Search

Identification of pre-transplant factors influencing delayed graft function (DGF) could have an important clinical impact. This could allow clinicians to early identify dialyzed chronic kidney disease (CKD) patients eligible for special transplant programs, preventive therapeutic strategies and specific post-transplant immunosuppressive treatments. To achieve these objectives, we retrospectively analyzed main demographic and clinical features, follow-up events and outcomes registered in a large dedicated dataset including 2,755 patients compiled collaboratively by four Italian renal/transplant units. The years of transplant ranged from 1984 to 2012. Statistical analysis clearly demonstrated that some recipients' characteristics at the time of transplantation (age and body weight) and dialysis-related variables (modality and duration) were significantly associated with DGF development (p ≤ 0.001). The area under the receiver-operating characteristic (ROC) curve of the final model based on the four identified variables predicting DGF was 0.63 (95 % CI 0.61, 0.65). Additionally, deciles of the score were significantly associated with the incidence of DGF (p value for trend <0.001). Therefore, in conclusion, in our study we identified a pre-operative predictive model for DGF, based on inexpensive and easily available variables, potentially useful in routine clinical practice in most of the Italian and European dialysis units.

Background: Kidney transplantation is the treatment of choice for chronic kidney disease (CKD), but in kidney transplant recipients (KTRs) cardiovascular events are the first cause of death with a functioning graft, ranging from 36 to 55%. The impact of vascular calcification (VC) on morbidity and mortality of KTRs is not appreciated enough nowadays., Summary: This review summarizes 13 important studies on VC in KTRs, comparing the results with CKD and dialysis populations. We focused on VC evaluation and use of coronary artery calcification (CAC) and aorta calcification (AoC) scores. We also evaluated the influence of traditional and non-traditional progression risk factors., Key Messages: VC strongly predicts cardiovascular events and all-cause mortality in KTRs. VC assessment is important in KTRs and based essentially on multislice computed tomography or electron beam computed tomography recognition of lesions. Quantitative measurement of CAC and AoC scores is essential for a correct definition of the calcium burden before and after kidney transplant. Progression of CAC slows down but does not halt after kidney transplant. A variable association of both traditional and non-traditional risk factors is shown. There is a strong association between baseline CAC score and CAC progression. A significant improvement in secondary hyperparathyroidism after transplantation favorably affects the progression of CAC. Low 25(OH)D3 levels are an independent determinant of CAC progression. Diabetes is a risk factor for the presence of CAC in KTRs, but has not been independently associated with CAC progression. The data published on the use of immunosuppressive drugs as progression factors are few and inconclusive.

Background: Numerous studies have established the importance of innate immunity, particularly natural killer (NK) cells, in transplantation tolerance. NK cells express killer cell immunoglobulin-like receptors (KIRs) on their surface. By recognizing and binding major histocompatibility complex class I antigens, KIRs prevent autologous cell killing and promote lysis of non-self antigen-presenting cells. This study investigated the role of 16 KIR genes and donor-recipient KIR/HLA combinations on 5-year outcomes in a population of deceased donor kidney transplant recipients., Material/methods: We genotyped 126 renal transplant patients and their donors for HLA A, B, C, DR, and KIR genes. Patients underwent standardized transplantation and immunosuppressive protocols and were followed-up for 5 years. Graft function was evaluated by serum creatinine level and glomerular filtration rate calculated using the 4-variable modification of diet in renal disease (MDRD) equation., Results: The presence of KIR2DS3 in the recipients was associated with better graft function indexes over time (p<0.05), but this effect was not confirmed by multivariate analysis. Conversely, the presence KIR2DS3 in the recipients combined with the presence of its HLA ligand in the donor had a detrimental effect on the trends of serum creatinine levels and eGFR trends, also confirmed by multivariate analysis. Kidney transplant recipients negative for the KIR2DL1 gene displayed higher creatinine levels after 5 years. Lastly, transplantation of HLA-A3/A11-negative donor kidneys into KIR3DL2-positive patients exerted a protective effect in terms of 5-years outcome (p<0.05)., Conclusions: The present study demonstrates an important role of the KIR immunogenetic system in the long-term immune response to kidney transplantation.

Background: Kidney transplant recipients (KTRs) manifest hypercoagulable state that contributes to an increased incidence of deep vein thrombosis (DVT), not only early but also late in their course. KTRs display an imbalance of hemostatic mechanisms with a multifactorial rise in procoagulant factors, partly related to traditional risk factors and partly to transplantation. The aim of this study was to evaluate the incidence of first episodes of DVT among KTRs, focusing on risk factors., Methods: From 2008 to 2011, we evaluated 30 kidney transplant patients who ≥4 months there after transplantation developed DVT in the lower limbs only, lower limbs complicated by pulmonary embolism or retinal thrombosis. We analyzed causes of primary nephropathy, immunosuppressive regimen, post-transplantation infections, and erythrocytosis. DVT was diagnosed by color Doppler ultrasound or eye examination., Results: A significantly increased incidence of DVT was observed among patients receiving cyclosporine or cyclosporine + mammalian target of rapamycin inhibitors, affected by polycystic kidney diseases, systemic lupus erythematosus or nephrotic syndrome, or displaying rapid and/or excessive correction of hematocrit values. DVT was not significantly related to an acute infection (cytomegalovirus) or to the prior dialysis modality., Conclusions: Hypercoagulability is a multifactorial condition in KTRs, representing a severe complication in stable patients. Prevention may consist of either accurate pretransplantation screening for thrombophilia or identification of patients at higher DVT risk., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: The progressive deterioration of kidney allograft function leads in most cases to transplant failure. Polymorphisms in genes encoding for inflammatory and apoptosis molecules may be one possible explanation for interindividual differences in kidney transplant outcomes. The objective of our work was to identify the possible effect of interleukin 6 (IL-6), transforming growth factor beta 1 (TGFB1), and Fas on graft function., Material and Methods: A case-control study was carried out to assess potential associations between polymorphisms in inflammation- and apoptosis-related genes and the risk for chronic impairment of kidney graft function. The study included 376 cadaveric kidney recipients, 256 of them with stable graft function and 120 who experienced renal deterioration during the follow-up period of 2.6 ± 1.4 years. Genotyping of IL-6/G-174C, TGFB1/L10P, TGFB1/R25P, and Fas/G-670A polymorphisms was performed by PCR-RFLP and direct sequencing., Results: Considering the single IL-6, TGFB1, and Fas polymorphisms, we found similar allelic and genotype frequencies between the 2 groups. To test the hypothesis of mutual effects of polymorphisms, multiple logistic regression was performed incorporating data for all the possible dual genotypic associations. The association of IL-6 high producer and Fas low producer genotype resulted in a protective effect against graft dysfunction (OR=0.79; 95% C.I.=0.72-0.86)., Conclusions: This study did not find significant associations of apoptosis and inflammation gene polymorphisms with transplanted kidney function in Italian renal transplant recipients. However, our data seem to indicate that the carriage of IL-6 high producer/Fas low producer genotype has a protective effect against graft function loss.

To assess incidence and risk factors for de novo cancers (DNCs) after kidney transplant (KT), we carried out a cohort investigation in 15 Italian KT centres. Seven thousand two-hundred seventeen KT recipients (64.2% men), transplanted between 1997 and 2007 and followed-up until 2009, represented the study group. Person years (PY) were computed from 30 days after transplant to cancer diagnosis, death, return to dialysis or to study closure. The number of observed DNCs was compared to that expected in the general population of Italy through standardised incidence ratios (SIR) and 95% confidence intervals (CI). To identify risk factors, incidence rate ratios (IRR) were computed. Three-hundred ninety five DNCs were diagnosed during 39.598PYs, with Kaposi's sarcoma (KS), post-transplant lymphoproliferative disorders (PTLD), particularly non-Hodgkin' lymphoma (NHL), lung, kidney and prostate as the most common types. The overall IR was 9.98/1.000PY, with a 1.7-fold augmented SIR (95% CI: 1.6-1.9). SIRs were particularly elevated for KS (135), lip (9.4), kidney carcinoma (4.9), NHL (4.5) and mesothelioma (4.2). KT recipients born in Southern Italy were at reduced risk of kidney cancer and solid tumors, though at a higher KS risk, than those born in Northern Italy. Use of mTOR inhibitors (mTORi) exerted, for all cancers combined, a 46% significantly reduced risk (95% CI: 0.4-0.7). Our study findings confirmed, in Italy, the increased risks for cancer following KT, and they also suggested a possible protective effect of mTORi in reducing the frequency of post transplant cancers., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Background/aims: The shortage in organ supply has required the use of expanded criteria donors (ECD) for kidney transplantation. Current pre-transplant evaluations of ECD organs are based on histological, clinical or mixed criteria. This monocentric study investigates the predictivity of Karpinski's histological score on 3-year graft function in renal transplant. Ex-post classification using Nyberg's score was carried out to assess the reliability of a purely clinical score and its applicability for organ allocation., Methods: We evaluated 407 deceased donors (251 optimal and 156 ECD) for renal transplants performed between 2001 and 2006. The differences in creatinine levels and MDRD-GFR at transplant and 1, 2 and 3 years post-transplant between optimal donors and ECD were recorded. Amongst ECD organs, the effect of different Karpinski score classes (0-1, 2, 3, 4, double transplants) on 3-year graft outcomes was analyzed. We then compared renal function over time across the Nyberg grades (A, B, C, and D)., Results: Karpinski scores 0-1 and 2 and double transplants were associated with improved graft function compared to scores 3 and 4. Nyberg's clinical score shows a good fit with medium-term outcome and Karpinski's score, but among the donors with a high Nyberg grade (C and D), it fails to differentiate between allocable or non-allocable organs (due to Karpinski's score ≥7)., Conclusions: Our data demonstrate a correlation of histological damage at the time of transplant with 3-year graft function, but at present we are unable to provide any supposition on the possible outcome of the discarded kidneys., (Copyright © 2013 S. Karger AG, Basel.)

Introduction: It is widely accepted that the risk of malignancies is significantly increased among patients with end-stage kidney disease (ESKD) and after kidney transplantation compared with the general population. Only a few data are available on kidney transplantation waiting list patients. The aim of this study was to investigate solid organ cancer incidence among subjects on the waiting list at a single center., Materials and Methods: We retrospectively reviewed the records of all patients enrolled on our kidney transplantation waiting list between August 1, 2008 and July 31, 2010, seeking to evaluate the causes of withdrawal from the list, incidence of cancer, type of neoplasm, and its correlation with clinical features. We estimated the ratio of observed to expected numbers of cancers, the standardized incidence ratio (SIR)., Results: Among 1184 patients, we excluded 569 patients from the waiting list including 26 (4.56%) who displayed malignancies. The overall incidence of cancer was 0.11 events/person-months and the overall prevalence of cancer was 2.2%. In 97% of patients, the malignant disease was confined to the primitive organ of origin without secondary dissemination. We observed a prevalence of cancers related to ESKD (17; 65.38%). The SIR for all cancer types in our population compared with the general population was 2.22. The SIR for native kidney and thyroid cancers among our population compared with the general population was >10., Conclusion: The incidence of cancer was significantly increased among kidney transplantation waiting list patients compared with the general population. Our study highlighted the importance of a careful, targeted neoplastic screening. It could be particularly important for ESKD-related malignancies like native kidney tumors or thyroid cancers., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background/aims: DNA fragmentation is one of the typical features of apoptosis, frequently induced by oxidative stress. Increased oxidative stress is known to be related to several pathological processes. In this study, we assessed oxidative damage in the early follow-up period after kidney transplantation measuring DNA oxidation and fragmentation of mononuclear cells and the circulating levels of inflammatory cytokines., Methods: Blood samples from 30 kidney transplant recipients were collected before transplantation and after 2 days, 1 month and 6 months. Oxidative DNA fragmentation was measured by Comet Assay, whereas DNA oxidation was evaluated measuring 8-OHdG leukocyte levels. Serum IL-1β, IL-4, IL-6, IL-8, IL-10, IFN-γ and TNF-α were assayed using a multiplex ELISA analysis., Results: At 6 months after transplantation, a significant reduction in DNA fragmentation and IL-6 plasma levels was observed; DNA oxidation was higher in patients with a worse outcome, with delayed graft function and low nutritional status. We also found a correlation of IL-6 and IL-10 levels with DNA fragmentation and of IL-10 levels with DNA oxidation., Conclusion: Low levels of oxidation and apoptosis at 6 months after transplantation correlate with a better recovery of renal function in kidney allografts. The measurement of cytokine levels confirmed a reduction of inflammatory parameters within 6 months of follow-up., (Copyright © 2011 S. Karger AG, Basel.)

Polyomavirus-associated nephropathy (PVAN) has become an important cause of graft loss in the last few years. The typical course of PVAN is characterized by an asymptomatic period of viruria followed, within weeks, by the development of viremia in the context of stable renal function. The persistence of viral replication characterized by high viremia, leads to parenchymal injuries and causes the development, within months, of PVAN that could lead to deterioration in graft function and graft loss. We reported, in a patient who received a renal transplant, an unusual presentation of PVAN characterized by the development of acute renal failurte earlier than would be expected after transplantation, where the histological presentation alone could be confused with an acute rejection. We underline the importance of the association of histological findings with the viral load in urine and blood and with ancillary techniques such as immunohistochemistry and polymerase chain reaction (PCR) in situ for virus detection. We also want to emphasize that decoy cells and PCR for BK virus DNA research could be considered among the diagnostic tools for possible acute renal failure in kidney transplant., (© 2010 John Wiley & Sons A/S.)

Despite their contribution in the success of organ transplantation, calcineurin inhibitors (CNIs) may be responsible for frequent and severe side effects that can affect graft survival and life expectancy. In this article, we have reviewed registry studies and randomized controlled trials (RCTs) that seek to avoid, withdraw, or minimize CNIs in renal transplant recipients. Attempts to completely avoid CNIs by administering mycophenolate mofetil (MMF) and/or sirolimus (SRL) have resulted in increased risks of rejection and side effects, with small advantage to improve renal graft function. Early withdrawal of CNIs after transplantation using administration of MMF can improve graft function but may be associated with a greater risk of acute or chronic rejection and graft failure. RCTs in which CNIs were replaced a few months after transplantation by SRL reported improved graft function among SRL-treated patients, but such a treatment was complicated by iatrogenic toxicity. Late replacement of CNIs with SRL did not produce a particular advantage and again was complicated by more frequent side effects. On the basis of these trials, it seems that CNI elimination can trigger rejection or side effects. Recent RCTs showed that minimization of CNI doses in association with everolimus does not increase the risk of rejection, allows one to obtain good graft function, and is well tolerated. Such an approach seems therefore preferable to complete elimination of CNIs with substitution of the current immunosuppressive drugs., (Copyright 2010 Elsevier Inc. All rights reserved.)

Background: Cardiovascular disease (CVD) represents the main cause of morbidity and mortality after renal transplantation. In view of the modern paradigm of atherosclerosis as an inflammatory disease, this study investigated the impact of inflammatory cytokine polymorphisms on posttransplant CVD., Methods: The association between cytokine polymorphisms and CVD was assessed in a case-control study to identify the differences in genotype distributions between kidney allografts with or without posttransplant CVD. To validate our results in two independent groups, we divided a cohort of 798 renal transplant recipients according to geographic area: an evaluation cohort of 478 patients from Emilia-Romagna and a validation cohort of 320 patients from the rest of Italy. Tumor necrosis factor (TNF)-alpha, transforming growth factor-beta1, interleukin (IL)-10, IL-6, interferon-gamma, and IL-8 polymorphisms were analyzed, and thereafter, the cytokine production genotype was assigned., Results: In the evaluation cohort, the patients in the CVD and no-CVD groups differed significantly in TNF-alpha and IL-10 genotype frequencies. Using multivariate analyses to test the association with CVD, the TNF-alpha high-producer genotype was associated with a significantly increased cardiovascular risk (odds ratio [OR]=4.41, 95% confidence interval (CI)=2.53-7.67). Conversely, the IL-10 high-producer genotype resulted protective against CVD (OR=0.07, 95% CI=0.02-0.29). These findings were confirmed in the validation cohort where the carriers of the TNF-alpha high-producer genotype proved to be at 2.45-fold increased cardiovascular risk (OR=2.45, 95% CI=1.29-4.63), whereas the IL-10 high-producer genotype was associated with a 0.08-fold reduced risk (OR=0.08, 95% CI=0.02-0.36)., Conclusions: This work suggests a prognostic value of TNF-alpha and IL-10 genotypes, which might represent cardiovascular risk markers in renal transplant.

Background: In combination with everolimus (EVL), cyclosporine A (CsA) may be used at low exposure, so reducing the risk of renal dysfunction in renal transplant recipients (RTR). We evaluated whether higher exposure of EVL could allow a further reduction of CsA., Methods: De novo RTR were randomized to standard exposure EVL (C0 3-8 ng/mL) with low-concentration CsA (C2 maintenance levels 350-500 ng/mL, group A) or higher EVL exposure (C0 8-12 ng/mL) with very low-concentration CsA (C2 maintenance levels 150-300 ng/mL, group B). The primary endpoints were 6-month creatinine clearance (CrCl) and biopsy-proven acute rejection (BPAR) rate. After 6 months, patients were followed up (observational extension) to 12 months., Results: Two hundred eighty-five RTR (97% from deceased donors) were enrolled. Two patients per group died (1.4%). The 6-month death-censored graft survival was 90.2% in group A and 97.9% in group B and was unchanged at 12 months (P=0.007). There was no significant difference between groups at 6 months in CrCl (59.9 vs. 57.8 mL/min) and BPAR rates (14.7% vs. 11.9%) and also at 12 months (CrCl 62.5+/-20.7 vs. 61.3+/-22.0 mL/min, BPAR 14.7% vs. 14.1%). No significant differences were seen in treated acute rejections, steroid-resistant acute rejections, treatment failures, or delayed graft function, although there was a trend to better results in group B., Conclusions: EVL given at higher exposure for 6 months plus very low CsA concentration may obtain low acute rejection rate and good graft survival in De novo renal transplantation. However, there was no difference between groups in CrCl.

Chronic allograft nephropathy (CAN) leads to the majority of late graft loss following renal transplantation. Detection of CAN is often too late to permit early intervention and successful management. Most current strategies for managing CAN rely on minimizing or eliminating calcineurin inhibitors (CNIs) once CAN has become established. The proliferation signal inhibitors everolimus and sirolimus have potent immunosuppressive and antiproliferative actions, with the potential to alter the natural history of CAN by reducing CNI exposure whilst avoiding acute rejection. Whilst data will be forthcoming from a number of clinical trials investigating this potential, we discuss early detection of CAN and the rationale for a role for this class of agent.

Cardiovascular disease is the leading cause of mortality and morbidity in renal transplant recipients as well as the leading cause of death with a functioning graft. The high cardiovascular risk is attributable to the prolonged exposure to multiple traditional and nontraditional risk factors in the pretransplant and posttransplant period. Particular attention must be paid to cardiovascular screening of candidates for kidney transplantation. After a transplant, treatment and prevention strategies should be focused on the modifiable risk factors including smoking, dietary habits, physical activity, weight control, hypertension, and dyslipidemia. Further studies on these factors are needed to better define the pharmacological approaches (hypotensive or hypolipemic drugs) and therapeutic targets. In view of the role of immunosuppressive therapy in the onset or worsening of several risk factors, it is important to tailor the treatment approach and dosage to the cardiovascular risk profile of the individual patient.

There is increasing proof that organ preservation by machine perfusion is able to limit ischemia/reperfusion injury in kidney transplantation. This study was designed to compare the efficiency in hypothermic organ preservation by machine perfusion or cold storage in an animal model of kidney autotransplantation. Twelve pigs underwent left nephrectomy after warm ischemic time; the organs were preserved in machine perfusion (n = 6) or cold storage (n = 6) and then autotransplanted with immediate contralateral nephrectomy. The following parameters were compared between the two groups of animals: hematological and urine indexes of renal function, blood/gas analysis values, histological features, tissue adenosine-5'-triphosphate (ATP) content, perforin gene expression in kidney biopsies, and organ weight changes were compared before and after preservation. The amount of cellular ATP was significantly higher in organs preserved by machine perfusion; moreover, the study of apoptosis induction revealed an enhanced perforin expression in the kidneys, which underwent simple hypothermic preservation compared to the machine-preserved ones. Organ weight was significantly decreased after cold storage, but it remained quite stable for machine-perfused kidneys. The present model seems to suggest that organ preservation by hypothermic machine perfusion is able to better control cellular impairment in comparison with cold storage.

When possible, living donor transplantation represents the best therapeutic strategy for patients suffering from chronic renal failure. Studying the donor allows a complete and thorough clinical, laboratory and instrumental assessment that guarantees good organ function whilst protecting the health of the donor. The main parameters considered within this framework are age, renal function, nephrological complications, comorbidities (diabetes, hypertension, obesity, etc.), malignancies, and infection. Moreover, particular attention is paid to the sociopsychological aspects of the donation, particularly related to the donor, the recipient, and the entire family situation.

The correct and constant management of transplant waiting lists is necessary for the optimal utilization of the limited number of organs available for transplantation. The guidelines regarding placement on transplant waiting lists (absolute and relative contraindications) are well documented, even though they are in constant development. The criteria for the monitoring of patients on waiting lists, however, are not so well defined; this aspect is subject to careful evaluation on account of the widening of the criteria for transplantation suitability, the increase in the average age of patients, a rise in the number of enrolments and, as a result, prolonged waiting time (in Italy, the average time spent on a waiting list is 37 months). During the waiting period, a greater risk of clinically significant comorbidities and mortality, above all from cardiovascular events, has been noted (the annual mortality is 5-7% in the US, 1.3% in Italy). An in-depth clinical and instrumental study of patients with chronic renal failure is necessary when screening eligible candidates for transplant programs, individualizing therapeutic strategies, and identifying patients for whom the risks outweigh the potential benefits. Clinical and instrumental monitoring, as well as adequate treatment of comorbidities during the waiting period, can help improve the post-transplant outcome. This work examines the study algorithms and monitoring procedures for patients on kidney transplant waiting lists.

Renal transplantation is the treatment of choice for patients with end-stage renal disease. In recent years a major improvement has been observed in short-term graft survival, but there has been no corresponding improvement in long-term survival. Chronic allograft dysfunction (CAD) is an anatomical and clinical alteration that can lead to the loss of the transplanted organ without any specific cause. The pathogenesis of CAD, which still remains to be fully clarified, involves both immunological factors (acute rejection, subclincial rejection, HLA mismatches between donor and recipient, noncompliance, etc) and non-immunological factors (marginal donor ischemia/reperfusion injury, infection, cardiovascular risk factors, nephrotoxicity, etc). Immunosuppressive therapy represents one of the strategies for the prevention of CAD. The introduction into clinical practice of novel immunosuppressive agents with no or lower nephrotoxicity, like mycophenolate mofetile, rapamycin and everolimus, will make therapeutic strategies aimed at decreasing the incidence of CAD feasible.

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.

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.

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 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%).

In isolated liver transplantation pretransplant renal failure is a major mortality risk, there are no guidelines at the moment to establish the indications for a combined liver-kidney transplantation (LKT). In irreversible chronic renal failure (CRF) not on dialysis, nephrological evaluation is required to assess the need for a simultaneous kidney transplantation. There are no experiences about the functional contribution of native kidneys post-LKT. Herein we have reported the case of two patients who underwent LKT in 2004 due to CRF, not yet on dialysis. At the moment of LKT, the first patient (polycystic kidney disease) had a glomerular filtration rate (GFR) = 29 mL/min, and the second recipient (vascular nephropathy and diabetes), a GFR = 33 mL/min. In both cases we did not observe delayed graft function. At discharge the serum creatinine was 1.1 and 1.0 mg/dL, respectively, which was maintained during follow-up. In both cases renal scintigraphy with Tc-99 DMSA was performed to evaluate the functional contributions of transplanted versus native kidneys. In the first case scintigraphy at 9 months after LKT demonstrated an 81% contribution from the transplanted kidney, 9% from the right and 10% from the left native kidneys. In the second case, at 3 months after LKT, the functional contributions were 76%, 10%, and 14%, respectively. The transplanted kidney nephron mass may avoid the need for hemodialysis in the early posttransplant period; in the midterm it may help to maintain residual renal function. As in other combined transplant programs (heart-kidney, kidney-pancreas) with irreversible CRF, a GFR < or = 30 to 35 mL/min may be an indication for LKT, but we need more experience.

Chronic allograft nephropathy (CAN) is characterized by progressive renal dysfunction leading in many cases to graft loss. The pathogenesis of CAN involves both immune and nonimmune factors. Concerning immune factors, one of the most remarkable predictors of CAN is acute rejection, which is associated with a worse prognosis if there are multiple episodes or when late onset occurs. Delayed graft function is also a major risk factor for CAN because of a correlation between late restoration of renal function after transplantation and long-term decreased graft survival. High creatinine levels at 6 months and 1 year after transplantation, proteinuria, viral infections, and cardiovascular risk factors are additional significant parameters for the development of CAN. Recent findings suggest that a high renal segmental arterial resistance index measured by Doppler ultrasonography in intrarenal vessels is associated with poor allograft function. Moreover, the study of patient genetic profile represents a new approach to identify predictive factors for CAN.

Chronic allograft nephropathy (CAN) is an anatomical and clinical alteration, characterized by proteinuria, hypertension and a progressive decline in kidney function, which begins at variable times (months, years) and can lead to the loss of the transplanted organ. CAN pathogenesis, which remains to be fully clarified, involves both immunological (early acute rejection, hyperimmunization, HLA-mismatches between donor and recipient, suboptimal immunosuppression, etc) and non-immunological factors (ischemia/reperfusion injury, reduced nephron mass, age differences between donor and recipient, dialysis time, hypertension, dislipidemia, proteinuria, etc). The possible prevention strategies for CAN consist of procedures aimed at the reduction of some potential risk factors: optimization of the conditions for organ explantation, diminution of ischemia/reperfusion injury, aggressive pharmacological treatment of acute rejection episodes, routine utilization of anti-hypertensive and hypolipidemic agents, and appropriate and rational immunosuppressive regimen. Moreover, some categories of immunosuppressive drugs, such as calcineurin inhibitors, can have a nephrotoxic effect, often regardless of therapeutic dosage. The introduction in clinical practice of novel immunosuppressive drugs with no nephrotoxicity, like mycophenolate mofetil and rapamycin, makes therapeutical strategies able to reduce the incidence of CAN feasible.

A 55-year-old Caucasian man who had received a second kidney graft in July 1993, was switched from cyclosporine to tacrolimus in June 2000 due to deterioration of renal function. Thereafter, he began to complain of muscle cramps in both quadriceps with an increased CPK and EMG findings of polyneuropathy. A muscle biopsy demonstrated acute myositis. Prednisone was administered with amelioration of the patient's symptoms, but with persistently increased CPK and myoglobin levels. In February 2001, mycophenolate mofetil was introduced and tacrolimus tapered to 3 mg daily to seek a toxic role of this immunosuppressant, since there was no other cause of myositis. A sudden decrease in CPK was observed, but the complete normalization took place only after its withdrawal in September 2002. This case represents a tacrolimus-associated myositis.

Background: In transplanted patients undergoing immunossuppressive therapy the incidence of malignant neoplasia is 3-4 times higher than in the general population. Aim of the present study was to evaluate the prevalence of different tumours and the links between modulation of immunosuppressive therapy and patient and graft survival., Patients: We evaluated 2029 kidney-transplanted patients from four Transplant Centres (Bari, Bologna, Modena, Novara) belonging to the Associazione InterRegionale Trapianti (AIRT)., Results: The incidence of neoplastic disease after transplantation was 3.9% in our population with a median time between transplantation and clinical onset of 23 months. We demonstrated a significant difference in the geographical distribution of different tumours. We did not observe any correlation with specific immunosuppressive drugs. Finally, dramatic reduction of the immunosuppression levels did not modify either the patients' or the graft's survival., Conclusions: Several factors can influence the post-transplant onset of neoplastic diseases with immunosuppressive therapy playing a pivotal role. The implementation of a National Registry would be the first step in an attempt to optimise immunosuppression in this particular group of patient's.

Background: MO2ART (monitoring of 2-hr absorption in renal transplantation) is the first prospective, multicenter trial of cyclosporine (CsA) blood level 2 hr postdose (C2) monitoring in de novo kidney recipients receiving CsA microemulsion (ME) (Neoral; Novartis, Basel, Switzerland). Efficacy and safety results from the first 3 months are presented here., Methods: MO2ART is a 12-month, open-label, randomized study involving 296 patients. In all patients, the dose of CsA-ME was adjusted to achieve protocol-defined C2 targets of 1.6 to 2.0 microg/mL for the first month, with subsequent tapering. Randomization into two target groups occurred at 3 months. All patients received steroids and mycophenolate mofetil (89%) or azathioprine. For patients with delayed graft function, the protocol permitted reduced C2 targets and prophylactic administration of antibodies., Results: At 3 months, overall incidence of biopsy-proven acute rejection was 11.5%. Median serum creatinine was 132 micromol/L. Patient and graft survival were 96.6% and 91.2%, respectively. C2 levels greater than 1.6 microg/mL were achieved within 5 days by 60.6% of patients with immediate graft function and 19.5% of patients with delayed graft function. Prophylactic antibodies were used in 15% of the total population. Twenty-four patients (8.1%) experienced serious adverse events with a suspected relation to CsA, and 26 patients (8.8%) discontinued the study because of adverse events (n=15) or after a switch in immunosuppression after rejection episodes (n=11)., Conclusions: Patient management by C2 monitoring resulted in a low incidence of biopsy-proven acute rejection in standard risk de novo kidney recipients, 85% of whom did not receive prophylactic antibodies. CsA-ME with C2 monitoring provides excellent short-term efficacy and safety among de novo renal transplant patients.

We present the study design of a prospective, multicenter, randomized trial aimed at comparing the effects of two different combinations of sirolimus. Renal transplant recipients will be allocated to receive either sirolimus and mycophenolate mofetil (group A) or sirolimus and cyclosporine (group B). The primary endpoint will be the graft function at 3, 6, 12, 24, 36, 48, and 60 months. A number of secondary endpoints will also be considered. To obtain a significant difference in the primary endpoint 180 patients will be enrolled.

Background: The prevalence of post-transplant malignancies, in renal transplant recipients, is higher than that expected in age and sex-matched controls from the general population, and there is a markedly increased incidence of certain cancers., Methods: In 1137 renal transplant recipients (1020 from cadaveric and 117 from living donors, M/F 771/366) performed at the S. Orsola Renal Transplantation Centre since 10/1976 to 9/2001, we studied the post-transplant cancer prevalence, the correlation between cancer prevalence and population characteristics, the risk factors (smoke, cancer history, positive HBsAg and antiHCV infection) and the immunosuppressive therapy., Results and Conclusions: The prevalence of malignancies was 3.86% (52 malignancies in 44 patients). The period between transplant and diagnosis of malignant disease was 59 +/- 85 months. Skin cancer was the most common (n=16; 30.7%), followed by lymphoproliferative disorders (n=8; 15.4%), Kaposi s sarcoma (n=6; 11.5%), uterine cancer (n=6; 11.5%), renal carcinoma of native kidney (n=5; 9.6%), cancer of breast/stomach/pancreas and urinary bladder (n=2; 3.8%) and other cancers (n=5; 9.6%). The mean duration of dialysis before transplantation was longer in cancer patients (41+/- 32.1 vs. 33.5 +/- 32.4 months). We found a correlation between types of malignancies and viral infection in NH-lymphoma (EBV positive 4/4) and skin cancer (HZV positive 13/16). We also detected a correlation between Aza and skin cancer (16/22) and CyA and lymphoproliferative disorders (7/8).

Purpose: To evaluate the value of CT-urography in the diagnosis and follow-up of the urological complications of renal transplantation., Materials and Methods: We performed 19 CT-urography examinations (3 of which were follow-up) on 15 patients by using a spiral multislice CT scanner and multiplanar reconstructions. The examinations were carried out directly after administration of 100 ml of iodinated contrast medium by slow iv infusion, with acquisitions starting 5 minutes after the end of the infusion. Surgery was regarded as the gold standard for the diagnosis of urological complications in the operated patients, whereas in patients who had undergone medical therapy or stent placement the gold standard was 1 month ultrasound and clinical follow-up with evaluation of diuresis and renal function., Results: Between January 1999 and December 2001 a total of 210 kidney transplantations were performed at our hospital. There were 34 urological complications in 28 patients with a 16.1% prevalence, consistent with the major international studies. The complications detected were 14 urine leaks and 19 ureteral obstructions secondary to stones, oedema, blood clots and stricture. We observed one case of reflux in the allograft ureter. Fourteen out of 16 CT-urography examinations yielded important clues for the diagnosis of urological complications in kidney allografts, completely replacing standard urography. In particular, CT-urography correctly detected 5 urinary fistulas by demonstrating iodinated contrast material leaks along the ureteral tract, and 8 cases of obstructive uropathy due to different causes (1 submucosal tunnel edema, 1 blood clot, 1 stone and 5 cases of ureteral stricture). One case of urinary fistula and one of obstructive uropathy were not detected., Discussion and Conclusions: CT-urography proved to be an important diagnostic tool in the evaluation of urological complications of kidney allografts, showing a diagnostic accuracy over 90%; it is useful for confirming the type and site of urological lesions, and therefore to provide guidance for a targeted surgical approach. Compared with excretory urography, which is no longer used in this diagnostic field, CT-urography is more complete and precise as it provides information not only about the urinary tract, but also about the kidney parenchyma and pararenal fluid collections. The only disadvantage, which limits its use to selected cases, is the risk associated with the use of iodinated contrast agents in patients with impaired renal function.

Three hundred sixty-five patients who underwent cadaver donor kidney transplantation between 1993 and 1998 were divided into four groups: 40 immunized patients with at least one peak panel-reactive antibody (PRA) value more than 50%, 11 hyperimmunized patients with more than three peak PRA values over 50%, 10 retransplanted patients and 304 control patients. Before transplantation, we ascertained the antibody specificities against individual HLA antigens (Prastat Sangstat ELISA method for HLA typing of first donor, husbands of multiparous women and potential donors against whom candidates gave positive cross-matches); thus, patients underwent transplantation excluding the presence of the HLA antigens previously detected and looking for high HLA (class I and II) compatibility. Actuarial graft survival after 12 months was satisfactory in all groups: 87% immunized, 81% hyperimmunized and 80% retransplanted vs 92% controls. Renal function at the end of the first year was similar and the number of rejection episodes in the first 3 months did not significantly differ.

Ureteral obstruction with impaired urine flow is the most common urological complication following renal transplantation. From December 1976 to December 1997, 869 kidney grafts were performed by our kidney transplantation group, 96 from living related donors and 773 from cadaver donors (736 first grafts and 37 regrafts). A stricture of the ureter (SU) was observed in 27 cases with a follow-up ranging from 18 months to 18 years after the graft and 11 months to 11 years after the treatment of the SU. In six patients, SU was immediately apparent and limited to the anastomosis: they were obviously technical flaws. In all the other patients, there was a free interval ranging from 2 months to 11 years after surgery; the SU usually involved the entire ureter, suggesting multiple etiologies. Repeated urinary infections could be a cause but immunological problems might be more determinant. In our series, acute rejection was more common than chronic so that the correction of SU was followed in many cases by a good and long lasting result (up to 11 years). In our experience, SU was not a dangerous complication even in patients in whom for different reasons (mainly refusal of treatment) the therapy was delayed - even if anuria occurred, no case of graft loss or serious damage were observed. At the beginning of our experience, the diagnosis of SU was based on urography, and therapy has always been re-operation. For 15 years, the diagnosis of SU has been based on routine echographic surveillance, which was intensified after each rejection, and the first treatment of SU in the last 8 years was re-operation in early technical SU and interventional radiology (balloon dilatation with or without temporary stent) in other cases. When it failed or in case of recurrence, surgical correction was performed utilizing the native ipsilateral or contralateral ureter for a uretero-ureterostomy.

We report on a kidney transplant recipient experiencing an unexpected early acute vascular graft rejection. Retrospective analysis of patient serum samples, utilizing a new ELISA HLA screening technique, revealed that the rejection crisis and the subsequent graft loss were due to a pretransplant donor-specific pre-sensitization caused by a non-complement-fixing antibody of IgG2 class. The case illustrates the clinical significance of non-complement-fixing anti-HLA antibodies. In addition it is shown that ELISA methods are suitable for detecting potentially harmful donor pre-sensitization in waiting-list patients not detectable by standard lymphocytotoxicity techniques. Hence ELISA could be an alternative to flow cytometry for this purpose. It is concluded that screening and cross-matching techniques which detect non-complement-fixing anti-HLA antibodies could improve graft outcome, and should form part of the immunological monitoring of kidney transplant waiting-list patients.

Diseases of the cardiovascular system are a common cause of death in renal transplanted patients. In this study we assessed the echocardiographic morphological and functional findings after renal transplantation of two homogenous groups of transplanted patients with normal renal function. The first (A) with spontaneously normotensive patients, the second (B) with moderate hypertension treated mainly with Ace inhibitors. Analysis of these data highlights two noteworthy results: the similar left ventricle hypertrophy found in both groups and the existence of better diastolic compliance among the hypertensive transplanted patients. If this is confirmed by studies currently in progress, the importance of Ace-inhibitors treatment in remodelling cardiac dysfunction after long term dialysis treatment might be seriously considered.