of donor renal function, the kidneyvolume/BSA should be included in the criteria when deciding for livingkidney donation.

Source of Funding: None

2272RHABDOMYOLYSIS WITH ACUTE RENAL FAILURE INDECEASED DONORS IS NOT A CONTRAINDICATION FORKIDNEY DONATION

Rajinikanth Ayyathurai*, Shivam Joshi, Obi Ekwenna,Junichiro Sageshima, Linda Chen, George Burke III,Gaetano Ciancio, Miami, FL

INTRODUCTION AND OBJECTIVES: The continuing shortageof kidneys available for transplantation requires major effort to expand thedonor pool. Grafts from deceased donors (DD) with rhabdomyolysis couldincrease the number of available kidneys, but it is unknown whether patientswho receive these kidneys will have good long term graft function.

METHODS: Three potential donors had rhabdomyolysis withacute renal failure (ARF) as evidenced by the presence of urinehemoglobin, levels of plasma creatinine phosphokinase (CK) five timesmore than normal and elevated serum creatinine. Two donors requireddialysis. All DD kidneys received machine perfusion (MP) preservation

e916 THE JOURNAL OF UROLOGY� Vol. 187, No. 4S, Supplement, Wednesday, May 23, 2012

with RM3 Renal Preservation Machine (Waters Instruments Inc., Roch-ester, MN). Kidneys were perfused with Belzer’s hypothermic preser-vation solution at 4°C at initial pressure of 50 mmHg (threshold for useafter 6 hours on the MP: flow rate �80mL/min and resistance �0.50).Pre-transplant biopsies of each graft were reviewed to evaluate chronicchanges or evidence of acute injuries.

The recipients were informed about the condition of the donorsand likelihood of delayed graft function (DGF). All the patients hadnegative T- and B-cell flow crossmatch. Induction immunosuppressionwas given with anti-thymocyte globulin and basiliximab. For mainte-nance immunosuppression, tacrolimus and mycophenolate were used.

RESULTS: Two out of 4 recipients received dual kidney trans-plantation. The mean cold ischemia time and perfusion machine timewere 33 hrs (24-40) and 28 hrs (18-36). Three out of 4 recipientsexperienced DGF requiring hemodialysis. They were tapered down onprednisone and maintained on low dose of steroids (4 mg daily). Thepatient with normal graft function was tapered off prednisone at the timeof discharge. The mean length of hospital stay for the 4 patients was 13days (6-18). At a mean of 32 months post transplant (4-79), all patientshave a good graft function with a mean creatinine of 1.1 (0.9-1.2). SeeTable 1 for more results.

CONCLUSIONS: Kidneys from donors affected by rhabdomy-olysis, even with ARF, may be used in kidney transplants with a goodlong term outcome. An accurate pre-transplant evaluation of the graft isessential before transplantation.

Characteristics of Recipient and Results

Recipient (Donor) 1 (1) 2 (2) 3 (2) 4 (3)

Age/Sex 40yo/M 60yo/M 64yo/M 48yo/M

Graft DKTx SKTx SKTx DKTx

Cold Ischemia Time (hours) 38-40 24 30 31-33

Perfusion Machine Time (hours) 34-36 18 24 28-30

Delayed Graft Function Yes No Yes Yes

Hemodialysis (days) 14 0 6 7

Hospital Stay (days) 18 6 13 14

Follow Up (months) 79 23 23 4

Creatinine at 1 month 1.1 0.9 1.2 0.9

Creatinine at 1 year 1.1 1.0 0.9 -

Creatinine at Last Follow Up 1.2 1.1 1.2 0.9

DKTx dual kidney transplnatation; SKTx single kidney transplantation; M male; Ffemale; yo year old

Source of Funding: None

2273FATE OF THE ACCESSORY RENAL ARTERIES OF GRAFTSWITH MULTIPLE RENAL ARTERIES DURING LIVE-DONORRENAL ALLO-TRANSPLANTATION

Ahmed Harraz*, Ahmed Shokeir, Ibrahim Shalaby, Shady Soliman,Ahmed El-Hefnawy, Mohamed Kamal, Ahmed Kamal,Mohamed Ghoneim, Mansoura, Egypt

INTRODUCTION AND OBJECTIVES: Donor grafts with multi-ple arteries are accepted alternative with equivalent outcome to graftswith single renal arteries. We aim at determining the effect of occlusionof the accessory artery on early graft function and delineating factorspredicting occlusions of the accessory artery.

METHODS: A retrospective review of 731 consecutive live-related renal transplants was conducted between November 2002 andJanuary 2011. A total of 105 consecutive grafts with multiple renal arterieswere identified. The patency of the accessory artery was evaluated usingDoppler US and MRA done at postoperative period. The frequency ofpatency was correlated with renographic clearance to delineate the effecton graft function. Factors predicting occlusion of the accessory artery werestudied using univariate and multivariate analyses.

RESULTS: Doppler US diagnosed occlusion of the accessoryarteries in 11 (10.5%) out of 105 grafts at a mean and median (range)of 8 and 9 (1-21) days post-transplantation, respectively. Mean � SDand median (range) of renographic clearance of grafts with occluded

accessory arteries were 50.5 � 26 and 40 (21-92) ml/min while thoseof grafts with patent accessory arteries ware 68.6 � 18.9 and 67.2(21-117) (p�0.01). The percentage change of renographic clearancebefore and after transplantation has increased for grafts with patentarteries and decreased for grafts with occluded arteries (p�0.03). Onmultivariate analysis, factors predicting the occlusion of the accessoryartery were delayed graft function (OR� 9.9, 95% CI� 1.6-58.6,p�0.01) and upper polar location of the accessory artery (OR�8.9,95% CI� 1.8-43.4, p�0.01). On the other hand, the site of anastomosis(to major or inferior epigastric arteries) or anastomosing the artery tothe main artery (bench surgery) had not affected the patency. Furtheranalysis showed that the mean � SD of the diameter of the upper polararteries was 0.14 � 0.09 cm and those of the hilar and lower polararteries were 0.2 � 0.06 and 0.2 � 0.08, respectively (p�0.03).

CONCLUSIONS: Occlusion of the accessory renal artery has anegative impact on the early graft function. When considering graftswith accessory arteries, grafts with upper polar arteries should be paidthe greatest attention and efforts should be exerted to avoid delayedgraft function.

Source of Funding: None

2274CLINICAL TRIAL OF RESTORED KIDNEY TRANSPLANT AFTERRESECTION OF RENAL CELL CARCINOMA: RESULTS OF THEINITIAL AND EXTENDED STUDIES

Yoshihide Ogawa*, Tomoharu Kobayashi, Akishima, Japan;Shinyu Shiroma, Keimei Kojima, Rensuke Mannami,Makoto Mannami, Uwajima, Japan; Keiichi Kitajima, Kagoshima,Japan; Mitsuo Nishi, Marugame, Japan; Seiichi Ito, Naoki Mitsuhata,Kure, Japan

INTRODUCTION AND OBJECTIVES: Kidneys from patientswith small renal cell carcinomas (RCC) have been considered as apotential source for solving the organ donor crisis. Buell, Mannami, andNicol respectively reported 14, 8, and 31 transplant procedures usingkidneys after resection of RCC. Nalesnik et al. recently performed thefirst step towards evaluating the risk of cancer transmission to optimizeorgan usage. However, no prospective data are available on thetransmission risk for RCC. To address this issue and raise awareness,we performed a prospective open trial that utilized resected kidneys fortransplant into third-party recipients after restoration.

METHODS: Our study of restored kidney transplant had anestimated enrollment of 5 patients with one year of follow-up and wasapproved by Tokushukai Joint Ethics Committee and registered withU.S. ClinicalTrials.gov. Donors were selected from among patients whoopted to undergo nephrectomy for small RCC after extensive discus-sion of other possible treatment modalities. After nephrectomy, thetumor was removed from each resected kidney, which was restoredand transplanted into an unrelated recipient who was selected by athird-party selection committee based on the blood group match, highclinical evaluation score, and negative cross-match test. The trial wasextended to enroll another 5 patients after the fifth transplant becauseof strong requests from other patients.

RESULTS: In the initial study, five male patients aged 51-79years were the kidney donors. The nephrometry RENAL scores fortheir renal tumors (Kutikov-Uzzo) were 6 or 7, suggestive of moderatecomplexity. A total of 56 dialysis patients aged 31-83 years (mean: 58.7years) were enrolled as candidate recipients. Two recipients had ahistory of kidney transplant. All patients received triple immunosuppres-sion. Four recipients have experienced rejection episodes so far andthe latest serum creatinine levels range from 1.22 to 1.67 mg/dl after 15to 23 months of follow-up. There has not been any recurrence of RCC.In the extended study, 4 patients aged 46-65 years have undergonerestored kidney transplant so far and their recent creatinine levelsrange from 1.06 to 1.80 mg/ml without tumor recurrence.

CONCLUSIONS: Selected candidates can benefit from re-stored kidney transplant, achieving good renal function without recur-

Vol. 187, No. 4S, Supplement, Wednesday, May 23, 2012 THE JOURNAL OF UROLOGY� e917