Combined spinal-epidural anesthesia for renal transplant in a lung transplant recipient: a case report.

A 67-year-old lung transplant recipient with severe comorbidities was admitted for renal transplant. As anesthesia technique, combined spinal-epidural at the T11-T12 level was chosen, associated with intravenous sedation. Graft's function initially results altered, bringing to pulmonary fluid overload. Beginning from the postoperative day 5 there was a slow but constant gain-of-function of the graft, proven by an improvement of renal function indexes and by the resolution of the pulmonary edema. Conclusions: Whereas general anesthesia remains the gold standard anesthesia technique for kidney transplant, a locoregional anesthesia, could be a feasible and effective option in patients at high risk of respiratory complications. (www.actabiomedica.it).

Allograft Vesicoureteral Reflux after Kidney Transplantation.

Allograft vesicoureteral reflux (VUR) is a leading urological complication of kidney transplantation. Despite the relatively high incidence, there is a lack of consensus regarding VUR risk factors, impact on renal function, and management. Dialysis vintage and atrophic bladder have been recognized as the most relevant recipient-related determinants of post-transplant VUR, whilst possible relationships with sex, age, and ureteral implantation technique remain debated. Clinical manifestations vary from an asymptomatic condition to persistent or recurrent urinary tract infections (UTIs). Voiding cystourethrography is widely accepted as the gold standard diagnostic modality, and the reflux is generally graded following the International Reflux Study Committee Scale. Long-term transplant outcomes of recipients with asymptomatic grade I-III VUR are yet to be clarified. On the contrary, available data suggest that symptomatic grade IV-V VUR may lead to progressive allograft dysfunction and premature transplant loss. Therapeutic options include watchful waiting, prolonged antibiotic suppression, sub-mucosal endoscopic injection of dextranomer/hyaluronic acid copolymer at the site of the ureteral anastomosis, and surgery. Indication for specific treatments depends on recipient's characteristics (age, frailty, compliance with antibiotics), renal function (serum creatinine concentration < 2.5 vs. ≥ 2.5 mg/dL), severity of UTIs, and VUR grading (grade I-III vs. IV-V). Current evidence supporting surgical referral over more conservative strategies is weak. Therefore, a tailored approach should be preferred. Properly designed studies, with adequate sample size and follow-up, are warranted to clarify those unresolved issues.

Aponeurotic-Cutaneous Tract Exeresis in Patients With Persistent Lymphorrhea After Kidney Transplantation: A Valid Approach in a Day Surgery Setting.

BACKGROUND: Lymphatic disorders (LDs) are the most common minor complications after kidney transplantation (KT), with an incidence rate between 0.6% and 33.9%, which appears to be related to both surgical and medical factors. LDs mostly resolve spontaneously, but occasionally a surgical approach may be required. MATERIALS AND METHODS: We report our experience with 7 KT recipients who developed persistent lymphorrhea (>150 mL/24 h) between October 2017 and March 2019. All cases were treated as outpatients with parietal fistulectomy (PF). The fibrotic aponeurotic-cutaneous tract was thoroughly excised, and the residual aponeurotic defect was closed by watertight suturing. Serial abdominal ultrasounds (US) were carried out after the procedure. RESULTS: A small perirenal graft lymphocele of <2 cm was detected by US in all patients after 48 to 72 hours, without any evidence of either vascular or ureteral compression. During the subsequent scheduled US follow-up, lymphoceles did not increase in size, and additional interventions were not needed. Neither superficial nor deep surgical-site infections were recorded in such patients. CONCLUSIONS: PF was found to be a safe and effective minimally invasive approach for persistent lymphorrhea after KT. It could be easily performed with local anesthesia in a day surgery setting and did not require patient hospitalization.

Outcomes and surgical complications following living-donor renal transplantation using kidneys retrieved with trans-peritoneal or retro-peritoneal hand-assisted laparoscopic nephrectomy.

The best minimally invasive procedure for living-donor kidney retrieval remains debated. Our objective was to assess trans-peritoneal (TP) and retro-peritoneal (RP) hand-assisted laparoscopic donor nephrectomy (HALDN). In this single-center retrospective study, we analyzed results from 317 living-donor renal transplants (RT) performed between 2008 and 2016. Donor and recipient outcomes were compared between TP-HALDN (n = 235) and RP-HALDN (n = 82). Conversion to open nephrectomy (0.4% vs 0%; P = 1.000), intra-operative complications (1.7% vs 1.2%; P = 1.000), and 1-year overall post-operative complications (11.9% vs 17.1%; P = .258) rates were similar in TP-HALDN and RP-HALDN. Overall surgical site infections were higher in RP-HALDN (6.1% vs 1.7%; P = .053), whereas incisional hernias were only recorded following TP-HALDN (3.4% vs 0%; P = .118). The duration of the procedure was 11-minute shorter for TP-HALDN than RP-HALDN (P < .001) but extraction time was equivalent (2, IQR 1.5-2.5 minutes; P = 1.000). RT following TP-HALDN and RP-HALDN showed comparable one-year death-censored allograft survival (97% vs 98.8%; P = .685), primary non-function (0.4% vs 0%; P = .290), delayed graft function (1.3% vs 4.9%; P = .077), and urological complications (2.6% vs 4.9%; P = .290) rates. In our series, donor and recipient outcomes were not substantially affected by the approach used for donor nephrectomy. TP-HALDN and RP-HALDN were both safe and effective.

Utility and safety of early allograft biopsy in adult deceased donor kidney transplant recipients.

INTRODUCTION: Delayed graft function (DGF) is considered a risk factor for rejection after kidney transplantation (KTx). Clinical guidelines recommend weekly allograft biopsy until DGF resolves. However, who may benefit the most from such an aggressive policy and when histology should be evaluated remain debated. METHODS: We analyzed 223 biopsies in 145 deceased donor KTx treated with basiliximab or anti-thymocyte globulin (rATG) and calcineurin inhibitor-based maintenance. The aim of the study was to assess the utility and safety of biopsies performed within 28 days of transplant. Relationships between transplant characteristics, indication, timing, and biopsy-related outcomes were evaluated. RESULTS: Main indication for biopsy was DGF (87.8%) followed by lack of improvement in graft function (9.2%), and worsening graft function (3.1%). Acute tubular necrosis was the leading diagnosis (89.8%) whereas rejection was detected in 8.2% specimens. Rejection was more frequent in patients biopsied due to worsening graft function or lack of improvement in graft function than DGF (66.7% vs. 3.5%; P = 0.0075 and 33.3% vs. 3.5%; P = 0.0104, respectively) and in biopsies performed between day 15 and 28 than from day 0 to 14 (31.2% vs. 3.7%; P = 0.0002). Complication rate was 4.1%. Management was affected by the information gained with histology in 12.2% cases (7% considering DGF). CONCLUSIONS: In low-immunological risk recipients treated with induction and calcineurin inhibitors maintenance, protocol biopsies obtained within 2 weeks of surgery to rule out rejection during DGF do not necessarily offer a favourable balance between risks and benefits. In these patients, a tailored approach may minimize complications thus optimizing results.

Implementing a Ureteric Magnetic Stent in the Kidney Transplant Setting: Report of 100 Consecutive Cases.

BACKGROUND: Kidney transplantation (KT) is the treatment of choice for end-stage kidney disease. The double-J-stent has been used to prevent urological complications (UCs), but it requires cystoscopy extraction. The novel magnetic black star (MBS) stent provided with a customized retrieval device (9 or 15 Fr) has been developed to spare cystoscopy. Scope of the paper is to analyze MBS in 100 consecutive KTs. METHODS: We report a retrospective analysis of 100 consecutive KT performed between April 2015 and September 2018 using MBS (4.8 Fr, 15 cm) to protect Lich-Gregoir ureteroneocystotomy. MBS was removed 4 weeks after KT by either the 9 Fr (61 cases) or the 15 Fr (39 cases) retrieval device. RESULTS: Intraoperative MBS insertion was straightforward in all cases, and its extraction was carried out in the outpatient setting in 93 patients. Extraction time was <30 seconds in 45 out of 61 patients (73.8%) and in 38 out of 39 patients (97.4%) using the 9 Fr and the 15 Fr retrieval device, respectively. In 15 patients, MBS removal took between 30 seconds and 3 minutes. Only 2 cases required extraction by cystoscopy. We observed 2 UC (ureteric leak and stenosis), 8 urinary tract infections, and 9 stent-related symptoms. 7 patients experienced distressing pain according to Visual Analog Scale for Pain. CONCLUSIONS: In our cohort, MBS appeared to be safe and cost-effective. We advocate its routine implementation in KT because of an easy and comfortable extraction in the outpatient setting even by nondedicated staff, without detrimental impact on UC and urinary tract infection rates.

Incidence, risk factors, and outcome of BK polyomavirus infection after kidney transplantation.

BACKGROUND: Polyomavirus-associated nephropathy is a leading cause of kidney allograft failure. Therapeutic options are limited and prompt reduction of the net state of immunosuppression represents the mainstay of treatment. More recent application of aggressive screening and management protocols for BK-virus infection after renal transplantation has shown encouraging results. Nevertheless, long-term outcome for patients with BK-viremia and nephropathy remains obscure. Risk factors for BK-virus infection are also unclear. AIM: To investigate incidence, risk factors, and outcome of BK-virus infection after kidney transplantation. METHODS: This single-centre observational study with a median follow up of 57 (31-80) mo comprises 629 consecutive adult patients who underwent kidney transplantation between 2007 and 2013. Data were prospectively recorded and annually reviewed until 2016. Recipients were periodically screened for BK-virus by plasma quantitative polymerized chain reaction. Patients with BK viral load ≥ 1000 copies/mL were diagnosed BK-viremia and underwent histological assessment to rule out nephropathy. In case of BK-viremia, immunosuppression was minimized according to a prespecified protocol. The following outcomes were evaluated: patient survival, overall graft survival, graft failure considering death as a competing risk, 30-d-event-censored graft failure, response to treatment, rejection, renal function, urologic complications, opportunistic infections, new-onset diabetes after transplantation, and malignancies. We used a multivariable model to analyse risk factors for BK-viremia and nephropathy. RESULTS: BK-viremia was detected in 9.5% recipients. Initial viral load was high (≥ 10000 copies/mL) in 66.7% and low (< 10000 copies/mL) in 33.3% of these patients. Polyomavirus-associated nephropathy was diagnosed in 6.5% of the study population. Patients with high initial viral load were more likely to experience sustained viremia (95% vs 25%, P < 0.00001), nephropathy (92.5% vs 15%, P < 0.00001), and polyomavirus-related graft loss (27.5% vs 0%, P = 0.0108) than recipients with low initial viral load. Comparison between recipients with or without BK-viremia showed that the proportion of patients with Afro-Caribbean ethnicity (33.3% vs 16.5%, P = 0.0024), panel-reactive antibody ≥ 50% (30% vs 14.6%, P = 0.0047), human leukocyte antigen (HLA) mismatching > 4 (26.7% vs 13.4%, P = 0.0110), and rejection within thirty days of transplant (21.7% vs 9.5%; P = 0.0073) was higher in the viremic group. Five-year patient and overall graft survival rates for patients with or without BK-viremia were similar. However, viremic recipients showed higher 5-year crude cumulative (22.5% vs 12.2%, P = 0.0270) and 30-d-event-censored (22.5% vs 7.1%, P = 0.001) incidences of graft failure than control. In the viremic group we also observed higher proportions of recipients with 5-year estimated glomerular filtration rate < 30 mL/min than the group without viremia: 45% vs 27% (P = 0.0064). Urologic complications were comparable between the two groups. Response to treatment was complete in 55%, partial in 26.7%, and absent in 18.3% patients. The nephropathy group showed higher 5-year crude cumulative and 30-d-event-censored incidences of graft failure than control: 29.1% vs 12.1% (P = 0.008) and 29.1% vs 7.2% (P < 0.001), respectively. Our multivariable model demonstrated that Afro-Caribbean ethnicity, panel-reactive antibody > 50%, HLA mismatching > 4, and rejection were independent risk factors for BK-virus viremia whereas cytomegalovirus prophylaxis was protective. CONCLUSION: Current treatment of BK-virus infection offers sub-optimal results. Initial viremia is a valuable parameter to detect patients at increased risk of nephropathy. Panel-reactive antibody > 50% and Afro-Caribbean ethnicity are independent predictors of BK-virus infection whereas cytomegalovirus prophylaxis has a protective effect.

Impact of Transplant Nephrectomy for Patient Survival Over the Past 15 Years: A Single-Center Study.

OBJECTIVES: How transplant nephrectomy affects patient survival after return to dialysis is unclear. Here, we compared patient survival after graft loss between patients with and without transplant nephrectomy. MATERIALS AND METHODS: We divided 171 patients who received transplant between 2000 and 2015 and had graft loss into 3 groups: 64 had graft failure left in situ (without nephrectomy), 51 had nephrectomy < 3 months posttransplant (early nephrectomy), and 56 patients had nephrectomy > 3 months posttransplant (late nephrectomy). The primary endpoint was patient survival. Risk factors for patient death were also analyzed. Secondary endpoints included relisting for transplant and immunosuppressive agent status. RESULTS: Patient survival rates at 1, 3, and 5 years posttransplant in those without nephrectomy, early nephrectomy, and late nephrectomy were 92.1% /90.5%/86.6%, 96.0%/89.7%/80.4%, and 100.0% /97.9%/ 95.6%, respectively. Rates in patients with early nephrectomy differed significantly from those with late nephrectomy (P = .005). On multivariate analysis, patient survival was affected by relisting for transplant (hazard ratio 0.17; 95% confidence interval, 0.06-0.41; P < .001) and graft survival duration (hazard ratio 0.36, 95% confidence interval, 0.13-0.93; P = .036). Relisting for transplant occurred in 46.9% of patients without nephrectomy, 56.9% of patients with early nephrectomy, and 51.8% of patients with late nephrectomy. Those with late nephrectomy took 14.7 months after graft loss to relist for transplant, with 7.8 months for those without nephrectomy (P = .039) and 6.3 months for those with early nephrectomy (P = .051). Only 10.9% of those without nephrectomy were immunosuppressive free, which was in contrast to 94.1% and 78.6% of those with early and late nephrectomy, respectively. CONCLUSIONS: After graft failure, patients without nephrectomy did not have inferior survival versus patients who received early or late nephrectomy. Graft survival time and relisting for transplant were associated with patient survival regardless of having transplant nephrectomy.

Impact of Donor Age on Clinical Outcomes of Primary Single Kidney Transplantation From Maastricht Category-III Donors After Circulatory Death.

BACKGROUND: Standard-criteria donation after circulatory death (DCD) kidney transplants (KTx) have higher primary nonfunction, delayed graft function (DGF), and rejection rates than age-matched donation after brain death (DBD) but similar graft survival. Data on expanded-criteria DCD are conflicting and many centers remain concerned regarding their use. METHODS: In this single-center observational study with 5-year follow-up, we analyzed data from 112 primary DCD Maastricht category-III single KTx receiving similar organ preservation and maintenance immunosuppression. Patients were sorted as young DCD (donor <60 years, 72 recipients) or old DCD (donor ≥60 years, 40 recipients). Old DCD outcomes were compared with young DCD and to a DBD control group (old DBD, donor ≥60 years, 40 recipients). RESULTS: After 5 years, old DCD showed lower patient survival (66% vs 85%; P = 0.014), death-censored graft survival (63% vs 83%; P = 0.001), and Modification of Diet in Renal Disease estimated glomerular filtration rate (34, 27.0-42.0 mL/min per 1.73 m2 vs 45.0, 33.0-58.0 mL/min per 1.73 m2; P = 0.021) than young DCD with higher DGF (70% vs 47.2%; P = 0.029) and graft thrombosis (12.5% vs 1.4%; P = 0.021). Comparison between old DCD and old DBD showed similar 5-year patient survival (66% vs 67%; P = 0.394) and death-censored graft survival (63% vs 69%; P = 0.518) but higher DGF (70% vs 37.5%; P = 0.007) and lower estimated glomerular filtration rate (34, 27.0-42.0 mL/min per 1.73 m2 vs 41, 40.0-42.0 mL/min per 1.73 m2; P = 0.029). Multivariate Cox regression analysis showed that donor 60 years or older (hazard ratio, 3.135; 95% confidence interval, 1.716-5.729; P < 0.001) and induction with anti-IL2-receptor-α monoclonal antibody (hazard ratio, 0.503; 95% confidence interval, 0.269-0.940, P = 0.031 in favor of induction with rabbit antithymocyte globulin) are independent predictors of transplant loss. CONCLUSIONS: Overall, single KTx from DCD Maastricht category-III donors 60 years or older have inferior outcomes than KTx from donors younger than 60 years. Comparison with age-matched DBD showed similar patient and graft survivals. However, the discrepancy in graft function between DCD and DBD deserves further investigation.

Multidisciplinary management of complicated bilateral renal artery aneurysm in a woman of childbearing age.

Ruptured renal artery aneurysm (RAA) during pregnancy is a rare condition associated with high mortality rates to both the mother and the foetus. We report on a 41-year-old woman at her second trimester who presented with shock to the emergency department as a result of a ruptured left RAA. While the bleeding was successfully treated with angiographic embolization, a contralateral RAA, also at risk of rupture, was discovered. Due to its position on the artery bifurcation, this lesion was considered not suitable for interventional radiology and was therefore managed by hand-assisted retroperitoneoscopic nephrectomy, ex-vivo repair and autotransplantation. This was done in order to preserve renal mass and give our patient a chance of having future pregnancies without risk of rupture. Three years later, her renal function is normal, there is no evidence of recurrence, and more importantly she had two successful and uncomplicated pregnancies.

Impact of Allograft Nephrectomy on Second Renal Transplant Outcome.

OBJECTIVES: The impact of allograft nephrectomy on the outcome of a subsequent renal transplant is unclear. This study was conducted to assess the effects of the first allograft nephrectomy on outcomes of a second transplant. MATERIALS AND METHODS: This study included 118 patients who received a second transplant between 1994 and 2015. Before the second transplant, 59 patients did not undergo a first allograft nephrectomy (group A). Group B comprised 59 patients who had undergone a first allograft nephrectomy. We compared sensitization, acute rejection, and survival of the second graft between groups. The risk factors of a second graft loss were assessed. RESULTS: The first graft survival was significantly longer in group A than in group B (100.6 vs 3.7 months; P < .001). Prevalence of preformed donor-specific antibodies before the second allograft was similar between both groups (28.8% vs 39.0% for group A vs group B; P = .243). Numerically higher acute rejection rates occurred in group B than in group A (23.7% vs 15.3%; P = .245). In group A, graft survival rates at 1, 3, and 5 years were 93.0%, 87.0%, and 82.3% and were significantly higher than for group B (76.7%, 69.1%, and 62.5%; P ⟨ .05). On multivariate analysis, survival of the second graft was affected by acute rejection (hazard ratio = 2.24; 95% confidence interval, 1.10-4.45; P = .027) and the interval from first graft loss to second transplant (hazard ratio = 1.11; 95% confidence interval, 1.02-1.19; P = .008). CONCLUSIONS: A first allograft nephrectomy was associated with inferior second graft survival. We recommend that recipients of second transplants should be considered as high risk if they had undergone prior allograft nephrectomy.

The UK National Registry of ABO and HLA Antibody Incompatible Renal Transplantation: Pretransplant Factors Associated With Outcome in 879 Transplants.

BACKGROUND: ABO and HLA antibody incompatible (HLAi) renal transplants (AIT) now comprise around 10% of living donor kidney transplants. However, the relationship between pretransplant factors and medium-term outcomes are not fully understood, especially in relation to factors that may vary between centers. METHODS: The comprehensive national registry of AIT in the United Kingdom was investigated to describe the donor, recipient and transplant characteristics of AIT. Kaplan-Meier analysis was used to compare survival of AIT to all other compatible kidney transplants performed in the United Kingdom. Cox proportional hazards regression modeling was used to determine which pretransplant factors were associated with transplant survival in HLAi and ABOi separately. The primary outcome was transplant survival, taking account of death and graft failure. RESULTS: For 522 HLAi and 357 ABO incompatible (ABOi) transplants, 5-year transplant survival rates were 71% (95% confidence interval [CI], 66-75%) for HLAi and 83% (95% CI, 78-87%) for ABOi, compared with 88% (95% CI, 87-89%) for 7290 standard living donor transplants, and 78% (95% CI, 77-79%) for 15 322 standard deceased donor transplants (P < 0.0001). Increased chance of transplant loss in HLAi was associated with increasing number of donor specific HLA antibodies, center performing the transplant, antibody level at the time of transplant, and an interaction between donor age and dialysis status. In ABOi, transplant loss was associated with no use of IVIg, cytomegalovirus seronegative recipient, 000 HLA donor-recipient mismatch; and increasing recipient age. CONCLUSIONS: Results of AIT were acceptable, certainly in the context of a choice between living donor AIT and an antibody compatible deceased donor transplant. Several factors were associated with increased chance of transplant loss, and these can lead to testable hypotheses for further improving therapy.

Do we need a different organ allocation system for kidney transplants using donors after circulatory death?

BACKGROUND: There is no national policy for allocation of kidneys from Donation after circulatory death (DCD) donors in the UK. Allocation is geographical and based on individual/regional centre policies. We have evaluated the short term outcomes of paired kidneys from DCD donors subject to this allocation policy. METHODS: Retrospective analysis of paired renal transplants from DCD's from 2002 to 2010 in London. Cold ischemia time (CIT), recipient risk factors, delayed graft function (DGF), 3 and 12 month creatinine) were compared. RESULTS: Complete data was available on 129 paired kidneys.115 pairs were transplanted in the same centre and 14 pairs transplanted in different centres. There was a significant increase in CIT in kidneys transplanted second when both kidneys were accepted by the same centre (15.5 ± 4.1 vs 20.5 ± 5.8 hrs p<0.0001 and at different centres (15.8 ± 5.3 vs. 25.2 ± 5.5 hrs p=0.0008). DGF rates were increased in the second implant following sequential transplantation (p=0.05). CONCLUSIONS: Paired study sequential transplantation of kidneys from DCD donors results in a significant increase in CIT for the second kidney, with an increased risk of DGF. Sequential transplantation from a DCD donor should be avoided either by the availability of resources to undertake simultaneous procedures or the allocation of kidneys to 2 separate centres.

ABO incompatible renal transplants: Good or bad?

ABO incompatible kidney transplantation (ABOi-KT) was previously considered to be an absolute contraindication for patients with end-stage kidney disease (ESKD) due to hyperacute rejection related to blood type barrier. Since the first successful series of ABOi-KT was reported, ABOi-KT is performed increasingly all over the world. ABOi-KT has led to an expanded donor pool and reduced the number of patients with ESKD awaiting deceased kidney transplantation (KT). Intensified immunosuppression and immunological understanding has helped to shape current desensitization protocols. Consequently, in recent years, ABOi-KT outcome is comparable to ABO compatible KT (ABOc-KT). However, many questions still remain unanswered. In ABOi-KT, there is an additional residual immunological risk that may lead to allograft damage, despite using current diverse but usually intensified immunosuppressive protocols at the expense of increasing risk of infection and possibly malignancy. Notably, in ABOi-KT, desensitization and antibody reduction therapies have increased the cost of KT. Reassuringly, there has been an evolution in ABOi-KT leading to a simplification of protocols over the last decade. This review provides an overview of the history, outcome, protocol, advantages and disadvantages in ABOi-KT, and focuses on whether ABOi-KT should be recommended as a therapeutic option of KT in the future.

Outcome and cost analysis of induction immunosuppression with IL2Mab or ATG in DCD kidney transplants.

BACKGROUND: Kidney transplantation from DCD now represents a significant part of the overall transplant activity in the UK. Outcome of different induction immunosuppression regimes and related cost benefit analysis has been reported by very few studies.This is a single centre study on frequency-matched patients who received a DCD kidney transplant between August 2007 and August 2009. METHODS: Data on 45 patients divided in 2 groups were collected prospectively and analyzed retrospectively. Group A (24 patients) received IL2Mab and Group B (21 patients) ATG as induction immunosuppression. Patient and graft survival were similar in both groups. RESULTS: In the ATG-induced group, there was a significant lower rate of DGF, BPAR, and infections requiring readmission.A cost analysis was performed including all immunosuppression-related costs, and it has shown remarkable savings in the ATG-induced group. CONCLUSION: Considering that the number of DCD kidney transplants is destined to rise in the UK, we believe that ATG is a valid option to continue optimizing outcomes of DCD kidney transplant. In our experience, ATG proved to be safe, effective, and contributed to significant cost savings.

Campath, calcineurin inhibitor reduction and chronic allograft nephropathy (3C) study: background, rationale, and study protocol.

BACKGROUND: Kidney transplantation is the best treatment for patients with end-stage renal failure, but uncertainty remains about the best immunosuppression strategy. Long-term graft survival has not improved substantially, and one possible explanation is calcineurin inhibitor (CNI) nephrotoxicity. CNI exposure could be minimized by using more potent induction therapy or alternative maintenance therapy to remove CNIs completely. However, the safety and efficacy of such strategies are unknown. METHODS/DESIGN: The Campath, Calcineurin inhibitor reduction and Chronic allograft nephropathy (3C) Study is a multicentre, open-label, randomized controlled trial with 852 participants which is addressing two important questions in kidney transplantation. The first question is whether a Campath (alemtuzumab)-based induction therapy strategy is superior to basiliximab-based therapy, and the second is whether, from 6 months after transplantation, a sirolimus-based maintenance therapy strategy is superior to tacrolimus-based therapy. Recruitment is complete, and follow-up will continue for around 5 years post-transplant. The primary endpoint for the induction therapy comparison is biopsy-proven acute rejection by 6 months, and the primary endpoint for the maintenance therapy comparison is change in estimated glomerular filtration rate from baseline to 2 years after transplantation. The study is sponsored by the University of Oxford and endorsed by the British Transplantation Society, and 18 centers for adult kidney transplant are participating. DISCUSSION: Late graft failure is a major issue for kidney-transplant recipients. If our hypothesis that minimizing CNI exposure with Campath-based induction therapy and/or an elective conversion to sirolimus-based maintenance therapy can improve long-term graft function and survival is correct, then patients should experience better graft function for longer. A positive outcome could change clinical practice in kidney transplantation. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01120028 and ISRCTN88894088.

Severe neurotoxicity in tacrolimus-treated living kidney transplantation in two cases.

Two living kidney-transplant recipients under tacrolimus-based immunosuppressive therapy experienced severe neurotoxicity, with tonic-clonic seizures. In both cases the dosage reduction did not result in improvement of symptoms, which completely disappeared after modification of the immunosuppressive regimen from tacrolimus to cyclosporine. Severe neurotoxicity, with seizures or uncommon clinical features, such as serious myalgias, is not foreseeable. We recommend the conversion to cyclosporine-based immunosuppression in such cases.

Renal allograft rupture caused by acute tubular necrosis.

Renal allograft rupture is a rare but potentially lethal complication of kidney transplantation. A renal allograft recipient receiving quadruple immunosuppressive therapy developed a spontaneous allograft rupture 13 days after kidney transplantation. Warm ischaemia time during the transplant was 80 minutes. The ruptured kidney graft could not be salvaged because of the patient's haemodynamic instability. The histopathological examination showed interstitial oedema with severe acute tubular necrosis with no signs of acute rejection. The most common causes of renal graft rupture are acute rejection and vein thrombosis, while acute tubular necrosis may only rarely be responsible for this complication. Renal graft rupture may be the result of interstitial damage attributed both to the prolonged warm ischaemia time during the transplant and to post-transplant acute tubular necrosis in the absence of graft rejection. In those patients whose haemodynamic status cannot be stabilized by appropriate aggressive haemodynamic support therapy, graft nephrectomy should be considered the only definitive treatment.