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.

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.

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.

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.

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.

Characterization of the APC gene in sporadic gastric adenocarcinomas.

The prominent role of the APC gene in colorectal tumor development is well established. However, its role in tumorigenesis in other tissues is not clear. Hence, DNA from 30 primary sporadic gastric adenocarcinomas was obtained from patients living in a high risk area of the world (North-Central Italy) in order to further define APC's role in gastric tumorigenesis. We thoroughly examined that region of APC which is commonly mutated in colorectal tumors using proven sensitive methods. The IVS protein assay and DNA sequence analysis of APC codons 686 through 1693 revealed no intragenic mutations. However, allelic loss of loci near APC was detected in 7 (28%) of 25 informative gastric adenocarcinomas using two 5q dinucleotide repeat markers for LOH analysis. These results suggest that genetic alteration of a region of APC commonly mutated in colorectal cancer is not a common event during sporadic gastric tumor development, at least in patients from North-Central Italy. Further analysis of chromosome 5q might identify another gene to be significantly altered in these gastric cancers.

Kidney transplantation from elderly donors: a prospective randomized study comparing celsior and UW solutions.

AIM: The aim of present study was to assess the effect of Celsior as compared with University of Wisconsin (UW) solution on immediate and long-term function of kidney transplants harvested from elderly donors. METHODS: A prospective multicenter randomized study was designed to evaluate the efficacy of Celsior versus UW solution for the clinical preservation of the kidney. Fifty renal transplants were performed from donors over 60 years old. Twenty-five kidneys were stored in Celsior and 25 in UW solution. The groups were comparable with regard to donor and recipient characteristics. Renal function outcomes were compared by evaluating delayed graft function rates, daily urinary output, as well as the evolution of mean serum creatinine at 1, 3, 5, 7, and 15 days. RESULTS: The warm ischemia time was 42.4 +/- 11 minutes among Celsior vs 46.9 +/- 17.9 minutes in the UW cohort (P = NS). The cold ischemia time was 18 +/- 4.5 hours in Celsior and 19 +/- 6.5 hours in UW (P = NS). Delayed graft function occurred in 48% of the Celsior group and in 52% of the UW group (P = NS). Mean serum creatinine levels and mean daily urinary output were also similar. One- and 5-year graft survivals of kidneys preserved with Celsior were 91.8% and 79.3% compared with 96% and 87.4% for UW without any significant statistical difference. CONCLUSIONS: Our data show that the preservation of kidneys from elderly donors in Celsior solution is equivalent to that of UW solution.

Urological complications in kidney transplantation: ureterocystostomy versus uretero-ureterostomy.

In our initial experience of kidney transplantation, we performed an extravesical uretero-cystostomy (U-C), but in 1997 we shifted to a uretero-ureterostomy (U-U) with the aim of reducing early and late urological complications. A data base was constructed to compare the incidence, donor and recipient risk factors, treatments, and outcomes of urological complications with the two techniques. From 1990 to the end of July 2004, 894 kidney transplants included 43 from living donors and 851 from cadaveric donors with 804 first and 47 second transplants. We observed 48 urinary fistulas (5.4%): 45 were successfully repaired and three were treated with a ureteral stent with two good results; and one failed at a late operation. We had 26 early stenoses (2.9%), all of which were successfully treated: 16 with surgery and 10 with a stent. Donor and recipient risk factors for fistula and early stenosis did not reach statistical significance, confirming the technical etiology of these complications. There were only six cases of late ureteral stenosis in patients operated after 1990, and in eight cases of U-C we observed vesico ureteral reflux. There were 88 urological complications, with only one kidney lost. The shift from U-C to U-U did not change the incidence of urological complications, but with U-U we observed a significant decrease in the number of postoperative urinary infections, an easier possibility to resolve ureteral stenosis with endourology and no reflux. It is now our first choice with a normal ureter.

[A case of relapsing cutaneous larva migrans transmitted by a cheetah (Acinonyx jubatus)]. / Un caso di larva migrans cutanea recidivante trasmesso dal ghepardo (Acinonyx jubatus).

A case of relapsing "creeping eruption" connected with parasites of the cheetah is reported in the man. The parasitological examination, carried out in two cheetahs liable of this syndrome, has shown two different helmintic species: Ancylostoma caninum and Ancylostoma tubaeforme.

[Personal approach in the surgical treatment of cancer of the gallbladder]. / Il nostro orientamento nella terapia chirurgica del cancro della colecisti.

The part played by surgery in the treatment of gallbladder cancer is conditioned by the delay in diagnosis and the rapid spread of the disease to non operable structures rather than to any particularly intrinsic malignity. In the face of a clinically ascertained cancer or one recognized at surgical exploration, exeresis is essential if possible. Cholecytectomy completed by cuneiform hepatic resection and extensive locoregional lymphadenectomy offers adequate radicality with acceptable risk. Vaster operations have high operative mortality which is out of proportion to the results possible, 43 personal cases are reported.

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.

Pulsatile perfusion of kidney allografts with Celsior solution.

BACKGROUND: Use of pulsatile perfusion (PP) to optimize outcomes in deceased donor renal transplantation remains controversial. This prospective analysis describes all cadaveric renal allografts transplanted at our center that were preserved with PP using Celsior solution. METHODS: We used the LifePort Kidney Transporter (Organ Recovery Systems) perfusion machine. Study outcomes included 1-year graft and patient survivals as well as rates of delayed graft function and need for posttransplant dialysis. RESULTS: Graft survival for PP was 90% and patient survival 100%. The incidences of delayed graft function was 10% and of posttransplant dialysis, 10%. CONCLUSION: These data support the use of PP with Celsior solution.

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.