[A retrospective analysis of functional and oncologic outcomes following surgical treatment of patients with pT1/pT2 renal cell carcinoma at a tertiary referral centre]. / Peri- und postoperatives Ergebnis nach Nierentumorchirurgie bei pT1/pT2 Nierenzellkarzinom ­ eine retrospektive Zentrumsanalyse der funktionellen und onkologischen Ergebnisse.

INTRODUCTION: In patients with localised renal cell carcinoma, the only curative treatment option is surgical tumour excision. The aim of this study was to evaluate peri- and postoperative outcomes as well as oncologic and functional long-term results following surgical treatment of patients with renal cell carcinoma (pT1/pT2) at a tertiary referral centre. PATIENTS AND METHODS: This retrospective study included a total of 758 patients with localised renal cell carcinoma (pT1 /pT2), who underwent radical (RN) or partial (PN) nephrectomy between 01/2008 and 10/2014. Pre-, peri- and postoperative parameters were recorded. Oncologic and functional long-term data were retrieved through questionnaires and structured telephone interviews. RESULTS: Laparoscopic RN or PN resulted in less blood loss and lower peri- and postoperative complication rates compared to open procedures. Regarding short- and long-term renal function, a higher increase in serum creatinine levels was detected after RN. No difference was noted in health status and quality of life. Median follow-up was 36 months. A total of 10.4 % of patients died during follow-up. 4.7 % and 8.4 % developed a relapse or metastatic disease. No difference was found between laparoscopic and open RN/PNs in terms of oncologic long-term results. DISCUSSION: In conclusion, all surgical techniques evaluated in this study provided good oncologic and functional short-/long-term outcomes.

Staging lymphadenectomy in patients with localized high risk prostate cancer: comparison of the laparoendoscopic single site (LESS) technique with conventional multiport laparoscopy.

BACKGROUND: In patients with localized high-risk prostate cancer awaiting radiation therapy, pelvic lymphadenectomy (PL) is a reliable minimally invasive staging procedure. We compared outcomes after laparoendoscopic single site PL (LESSPL) with those after conventional multiport laparoscopic PL (MLPL). METHODS: A retrospective case-control study was carried out at the authors' center. For LESSPL the reusable X-Cone single port was combined with straight and prebent laparoscopic instruments and an additional 3 mm needlescopic grasper. MLPL was performed via four trocars of different sizes using standard laparoscopic instruments. RESULTS: Patients who underwent either LESSPL (n = 20) or MLPL (n = 97) between January 2008 and July 2013, were included in the study. Demographic data were comparable between groups. Patients in the LESSPL group tended to be older and had a significantly higher ASA-score. The mean operating time was 172.4 ± 34.1 min for LESSPL and 116.6 ± 40.1 min for MLPL (P < .001). During LESSPL, no conversion to MLPL was necessary. An average of 12 lymph nodes per patient was retrieved, with no significant difference between study groups. Postoperative pain scores were similar between groups. The hospital stay was 2.3 ± 0.7 days after LESSPL and 3.1 ± 1.2 days after MLPL (P = .01). Two days postoperatively, significantly more patients after LESSPL than after MLPL recovered their normal physical activity (P < .001). Six months postoperatively, no complications were registered in the LESSPL group and cosmetic results were excellent. CONCLUSIONS: In the present study, shorter hospitalization and quicker postoperative recovery were major benefits of LESSPL over MLPL. In patients with localized prostate cancer, staging LESS pelvic lymphadenectomy may be a safe alternative to conventional multiport laparoscopy.

Volume matters: CT-based renal cortex volume measurement in the evaluation of living kidney donors.

Currently, no international standard for the pre-transplant evaluation of living donor renal function exists. Following a standardized questionnaire on current practice in all Eurotransplant (ET) centers, we compared a new CT-based technique to measure renal cortex volume with our standard of DTPA-clearance combined with MAG3-scintigraphy (DTPA × MAG3) and with creatinine-based methods in 167 consecutive living kidney donors. Most ET centers use creatinine-clearance (64%) to measure total renal function and radioistopic methods (82%) to assess split renal function. Before transplantation, CT-measured total cortex volume (r = 0.67; P < 0.001) and estimated GFR using the Cockcroft-Gault formula [eGFR(CG)] (r = 0.55; P < 0.001) showed the strongest correlation with DTPA-clearance. In contrast, the correlation between DTPA-clearance and creatinine clearance was weak (r = 0.21; P = 0.02). A strong correlation was observed between CT-measured split cortex volume and MAG3-measured split renal function (r = 0.93; P < 0.001). A strong correlation was also found between pre-transplant split renal function assessed by eGFR(CG) together with cortex volume measurement and post-transplant eGFR(CG) of both, the donor (r = 0.83; P < 0.001) and the recipient (r = 0.75; P < 0.001). In conclusion CT-based assessment of renal cortex volume bears the potential to substitute existing methods to assess pre-transplant living donor split renal function.

Outcomes after laparoscopic living donor nephrectomy: comparison of two laparoscopic surgeons with different levels of expertise.

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.

Long-term outcomes of living donor kidney transplants in pediatric recipients following laparoscopic vs. open donor nephrectomy.

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.

Successful repair of post-transplant mycotic aneurysm of iliac artery with renal graft preservation: a case report.

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.

Impact of surgeon experience on complication rates and functional outcomes of 484 deceased donor renal transplants: a single-centre retrospective study.

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.

Inhibition of 20-HETE synthesis and action protects the kidney from ischemia/reperfusion injury.

20-Hydroxyeicosatetraenoic acid (20-HETE) production is increased in ischemic kidney tissue and may contribute to ischemia/reperfusion (I/R) injury by mediating vasoconstriction and inflammation. To test this hypothesis, uninephrectomized male Lewis rats were exposed to warm ischemia following pretreatment with either an inhibitor of 20-HETE synthesis (HET0016), an antagonist (20-hydroxyeicosa-6(Z),15(Z)-dienoic acid), an agonist (20-hydroxyeicosa-5(Z),14(Z)-dienoic acid), or vehicle via the renal artery and the kidneys were examined 2 days after reperfusion. Pretreatment with either the inhibitor or the antagonist attenuated I/R-induced renal dysfunction as shown by improved creatinine clearance and decreased plasma urea levels, compared to controls. The inhibitor and antagonist also markedly reduced tubular lesion scores, inflammatory cell infiltration, and tubular epithelial cell apoptosis. Administering the antagonist accelerated the recovery of medullary perfusion, as well as renal medullary and cortical re-oxygenation, during the early reperfusion phase. In contrast, the agonist did not improve renal injury and reversed the beneficial effect of the inhibitor. Thus, 20-HETE generation and its action mediated kidney injury due to I/R. Whether or not these effects are clinically important will need to be tested in appropriate human studies.

Cytoprotective Actions of FTY720 Modulate Severe Preservation Reperfusion Injury in Rat Renal Transplants.

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.

The 'blood group O problem' in kidney transplantation--time to change?

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.

Outcomes of transplanting deceased-donor kidneys between elderly donors and recipients.

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.

Kidney transplantation into urinary conduits with ureteroureterostomy between transplant and native ureter: single-center experience.

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.

Glutamine donor pretreatment in rat kidney transplants with severe preservation reperfusion injury.

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.

Ureteral complications in the renal transplant recipient after laparoscopic living donor nephrectomy.

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.

End stage polycystic kidney disease: indications and timing of native nephrectomy relative to kidney transplantation.

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.

H-NMR-based metabolic signatures of mild and severe ischemia/reperfusion injury in rat 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.

Increased rejection in living unrelated versus living related kidney transplants does not affect short-term function and survival.

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.

Early graft function after living donor kidney transplantation predicts rejection but not outcomes.

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.

Influence of donor pretreatment with N-acetylcysteine on ischemia/reperfusion injury in rat kidney grafts.

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.