Prediction of tumor-reactive T cell receptors from scRNA-seq data for personalized T cell therapy.

The identification of patient-derived, tumor-reactive T cell receptors (TCRs) as a basis for personalized transgenic T cell therapies remains a time- and cost-intensive endeavor. Current approaches to identify tumor-reactive TCRs analyze tumor mutations to predict T cell activating (neo)antigens and use these to either enrich tumor infiltrating lymphocyte (TIL) cultures or validate individual TCRs for transgenic autologous therapies. Here we combined high-throughput TCR cloning and reactivity validation to train predicTCR, a machine learning classifier that identifies individual tumor-reactive TILs in an antigen-agnostic manner based on single-TIL RNA sequencing. PredicTCR identifies tumor-reactive TCRs in TILs from diverse cancers better than previous gene set enrichment-based approaches, increasing specificity and sensitivity (geometric mean) from 0.38 to 0.74. By predicting tumor-reactive TCRs in a matter of days, TCR clonotypes can be prioritized to accelerate the manufacture of personalized T cell therapies.

Analysis of 80 dual-kidney transplantations: a multicenter experience.

INTRODUCTION: The use of kidneys from expanded criteria donors (ECD) is an attractive strategy to enlarge the pool of organs available for transplantation. Considering the fact that ECD organs have a reduced nephron mass, they are preferentially allocated for dual-kidney transplantation (DKT). Authors have reported excellent results of DKT when pretransplant ECD organs are evaluated for histological scores. The aim of this study was to evaluate DKT donor and recipient characteristics for comparison with DKT posttransplant outcomes versus those of recipients of single-kidney transplantations from expanded criteria (edSKT) and ideal donors (idSKT). We analyzed the potential prognostic factors involved in DKT among a population derived from three transplant centers. MATERIALS AND METHODS: Between 2001 and 2007, DKT (n = 80) were performed based upon the ECD kidney allocation assessed by biopsy. RESULTS: The average donor ages for the DKT, edSKT, and idSKT groups were 68.8 ± 7.8, 65.3 ± 7.2, and 40.1 ± 13.8 years, respectively (P < .001). The number of human leukocyte antigen mismatches was greater in the DKT group (3.1 ± 1.2, P < .05). Patient and graft 5-year survival rates were similar among DKT, edSKT, and idSKT recipients, namely, 97.5% versus 95.8% versus 96.9% and 93.7% versus 87.4% versus 86.9%, respectively. Mean serum creatinine values at discharge were lower in the DKT and idSKT recipients (1.5 ± 0.9 and 1.6 ± 0.7 mg/dL; P < .05) compared with the edSKT group (1.9 ± 0.7 mg/dL). Correlations between supposed prognostic factors and survival among the DKT group noted worse outcomes in reoperation cases (P < .05). CONCLUSION: We confirmed that DKT produced successful outcomes. An accurate surgical procedure is particularly important to try to avoid reoperations. In our experience, the use of a biopsy as an absolute criterion to allocate ECD kidneys may be too protective.

Importance of renal mass on graft function outcome after 12 months of cadaveric donor kidney transplantation.

BACKGROUND: Few studies have measured cadaveric kidney weight to investigate its relation to recipient kidney function related to it. The aim of this study was to evaluate kidney weight (cadaveric donor) and its relationship to creatinine clearance (CrCl) after 12 months posttransplantation. METHODS: We evaluated 81 renal transplantation recipients from cadaveric donors. We collected donor and recipient demographic, clinical and anthropometric data. Data about kidney weight were obtained through kidney measurement using an electronic machine at the moment of transplantation. RESULTS: The mean kidney weight was 201.4 +/- 10.2 g (200.5 +/- 11.6 g in women and 210.3 +/- 14.1 g in men). Kidney weight correlated with CrCl at 12 months (0.001). The CrCl at 12 months showed a significant correlation of graft weight/recipient weight ratio (P < .01). CONCLUSION: The cadaveric donor kidney weight significantly influenced the CrCl at 12 months after transplantation.

Hand-assisted laparoscopic donor nephrectomy: analysis of the learning curve in a training model in vivo.

INTRODUCTION: Hand-assisted laparoscopic donor nephrectomy (HALDN) outcomes are impaired mainly by the risks associated with the learning curve. Considering that practice by in vivo training may reduced this risk, we recently assessed a swine model of HALDN. The aim of this study was to analyze the learning curve of HALDN using an in vivo training model. MATERIALS AND METHODS: Ten female white pigs underwent a left and then a right HALDN in the same session for a total of 20 procedures by the same first operator. The HALDN were divided into 2 groups: group A, the first 10 nephrectomies and group B, the latter 10. For each group, we assessed operative times, intraoperative complications, estimated blood loss (EBL), warm ischemia time (WIT), and graft quality. RESULTS: We observed a significant decrease in operative times among group B. Two right HALDN of group A were converted to open procedures owing to bleeding. The EBL was consequently lower in group B (P < .05); the mean WIT was not significantly different between the 2 study groups. The graft quality was good in 5/8 kidneys evaluated in group A and 9/10 in group B. DISCUSSION: Standardization of analyzed parameters after a number of procedures, which were comparable to the clinical settings, confirmed the validity of this in vivo training model and its potential utility to allow many transplantation centers to adopt this technique by reducing the risk of the learning curve.

Colonic perforation after renal transplantation: risk factor analysis.

INTRODUCTION: The incidence of gastrointestinal (GI) complication in renal transplantation is relatively high. These complications may be severe, leading to graft loss and patient death. MATERIALS AND METHODS: We reviewed 1651 patients who underwent renal transplantation between 1976 and 2007, analyzing the incidence of colonic perforations and the clinical prognostic factors. RESULTS: Twenty-one patients (1.3%) developed colonic perforations with 7 subsequent deaths. Diverticulitis and ischemia were the most common causes of perforation. Eleven patients (52.3%) were diagnosed and treated within the first 24 hours; their mortality was 18.1%. The 10 patients (47.7%) who were diagnosed and treated 24 hours after the clinical event displayed an high mortality rate (50%). Diverting stoma procedures were performed in all cases. CONCLUSIONS: The follow-up of the kidney transplant patients should include a careful evaluation for possible GI complications and colonic perforations. Early diagnosis and timely treatment were associated with improved outcomes, regardless of the surgical procedures, the cause of perforation or the clinical and laboratory parameters.

Urological complications after kidney transplantation: experience of more than 1,000 transplantations.

OBJECTIVE: Urinary fistulas and stenoses are the most common complications that may require surgical revision after kidney transplantation. The aim of this study was to retrospectively assess the incidence of and risk factors for early (within 30 days) or late major urological complications (stenoses and fistulas) after kidney transplantation. PATIENTS AND METHODS: The study population comprised 1142 consecutive patients who underwent kidney transplantation between January 1990 and September 2007. Endpoints were early and late urological complications (stenoses and fistulas). The variables considered upon multivariate and univariate analyses were: recipient age, sex, etiology of renal failure, number (first/second) and type (single/double/combined with other organs) of kidney transplantations, cold ischemia time, type of urinary reconstruction, stent positioning, as well as donor cause of death, sex, age, and serum creatinine and clearance. We also examined the presence of graft polar arteries, acute rejection episodes, and postoperative graft function. RESULTS: Among 1142 transplantation performed at our center, 100 patients (8.7%) experienced 107 urological complications: 85 (79.4%) were early (56 fistulas, 29 stenoses) and 22 (20.5%) late (7 fistulas and 15 stenoses). Multivariate analysis for all complications revealed significant associations with male recipient sex (P = .00, HR = 2), while first kidney transplantation was protective (P = .00, HR = .4). Male gender both of the recipient and of the donor was significantly associated with early fistulas (P = .01, HR = 2.5 and P = .02, HR = 2, respectively). First (versus second) kidney transplantation had a protective effect on early stenoses (P = .01, HR = .27). Late fistulas were associated with anastomotic stenting (P = .03) in univariate but not multivariate analysis. Multivariate analysis for late stenoses did not demonstrate any significant association with the considered variables; however, the late stenosis cases showed significantly higher recipient and donor ages (P < .05) and a lower donor creatinine clearance (P < .05). The type of urinary anastomosis, stenting, cold ischemia time, presence of polar arterial branches, and type of transplantation did not influence the incidence of urinary fistulas or stenoses. CONCLUSIONS: Our data confirmed that older recipients and organs from older donors, especially of male gender, and retransplantations are to be considered risk factors for urological complications. The present analysis cannot suggest any modification of the actual surgical strategy that would prevent urological complications in kidney transplantation.

Dielectrophoretic trapping in microwells for manipulation of single cells and small aggregates of particles.

In this work we present a novel concept of active microwells based on cylindrical wells able to vertically trap and control single particles by means of negative dielectrophoresis. The device is fabricated by drilling through holes on a polyimide substrate with copper-gold or aluminum metals, forming three annular electrodes within the well. A channel under the device provides a fluid flow filling the microwell by capillarity. Particles are delivered from the top by a microdispenser and applying sinusoidal signals to the electrodes at frequencies ranging from 100kHz to 1.5MHz and amplitudes between 2V and 7V they are successfully trapped and levitated at the level of the central electrode in the middle of microwells with a diameter of 125mum. By changing signal phases, other configurations are also enabled to load particles in the well or eject them from the bottom. The extension to an array of microwells is presented and design rules are described for routing electrode connections and setting signal parameters. K562 cells cultured with Ara-C 1000nM were successfully trapped and controlled in physiological media. Polystyrene beads were also levitated in water and were used for experimental measurements on minimum amplitudes and phase differences in the signals required to levitate beads, confirming the results obtained by simulation.

Hyperimmunized patients awaiting cadaveric kidney graft: is there a quick desensitization possible?

On all kidney waiting lists the 10% to 20% of patients who have antibodies against more than 80% of a panel of HLA antigens (panel reactive antibody [PRA] >80%) are difficult to transplant. The best solution for these patients is to find a compatible donor, ideally a full match, who yields a negative crossmatch test (CMX). If this is not possible, desensitization treatment (high-dose) intravenous immunoglobulin (IVIG) or plasmapheresis (PP) + low-dose IVIG is possible with good results in living donor kidney transplantation mainly if the antibody titer is low. It may also be offered to patients awaiting cadaveric donors too after a long waiting time; however, when applied for several months, it has the obvious disadvantage of giving the patient the risk for long-lasting immunologic weakness without the certitude of finding a kidney. In one of our recent cases of combined liver plus kidney transplantation, a positive CMX became negative 8 hours after the liver operation; the kidney was transplanted with a good result which lasted over 3 years. This observation suggested the possibility of a quick desensitization protocol in selected patients with a large (but not strong) immunization who probably are the majority. Patients sensitized to IVIG and with low titer PRA could be given a single PP + low-dose IVIG (what can be done within the time limit of cadaveric donor kidney transplantation) with good probability of turning an initial positive CMX to negative with the possibility of performing the operation and the advantage of giving the immunosuppression only when the kidney is present.

Kidney transplantation combined with other organs in Bologna: an update.

BACKGROUND: We retrospectively reviewed our experience in combined liver-kidney (L-KT) and heart-kidney (H-KT) transplantations. PATIENTS AND METHODS: Between January 1997 and April 2007, we performed 25 L-KT and 5 H-KT. Patient mean age was 51+/-8 years in L-KT and 43+/-11 years in H-KT. The main cause of liver failure was chronic viral hepatitis (14 cases). Etiology of heart failure was dilated cardiomyopathy and hypertrophic cardiomyopathy (4 and 1 patients, respectively). The main causes of renal failure in L-KT were chronic glomerulonephritis (n=8) and polycystic disease (n=7). Etiology of renal failure in H-KT was interstitial nephropathy (n=2), vascular nephropathy (n=2), and chronic glomerulonephritis (n=1). RESULTS: Mean follow-up was 32+/-26 months in L-KT and 24+/-17 months in H-KT. Immunosuppression was cyclosporine-based (n=4) or tacrolimus-based (n=21) in L-KT and cyclosporine-based in H-KT. Acute rejection rate was 8% for both liver and kidney in L-KT; 80% (mild) for heart and 40% for kidney in H-KT. In the L-KT group, there was no primary graft nonfunction (PGNF). Two patients experienced liver delayed graft function (DGF); 1 patient required postoperative dialysis. One-year graft and patient survivals were both 84% and overall graft and patient survival was 76%. In the H-KT group, 3 patients needed postoperative dialysis and 1 required a cardiac assistance device for 48 hours; overall graft and patient survival was 100% with good cardiac and renal functions. CONCLUSION: Our experience confirmed that H-KT and L-KT are safe procedures, offering good long-term results.

Multicenter study on double kidney transplantation.

BACKGROUND: Marginal organs not suitable for single kidney transplantation are considered for double kidney transplantation (DKT). Herein we have reviewed short and long-term outcomes of DKT over a 7-year experience. PATIENTS AND METHODS: Between 2001 and 2007, 80 DKT were performed in the transplant centers of Bologna, Parma, and Modena, Italy. Recipient mean age was 61+/-5 years. The main indications were glomerular nephropathy (n=33) and hypertensive nephroangiosclerosis (n=14). Mean HLA A, B, and DR mismatches were 3.1+/-1.2. Donor mean age was 69+/-8 years and mean creatinine clearance was 75+/-27 mL/min. Almost all kidneys were perfused with Celsior solution. Mean cold ischemia time was 17+/-4 hours and mean warm ischemia time was 41+/-17 minutes. Mean biopsy score was 4.4. Immunosuppression was based on tacrolimus (n=52) or cyclosporine (n=26). RESULTS: Fifty (62.5%) patients displayed good postoperative renal function. Thirty (37.5%) experienced acute tubular necrosis and required postoperative dialysis treatment; 8 acute rejections occurred. Urinary complications were 13.7% with 8/11 requiring surgical revision. There were 6 surgical reexplorations: intestinal perforation (n=2), bleeding (n=3), and lymphocele (n=1). Two patients lost both grafts due to vascular and infectious complications at 7 or 58 days after transplantation. Two patients underwent intraoperative transplantectomy due to massive vascular thrombosis. Four (5%) patients underwent transplantectomy of a single graft due to vascular complications (n=2), bleeding (n=1), or infectious complications (n=1). Graft and patient survivals were 95% and 100% versus 93% and 97% at 3 versus 36 months, respectively. CONCLUSIONS: DKT is a safe approach for organ shortage. The score used in this study is useful to determine whether a kidney should be refused or accepted.

Gastrointestinal perforations following kidney transplantation.

This study reports major gastrointestinal (GI) complications among a group of 1611 patients following kidney transplantation. The immunosuppressive regimen changed somewhat during the course of the study but included azathioprine, prednisolone, antilymphocyte globulin, cyclosporine, tacrolimus, mycophenolate mofetil, and sirolimus. Perforations occurred in the colon (n=21), small bowel (n=15), duodenum (n=6), and stomach (n=4). Nearly 50% of the complications occurred while patients were being given high-dose immunosuppression to manage either the early postoperative period or acute rejection episodes. Of the 46 patients affected, 11 (24%) died as a direct result of the GI complication. This high mortality appeared to be related to the effects of the immunosuppression and the associated response to sepsis. Reduction of these complications may be achieved by improved surgical management, preventive measures, prompt diagnosis, and a reduced immunosuppressive protocol.

A new swine training model of hand-assisted donor nephrectomy.

INTRODUCTION: Despite the described advantages of hand-assisted laparoscopic donor nephrectomy (HALDN), the learning curve risks discourage many transplant centers to switch from the traditional technique to the laparoscopic approach. Considering that the learning curve risk may be softened with practice on a training model the aim of this study was examine a low-cost, high-fidelity model of HALDN in pigs. METHODS: Ten female white pigs underwent a left and then a right HALDN in the same session for a total of 20 procedures. For each nephrectomy, we assessed operative times and intraoperative complications. All nephrectomies were performed by a single senior transplantation surgeon. RESULTS: All animals that survived bilateral nephrectomy were sacrificed. Two right HALDNs were converted to open procedures due to bleeding. One spleen lesion and one lumbar vein injury were treated laparoscopically. Considering only the 18 HALDN completed, we registered a mean total operative time of 75.4 min (range=52 to 120). DISCUSSION: The in vivo training model described herein made it possible to reproduce the positions and operative difficulties similar to those encountered in clinical practice. Moreover, the costs can be considerably reduced by performing two procedures in each animal employing reusable instruments. Our model represented a valid high-fidelity training procedure that was useful and convenient to achieve skills for HALDN that may help transplantation centers adopt this technique to reduce the learning curve risk.

Protective effect of an inhibitor of interleukin-8 (meraxin) from ischemia and reperfusion injury in a rat model of kidney transplantation.

INTRODUCTION: Since the ischemia and reperfusion injury is one of the main causes of delayed graft function after transplantation, research efforts have focused on studying the molecules involved in this inflammatory process. The chemokine interleukin-8 (IL-8) seems to be the main one responsible through a chemoattractive action toward neutropils. Therefore, one of the strategies adopted to prevent this process is blocking the binding between IL-8 and its receptors. The aim of our study was to test the effect of meraxin, a new derivative from repertaxin, to protect the renal graft from ischemia and reperfusion injury. MATERIALS AND METHODS: Eighty male syngenic rats were divided into four groups. The control group underwent only kidney transplantation, while the other groups were treated with meraxin at various dosages 2 hours before graft reperfusion. Blood and histological samples were taken at sacrifice 24 hours after transplantation. RESULTS: Creatinine was significantly lower in the group treated with the high dosage of meraxin. Histological observation of the grafted tissue showed instead only a mild and not significant neutrophilic infiltration, equal in each group. CONCLUSIONS: Graft function was improved by the administration of meraxin at high dosage, but this effect did not seem to be connected to a reduction in inflammatory infiltration in the parechymal tissue. Maybe the cause is in the mechanisms of clotting activation, due to alteration of adhesion molecules and endothelial cells.

Metabolic syndrome after kidney transplantation.

BACKGROUND: Metabolic syndrome (MS) includes some risk factors for development of diabetes and cardiovascular disease, obesity (BMI > 30), high triglycerides, low HDL cholesterol, hypertension and impaired glucose tolerance. Following the definition of the Adult Treatment Panel III criteria, a diagnosis of MS was established when 3 or more factors were present. In renal transplant patients MS has been reported to negatively influence both patient and graft survivals. The present study sought to verify the effect of MS among our cases. METHODS: 298 cadaveric renal transplant recipients operated between January 1, 1996 and December 31, 2001 with absence of diabetes before transplantation, stable renal function 1 year posttransplantation and at least 4 years follow up were retrospectively evaluated from the end of the first post-operative year. RESULTS: 50 patients out of 298 (16,7%) had MS at the beginning of the study, including 37 of them with 3 and 13 with 4 risk factors. Only one patient with MS died of cardiovascular disease. Graft failure was observed in 23.5% MS patients versus 9,7% patients without the Syndrome (p:n.s.) Only Creatinine and the incidence of Cardiovascular Diseases at 4 years were statistically higher in MS patients (P < .001). CONCLUSIONS: These results suggested that MS is a risk factor for increasing CVD morbidity and decreased graft function, but early treatment of risk factors as soon as they become apparent can limit the adverse effects on patient and graft survival.

Bologna transplant center results in double kidney transplantation: update.

INTRODUCTION: Double-kidney transplantation is performed using organs from marginal donors with a histological score not suitable for single kidney transplantation. The aim of this study was to verify the results obtained with double-kidney transplantation in terms of graft/patient survivals and complications. PATIENTS AND METHODS: Between September 2001 and September 2006. 26 double-kidney transplantations were performed in our center. Indications for surgery were: chronic glomerulonephritis (n = 17), polycystic disease (n = 4), reflux nephropathy (n = 1), hypertensive nephroangiosclerosis (n = 4). The kidneys were all perfused with Celsior solution and mean cold ischemia time was 16.7 +/- 2.5 hours. In all cases, a pretransplant kidney biopsy was performed to evaluate the damage (mean score: 4.3). Immunosuppression was tacrolimus-based for all patients. RESULTS: Eighteen patients had good renal postoperative function, while the other eight displayed acute tubular necrosis. Two of the patients who had severe acute tubular necrosis never recovered renal function. There was only one episode of acute rejection, while the incidence of urinary complications was 31%. There were two surgical reoperations for intestinal perforation. Graft and recipient survivals were 82.7% and 100%, and 78.9% and 94% at 3 and 36 months, respectively. CONCLUSIONS: Double-kidney transplantation is a safe strategy to face the organ shortage. The score used in this study is useful to determine whether a kidney should be refused or suitable for single- or dual-kidney transplantation. The results of our experience are encouraging, but the series is too small to allow a conclusion.

The first case of ureteral duplication in a combined liver-kidney transplantation.

AIM: Kidney transplantation with ureteral duplication may represent a doubled risk factor in terms of ureteral stenosis or necrosis with urinary leakage usually from the site of ureteroneocystostomy. The incidence of complete duplication is very low at 0.19%. We report a kidney with ureteral duplication in the specific setting of multiorgan transplantation since it could be considered an adjunctive risk factor for urological complications. METHODS: The recipient was a 67-year old man, suffering from terminal renal insufficiency. He was also affected by HCV-related cirrhosis. The patient had been waiting for the combined transplantation for 27 months and in the last two months his hepatic function dramatically worsened. The donor was a 53-year old man who died of non-traumatic subarachnoid hemorrhage. Good HLA compatibility was observed between donor and recipient. During harvest both kidneys presented a complete ureteral duplication. So the ureters were freed together with a wide cuff of periureteral tissue and dissected distally. No vascular abnormalities were noted during the removal of either kidney. The grafts were flushed with University of Wisconsin solution and stored in the same solution. RESULTS: The liver was reperfused after 9 hours of cold ischemia. Subsequently the kidney was vascularized after 15 hours of cold ischemia. Urine production occurred immediately after revascularization. Two separated ureteroneocystostomies with a single antireflux technique were performed. Cyclosporine and steroids were given. Post-operative course was uneventful and liver and kidney function were normal. The 7-day cystography was normal. The 6, 12, 24 month ultrasonographies showed no signs of hydronephrosis or hydroureter. After 28 months renal cancer was diagnosed and the patient underwent a right nephrectomy. The liver-kidney recipient had excellent hepatic and renal function for 84.7 months. He died of malignancy from de novo tumor. CONCLUSIONS: On the basis of this experience, a kidney with an ureteral duplication, while rare, can be satisfactorily used also in combined liver-kidney transplantation.

Double kidney transplantation: initial experience of the Bologna Transplant Center.

AIM: Double-kidney transplantation is performed using organs from marginal donors with a histological score not suitable for single kidney transplantation. The aim of the study is to verify the results obtained with double-kidney transplantation in terms of graft and patient survival and complications. METHODS: Between September 2001 and September 2004, 16 double-kidney transplantations were performed in our center. The kidneys were all perfused with Celsior solution and the mean cold ischemia time was 17.6+/-2.7 hours. In all cases a pre-transplant kidney biopsy was performed to evaluate the damage. Immunosuppression was tacrolimus based for all patients. RESULTS: Eight patients had good renal postoperative function while the other eight had acute tubular necrosis. Two of the patients who had severe acute tubular necrosis never recovered renal function. There was only one episode of acute rejection, while the incidence of urinary complications was 31.2%; there were two surgical revisions for intestinal perforation. The graft and recipient survival was 78.1% and 100% and 78.1% and 93.7% at 3 and 36 months. CONCLUSIONS: Double-kidney transplantation is a safe way to face the organ shortage. Moreover the score used in this study is useful to determine whether a kidney should be refused or suitable for single or dual-kidney transplantation. The results of our initial experience are encouraging, but this series is too small in number to consent a conclusive statement.

Combined liver transplants: main characteristics from the standpoint of anesthesia and support in intensive care.

Combined transplants with the liver represent a small number of associated pathologies with little chance of resolving with a single transplant. The small case number prevents us from establishing homogeneous criteria for the procedure. The insertion of the Model for End-Stage Liver Disease in the preoperative evaluation of the patients awaiting liver transplant has definitely increased the number of combined liver-kidney transplants, which have reached more significant numbers. The number of heart-liver transplants is still too low to establish the efficacy of the measure. The multiorgan transplant with the liver represents a rare event entrusted to a series of case reports, each one of which has a history unto itself. Our experience in this field includes 14 combined liver-kidney, six combined heart-liver, and two multiorgan transplants with liver among 36 intestine transplants. We have examined the main pre-, intra-, and postsurgical problems for each one of these transplants, particularly relating to the anesthetic and intensive-care aspects.

Combined liver-kidney transplantation: the experience of the University of Bologna and the case of preoperative positive cross-match.

Combined liver and kidney transplantation (CLKT) has been increasingly used in recent years: 13 of our 19 cases were performed in the last 2 years being 3.2% of our liver transplantation (LT) and kidney transplantation (KT) activity. Only three of them were not on hemodialysis and the scheduling of a CLKT meant being at the top of the waiting list. We accepted only ideal donors and had no case of liver and only one case of kidney delayed graft function. Two deaths occurred during the first postoperative month, due to acute respiratory distress syndrome and multiorgan failure, both in patients with adult polycystic disease who were in poor nutritional condition due to a late indication for CLKT. We had two late deaths, one due to a native kidney tumor at 7 years and one at 8 years due to alcoholic cirrhosis recurrence. The late survival of our patients was 77.3% with all surviving patients showing good liver and kidney function. We planned not to do the KT in the case of a positive preoperative cross-match; but the only positive case became negative 8 hours after LT when we performed the KT. The patient is well after 2 years. The liver does not always protect the kidney if there are preformed antibodies, but we should try every possible technique not to lose the possibility of doing both transplants, because in case of LT alone the patients loses his top position on the CLKT waiting list and often waits years for a kidney.

Combined liver-kidney transplantation--S. Orsola experience: nephrological aspects.

Combined liver kidney transplantation (LKT) has the potential to provide a complete recovery of liver and kidney failure; the literature reports an increase in LKT in the last few years and an improvement in patient and graft survival. In our experience 15 patients underwent LKT from 1997 to 2005. The mean age was 50 +/- 9 years (range 34 to 63). The patients were affected by viral (n = 9), alcoholic (n = 1), polycystic (n = 2), cholangitis (n = 1), cholestatic (n = 1), or amyloidotic (n = 1) chronic hepatopathy. Chronic renal failure (CRF) was due to polycystic kidney disease (n = 4), IgA (n = 2), interstitial nephropathy (n = 2), glomerulonephritis (n = 4), amyloidosis (n = 1), vascular nephropathy (n = 1), of unknown end-stage renal disease (n = 1). Twelve of 15 patients were on renal dialysis treatment, three patients had moderate/severe CRF. Two patients had previously been transplanted (kidney). All patients were selected based upon blood group identity and negative cross-match before kidney transplant. Histocompatibility matching (HLA) was not included in the selection criteria. We did not observe delayed graft function. After a mean follow-up was 23 +/- 32 months (range 5 to 99), 12 subjects show, normal hepatic and renal function. At the beginning of our experience two patients in bad clinical condition died within 3 months because of sepsis, and one died because of a malignancy after 7 years. Both organs were functioning well in the deceased patients. Survival analysis confirms LKT efficacy: at 5 years follow-up patient survival is 86%, graft survival censored for death 100%. Only two subjects had an acute rejection episode in the first year; the kidney rejection incidence was lower than that reported for an isolated kidney transplant (13% vs 21%).