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Purpose: To compare current technology multislice computed tomography angiography (CTA) with magnetic resonance angiography (MRA) in the pre-operative evaluation of vascular anatomy of living renal transplant donors., Methods and Materials: Two hundred and thirty-six kidneys were included in the CTA and MRA analysis. Renal vasculature was evaluated independently by two readers in each modality with a delay of 4 weeks between reading sessions. Surgical correlation on the operated side was available in all patients. The reference standard was defined by surgical correlation and consensus reading of both modalities., Results: Detection rate of CTA for arteries was 99.1 and 95.0 % for reader 1 and reader 2, respectively. Detection rate of MRA for arteries was 95.0/94.3 %. Most of the undetected arteries were ≤ 1 mm diameter (reader 1: 2 of 3 in CTA and 9 of 16 in MRA; reader 2: 11 of 16 in CTA, and 8 of 18 in MRA). Detection rates for arteries ≥ 2 mm for reader 1/reader 2 were 99.7/98.7 % in CTA and 99.1/97.8 % in MRA, respectively. Detection rates for veins were 99.6/97.4 % in CTA and 97.8/96.9 % in MRA, respectively. Both readers misdiagnosed between 0 and 1 non-present arteries and between 2 and 3 non-present veins in both modalities., Conclusions: Modern multislice CT and MRI scanners allow highly accurate evaluation of the vascular anatomy, especially for vessels of ≥ 2 mm diameter. CTA may provide slightly better depiction of very small arteries; however, this may be reader-dependent. Additional factors affecting the choice of imaging modality should include local availability, cost, and the desire to avoid ionizing radiation in healthy transplant donors.

Purpose: There is a growing discrepancy between the demand for renal transplants and the number of transplants conducted. For the many patients on the renal transplant waiting list, this means increased dialysis-associated morbidity, mortality and a reduced quality of life. The aim of this study was to ascertain whether it is justifiable for transplant centers to reject cadaveric donor organs on hand of marginal organ quality., Methods: We identified 110 kidneys that were primarily rejected for transplantation at Charité Universitätsmedizin Berlin, Campus Mitte, and later transplanted at another center within the Eurotransplant zone. Using data from the Collaborative Transplant Study, we analyzed various demographic donor data including cold ischemia times, as well as graft and recipient outcomes., Results: The median follow-up was 54 months. The cold ischemia time averaged 16 h. The organs that were primarily rejected by our center and then transplanted at other Eurotransplant centers showed 31 % of recipients had creatinine levels under 1.47 mg/dl and 94 % had levels under 2.97 mg/dl at 3-year follow-up. The mean death-censored graft survival was 71.4 months. The mean renal transplant recipient survival was 87.5 months., Conclusions: Based on our findings, we propose that acceptance criteria for marginal donor kidneys need to be widened.

Objective: To test the effect of surgeon experience on donor and recipient outcomes after laparoscopic living donor nephrectomy (LLDN). Results of a LLDN expert were compared with those of an LLDN novice., Patients and Methods: Between October 2008 and October 2010 the last 20 cases of a series of 130 consecutive LLDNs, performed by an expert (EXP) were compared with the first 20 cases of an LLDN novice (NOV). Donor and recipient outcomes were evaluated. The novice was mentored by the expert during his initial four LLDN cases., Results: Donor and recipient demographics were not different between the two surgeon groups. Total operating time and warm ischaemia time during LLDN was significantly longer in the NOV group compared with the EXP group (273 min vs 147 min and 213 s vs 162 s, respectively). The incidence of donor complications was low in both groups. Length of hospital stay among donors did not differ between groups. Although delayed graft function, rejection rates and postoperative serum creatinine levels indicated slightly poorer recipient outcomes in the NOV group, differences did not reach statistical significance., Conclusions: Mentoring by an experienced urological laparoscopist may help an LLDN novice to generate acceptable donor and recipient outcomes. Whether or not prolonged operating times and warm ischaemia times during the early phase of an LLDN experience are risk factors for impaired graft function needs further evaluation., (© 2012 The Authors BJU International © 2012 BJU International.)

We compared long-term outcomes of LDKT in pediatric recipients following either laparoscopic (LDN) or ODN. In our retrospective single-center study, we compared 38 pediatric LDKT recipients of a laparoscopically procured kidney with a historic ODN group comprising 17 pediatric recipients. In our center, the first pure laparoscopic non-hand-assisted LDN for a pediatric LDKT recipient was performed in June 2001. Demographic data of donors and recipients were comparable between groups. Mean follow-up was 64 months in the LDN group and 137 months in the ODN group. Patient survival was comparable between groups. Graft survival at one and five yr was 97% (LDN) vs. 94% (ODN) and 91% (LDN) vs. 88% (ODN; p = n.s.), respectively. Serum creatinine at one and five yr was 1.16 ± 0.47 mg/dL (LDN) vs. 1.02 ± 0.38 mg/dL (ODN) and 1.38 ± 0.5 mg/dL (LDN) vs. 1.20 ± 0.41 mg/dL (ODN), respectively. The type and frequency of surgical complications did not differ between groups. DGF and acute rejection rates were similar between groups. In the ODN group, a higher proportion of right donor kidneys was used. In the ODN group, all kidneys had singular arteries, whereas in the LDN group five kidneys had multiple arteries. Arterial multiplicity was associated with a higher incidence of DGF. In our experience, LDN does not compromise long-term graft outcomes in pediatric LDKT recipients. Arterial multiplicity of the donor kidney may be a risk factor for impaired early graft function in the pediatric population., (© 2012 John Wiley & Sons A/S.)

Objective: To describe the successful repair of a post-transplant iliac artery aneurysm with renal graft preservation., Methods: An aneurysm was detected in an asymptomatic 47-year-old male recipient on routine Doppler ultrasonography that involved the right external iliac artery and the distal portion of the renal artery. Aneurysm resection was performed immediately after diagnosis 3 months after transplantation. A polytetrafluorethylene tube graft was used for reconstruction of the right external iliac artery. Reconstruction of the renal artery required interposition of a vena saphena graft between the proximal portion of the renal artery and the polytetrafluorethylene tube., Results: The total warm ischemia time used for aneurysm repair and renal transplant revascularization was 90 minutes. The postoperative Doppler ultrasound scan showed homogeneous graft perfusion. Pathologic and microbiologic examination of the resected aneurysm revealed Candida albicans arteritis. The center in which the contralateral donor kidney was transplanted had previously reported Candida albicans contamination of the preservation solution. The recipient of the contralateral kidney lost his graft owing to bleeding complications. Information on this incident was acquired by our center only after aneurysm repair. Postoperatively, our recipient was given systemic antifungal therapy. At 6 months, the serum creatinine level was 1.7 mg/dL., Conclusion: Although a high-risk procedure, repair of a mycotic aneurysm with renal graft preservation is feasible. Routine microbiologic screening of the preservation solution might help to detect and treat donor-transmitted infections in renal transplant recipients., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Objective: To determine how postoperative and functional outcomes after deceased donor renal transplantation (DDRT) are related to surgeon experience., Patients and Methods: The outcomes of 484 adult DDRT performed by 13 urological surgeons were retrospectively reviewed. After completion of a staged renal transplant training programme under supervision of an attending urological transplant surgeon, the 13 surgeons were either assigned to the inexperienced group (n = 8) or the experienced group (n = 5). Surgeons in the experienced group had performed more than 30 unsupervised DDRT in a standard fashion with routine ureteric stenting. Between 1988 and 2005, inexperienced surgeons performed 152 DDRT, whereas experienced surgeons performed 332 DDRT., Results: Patient and graft survival at 2 hyears were 98% and 94.7%, respectively. Early graft loss in five recipients was unrelated to surgeon experience. Delayed graft function occurred in 29% of cases and median 1-year serum-creatinine was 1.48 mg/dL, with no difference between surgeon groups. Postoperative bleeding and lymphocele formation were the most frequent surgical complications, with an equal distribution between groups. Ureteric complications had a significantly higher incidence among inexperienced surgeons (6.6% versus 2.7%; P = 0.04)., Conclusion: We conclude that DDRT as performed by inexperienced urological renal transplant surgeons has both acceptable short- and long-term outcomes., (© 2012 THE AUTHORS. BJU INTERNATIONAL © 2012 BJU INTERNATIONAL.)

Purpose: Systemic heparin administration during laparoscopic donor nephrectomy (LDN) may prevent microvascular thrombus formation following warm ischemia. We herein present our experience with and without systemic heparinization during LDN., Methods: We retrospectively reviewed donor complications and graft outcomes in 119 consecutive live donor kidney transplantations between January 2005 and December 2009. Systemic heparin was administered to the first 65 donors. LDN was carried out by 2 surgeons using a pure laparoscopic technique., Results: Total operating time for LDN was significantly longer in the heparin group (202 vs. 157 min). The incidence of renal artery multiplicity was significantly higher in the heparin group. Mean warm ischemia time was 160 s, and mean hospital stay was 5 days with no differences between groups. Postoperative hemorrhage occurred in 3 donors with systemic heparinization and in 1 without heparinization. Two donors received blood transfusions, and 2 underwent laparoscopic reexploration. Three grafts were lost in the heparin group and 1 in the non-heparin group. Graft loss was due to early vascular thrombosis (n = 3) and due to acute rejection (n = 1). Overall, 1-year graft survival was 96.6%, and 1-year serum creatinine was 1.41 mg/dl (P = n. s. between groups)., Conclusions: Abandoning systemic donor heparinization in LDN with short warm ischemia has a low complication rate without adverse effects on short- and long-term graft outcomes.

Background: Kidney allograft function crucially depends on the quality of organ perfusion. Duplex sonography, however, frequently reveals hypoperfused segments that remained undetectable to visual inspection intraoperatively. To date, no imaging system supplementing the surgeon's experience has achieved clinical acceptance. The present work examines whether laser-assisted indocyanine green (ICG) fluorescence-videography can be used as a safe and sensitive technique for the intraoperative assessment of renal allograft perfusion., Methods: Intraoperative assessment of organ perfusion by laser-assisted ICG fluorescence videography (IC-VIEW) was performed in 10 consecutive de novo renal transplantations. The IC-VIEW system allows the visualization of graft perfusion by the fluorescein dye ICG that emits infrared light after exposure to laser light., Results: Perfusion measurements were successful in all 10 transplant recipients. Fluorescence videography produced brilliant, sharply contrasted images of the organs, allowing the detection of even small perfusion deficits. Remarkably, this technique detected 1 large perfusion defect that had remained imperceptible to visual inspection. Repositioning of the graft led to a homogeneous overall perfusion. There were no complications with the ICG injection or the imaging device., Conclusion: Laser-assisted ICG fluorescence videography is a feasible and safe technique for the intraoperative assessment of renal allograft perfusion.

Background: Patients with blood group O have disadvantages in the allocation of deceased donor organs in the Eurotransplant Kidney Allocation System and fewer ABO-compatible living donors. In order to investigate the consequences of this dilemma, we analysed the outcome of patients with blood group O in our transplantation programme., Methods: A single-centre analysis of 1186 waitlisted patients for first deceased donor kidney transplantations between 1996 and 2008 was performed, and the mechanisms of blood group-dependent differences for graft and recipient outcome were assessed., Results: Median follow-up time until death or end of observation for all waitlisted patients was 66 months (range, 0-158 months) and for 589 recipients of a kidney graft was 61 months (range, 0-158 months). Patients with blood group O had significantly longer waiting times for deceased donor kidney grafts, compared to non-group O recipients (median waiting time, 85 vs 59 months). As a consequence, blood group O patients had an increased risk for death without transplantation (13.1% for O patients vs 9.6% for non-O patients; P < 0.05). Despite a good human leukocyte antigen match, graft outcome tended to be worse in O recipients; 14.1% (95% CI, 8.2-19.9%) of all O kidneys from deceased donors were transplanted into non-O recipients, leading to the accumulation of O recipients on the waiting list., Conclusions: The export of blood group O donor kidneys to other blood groups leads to longer waiting times, to a higher death rate and to accumulation of blood group O patients on the waiting list, which will further aggravate the problem in the future. Our results should prompt further research on the issues associated with blood group O. Current allocation systems and living donor kidney exchange programmes should be re-evaluated to address this problem.

Background: Fingolimod (FTY720) is a potent agonist of sphingosine 1 phosphate receptors and thereby interferes with lymphocyte trafficking. We previously showed that FTY720 protects from mild preservation reperfusion injury induced by 4 hr of cold ischemia. The purpose of this study was to explore the role of FTY720 in ischemic injury and regeneration using a clinically relevant rat renal transplant model with 24 hr of cold ischemia., Methods: Donor kidneys were cold stored in the University of Wisconsin solution for 24 hr before transplantation into bilaterally nephrectomized syngeneic recipients (n=6 per group), which received 0.5 mg/kg/d FTY720 or vehicle through oral gavage. Grafts were harvested 2 or 7 days posttransplantation. Renal tissue was examined histologically, stained for apoptosis, proliferation, inflammatory cell infiltrates, and studied for transforming growth factor-beta, and tumor necrosis factor-alpha expression. Rat proximal tubular cells were incubated with 0.1 to 30 micromol/L of phosphorylated FTY720 to test for in vitro cytopathic effects., Results: FTY720 induced peripheral lymphopenia and significantly reduced intragraft CD3 and ED1 infiltrates. Acute tubular damage scores and graft function were not influenced by FTY720. Tubular apoptosis was significantly reduced, whereas the number of proliferating cell nuclear antigen-positive tubular cells were markedly increased. FTY720 attenuated renal tumor necrosis factor-alpha and transforming growth factor-beta expression. In vitro, pharmacologic concentrations up to 1 micromol/L of phosphorylated FTY720 did not affect tubular cell viability., Conclusion: FTY720 confers tubular epithelial protection in the presence of severe preservation reperfusion injury. Beneficial effects may in part be due to reduction in cell-mediated immune mechanisms. Furthermore, FTY720 could be helpful in patients with delayed graft function.

Objectives: To evaluate the functional outcomes and complications after allogeneic kidney transplantation into recipients with a urinary conduit using ureteroureterostomy between the transplant and native ureter., Methods: We performed a retrospective study of 6 patients with a pre-existing urinary conduit undergoing kidney transplantation at a single tertiary academic center from May 1982 to February 2007., Results: The study included 1 female and 5 males aged 16 to 65 years. Two patients received a living donor transplant. The indications for pretransplant conduit formation were neurogenic bladder in 3 and bladder contraction with vesicoureteral reflux in 3. One patient received a colon conduit. All patients underwent kidney transplantation into a urinary conduit using ureteroureterostomy between the transplant ureter and the ipsilateral native ureter. The average interval between conduit formation and kidney transplantation was 83.5 months and the average time of requiring hemodialysis was 56.3 months. The mean follow-up was 5.3 years. The patient and graft survival rate was 100% and 83.3%, respectively. The 3-year serum creatinine averaged 1.4 mg/dL. One graft was lost because of chronic rejection. Transplant ureter obstruction occurred in 2 patients and required endoscopy or open revision. Four patients underwent post-transplant native nephrectomy for recurrent pyelonephritis. Three patients were hospitalized for treatment of graft pyelonephritis., Conclusions: In our experience, ureteroureterostomy between the transplant and native ureter is technically feasible and provides good functional results despite a high incidence of urinary tract infection. We recommend this approach in renal transplant recipients with a short contracted conduit or in those in whom the donor ureter is too short to warrant a tension-free ureteroileal anastomosis.

Rate of acceptance of deceased-donor kidneys decreases with donor age despite the growing number of aged transplant candidates on the waiting list. In the Eurotransplant Senior Program, HLA-unmatched kidneys from deceased donors aged > or = 65 yr are transplanted regionally into recipients aged > or = 65 yr. Because we have become more willing to accept kidneys from donors aged > or = 75 yr than previous years, we performed a retrospective analysis of this subgroup. Kidneys were accepted from donors aged > or = 75 yr provided a normal creatinine on admission to the hospital, a Cockcroft-Gault creatinine clearance > 80 ml/min, and an absence of comorbidities. We compared outcomes of kidneys from donors aged > or = 75 yr with both younger-donor kidneys transplanted in the Eurotransplant Senior Program and with younger-donor HLA-matched kidneys transplanted into recipients > or = 60 yr. There were no differences in 5-yr graft and patient survival or rate of delayed graft function between groups. Graft function, measured by creatinine and creatinine clearance, differed without pattern at only three of 12 time points during 5 yr of follow-up. In conclusion, our data suggest that kidneys from deceased donors aged > or = 75 yr can be transplanted safely into recipients aged > or = 65 yr if similar donor criteria and local allocation practices are used.

Background: Glutamine (GLN) has been shown to confer cytoprotection by enhancing endogenous heat shock protein (HSP) expression. We hypothesized that GLN donor pretreatment protects rat renal grafts against severe preservation reperfusion injury (PRI)., Materials and Methods: GLN (0.75 g/kg) or saline was administered i.p. to male donor rats 24 h and 6 h before donor nephrectomy. Kidneys (n = 6/group) were cold-stored in UW solution for 40 h and transplanted into bilaterally nephrectomized syngeneic recipients. Grafts were removed after 24 h. Renal HSP 70 expression was determined by Western blotting. Graft function was assessed by serum creatinine. Renal cross sections were microscopically examined for acute tubular necrosis, apoptosis, tubular proliferation, and macrophage infiltration., Results: GLN donor pretreatment significantly increased intragraft HSP 70 expression. Serum creatinine was not different between groups: 2.6 +/- 0.2 mg/dL (saline) versus 2.7 +/- 0.5 mg/dL (GLN). Both treatment groups showed severe tubular damage with significantly less papillary necrosis in the GLN group (P < 0.05). GLN significantly reduced the number of apoptotic tubular cells in the cortex, medulla, and papilla (P < 0.001 versus saline). Postinjury tubular proliferation, measured by PCNA antigen expression, and intragraft macrophage infiltration was not influenced by GLN., Conclusions: In rat renal grafts suffering severe PRI pharmacological preconditioning with GLN attenuates early structural damage, especially tubular cell apoptosis. Stimulation of renal HSP 70 expression could be an important mechanism of GLN-induced cytoprotection. Our findings may have implications for the treatment of delayed graft function in recipients of marginal donor kidneys.

Many transplant physicians believe that transplant candidates who enroll in clinical trials may have better outcomes than those who do not enroll. We examined a 7-year cohort (1997-2003) of adult primary, non-HLA identical, living donor kidney transplant (LDKT) recipients to determine whether demographic characteristics predisposed to enrollment and whether participation affected posttransplant care intensity and/or allograft function. Overall, 146 of 512 (28.5%) LDKT recipients enrolled in clinical trials. LDKT recipients who were male and those who lived <100 miles from our transplant center were significantly more likely to participate. During the first post-transplant year, study patients (SPs) had more clinic visits (p < 0.0001) and more allograft biopsies (p = 0.024) compared to nonstudy patients (NSPs), but comparable numbers of hospital readmissions and allograft ultrasounds. SPs and NSPs did not differ in 1-year creatinine clearance, delta creatinine or rejection incidence. Overall graft and patient survival were comparable. We conclude that clinical trial participants were disproportionately male, had increased intensity of post-transplant care but comparable outcomes to nonparticipants.

Objectives: We report on ureteral and surgical complications in our first 110 consecutive recipients of kidneys procured with laparoscopic living donor nephrectomy (LLDN)., Methods: The records of all living donor transplants with LLDN performed between February 1999 and December 2004, including 10 pediatric transplants, were reviewed retrospectively. Three urologists performed LLDN using a pure laparoscopic non-hand-assisted transperitoneal technique. Kidney transplantation was performed in a standard fashion. For ureteroneocystostomy, the intravesical Politano-Leadbetter (P-L) technique was used., Results: Two-year patient and graft survival was 99% and 98%, respectively. Serum creatinine at 12 months was 1.36+/-0.1mg/dl in adult and 0.99+/-0.23 mg/dl in pediatric recipients. Nineteen right donor kidneys were transplanted into adult recipients. Surgical complications included three symptomatic lymphoceles, one peritransplant haematoma and one kinking of a lower pole artery. All five (4.5%) ureteral complications occurred in adult recipients with a mean age of 33.2+/-2.8 years. The incidence of ureteral complications was not clustered around the early phase of our LLDN experience. Of the three (2.7%) patients diagnosed with ureteral obstruction, two required ureteral reimplantation, and one was managed conservatively. Another two patients (1.8%) with a urinary leak received a double J stent and a cystostomy catheter for 3 and 5 months, respectively. Of the five patients with a ureteral complication, three had received a donor kidney with more than one renal artery., Conclusions: LLDN combined with the intravesical (P-L) ureteral implantation technique provides excellent graft outcomes with low recipient morbidity. Renal artery multiplicity may increase the risk of ureteral complications.

The impact of mycophenolate mofetil (MMF) on initial renal transplant function is not well characterized. We tested how MMF may modulate graft function and survival in a syngeneic rat kidney transplantation model after prolonged cold preservation. Donor kidneys were preserved in University of Wisconsin for either 24 or 39 h prior to transplantation into nephrectomized rats. Recipients received MMF (20 mg/kg/day) or vehicle. Mycophenolic acid (MPA) blood concentrations were measured by high-performance liquid chromatography. The inflammatory response, tubular epithelial proliferation, and histologic damage 3 days post-transplantation were assessed microscopically. In the 24 h cold storage (c.s.) group serum-creatinine was measured. In the 39 h c.s. group 1-week recipient survival was determined. After 24 h of c.s., recipient survival was 100%. The number of T-cell infiltrates was low and not influenced by MMF, whereas renal ED1+ cell infiltration was significantly suppressed by MMF. Tubular cell proliferation was enhanced by MMF. Serum-creatinine levels and renal histology were comparable between MMF and vehicle-treated animals. In the 39 h c.s. group, recipient survival was 20% in MMF-treated vs 90% in vehicle-treated animals (P=0.001). MMF effectively suppressed inflammatory cell infiltration and inhibited tubular cell proliferation. MMF-induced structural damage was most striking in the renal papilla. In rat kidney grafts with moderate preservation injury (24 h c.s.), MMF, given at an immunosuppressive dose, showed predominantly antiinflammatory effects without compromising graft function. In grafts with severe preservation injury (39 h c.s.), MMF caused irreversible structural damage and inhibited tubular cell regeneration resulting in renal failure.

Patients with end-stage renal disease awaiting kidney transplantation require regular urological evaluation. The urologist's main task is early diagnosis and treatment of genitourinary malignancies and evaluation of the lower urinary tract. Furthermore, urologists are often confronted with the question of whether or not to perform pretransplant urological surgery, i.e., native nephrectomy for polycystic kidney disease. Urological care after kidney transplantation involves diagnosis and treatment of ureteral complications, malignancies, lower urinary tract symptoms, and last but not least erectile dysfunction, which has a prevalence of 20-50% among kidney transplant recipients. For the evaluation and follow-up of the living kidney donor, international guidelines have been developed in recent years to also help the urologist to perform a correct evaluation and follow-up of the kidney donor.

Ten years ago the first laparoscopic living donor nephrectomy (LDN) was performed. Today, LDN is a routine operation in many US-American transplantation centers and an increasing number of centers in Europe are practicing LDN. In this article the different aspects of LDN for donor, kidney, recipient and operating surgeon are evaluated. We performed a literature research concerning LDN and the different aspects. Our own experience, as the largest LDN center in Germany, is part of the evaluation. Laparoscopic extraction of a kidney from a living donor is as safe for the donor as the open approach. At the same time, LDN offers multiple advantages like reduced pain and shorter convalescence. For the donated kidney and the recipient no disadvantages occur from the laparoscopic technique, as long as special intra- and perioperative demands are met. For the operating surgeon multiple developments have expanded the technical armentarium. LDN is safe for donor, recipient and kidney. Central issue of an optimal LDN is sufficient experience with laparoscopic urological techniques.

Purpose: We evaluated the indications for and outcome of pre-transplant, concomitant and post-transplant native nephrectomy in patients with end stage polycystic kidney disease (PCKD)., Materials and Methods: The records of 32 patients were retrospectively reviewed using the electronic database at our institution., Results: Between January 1992 and December 2002, 171 patients with end stage PCKD received a kidney transplant at University of California-San Francisco. A total of 32 patients (18.7%) underwent pre-transplant (7, group 1), concomitant (16, group 2) or post-transplant (9, group 3) native nephrectomy. Of these patients 25 underwent bilateral nephrectomy. Median followup was 18 months. Indications for nephrectomy were hematuria, a renal mass and chronic pain in group 1, lack of space in group 2 and urinary tract infection in group 3. Mean operative time +/- SEM was 231 +/- 14, 370 +/- 24 and 208 +/- 14 minutes in groups 1 to 3, respectively (p = 0.001). Mean intraoperative blood loss was 533 +/- 105, 573 +/- 155 and 522 +/- 181 ml in groups 1 to 3, respectively (p not significant). Two group 2 patients required blood transfusions. Postoperative complications requiring surgical intervention included wound dehiscence in group 1 and abdominal bleeding in group 3. Mean hospital stay was comparable among groups 1 to 3 at 7 +/- 0.7, 8.6 +/- 1.2 and 6.3 +/- 0.6 days, respectively (p not significant). At 3 months mean serum creatinine was not significantly different between groups 2 and 3 at 1.3 +/- 0.1 and 1.5 +/- 0.2 mg/dl, respectively., Conclusions: Unilateral or bilateral nephrectomy for PCKD at transplantation is safe in terms of postoperative patient morbidity and graft function. We perform concomitant native nephrectomy when indicated, preferably in recipients of living donor kidney transplants.

Background: Severe ischemia/reperfusion (IR) injury is a risk factor for delayed graft function. Delayed graft function remains difficult to predict, and it currently relies primarily on serum creatinine (SCr), urine output, and occasionally on graft biopsy. (1)H-NMR (nuclear magnetic resonance spectroscopy) based metabolomics was used to establish IR-specific metabolic markers in both blood and kidney tissue. These markers were compared to SCr and graft histology., Methods: Male Lewis rats were used for kidney transplantation. Two cold ischemia (CI) groups (24- and 42-hour) and two transplantation groups [after 24 (TX24) and after 42 hours (TX42) of CI] were compared to a control group. Whole blood and kidney tissue were collected for further analysis., Results: SCr levels taken 24 hours after transplantation were 1.6 +/- 0.12 mg/dL (TX24) and 2.1 +/- 0.5 mg/dL (TX42), (P= n.s.). Histology samples revealed mild injury in the TX24 group and severe injury in the TX42 group. A significantly decreased level of polyunsaturated fatty acids (PUFA) and elevated levels of allantoin, a marker of oxidative stress, was found in the renal tissue. In the blood, both trimethylamine-N-oxide (TMAO), a marker of renal medullary injury, and allantoin were significantly increased. Allantoin levels were low in both the control and CI groups. Levels were significantly increased after reperfusion (control 0.02 +/- 0.03 micromol/mL, TX24 1.13 +/- 0.22, and TX42 1.89 +/- 0.38, P < 0.001), and correlated with cold ischemia time (r= 0.96) and TMAO (r= 0.94)., Conclusion: The (1)H-NMR metabolic profiles of both the mild and severe IR groups revealed significant changes consistent with graft histology, while the SCr did not.

Unlabelled: Ischemic preconditioning (IP) has been shown to ameliorate renal ischemia reperfusion injury. Using a rat kidney transplantation model we determined if IP improves graft function after prolonged cold storage., Materials and Methods: Syngeneic rat kidneys were divided into two groups. Prior to 42 hours of cold storage in UW and transplantation, one group (n = 10) received IP (15 minutes of warm ischemia/10 minutes of reperfusion), whereas another group (n = 10) received no treatment. Early graft function and 1-week recipient survival were assessed., Results: Recipient survival was not significantly different between groups [70% (IP) vs 40% (non-IP); P = .28]. IP treatment led to a quicker recovery of renal function. On PODs 3 and 6, serum creatinine levels in the IP group were significantly lower compared with the untreated group. In conclusion, one cycle of IP (15/10) accelerates recovery of renal graft function after severe ischemia reperfusion injury. This simple treatment modality may improve outcomes of renal transplants with prolonged cold storage.

Background: At our institution, increased kidney donation from unrelated donors accounts for a steady rise in live donor kidney transplantation rates. We compared outcomes of living related (LRT) versus living unrelated kidney transplants (LURT) and analyzed the effect of early rejection upon graft survival., Methods: A retrospective analysis on 428 adult living donor kidney transplants was performed. Graft function and survival were compared between LRT and LURT and risk factors for 1-year rejection were defined by multivariate analysis., Results: Between 1/1/97 and 12/31/01, 308 LRT and 120 LURT were performed at the University of California San Francisco. Donor age and number of mismatches were significantly higher in the LURT group. Patient and graft survival were similar in both groups. After a median follow-up of 26 months, graft survival was 94.8% (LRT) versus 93.3% (LURT). Five-year serum creatinine levels were comparable in both populations. One-year rejection was higher in the LURT group (30% vs. 18.5%; P<0.01). Rejection was influenced by the number of human leukocyte antigen mismatches. Other independent risk factors for early rejection were poor initial graft function, donor age greater than 55 years, and recipient body mass index greater than 30. Patients with poor initial graft function and early rejection had a statistically greater incidence of subtherapeutic tacrolimus trough levels on postoperative day 7., Conclusions: Despite a higher incidence of early rejection, LURT show similar function and survival compared with LRT. In high-risk patients receiving living unrelated renal transplants, consideration should be given to intensify initial immunosuppression to prevent early rejection episodes.

Poor early graft function (EGF) after deceased donor kidney transplantation (DDKT) has been intensely studied. Much less is known about poor EGF after living donor kidney transplantation (LDKT). Data were collected on 469 LDKTs performed between 1/1/97 and 12/31/01 to determine risk factors for and outcomes associated with poor EGF, defined as either delayed or slow graft function (DGF or SGF). The incidence of DGF and SGF were 4.7% and 10.7%, respectively. Diabetic etiology (OR 2.22; p = 0.021) and warm ischemia time (WIT) (OR 1.05 per min increment; p = 0.0025) emerged as independently associated with poor EGF. Neither functional graft survival nor 1-year graft function differed among the EGF groups. However, DGF and SGF strongly predisposed to acute rejection (AR), which compromised functional graft survival (p = 0.0007) and 1-year graft function. Therefore, we conclude that diabetic etiology of renal disease and WIT are the dominant risk factors for poor EGF after LDKT. Poor EGF did not directly compromise functional graft survival but strongly predisposed to AR. We suggest that immunosuppression should be intensified in the poor EGF setting to maximize LDKT longevity, as AR does impair functional graft survival.

Purpose: N-acetylcysteine (NAC) has been shown to ameliorate ischemic acute renal failure. We determined the effect of donor pretreatment with NAC on ischemia reperfusion (I/R) injury in rat kidney grafts., Materials and Methods: Lewis rats were divided into 3 groups (8 per group) and treated with saline, mannitol (1 gm/kg) or NAC (1 gm/kg intravenously) prior to donor nephrectomy. Cold stored kidneys (24 hours in UW solution) were transplanted into bilaterally nephrectomized recipients. Blood and graft tissue samples were taken 24 hours after transplantation for assessment of metabolic changes, histological damage and renal function. Metabolites associated with renal I/R injury were quantified in blood and renal tissue by magnetic resonance spectroscopy., Results: The degree of histological damage was similar between the treatment groups. Of the counted tubules 60%were mildly damaged, whereas 40% showed moderate damage. Measurement of the metabolites allantoin and trimethylamine-N-oxide (TMAO) indicated a beneficial effect of NAC treatment. In graft tissue and recipient blood allantoin, a uric acid metabolite, was significantly lower in the NAC group vs the mannitol and saline groups (p <0.05). In recipient blood TMAO, an established marker of renal medullary injury, was significantly decreased in the NAC group vs mannitol and saline (p <0.05). Serum creatinine levels were not different between treatment groups., Conclusions: Donor pretreatment with NAC preserves renal metabolism and may improve outcomes of I/R injured kidney transplants. Allantoin and TMAO are sensitive metabolic markers of renal I/R injury that can be detected before the onset of functional and morphological changes.

Background: Sirolimus (SRL) seems to impair renal recovery from ischemic injury in animal models and delayed graft function after clinical renal transplantation. This study determined the impact of SRL on renal recovery after ischemia-reperfusion injury in a rat kidney transplant model., Methods: Syngeneic kidneys were preserved in University of Wisconsin solution before transplantation into bilaterally nephrectomized rats. Recipients received vehicle or SRL targeting for whole-blood trough levels of 10 to 20 ng/mL as measured by high-performance liquid chromatography. Renal function was assessed by animal survival or daily serum creatinine. Tissue samples were collected for histologic examination., Results: Median SRL whole-blood concentrations were 16.6 +/- 1.6 ng/mL on postoperative day (POD) 1 and 12.0 +/- 0.9 ng/mL on POD 3. Transplantation of kidneys after 39 hr of cold storage resulted in 30% survival in the SRL-treated group compared with 100% survival in the control group (P=0.002). Transplantation of kidneys after 24 hr of cold storage resulted in no survival differences, but there were significant differences in renal function. Daily serum creatinine (PODs 1-4) was higher in the SRL-treated group compared with the control group (P<0.05 at all time points). Grafts from SRL-treated animals showed more severe tubular necrosis compared with control animals., Conclusions: When given at therapeutic immunosuppressive doses, SRL compromises renal function after ischemia-reperfusion injury in a rat kidney transplant model. The antiproliferative effect of SRL may translate into impairment of tubular repair and regeneration necessary for recovery after such injury.

Purpose: Laparoscopic surgery has become widely accepted for the treatment of lymphoceles following kidney transplantation. In this single center study we retrospectively reviewed our results of the surgical management of post-transplant lymphoceles, assessing indication and outcome of laparoscopic versus open drainage., Materials and Methods: The records of 60 patients who underwent surgical treatment for a symptomatic lymphocele following kidney transplantation or combined kidney/pancreas transplantation were retrospectively reviewed., Results: Between 1995 and 2002, 1,836 patients received a kidney transplant at the University of California San Francisco. In 60 patients (3.3%) a symptomatic lymphocele developed and either laparoscopic (20) or open drainage (40) was completed. The conversion rate from laparoscopic to open drainage was 16.5%. The most common indications for open lymphocele drainage were noninfectious wound complications (13 patients) and a high risk of vessel or ureter injury (8) due to proximity of the lymphocele to hilar structures. Additional surgery on the graft was required in 5 patients. Intraoperative blood loss was significantly lower in the laparoscopy group. Median hospital stay was 1 day in the laparoscopy group versus 4 days in the open drainage group. No perioperative complications were observed in either group. After a median followup of 38 months, 2 patients in each treatment group had a symptomatic recurrence., Conclusions: Although both surgical approaches are safe and effective, laparoscopic drainage should remain the method of choice for the treatment of post-transplant lymphocele. However, open drainage should be performed in patients with wound complications and in those with a small lymphocele adjacent to vital renal structures.

Fifteen blood group O and B recipients have been transplanted with kidneys from subtype A2 living donors since April 1992. ABO red cell grouping was performed by local licensed blood banks with A2 subtype determined using an anti-A1 lectin and, retrospectively, by a polymerase chain reaction (PCR)-based molecular method. All grafts functioned immediately and no patient has required dialysis. Three patients each experienced one reversible rejection episode. With the exception of one cardiac death at 9months and one patient with profound toxicity to calcineurin inhibitors, all allografts continue to function normally. One donor, mistyped as a group A2 using lectin, was by PCR typing an A1O1 nonsecretor; the graft continues to function normally at 30 months. Transplantation of living donor A2 renal allografts into non-A recipients produces excellent long-term allograft survival and expands the potential living donor pool for nonblood group A recipients.

Background: Inflammatory leukocyte-endothelium interactions, mediated by selectins, contribute to renal ischemia/reperfusion (I/R) injury. We examined the influence of the soluble P-selectin glycoprotein ligand 1 (sPSGL) on early I/R-induced changes in a rat kidney transplantation model with long cold ischemia., Methods: After 24 hr of cold storage, syngeneic kidneys were grafted into bilaterally nephrectomized rats. Before transplantation, recipients received either 1 mg/kg of sPSGL or vehicle (n=8 per group). Six hours after reperfusion, grafts were removed for light microscopy and immunohistochemistry. Capillary blood flow was measured under a fluorescence microscope by using the concentric-circles method., Results: A greater proportion, 74.7+/-7.2% (sPSGL) vs. 28+/-7.4% (controls), of all dye-labeled outer medullary capillaries appeared in the 12-microm radius (P<0.01), indicating dense blood flow, whereas 7.6+/-2.9% vs. 43.3+/-9.7%, respectively, appeared in the 60-microm radius (P<0.05), indicating rarefied blood flow. In the sPSGL-treated group, the extent of severe tubular damage within the inner stripe of the outer medulla was lower compared with controls (37.5+/-8.3% vs. 78.4+/-3.5%, P<0.01). Outer medullary heat shock protein 72 expression was 14.5+/-1.6% in the sPSGL-treated group compared with 9.6+/-1.4% in controls (P<0.05). The number of infiltrating polymorphonuclear leukocytes was similar in both groups. Treatment with sPSGL had no influence on the serum creatinine level., Conclusions: Our data suggest that impairment of outer medullary blood flow is crucial in I/R injury of kidney grafts with prolonged cold storage. Reduction of capillary blood flow perturbations by sPSGL protects tubular cells from severe structural damage. Blocking early selectin-mediated leukocyte adhesion may have therapeutic implications in improving the prognosis of renal transplants with severe I/R injury.

Introduction: Data from the UCLA/UNOS and Collaborative Transplant Studies Registries indicate that mismatched HLA-DR alloantigens expressed on a former donor renal allograft should not be repeated because of significantly poorer long-term survival., Methods: Retransplant candidates waiting for another renal allograft were screened for HLA class II alloantibodies (aAb) using direct complement-dependent cytotoxicity and several sensitive aAb binding assays., Results: When screened by complement-dependent cytotoxicity, 46% of the patients were aAb negative. In contrast, using aAb binding assays, 90% of the patients had HLA-DR aAb specific for previous HLA-DR allograft mismatches. Most important, no directly cytotoxic HLA-DR antibody was detected in 9 of 27 patients., Conclusion: Our studies suggest that crossing the same HLA-DR mismatch in a subsequent transplant may result in poorer survival due to underlying donor-specific HLA-DR aAb. If confirmed in a retrospective study of retransplant patients, B cell donor cross-matches using antiglobulin complement-dependent cytotoxicity or flow cytometry would appear essential if this barrier were to be crossed.

The stability of HLA alloantibodies was studied in 128 antibody-positive, potential kidney transplant recipients over an average period of 3 years. Antibody detection was performed using an anti-human globulin-complement-dependent cytotoxicity technique. In this study, the specificity of antibodies was categorized as against either private epitopes or cross-reactive group (CREG) epitope clusters. Definable antibodies were found in 94% of patients, and 89.5% of the definable antibodies had specificity for CREG clusters. Patterns of antibody reactivity were stable in most of the patients evaluated, even though the percentage of panel-reactive antibody (PRA) often demonstrated considerable fluctuations. Of the 220 definable private-specific or CREG cluster-specific antibodies identified in the patients, nearly 80% persisted throughout the observation period. The fluctuations in % PRA were common, but usually were not due to the acquisition of new HLA antibodies. Most fluctuations were attributable to variable detection of specificities within the same CREG cluster, possibly due to technique variation or changes in antibody avidity or titer or in cell panel composition. This study demonstrates that patterns of antibody specificity are remarkably stable in this patient population, even though PRA values fluctuated. This study further suggests that HLA antibody specificity analysis is a more useful clinical parameter of lymphocytotoxicity testing than simple reporting of % PRA when identifying potential donors for individual patients.

Excellent allograft survival is now routinely accomplished following renal transplantation. Changes in immunosuppression have resulted in a significant improvement in early survival for recipients of primary LRD and CD allografts. In our series, crossmatching techniques which accurately assess alloantibody reactivity and not the degree of HLA mismatch have also permitted successful transplantation of such high-risk groups as recipients of second transplants and highly sensitized recipients. However, a yearly attrition rate of allograft loss persists for all recipients. These long-term observations stress the need for newer approaches to immunosuppression in the future, which include protocols that allow for an indefinite tolerance to incompatible donor antigens.

The sera of 37 renal and 12 liver allograft recipients treated with OKT3 (42), Leu2a (7), or both (2) monoclonal antibodies were serially analyzed by an enzyme-linked immunosorbent assay to determine the humoral response (IgG) to mAb. Anti-mAb IgG to the treatment mAb was detected in the serum of 23 (76%) renal and 6 (50%) liver OKT3 recipients, and all 7 Leu2a renal recipients, usually within 14 days of mAb completion, but never during the first week of Rx. Each of the 7 Leu2a recipients developed reactivity not only to Leu2a isotype (IgG1), but also to OKT3 isotype (IgG2a). In contrast, only 1 of the 42 renal and liver allograft recipients treated with OKT3 developed reactivity to the Leu2a isotype. Blocking studies indicated that the specificity of the response to the treatment mAb was directed at the idiotype--and, in some patients, to the constant domain (isotype) of the mAb administered. The antibody response to an alternate isotype (IgG2a) observed in Leu2a (IgG1)-treated patients most likely resulted from irrelevant immunoglobulin (IgG2a) in the Leu2a preparation. This reactivity appeared to be specific for the IgG2a subclass. Clinicians administering mAb therapy should be aware that various mAb preparations may contain immunoglobulin isotypes unrelated to the therapeutic mAb. Crossimmunization to the irrelevant immunoglobulins may occur, precluding subsequent use of other mAbs sharing similar isotype.

A component of the interleukin 2 receptor (IL-2R) is released in soluble form during T cell activation and can be detected in the blood during acute renal allograft rejection. This study evaluates the diagnostic utility of a sandwich enzyme immunoassay test for serum and urine IL-2R in renal allograft recipients. A rise in serum IL-2R during the week prior to the clinical diagnosis of rejection correlated better with rejection than did isolated serum IL-2R levels or urine values. For the diagnosis of acute rejection, a rise in serum IL-2R (sensitivity 73%, specificity 87%) was comparable in overall test performance to a rise in serum creatinine (sensitivity 70%, specificity 84%). Overall, the two tests had equivalent receiver operating characteristic curves. Because the etiology of false positives in creatinine and IL-2R assays differed (primarily cyclosporine toxicity and infection, respectively), the predictive value of the combined tests was superior to either alone.

The phenotype and function of T lymphocyte cell lines established in vitro from kidney biopsies at the time of acute cellular rejection were studied using a nonhuman primate renal allograft model. Our objectives were to investigate the function and surface phenotype of cells that infiltrate renal allografts in animals that were untreated, that were given subtherapeutic cyclosporin, or that developed rejection after treatment with monoclonal antibodies to IL-2R B chain (CD25), immune cell adhesion molecule-1 (ICAM-1), or CD8. Lines from allograft biopsies and peripheral blood were expanded in vitro using solely human recombinant IL-2 and analyzed after 6-20 days in culture. We found that the large majority of cells cultured from cynomolgus allografts at the time of acute rejection or, when possible, assayed directly without culture, were CD3+4-8+ T lymphoblasts that possessed donor-specific cytolytic function and an NK-line, cytotoxic activity. In contrast, it was rarely possible to establish T cell lines exhibiting donor-specific cytotoxic activity from the blood except in the absence of immunosuppression or during CsA taper. A stable number of graft-derived CD4+8- cells was only observed in an unsuppressed animal 2 days after transplantation in the absence of manifest signs of rejection. Taken together, the above data indicate that similar T lymphocyte populations associated with allograft rejection are present in acutely rejecting allografts after the various types of immunosuppressive therapy. Since the infiltrating cells were similar to those obtained prior to therapy, recurrent rejection most likely represents cells that have escaped elimination. The T cells derived from monkey grafts differ from those from human renal allografts by the decreased frequency of CD4+ cells. Whether this difference is species-related or therapy-related is not known.

The relationship between transfusion of different preparations of blood, sensitization to HLA antigens and survival of subsequent kidney transplants was investigated in 90 consecutive recipients. HLA lymphocytotoxins in transplant candidates precluded or greatly delayed receipt of an allograft (p less than 0.0005). Furthermore, only 17% of such sensitized recipients had functioning grafts one year after transplantation compared to 57% survival for nonsensitized recipients (p less than .02). A small number of nonsensitized patients who were never transfused had surprisingly poor one year graft survival (25%). If frozen blood is used for transfusion rather than whole/packed RBC, the incidence of patient sensitization can be markedly reduced without subsequent compromise in transplant survival (51%). It is concluded that as a consequence of avoiding HLA sensitization by transfusion of frozen blood (processed by agglomeration), the period of hemodialysis required for potential graft recipients will be shortened and an increased proportion of potential recipients will be successfully treated by transplantation.

In 3 cases of Listeria cerebritis, two of the patients had relapse with cerebritis after antimicrobial therapy for acute Listeria septicemia or meningitis. Each had received ten to 14 days of intravenous penicillin. Relapse occurred with fever and sudden focal cerebral dysfunction. Brain scans showed focal uptake; arteriograms and computerized tomography were normal. Cerebrospinal fluids were nondiagnostic; blood cultures yielded Listeria in two patients. Penicillin treatment for six weeks produced rapid clinical responses that were complete in one and minimal residual in two. Progress brain scans were normal. A relapse rate of 35% is reported in transplant patients with Listeria meningitis and/or bacteremia who are treated for less than three weeks; to our knowledge, cerebritis in such patients has not been reported previously. High-dose penicillin or ampicillin therapy for four to six weeks is recommended for Listeria infections in this select group.

Angiograms of 34 kidney transplant patients with progressive decrease in renal function after multiple doses of intravenous methylprednisolone (MP) were evaluated retrospectively in regard to the prognostic value of angiography. The following parameters were included in evaluation: prolonged arterial washout time, large vessel vasculitis, presence of arteriovenous shunting, poor cortical perfusion as evidenced by non-filling of cortical vessels, poor definition of cortico-medullary junction, and a poor nephrogram. When 1 to 3 of these abnormalities existed in angiogram, 67% of living related donor transplants (LRD) recovered under continued MP-therapy. With 4-6 angiographic abnormalities the recovery rate was reduced to 30%. The overall recovery rate for LRD transplants was 44%. Cadaveric transplants (CAD) had a statistically significant poorer prognosis as evidenced by only 8% recovery rate under continued MP-therapy.

Fibrolipomatosis of varying degree was observed in 24 transplanted kidneys. In 8 patients there was no history of urinary tract obstruction or multiple infections, leaving earlier rejection periods as the probable factor responsible for development of fibrolipomatosis after transplantation.

Of 158 renal transplant recipients, 75 underwent excretory urography at some point during a six-year period, 24 hours to 7 years after transplantation. In 11 patients, renal papillary necrosis (RPN) was found. RPN was associated in 9 patients with one or more disease entities known to be the etiologic factor to RPN in nontransplanted kidneys. In 2 patients, previous rejection episodes were the probable case for RPN. Renal papillary necrosis, a rather late complication with renal allograft, was demonstrated in this population on an average of 28.1 months after transplantation.

To evaluate in situ lymphocyte responses in cell-mediated immune tissue injury, we have developed an approach for propagation of human allospecific T lymphocytes directly from tissue biopsies. We have utilized renal allograft tissue obtained from eight patients undergoing cellular rejection. Needle biopsy tissue was cultured in medium containing interleukin 2 (IL 2), including recombinant-DNA-produced IL 2. In each case, lymphoblasts migrated out of the tissue and increased in numbers, especially adjacent to the tissue. In two cases in which there was no cellular infiltrate present in the biopsy, no lymphocytes proliferated in vitro. Instead, fibroblasts eventually filled the wells from these allograft biopsies. The continued presence of the allograft tissue enhanced the viability and growth of the lymphoblasts in cultures from rejecting allografts. The isolated lymphoblasts had surface markers of mature OKT3+ lymphocytes of either OKT4+ or OKT8+ subsets. OKT8+ cells predominated. There was variability (41 to 97%) in the percentage of T lymphoblasts that bore surface HLA-DR antigens. In assays of lymphoblasts obtained from eight separate renal allografts, there was donor-specific cytotoxicity, and in all but two of the cases there was donor-induced proliferation. The specificity of the cytotoxic reaction was tested by using 51Cr-labeled, PHA-stimulated target cells prepared from a panel of HLA-typed donors. Proliferation was tested after 48 hr in the presence of mitomycin C-treated peripheral blood mononuclear cells as stimulator cells by using only 10(4) responder T lymphoblasts. Of particular note was that the cytotoxicity of the isolated lymphoblasts showed specificity against both "private" HLA class I alloantigens (of the allograft donor) as well as "public" cross-reacting epitopes. This method permits the propagation and functional characterization of in vivo-activated T lymphoblasts that are obtained from the actual sites of immune-mediated injury. Preliminary studies of other tissues with diverse inflammatory processes indicate the possible widespread applicability of obtaining in vivo-activated lymphocytes.