Search

Background and Objectives: Extended criteria donors represent nowadays a main resource for kidney transplantation, and recovery criteria are becoming increasingly inclusive. However, the limits of this approach are not clear as well as the effects of extreme donor ages on long-term kidney transplantation outcomes. To address these issues, we performed a retrospective study on extended criteria donor kidney transplantation., Design, Setting, Participants, & Measurements: In total, 647 consecutive extended criteria donor kidney transplantations performed over 11 years (2003-2013) were included. Donor, recipient, and procedural variables were classified according to donor age decades (group A, 50-59 years old [n=91]; group B, 60-69 years old [n=264]; group C, 70-79 years old [n=265]; and group D, ≥80 years old [n=27]). Organs were allocated in single- or dual-kidney transplantation after a multistep evaluation including clinical and histologic criteria. Long-term outcomes and main adverse events were analyzed among age groups and in either single- or dual-kidney transplantation. Kidney discard rate incidence and causes were evaluated., Results: Median follow-up was 4.9 years (25th; 75th percentiles: 2.7; 7.6 years); patient and graft survival were comparable among age groups (5-year patient survival: group A, 87.8%; group B, 88.1%; group C, 88.0%; and group D, 90.1%; P=0.77; graft survival: group A, 74.0%; group B, 74.2%; group C, 75.2%; and group D, 65.9%; P=0.62) and between dual-kidney transplantation and single-kidney transplantation except for group D, with a better survival for dual-kidney transplantation (P=0.04). No difference was found analyzing complications incidence or graft function over time. Kidney discard rate was similar in groups A, B, and C (15.4%, 17.7%, and 20.1%, respectively) and increased in group D (48.2%; odds ratio, 5.1 with A as the reference group; 95% confidence interval, 2.96 to 8.79)., Conclusions: Discard rate and long-term outcomes are similar among extended criteria donor kidney transplantation from donors ages 50-79 years old. Conversely, discard rate was strikingly higher among kidneys from octogenarian donors, but appropriate selection provides comparable long-term outcomes, with better graft survival for dual-kidney transplantation., (Copyright © 2017 by the American Society of Nephrology.)

Contamination of perfusion fluid (PF) could lead to serious infections in kidney transplant recipients. Preemptive therapy (PE-T) in case of yeast contamination of PF is mandatory. The usefulness of PE-T in presence of bacteria remains unclear. In this study we evaluated the incidence of PF bacterial contamination and the impact of PE-T on clinical outcome. Microbiological data of 290 PF and clinical data of the corresponding recipients collected in our hospital from January 2010 and December 2012 were analyzed. Recipients with bacterial contaminated PF (101) were divided in 3 groups: group 1 (n = 52) PE-T treated bacteria resistant to perioperative antibiotic prophylaxis (PAP), group 2 (n = 28) bacteria sensitive to PAP, group 3 (n = 21) PE-T-untreated bacteria resistant to PAP. Incidence of positive PF was 34.8 %, 50.4 % staphylococci, 9.9 % C. albicans. No significant differences in the rate of PF-related infections between the three groups were found. In conclusion, although PF contamination is frequent, the incidence of PF-related infections is very low. In addition, in this study PE-T did not help to reduce the rate of PF-related infection suggesting that a resonable reduction in the use of antibiotic terapy could be made. However, waiting for largest and prospective clinical trials to confirm our findings, a closely clinical and microbiologic monitoring of the recipient is highly recommended in case of PF contamination.

In renal transplanted patients, lymphoceles and lymphorrhea are well-known lymphatic complications. Surgical damage of the lymphatics of the graft during the procurement and of the lymphatic around the iliac vessels of the recipients has been associated with development of lymphatic complications. However, lymphatic complications may be related to medical factors such as diabetes, obesity, blood coagulation abnormalities, anticoagulation prophylaxis, high dose of diuretics, delay in graft function and immunosuppressive drugs. Consistently, immunosuppression regimens based on the use of mTOR inhibitors, especially in association with steroids and immediately after transplantation, has been associated with a high risk to develop lymphocele or lymphorrhea. In addition, several studies have demonstrated the association between rejection episodes and lymphatic complications. However, before the discovery of reliable markers of lymphatic vessels, the pathogenic mechanisms underlining the development of lymphatic complications during rejection and the influence of mTOR inhibitors remained not fully understood. The recent findings on the lymphatic systems of either native or transplanted kidneys together with the advances achieved on lymphangiogenesis shared some lights on the pathogenesis of lymphatic complications after renal transplantation. In this review, we describe the surgical and medical causes of lymphatic complications focusing on the rejection and immunosuppressive drugs as causes of lymphatic complications.

Background: Delayed graft function (DGF) is an early complication of kidney transplantation (KT) associated with increased risk of early loss of graft function. DGF increases using kidneys from extended criteria donors (ECD). NGAL is a 25KDa protein proposed as biomarker of acute kidney injury. The aim of this study was to investigate the role of NGAL as an early and accurate indicator of DGF and Tacrolimus (Tac) toxicity and as a mediator of tissue regeneration in KT from ECD., Methods: We evaluated plasma levels of NGAL in 50 KT patients from ECD in the first 4 days after surgery or after Tac introduction., Results: Plasma levels of NGAL at day 1 were significantly higher in DGF group. In the non DGF group, NGAL discriminated between slow or immediate graft function and decreased more rapidly than serum creatinine. NGAL increased after Tac introduction, suggesting a role as marker of drug toxicity. In vitro, hypoxia and Tac induced NGAL release from tubular epithelial cells (TEC) favoring an autocrine loop that sustains proliferation and inhibits apoptosis (decrease of caspases and Bax/Bcl-2 ratio)., Conclusions: NGAL is an early and accurate biomarker of graft function in KT from ECD favoring TEC regeneration after ischemic and nephrotoxic injury.

Measurement of inosine-monophosphate dehydrogenase (IMPDH) activity or gene expression was used as a further approach in pharmacokinetics (PK)/pharmacodynamic (PD)-guided mycophenolate mofetil (MMF) therapy. Forty-four de novo kidney transplant patients were enrolled; 35 of these completed the study, and were followed for 24 weeks for clinical status, PK parameters, IMPDH activity and IMPDH1/2 gene expression. IMPDH activity and expression were measured in peripheral blood mononuclear cells before transplant and at week 2,4,12 and 24, drawn before (t0) and 2 h (t2 h) after MMF administration. No significant correlation was found between IMPDH activity/expression and PK parameters. For both genes, significant enhancement in t2 h expression was observed, then decreases towards week 24 with a trend following steroid dosages. Seven patients experienced acute rejection (AR) and exhibited significantly higher pre-transplant expression of both IMPDH1 (median 3.42 vs. 0.84; p=0.0025), and IMPDH2 genes (135 vs. 104; p=0.0218) with respect to non-rejecting patients. A significant association was also found between pre-transplant IMPDH1 mRNA and haematological complications (p=0.032). This study suggests that high steroid dosages may influence IMPDH1/2 expression, hampering their use as a PD biomarker, particularly during the early post-transplant period. The measurement of pre-transplant levels of IMPDH1/2 may contribute to prediction of individual drug responsiveness to improve the clinical management of patients in MMF therapy.

The development of proteinuria has been observed in kidney-transplanted patients on m-TOR inhibitor (m-TORi) treatment. Recent studies suggest that m-TORi(s) may alter the behavior and integrity of glomerular podocytes. We analyzed renal biopsies from kidney-transplanted patients and evaluated the expression of nephrin, a critical component of the glomerular slit-diaphragm. In a group of patients on 'de novo' m-TORi-treatment, the expression of nephrin within glomeruli was significantly reduced in all cases compared to pretransplant donor biopsies. Biopsies from control transplant patients not treated with m-TORi(s) failed to present a loss of nephrin. In a group of patients subsequently converted to m-TORi-treatment, a protocol biopsy performed before introduction of m-TORi was also available. The expression of nephrin in the pre-m-TORi biopsies was similar to that observed in the pretransplant donor biopsies but was significantly reduced after introduction of m-TORi(s). Proteinuria increased after the m-TORi inititiation in this group. However, in some cases proteinuria remained normal despite reduction of nephrin. In vitro, sirolimus downregulated nephrin expression by human podocytes. Our results suggest that m-TORi(s) may affect nephrin expression in kidney-transplanted patients, consistently with the observation in vitro on cultured podocytes., (© 2010 The Authors Journal compilation © 2010 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Introduction: A pro-apoptotic effect of circulating mediators on renal tubular epithelial cells has been involved in the pathogenesis of sepsis-associated acute kidney injury (AKI). Adsorption techniques have been showed to efficiently remove inflammatory cytokines from plasma. The aim of this study was to evaluate the efficiency of the hydrophobic resin Amberchrom CG161 M to adsorb from septic plasma soluble mediators involved in tubular injury., Methods: We enrolled in the study 10 critically ill patients with sepsis-associated AKI and we evaluated the effects of their plasma on granulocyte adhesion, apoptosis and functional alterations of cultured human kidney tubular epithelial cells. We established an in vitro model of plasma adsorption and we studied the protective effect of unselective removal of soluble mediators by the Amberchrom CG161 M resin on septic plasma-induced tubular cell injury., Results: Plasma from septic patients induced granulocyte adhesion, apoptosis and altered polarity in tubular cells. Plasma adsorption significantly decreased these effects and abated the concentrations of several soluble mediators. The inhibition of granulocyte adhesion to tubular cells was associated with the down-regulation of ICAM-1 and CD40. Resin adsorption inhibited tubular cell apoptosis induced by septic plasma by down-regulating the activation of caspase-3, 8, 9 and of Fas/death receptor-mediated signalling pathways. The alteration of cell polarity, morphogenesis, protein reabsorption and the down-regulation of the tight junction molecule ZO-1, of the sodium transporter NHE3, of the glucose transporter GLUT-2 and of the endocytic receptor megalin all induced by septic plasma were significantly reduced by resin adsorption., Conclusions: Septic plasma induced a direct injury of tubular cells by favouring granulocyte adhesion, by inducing cell apoptosis and by altering cell polarity and function. All these biological effects are related to the presence of circulating inflammatory mediators that can be efficiently removed by resin adsorption with a consequent limitation of tubular cell injury.

We present the first case in which magnetic resonance imaging (MRI) has been utilized to rule out lesions compatible with acute pyelonephritis in kidneys from a cadaveric organ donor before transplanting them. A 40-year-old female underwent diagnosis of brain death following a septic shock. The ecotomography of the kidneys showed areas compatible with micro-abscesses raising the hypothesis of acute pyelonephritis. Our radiologist proposed to perform a bench-MRI (maintaining kidneys within the sterile preservation bags constantly on ice); this did not show lesions except little cysts not relevant by the clinical point of view. We transplanted kidneys without infective complications and results were very good.

Background: BK virus-associated nephropathy (BKVAN) is one of the most common viral diseases affecting renal allografts. Screening for viral replication may allow for earlier intervention with reduced allograft loss. A plasma viral load >10(4) copies/mL of BKV DNA is recommended for a presumed diagnosis of BKVAN., Methods: We monitored BKV load on serum and urine samples by Real-Time TaqMan PCR in 229 renal transplant recipients in the first year post-transplantation. Overall, 2025 serum and 2025 urine samples were evaluated. A graft biopsy was performed in 47/229 patients to investigate the declining renal function. Operating characteristics [sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV)] and receiver operating characteristic (ROC) curve analysis at different viral load values were calculated., Results: Serum BKV viral load was >10(4) in 5/229 patients (2.2%). A histological diagnosis of BKVAN was made in 3/229 patients (1.3%): 3/5 (60.0%) among those with serum viral load >10(4) and 3/4 (75.0%) in those with >1.6 x 10(4). Operating characteristics of a serum BK load of 10(4) for the diagnosis of BKVAN were as follows: sensitivity, 100%; specificity, 99.1%; NPV, 100%; PPV, 59.4%. Specificity and PPV rose to 99.6% and 75.0% when using a cut-off level of 1.6 x 10(4) copies/mL., Conclusions: The recommended level of BK viraemia of 10(4) copies/mL is useful to identify patients at risk of BKVAN, although specificity and PPV increase by using a cut-off level of 1.6 x 10(4) copies/mL. BK replication may occur in the first 3 months post-transplantation and subsequently recede. Therefore, the temporal profile of BKV replication has to be accurately evaluated and occasionally elevated values should prompt a closer monitoring.

Macrophage-stimulating protein (MSP) exerts proliferative and antiapoptotic effects, suggesting that it may play a role in tubular regeneration after acute kidney injury. In this study, elevated plasma levels of MSP were found both in critically ill patients with acute renal failure and in recipients of renal allografts during the first week after transplantation. In addition, MSP and its receptor, RON, were markedly upregulated in the regenerative phase after glycerol-induced tubular injury in mice. In vitro, MSP stimulated tubular epithelial cell proliferation and conferred resistance to cisplatin-induced apoptosis by inhibiting caspase activation and modulating Fas, mitochondrial proteins, Akt, and extracellular signal-regulated kinase. MSP also enhanced migration, scattering, branching morphogenesis, tubulogenesis, and mesenchymal de-differentiation of surviving tubular cells. In addition, MSP induced an embryonic phenotype characterized by Pax-2 expression. In conclusion, MSP is upregulated during the regeneration of injured tubular cells, and it exerts multiple biologic effects that may aid recovery from acute kidney injury.

Polyomavirus BK reactivation is common in renal transplant recipients and may cause nephropathy with significant graft dysfunction. The induction of anti-double stranded DNA (anti-dsDNA) antibodies by BKV has been described in experimental animals and during primary infection, and has been implicated in the pathogenesis of systemic lupus erythematosus. This study evaluated the occurrence of anti-dsDNA antibodies and non-organ-specific autoantibodies (NOSA) by indirect immunofluorescence before transplantation and at 3 and 6 months post-transplantation in 90 renal transplant recipients and the association with BKV reactivation, demographic and clinical features. Moreover, the relation to HCMV infection, as detected by pp65-antigenemia, was also evaluated. Post-transplantation NOSAs were present in 23/90 (25.6%) and anti-dsDNA antibodies in 17/90 (18.9%). BK viremia was detected in at least one serum sample in 22 patients: 9 anti-dsDNA antibody-positive vs 13 negative (p<0.01). No significant correlation between the occurrence of NOSAs and anti-dsDNA antibodies and demographic and clinical features was found. No significant association with pp65-antigenemia-positivity was found, although antigenemia was positive in 6/23 NOSA-positive patients (26.1%). Although a relation seems to exist between BKV and the occurrence of anti-dsDNA antibodies in renal transplant patients, the lack of correlation with other epidemiological and clinical features does not allow any conclusion. The role of autoimmune response in this context and the relation with other patient-related factors and infectious agents should be further investigated.

Background: Human herpes virus 8 (HHV-8) infection is associated with Kaposi sarcoma (KS) and other neoplastic and non-neoplastic manifestations. A strong association between HHV-8 and KS has been evidenced in transplant recipients, particularly kidney recipients., Methods: We have investigated the HHV-8 seroprevalence by an immunoenzymatic assay in 408 patients awaiting kidney transplantation and in the corresponding 356 donors; moreover, we have tested for the presence of HHV-8 DNA by nested PCR in available serum samples of the same graft recipients at 6, 12 and >18 months post-transplantation (overall 156 specimens). Associated factors, such as age, sex, area of residence, potential for HHV-8 transmission via organ transplantation and development of KS were also investigated., Results: Twenty (4.9%) of 408 patients and 7 (1.9%) of 356 donors were seropositive. HHV-8 seropositive patients were on average about 6 years older than seronegative individuals. No difference in prevalence by gender was found. Considering the area of residence of seropositive patients, 4/161 (2.48%) were resident in Piemonte vs 16/247 (6.47%) in other areas of Italy (P = n.s.). During the follow-up post-transplantation, HHV-8 DNA was found only in four patients who were seropositive before transplantation, in three cases the corresponding donor was seronegative, in one the corresponding donor was also seropositive and the recipient developed KS. At >18 months post-transplantation, two patients were HHV-8 DNA positive, both were seronegative pre-transplantation and their corresponding donors were seronegative., Conclusions: HHV-8 seroprevalence in the Piemonte region seems to be low, also in a population of kidney transplant recipients. Based on our data, it does not seem that the immunosuppressive regimen favours the reactivation of HHV-8. Our results do not suggest the possibility of HHV-8 transmission via organ transplantation. Incidence of KS among HHV-8 seropositive patients was very low.

Microscopic sediment analysis of urine from a 56-year-old woman who underwent renal transplantation showed many uncommon clusters of rounded and translucent cells containing globular mucous cytoplasmic inclusions (HPF, x400). These cells were bigger than leukocytes and, compared with uroepithelial cells, showed a smaller nucleus to cytoplasm ratio and appeared eosinophilic, being pink rather than azurophilic with Sternheimer-Malbin stain. They were also unlikely to be tubular cells, which are usually smaller, singly distributed and associated with dysmorphic erythrocytes and/or casts and/or a worsening in renal function. A review of the patient's history showed that a pretransplantation urologic surgical treatment, including ileal bladder reconstruction, had been performed. Intestinal epithelial cells should be remembered when examining urinary sediment.

Donor intra-islet endothelial cells contribute to neovascularization after transplantation. Several factors may interfere with this process and ultimately influence islet engraftment. Rapamycin, a central immunosuppressant in islet transplantation, is an mTOR inhibitor that has been shown to inhibit cancer angiogenesis. The aim of this study was to evaluate the effects of rapamycin on islet endothelium. Rapamycin inhibited the outgrowth of endothelial cells from freshly purified human islets and the formation of capillary-like structures in vitro and in vivo after subcutaneous injection within Matrigel plugs into SCID mice. Rapamycin decreased migration, proliferation and angiogenic properties of human and mouse islet-derived endothelial cell lines with appearance of apoptosis. The expression of angiogenesis-related factors VEGF, alphaVbeta3 integrin and thrombospondin-1 on islet endothelium was altered in the presence of rapamycin. On the other hand, rapamycin decreased the surface expression of molecules involved in immune processes such as ICAM-1 and CD40 and reduced the adhesion of T cells to islet endothelium. Our results suggest that rapamycin exerts dual effects on islet endothelium inducing a simultaneous inhibition of angiogenesis and a down-regulation of receptors involved in lymphocyte adhesion and activation.

Rejection prevention and control have been pivotal aims of medical research since the time that renal transplant was first developed. While acute rejection rates have generally fallen to 10%-15% at 1 year, chronic rejection and chronic allograft nephropathy (CAN) still erode long-term transplant potential. Furthermore, drug tolerability and their 'secondary' effects other than immunosuppression have become as important as their effectiveness in a recipient population that is increasingly old and burdened by cardiovascular morbidity. We review the state of the art of new immunosuppressive drugs: some of them have already entered clinical practice (e.g., mycophenolate mofetil, anti-CD25 monoclonal antibodies and sirolimus [SRL]); others are at different stages of the pre-registration phase (everolimus, mycophenolic acid, FTY 720, leflunomide-FK 778 and Campath-1H), and many others show promising potential for the future (rituximab, monoclonal antibodies against costimulatory molecules). Especially, new drugs with antiproliferative and antifibrogenic effects (SRL, everolimus, leflunomide and mycophenolic acid) could to be decisive in still challenging areas such as CAN and cardiovascular and neoplastic transplant complications. The key to solving these open issues probably lies in the possibility of relying on a wide repertoire of drugs with different profiles, to be exploited in several associations, and in our capacity to integrate new and old immunosuppressive drugs.

Context: Organ shortage for transplantation is a crucial problem; educational interventions may increase donations and decrease opposition., Objective: To test the efficacy of an educational programme on opinions on organ transplantation and kidney donation., Design and Participants: Cluster Randomized Controlled Trial: eight intervention and eight control schools were randomly selected from the 33 public schools that agreed to participate. Targets: students in the last 2 years of secondary school (17-18 years); seven schools per group completed the study. EDUCATIONAL PROGRAMME:, Intervention: first questionnaire (anonymous); 2 h lesson in each class; 2 h general session with patients and experts; second questionnaire., Control: questionnaires., Main Outcome Measures: Differences between questionnaires (comparative analysis); interest; satisfaction with the programme; (cross-sectional analysis)., Results: 1776 first, 1467 second questionnaires were retrieved. Living kidney donation: at baseline 78.8% of students would donate a kidney to a relative/friend in need. The answers were unaffected by type of school but depended on sex (females more prone to donate, P<0.001); the answers did not change after the lessons. Cadaveric kidney donation: baseline opinions were mixed (intervention schools: 31.5% yes, 33.7% no, 34.8% uncertain), depending on type of school (classical-scientific high schools more positive than technical institutes, P<0.001), sex (males more prone to donate, P<0.001). Answers on living and cadaveric donation were correlated (P<0.001). The educational intervention increased favourable (31.5 to 42.9%) and uncertain (34.8 to 41.1%) opinions and decreased negative ones (33.7 to 16%) (P<0.001)., Conclusions: Educational interventions are effective in increasing interest and improving opinions about cadaveric organ donation.

Background: Predialysis care is vital for the patient and is crucial for dialysis choice: empowered, early referred patients tend to prefer out-of-hospital and self-care treatment; despite these claims, early referral remains too often a program more than a reality. Aim of the study was to evaluate the pattern and reasons for RRT choice in patients treated in a long-standing outpatient network, presently following 850 chronic patients (about 80% diabetics), working with an early referral policy and offering a wide set of dialysis options (home hemo and PD; self care and limited care hemodialysis; hospital hemodialysis)., Methods: Prospective historical study. All patients who started RRT in January 2001-December 2003 were considered. Correlations between demographical (sex, age, educational level) or clinical variables (pre-RRT follow-up, comorbidity, SGA and Karnofsky) and treatment choice have been tested by univariate (chi-square, Kruskal-Wallis) and multivariate models (logistic regression), both considering all choices and dichotomising choice into "hospital" versus "out of hospital dialysis"., Results: Hospital dialysis was chosen by 32.6% of patients; out of hospital in 67.4% (PD 26.5%, limited-care 18.4%, home hemodialysis 4.1%, self-care 18.4%). Hospital dialysis and PD were chosen by elderly patients (median age: 67.5 and 70 years respectively) with multiple comorbidities (75% and 92.3%); no difference for age, comorbidity, Karnofsky, SGA and educational level. 6/13 PD patients needed the help of a partner. Self-care/home hemodialysis patients were younger (median age 52), had higher educational level (p = 0.014) and lower prevalence of comorbidity (63.6% vs 94.7% in the other dialysis patients, p = 0.006). In the context of a long follow-up period (3.9 years) a statistically significant difference was found comparing hospital dialysis (3.3 years) vs out of hospital dialysis (4.9 years) (p = 0.035). In a logistic regression model, only pre-RRT follow-up was correlated with dialysis "hospital vs "out of hospital" choice (p = 0.014)., Conclusion: Early nephrological follow-up may enhance self and home-based dialysis care.

The number of women who decide to have a child after organ transplantation has increased. We determined the outcomes of 67 pregnancies of women who had undergone kidney, liver or heart transplantation. All recipients had been maintained on immunosuppressive therapy before and during pregnancy. Pregnancy complications at term were observed in 17 out of 67 women (25%), hypertension being the most frequent complication (16.17%). Two transplant rejections were reported. Sixty-eight infants were delivered (including one pair of twins); five women had two pregnancies at term. Twenty-eight miscarriages (29.2%) were recorded. Of these 68 babies (including the pair of twins), 40 (58.8%) were born at term and 28 (41.2%) before term. The babies were followed-up for 2 months to 13 years. According to our previous experience, our study shows that patients who have undergone organ transplantation can give birth to healthy infants as long as they are monitored accurately during pregnancy.

Unlabelled: Living kidney donation is an important clinical option, encountering different fortunes in the world., Aim: To analyse the opinions of a large subset of older teenagers attending high school (7999 students, median age 18) on different aspects of living kidney transplantation., Methods: Analysis of semistructured questionnaires submitted within an educational campaign on dialysis and transplantation in the high schools of Torino and its county (about 2,000,000 inhabitants)., Results: Over 90% of the students had already heard of transplantation, mainly via television (88.4% county, 84.5% city). 80% would donate a kidney to a family member (3.5% wouldn't, 16.5% uncertain); answers were correlated with sex (females more than males p<0.0001), school type (istituti tecnici versus licei p=0.007), interest (yes versus other p<0.0001). A lower percent of individuals would receive a kidney (58.4% county, 59.4% city), only 10% would ask for donation. Over 40% of students consider legally buying a kidney a patient's right, only 26.6% would discourage this choice. The answers were correlated with the reverse pattern as for non-mercenary donation with type of school (licei more than istituti tecnici: p<0.0001), sex (males versus females p<0.0001), interest (not versus yes: p=0.002)., Conclusions: Teenagers are favourable towards all forms of living kidney donation. The lower prevalence of positive answers on acceptance versus donation suggests that fears of endangering the donor's health may be one of the causes for a low living donation rate in our setting. The mixed answers on mercenary donation suggest discussing this complex issue in future educational programs.

Background: Recent improvements in simultaneous pancreas-kidney transplantation (SPK) and the striking decrease in acute rejection lead us to focus on the effects of long-term immunosuppression., Aim of This Study: Evaluation of a policy of steroid withdrawal and tailored immunosuppression in pancreas-kidney patients treated in a single center., Methods: review of the clinical charts in 9 SPK recipients (male/female = 5/4, median age 41 years, median follow-up 42 months), by the same operator, under supervision of the two usual caregivers. Therapeutic protocols. Induction phase: all patients received mycophenolate mophetil (starting dose: 2 grams), tacrolimus and steroids, 8 received Simulect, 1 received thymoglobulins. Maintenance therapy was slowly reduced, with the goal of steroid withdrawal., Results: The therapeutic adjustments were mainly determined by two almost opposing elements: 1. Rapid adjustments in the case of side-effects (gastrointestinal problems, infections and neoplasia); 2. Slow tapering off in the case of good organ function. On the other hand, a switch to cyclosporine A and to rapamycine was considered in the case of chronic organ malfunction. By these means, over a median of 42 months follow-up, steroid withdrawal was slowly obtained in 6/9 patients (at a median time of 25 months)., Conclusions: Within the limits of this small-scale study, a tailored immunosuppressive policy allows at least some "positively selected" patients to reach the "dream" of steroid withdrawal after SPK.

Background: Concerns about vascular access failure may have limited the widespread use of daily haemodialysis (DHD). We assessed the incidence and type of vascular access complications during DHD and other schedules, both at home and on limited care haemodialysis., Methods: All patients were treated in a limited care and home haemodialysis unit with a stable caregiver team (November 1998-November 2002). Vascular access failure, surgical treatment, angioplasty and declotting were studied alone or in combination by univariate and multivariate models. We analysed the effects of age, sex, comorbidity, previous vascular events, schedule, setting of treatment (home, limited care), dialysis follow-up, vascular access (native vs prosthetic, first vs subsequent) and setting of vascular access creation. 'Intention to treat' and 'per protocol' analyses were performed., Results: In 2160 patient-months (home dialysis: DHD 400 months, non-DHD 655 months; limited care: DHD 208 months; non-DHD 897 months), 57 adverse events occurred (27 failures), in which 30 were at home (nine DHD) and 27 were in limited care (five DHD). The probability of remaining free from adverse events at 6 and 12 months was 89% and 80% on DHD and 79% and 76% on other schedules ('intention to treat'). Univariate analyses revealed a significant difference for the setting of the vascular access creation (lower risk of vascular access complications in our centre) and sex (male sex was protective). Logistic regression and Cox analyses confirmed the role for the setting of the vascular access creation., Conclusions: Although DHD did not appear as a risk factor for vascular access morbidity or failure at home or in a limited care centre setting, the setting of vascular access creation may influence its success.

Background: Pre-emptive pancreas-kidney transplantation is increasingly considered the best therapy for irreversible chronic kidney disease (CKD) in type 1 diabetics. However, the best approach in the wait for transplantation has not yet been defined., Aim: To evaluate our experience with a low-protein (0.6 g/kg/day) vegetarian diet supplemented with alpha-chetoanalogues in type 1 diabetic patients in the wait for pancreas-kidney transplantation., Methods: Prospective study. Information on the progression of renal disease, compliance, metabolic control, reasons for choice and for drop-out were recorded prospectively; the data for the subset of patients who underwent the diet while awaiting a pancreas-kidney graft are analysed in this report., Results: From November 1998 to April 2004, 9 type 1 diabetic patients, wait-listed or performing tests for wait-listing for pancreas-kidney transplantation, started the diet. All of them were followed by nephrologists and diabetologists, in the context of integrated care. There were 4 males and 5 females; median age 38 years (range 27.9-45.5); median diabetes duration 23.8 years (range 16.6-33.1), 8/9 with widespread organ damage; median creatinine at the start of the diet: 3.2 mg/dl (1.2-7.2); 4 patients followed the diet to transplantation, 2 are presently on the diet, 2 dropped out and started dialysis after a few months, 1 started dialysis (rescue treatment). The nutritional status remained stable, glycemia control improved in 4 patients in the short term and in 2 in the long term, no hyperkalemia, acidosis or other relevant side effect was recorded. Proteinuria decreased in 5 cases, in 3 from the nephrotic range. Albumin levels remained stable; the progression rate was a loss of 0.47 ml/min of creatinine clearance per month (ranging from an increase of 0.06 to a decrease of 2.4 ml/min) during the diet period (estimated by the Cockroft-Gault formula)., Conclusions: Low-protein supplemented vegetarian diets may be a useful tool to slow CKD progression whilst awaiting pancreas-kidney transplantation.

Background: Type 1 diabetic patients are a small but challenging subset of chronic kidney disease. The new frontiers of pancreas-kidney transplantation may enhance the need for early referral., Objective: To analyze the referral pattern of type 1 diabetics to a specialized Nephrology Unit, and to quantify the indications for pancreas or pre-emptive pancreas-kidney transplantation at referral in this population., Patients and Methods: Setting of study was a Nephrology Outpatient Unit, dedicated to diabetics, active since 1986; period of study 1991--2002. The main biochemical and clinical parameters were analyzed at referral. Indications for transplantation were put at: serum creatinine (sCr)> or =2 mg/dL or > or =3 mg/dL and/or nephrotic syndrome. Pancreas: lesser degrees of functional impairment without worsening after FK-506 challenge., Results: 90 type 1 diabetics were referred: 48 males, 42 females; median age: 38 (18-65) years; median diabetological follow-up 20 (3-37) years; sCr 1.2 (0.6-7) mg/dL, proteinuria 0.9 (0-12.3) g/day; creatinine clearance: 58 (6-234) ml/min; Hbalc: 8.8% (5.9-14), diastolic blood pressure: 80 (55-100) mmHg, systolic blood pressure: 137.5 (70-180) mmHg. 85.6% had signs of end-organ damage due to diabetes. 67% of the patients had diabetic nephropathy, 20.7% hypertensive with or without diabetic nephropathy. According to the chosen criteria, 30.6% had indications for pancreas-kidney graft (sCr > or = 2 mg/dL), 25.9% considering sCr > or = 3 mg/dL; 28.2% further patients could be considered for isolated pancreas graft., Conclusions: At referral to the nephrologist, over 50% of type 1 diabetics may have indications for pancreas-kidney or pancreas graft; an earlier multidisciplinary work-up is needed to optimize an early pre-emptive transplant approach.