Chemical characterization of exhaled breath to differentiate between patients with malignant plueral mesothelioma from subjects with similar professional asbestos exposure.

Malignant pleural mesothelioma (MPM) is an aggressive tumour whose main aetiology is the long-term exposure to asbestos fibres. The diagnostic procedure of MPM is difficult and often requires invasive approaches; therefore, it is clinically important to find accurate markers for MPM by new noninvasive methods that may facilitate the diagnostic process and identify patients at an earlier stage. In the present study, the exhaled breath of 13 patients with histology-established diagnosis of MPM, 13 subjects with long-term certified professional exposure to asbestos (EXP) and 13 healthy subjects without exposure to asbestos (healthy controls, HC) were analysed. An analytical procedure to determine volatile organic compounds by sampling of air on a bed of solid sorbent and thermal desorption GC-MS analysis was developed in order to identify the compounds capable of discriminating among the three groups. The application of univariate (ANOVA) and multivariate statistical treatments (PCA, DFA and CP-ANN) showed that cyclopentane and cyclohexane were the dominant variables able to discriminate among the three groups. In particular, it was found that cyclohexane is the only compound able to differentiate the MPM group from the other two; therefore, it can be a possible marker of MPM. Cyclopentane is the dominant compound in the discrimination between EXP and the other groups (MPM and HC); then, it can be considered a good indicator for long-term asbestos exposure. This result suggests the need to perform frequent and thorough investigations on people exposed to asbestos in order to constantly monitor their state of health or possibly to study the evolution of disease over time.

ID2-VEGF-related pathways in the pathogenesis of Kaposi's sarcoma: a link disrupted by rapamycin.

The Id-proteins are a family of four related proteins implicated in the control of differentiation and cell-cycle progression. Down-regulation of Id-gene expression is essential for the differentiation of several cell types. In addition, deregulated Id2 activity inhibits the Rb tumor suppressor pathway and promotes the expression of vascular endothelial growth factor (VEGF). Several members of VEGF family could be involved in Kaposi's sarcoma (KS) development and progression. Lymphatic vascular endothelial hyaluronan receptor-1 (LYVE-1) is the first marker of lymphatic endothelial competence during development in the mature vasculature, and is also expressed on KS spindle cells. Rapamycin (RAPA), an immunosuppressive drug, has been shown to reverse KS growth and to reduce tumor angiogenesis. We evaluate, in transplantation-associated KS and in cultured KS-cells the RAPA effect on Id2 and on de novo lymphangiogenesis. Markers of lymphatic-endothelial-cells (VEGFR-3, LYVE-1) and Id2, expressed at low levels within the normal skin, were up-regulated in KS and returned to normal levels after RAPA introduction. The association between Id2 and lymphangiogenesis is suggested by co-localization of Id2, VEGFR-3 and LYVE-1. RAPA inhibition on Id2 expression was confirmed in vitro in KS-cells, both in basal conditions and upon stimulation with VEGF. In conclusion, our data would suggest a novel molecular mechanism for the antineoplastic effects of RAPA in posttransplant KS.

Waist-to-height ratio is the best anthropometric index in association with adverse cardiorenal outcomes in type 2 diabetes mellitus patients.

BACKGROUND/AIMS: Visceral obesity is a potent risk factor for both chronic kidney disease (CKD) and myocardial infarction (MI) in type 2 diabetes mellitus patients (T2DM). Short stature is also associated with higher risk for either coronary or kidney diseases. Thus, the aim of our study was to investigate the association of the frequency of cardiorenal complications with waist-to-height index (W/Ht) in T2DM. METHODS: This was a cross-sectional study where 958 T2DM patients were studied. Subjects with cardiorenal disease (CRD) were defined as those with both kidney dysfunction (KD) and MI. RESULTS: We found a significant excess of MI in patients with KD as compared to those without KD (28 vs. 14%, p < 0.0001). Interestingly, among the commonly used indices of obesity, only W/Ht and BMI were significantly associated with CRD risk. Moreover, only the W/Ht index (but neither BMI nor WC) was significantly associated with the risks for every component of CRD. Lastly, in the multivariate logistic regression analysis, W/Ht proved superior to the other traditional factors associated with risk for CRD. CONCLUSIONS: Our study in a large cohort of subjects demonstrated that a higher W/Ht index is the best anthropometric measure associated with adverse CRD outcomes of T2DM patients.

The impact of age on intravesical instillation of Bacille Calmette-Guerin treatment in patients with high-grade T1 bladder cancer.

Intravesical instillation of Bacille Calmette-Guèrin (BCG) is the standard adjuvant treatment for high-risk non muscle invasive bladder cancer (NMIBC). Since its mechanism of action is supposed to be linked to the immune system efficiency and senescence could negatively affect this efficiency, BCG efficacy in the elderly has been questioned. This study aimed to assess the impact of age on BCG efficacy and safety in patients with high-grade T1 bladder cancer (BC).Among 123 patients with high-grade T1 BCG scheduled for BCG treatment, 82 were <75 year-old (group A) and 41 were ≥75 year-old (group B). Follow-up: urine cytology and cystoscopy every 3 months for the first 2 years, every 6 months for the third year, and then yearly. Tumor recurrence was defined as pathological evidence of disease at the bladder biopsy; tumor progression was defined as pathological shift to muscle invasive disease at the bladder biopsy or the imaging techniques showing recurrent BC and distant metastasis likely related to it.The median follow-up was 65 months (range 11-152). Recurrence occurred in 35 patients, 19 (23.2%) in the group A and 16 (39%) in the group B. Progression occurred in 18 patients, 12 (14.6%) in the group A and 6 (14.6%) in the group B. Recurrence free rate was similar in both groups up to 2 years. The 5 years progression rate was almost the same in both groups A and B (85.9% vs 84.7%), whereas the 5 years cancer-specific survival (CSS) was 92.6% in the group A and 85.4% in the group B. Of the 18 patients with progression, 11 underwent cystectomy; 12 patients died because of their BC. Kaplan-Meier plots pointed out no difference in recurrence-free, progression-free, and CSS between the 2 groups. Adverse events were similar in the 2 groups. Only 4 (3.3%) patients, 2 (2.4%) in the group A and 2 (4.8%) in the group B, experienced mild adverse reactions compatible with treatment.Elderly patients with high-grade T1 BC are not poorer candidates to BCG treatment, as they had similar benefit and adverse reactions than those aging ≥75 years.

[Nocturnal hemodialysis: an alternative treatment for a better quality of life]. / Emodialisi notturna: un trattamento alternativo per una migliore qualità della vita.

The interest of investigators in intensified dialysis regimens has been growing in recent years, especially since the HEMO Study Group showed that a higher dose of thrice-weekly hemodialysis fails to reduce mortality and morbidity but improves clinical outcomes. Alternative hemodialysis strategies including short daily hemodialysis (SDHD), long hemodialysis (LHD) and nocturnal daily hemodialysis (NDHD) have been developed in the hope to improve patients' outcomes. A growing number of investigators are studying patients on alternative dialysis regimens and most publications in this field have reported significant improvements in clinical outcomes including left ventricular hypertrophy, blood pressure control, anemia, calcium-phosphate metabolism, and fluid and electrolyte balance; all of these parameters can be considered as indirect signs of improvement in quality of life. However, the strength of these results is often limited by shortcomings in study design. Indeed, in most of these studies an adequate control group is missing, the patient groups are not properly matched, and the number of patients enrolled is small. Similarly, most studies have evaluated the effects of NDHD and/or nocturnal LHD on health-related quality of life (HRQoL) by questionnaire administration. Even though better results might be achieved with nocturnal hemodialysis, no conclusive data exist to prove statistically significant differences in HRQoL between conventional and intensive hemodialysis. In conclusion, all of these novel dialysis strategies offer reliable opportunities for uremic patients, but further trials are needed to determine whether alternative hemodialysis can reduce morbidity and mortality in this high-risk population of patients.

[Pro and anti-neoplastic effects of immunosuppressive drug in renal transplantation]. / Effetti pro ed anti-neoplastici dei principali farmaci immunosoppressori usati nella pratica clinica trapiantologica.

The increased efficiency of immunosuppressive drugs obtained in the last few years has significantly reduced the incidence of acute rejection, prolonging transplant survival rates. The inevitable trade-off was however an increased rate of post-transplant infections and malignancies. Furthermore, this problem might get more and more serious in the next future due to the increasing incidence of cancer in immunosuppressed transplant recipients; the introduction of new immunosuppressive strategies is expected to extend significantly allograft survival. The inclusion of older recipients in transplant programs will also likely increase this problem. Thus, cancer may represent a serious cause of morbidity and mortality in patients otherwise successfully treated by organ transplantation. Nevertheless, effective approaches to deal with malignancies in immunosuppressed patients are still far from the clinical arena. Therefore, once cancer occurs in a transplant recipient, clinicians only have two options: to reduce or withdraw the immunosuppression eventually causing acute or chronic allograft rejection, or to continue the standard immunosuppressive therapy while beginning specific therapy for the malignancy. Several clinical studies suggest that the use of immunosuppressive drugs may result in increased cancer incidence, in transplant as well as autoimmune disease patients. This clinical observation is supported by experimental data showing that these drugs enhance cancer cell growth characteristics and inhibit DNA repair mechanisms, clearly suggesting that the increased incidence of neoplastic disease in patients treated with several immunosuppressive drugs is at least partially independent of their immunosuppressive action. In this scenario it is of particular interest the fact that some immunosuppressive drugs have both an anti-rejection and anti-neoplastic activity. In this review we focus our attention on this potential dual role of immunosuppressive therapy in the development of neoplasia in transplanted patients.

Double J stent with antireflux device in the prevention of short-term urological complications after cadaveric kidney transplantation: single-center prospective randomized study.

The placement of a double J stent to protect a uretero-vesical anastomosis in a kidney transplant is a widespread procedure performed to reduce the incidence of fistula and stenosis at the anastomosis. However, the presence of a double J stent may cause vesicoureteral reflux (VUR), predisposing one to urinary tract infections (UTIs), which may be a significant source of morbidity for the graft. We evaluated whether a ureteral stent incorporating an antireflux device can reduce the incidence of ureteral reflux and UTIs. From January to December 2003, 44 kidney transplant recipients were randomized to receive a 14-cm 4.8-F double J stent with (group A) or without an anti-reflux device (group B). Primary end points were the reduction of the incidence of VUR and of UTIs. The secondary end point was the graft function, on the basis of mean serum creatinine level at 3, 6, and 12 months. We failed to observe statistically significant differences in terms of either the incidence of VUR and UTIs, or the short-term outcomes of the grafts. We concluded that the anti-reflux device does not have an impact on the incidence of stent-related side effects.

[Immunosuppressive drugs and renal transplantation]. / Farmaci immunosoppressori e trapianto renale.

Although the use of new immunosuppressive drugs, and their combination have drastically reduced the incidence of acute rejections, the graft survival is unchanged in the last ten years. The immunosuppressive drugs can be divided in four classes, according to their different site of molecular action: proliferative signal inhibitors, amplification signal inhibitors; STATs inhibitors, DNA synthesis inhibitors. Steroids act on immune system through several mechanisms. Azathioprine is an anti-metabolite that inhibits de-novo synthesis of purins, acting on S-phase of cellular cycle. Mycophenolate-Mofetil (MMF) is also an anti-metabolite, purine synthesis inhibitor that, differently from azathioprine, acts specifically on IMPDH (Inositolmonophosphate-dehydrogenasis) through a non-competitive mechanism. Calcineurin inhibitors (cyclosporin and tacrolimus) act on amplification of intracellular signal. The most important therapeutic side-effect of calcineurin inhibitors is the nephrotoxicity. Other inhibitor agents of the amplification signal are monoclonal antibodies anti-á chain of IL-2 (CD25). Another drug used in the last years, is sirolimus (SRL) or rapamycine, an immunosuppressive agent that act, through the inhibition of T lymphocyte activation.

Monocyte chemotactic peptide-1 expression and monocyte infiltration in acute renal transplant rejection.

Mononuclear cell infiltration is a common histopathological feature of acute renal transplant rejection, in which it seems to play a key role in the pathogenesis of tubulointerstitial lesions. Monocyte chemotactic peptide-1 (MCP-1) is a specific chemotactic and activating factor for monocytes. Thus, the present study was aimed at evaluating MCP-1 gene and protein expression in renal biopsies of kidney transplant recipients with acute deterioration of graft function, and to correlate it with the extent of monocyte infiltration. We studied 20 kidney transplant recipients with acute graft dysfunction (13 with acute rejection, seven with acute tubular damage). MCP-1 gene and protein expression were analyzed by in situ hybridization and immunohistochemistry, respectively. CD68-positive cells were identified as monocytes. CD68-positive cell number and MCP-1 expression were quantified by a computerized image analysis system. MCP-1 gene expression, undetectable in normal human kidneys, was strikingly increased in patients with acute rejection. The chemokine localized mainly to the proximal tubular cells and to mononuclear-infiltrating cells. In patients with acute tubular damage, the MCP-1 expression, even if higher than in controls, was significantly lower than in acute rejection. The expression of the chemokine strictly correlated with the number of infiltrating monocytes (r=0.87, P<0.05). Moreover, we measured MCP-1 urinary excretion by ELISA, in eight normal subjects (36+/-16 pg/mg urine creatinine), in 13 clinically stable transplant recipients (33+/-9 pg/mg, ns vs. normal patients), in 12 transplant recipients with acute rejection (250+/-46 pg/mg, P<0.01 vs. normal patients), and in five transplant recipients with acute tubular damage (97+/-33 pg/mg, P<0.05 vs. controls and patients with acute rejection). Urinary MCP-1 excretion directly correlated with renal MCP-1 gene expression (r=0.65, P=0.05). Finally, we observed a significant reduction in MCP-1 urine levels in patients with acute rejection, who responded to the antirejection treatment. In conclusion, our data suggest that MCP-1 may play a critical role in modulating monocyte influx and consequent tubulointerstitial damage in acute rejection. Therefore, an increase in urinary MCP-1 excretion may represent an early signal of ongoing acute graft rejection.

Interference of angiotensin-converting enzyme inhibitors on erythropoiesis in kidney transplant recipients: role of growth factors and cytokines.

BACKGROUND: Recent data indicate that factors other than erythropoietin (EPO), such as insulin-like growth factor 1 (IGF-1), can promote erythropoiesis in vitro and correct the anemia of chronic renal failure in vivo. IGF-1 is produced by the liver under growth hormone control, as well as by other sources, including the kidney. The erythropoietic role of growth factors and cytokines and their possible modulation by angiotensin-converting enzyme inhibitors (ACEI) has never been explored. METHODS: This study evaluated the serum levels of EPO, IGF-1, interleukin (IL)-2, IL-3, and granulocyte macrophage-colony-stimulating factor in 40 kidney transplanted patients with or without posttransplant erythrocytosis (PTE) and in 10 living kidney donors. Then, the effect of ACEI therapy on the above pattern was examined in patients with PTE. RESULTS: EPO and IGF-1 serum levels were significantly higher in patients with PTE than in patients without PTE and in living kidney donor subjects. ACEI therapy significantly reduced hematocrit (Hct) as well as circulating IGF-1 and EPO levels. Of note, the decrease in IGF-1 was prominent mainly in those patients whose EPO levels were not significantly modified by ACEI therapy. In all of the patients Hct levels displayed a direct relationship with circulating IGF-1 levels, but not with EPO concentration. Growth hormone did not significantly differ among the groups examined, whereas it steeply increased under ACEI. Finally, no significant difference in IL-2, IL-3, and granulocyte macrophage-colony-stimulating factor serum levels was detected. CONCLUSIONS: IGF-1 seems to play a role in the ACEI-related decrease of Hct in patients with PTE, chiefly in patients without any modification of EPO serum levels.

Protease-activated receptor 1 and plasminogen activator inhibitor 1 expression in chronic allograft nephropathy: the role of coagulation and fibrinolysis in renal graft fibrosis.

BACKGROUND: Chronic allograft nephropathy (CAN), the major cause of renal graft failure, frequently displays extensive interstitial fibrin deposition. Little is known in regard to the cause of the altered coagulation/fibrinolysis balance and its relevance in the pathogenesis of CAN. Thrombin, present within the fibrin clots, can interact with a specific receptor, protease-activated receptor 1 (PAR-1), and modulate a variety of cell functions. On the other hand, the derangement of the fibrinolytic system may directly affect extracellular matrix (ECM) degradation. METHODS: In the present study, we investigated, by in situ hybridization, PAR-1 gene expression and the mRNA levels for tissue factor and plasminogen activator inhibitor 1 (PAI-1), two key regulatory molecules of coagulation and fibrinolysis, in 16 CAN biopsies and in 10 normal human kidney grafts. The thrombin-induced transforming growth factor beta (TGF-beta) gene and protein expression in proximal tubular cells (PTC) was investigated by Northern blotting and ELISA, respectively. RESULTS: Fibrin deposits, absent in normal grafts, were observed in the interstitial space and arterial wall of CAN. Tissue factor gene expression was not increased either at the vascular or at the interstitial level in CAN. On the contrary, PAI-1 gene expression, barely detectable in control tissue, was strikingly increased in CAN, with a distribution resembling the pattern of fibrin deposition. Note that PAI-1 gene expression was directly correlated with the degree of interstitial fibrosis. In addition, fibrin deposits were strictly associated with a marked increase of PAR-1 gene expression in endothelial cells and PTC. The tubular expression of PAR-1 was significantly higher in Banff grade II-III than in grade I. In vitro, incubation of PTC with thrombin caused a significant up-regulation of TGF-beta gene expression, followed by an increased TGF-beta release into the supernatant. Interestingly, urine from CAN patients contained significantly higher levels of TGF-beta. CONCLUSIONS: Fibrin deposits in CAN may result from the increased expression of PAI-1 and the subsequent inhibition of fibrinolysis. The reduced fibrinolysis may cause, in turn, a decreased ECM turnover. Finally, thrombin, preserved in the active form within the fibrin clots, may interact with PAR-1 highly expressed on PTC and induce an up-regulation of ECM deposition in a TGF-beta-dependent manner.

Immunologic evaluation during the first year of life of infants born to cyclosporine-treated female kidney transplant recipients: analysis of lymphocyte subpopulations and immunoglobulin serum levels.

BACKGROUND: In rodents, CsA has been shown to affect T-cell development, giving rise to an abnormal production of mature T cells and the absence of many T-cell subsets as well as to autoimmunity. Surprisingly, only a few studies investigated the effect of the immunosuppressive drug on the immune system of the human fetus. METHODS: We examined six infants born to female kidney transplant recipients who had received cyclosporine and methylprednisolone throughout their pregnancies. Peripheral blood was obtained 1 day and 2, 4, 6, and 12 months after birth, and two-color flow cytometric immunophenotyping of lymphocytes was performed. RESULTS: Total T cells, as well as CD4+ and CD8+ T cells, were low at birth, but normalized thereafter. Among T-cell activation markers, the expression of CD25, the alpha chain of the interleukin-2 receptor, was below the normal range or low range throughout the study period, and HLA-DR expression was extremely low at birth and failed to increase up to 12 months. The number of total B cells was lower than normal at birth, but steeply increased over time. In contrast, B-cell subset bearing CD5 antigen was severely depleted throughout the first year of life. Total IgG concentration was significantly lower than in controls at 2 months, mainly because of subnormal levels of IgG1 and IgG3 subclasses, which remained in the low range up to 6 months. Finally, infants showed normal numbers of true natural killer (NK) cells (CD3-CD16+CD56+), whereas the expression of CD57 antigen, defining non-MHC-restricted cytotoxic lymphocytes, was barely detectable at birth and failed to increase over time, in both CD8+ and CD8- subsets. Of note, none of the infants had clinical evidence of an immunodeficient state. CONCLUSIONS: continuous exposure to CsA in utero seemingly impairs T-, B-, and NK-cell development and/or maturation, and most of its effects are still apparent at 1 year, which might suggest that conventional vaccinations should be delayed in these infants.

Pregnancy in renal transplantation: immunologic evaluation of neonates from mothers with transplanted kidney.

The occurrence of pregnancy in young female organ transplant recipients may sustain a high risk for prematurity and low rate of malformations in neonates. Therefore, it is necessary to counsel couples who want a child. In case of pregnancy, strict guidelines must be observed. Continuous exposure to CsA in utero seems to impair T-, B- and NK-cell development and function in neonates. This effect is prolonged throughout the first year of life. In addition, low levels of serum immunoglobulins occur at the same time. This leads to suggest a delayed administration of classical vaccinations (after the first 6 months of life) in view of the potential risks of both sub-optimal immunologic responses, and adverse events after the administration of live, attenuated vaccines in infants born from young female organ transplant recipients.

Primary renal lymphoma does exist: case report and review of the literature.

Primary renal lymphoma (PRL) is a controversial and rare disease and there is still no agreement on its existence. Many cases have been reported in the literature, but clear diagnostic criteria have not yet been established. Most of the reported cases are questionable because of incomplete staging or the presence of extrarenal disease. Here we report a new case and a review of the literature based on a critical examination of the diagnostic procedure. Thus, probably only 29 cases, ours included, should be recognized as PRL, because only these cases fulfil the three diagnostic criteria and underwent complete diagnostic screening, including renal biopsy, bone marrow biopsy and thoraco-abdominal computerised tomography (CT).

Kidney transplants from infected donors: our experience.

Organ procurement from infected donors may transmit a disease to the recipient that could cause a graft loss and/or recipient morbidity. Retrospectively, all kidney transplants from infected donors at our center in the last 4 years were reviewed. A donor was considered infected in the presence of at least one positive culture before procurement. From January 1999 to 2003, 23 of 160 donors (14.5%) were infected: in 10 donors a positive blood culture; in 3, a urine culture; and in 13, a bronchial culture. In a further 12 (7%) donors, only the preservation solution was contaminated. Organisms isolated were: Staphylococcus coagulase.neg. (n = 7); Staphylococcus epidermidis (n = 3); Staphylococcus aureus (n = 6); Klebsiella pneumoniae (n = 3); Pseudomonas aeruginosa (n = 4); Acinetobacter (n = 1); Candida albicans (n = 13); Aspergillus (n = 1); and Escherichia coli (n = 1). All except 2 kidneys were transplanted with positivity in all cultures. All recipients received general, nonspecific, antibacterial and antifungal prophylaxis until the antibiotic and antifungal spectrum was ready. Patient and graft survival rates at 6 months were 94% and 93%, respectively. Two deaths occurred due to bacterial arteritis (P aeruginosa), and 2 acute graft losses due to fungal arteritis. Kidneys from infected donors seem suitable for transplants. Only grafts infected by vasculotropic agents (S aureus, P aeruginosa, and C albicans) should be discarded.

Medical and surgical complications after kidney transplantation from "suboptimal donors": one centre's experience.

To overcome the organ shortage, the pool of donors can be expanded to include aged donors (>55 years old) or patients with diabetes and long-standing hypertension, the so-called "suboptimal donors." Our experience on medical and surgical complications in kidney recipients from such donors and their impact on the graft and patient survival rates is reported. From January 1998 to April 2003, 276 kidney transplantation were performed: 107 from suboptimal donors (group A) and 169 from optimal ones (group B). After a mean follow-up of 26.8 months (range, 1-63 months), the 1-year graft survival rate was 89.3% and 97% for groups A and B, respectively. Medical complications were observed in 18.8% of group A and 6% of group B and surgical complications in 34.5% and 20%, respectively. In conclusion, even if the complication rate is higher among the suboptimal donor group, the patient and graft survival rates appear to be only slightly affected, therefore, validating the use of marginal donors.

Experience with cyclosporine: approaching the therapeutic window for C2 levels in maintenance kidney transplant recipients.

This study was aimed to evaluate the clinical benefit of C2 monitoring in 191 stable renal transplant patients previously monitored by C0. All patients had been transplanted for at least 1 year and received cyclosporine (CsA)-based immunosuppression since the start. At the inceptions C0 levels were significantly correlated with C2 values (P<.0001). Patients with starting C2 levels >1000 ng/mL showed significantly higher levels of serum creatinine (sCr) both at inception (1.66 +/- 0.50 vs 1.44 +/- 0.41 mg/dL; P=.0021) and at the end of a 2-year follow-up (1.84 +/- 0.80 vs 1.46 +/- 0.51 mg/dL; P=.005). C2 monitoring revealed that a high percentage of patients were overexposed to CsA, mainly in the subgroup with most recent renal engraftments (12 to 24 months). The switch to C2 monitoring was associated with a slower deterioration of graft function (P=.02). Further, the mean values of C2 over a 2-year follow-up were inversely correlated with sCr at the end of follow-up (P=.0005). Finally, patients with mean threshold C2 levels above 720 ng/mL, roughly corresponding to the median value of C2, showed significantly lower levels of sCr at the end of follow-up (P=.0004). In conclusion, C2 monitoring of maintenance renal transplant patients allows one to identify a significant percentage of overexposed subjects, possibly limiting the rate of progression of chronic graft dysfunction. Target range values between 700 and 900 ng/mL appear to be associated with better long-term kidney graft function.

[Cardiovascular risk and renal transplantation]. / Il rischio cardiovascolare nel paziente con trapianto renale.

Cardiovascular disease after renal transplantation is often the expression of a disease process that first started with the onset of renal dysfunction many years before, and its prevention starts with the early predialysis phase of chronic renal failure and with the aggressive treatment of hypertension and dyslipidemia. The evidence that dialysis treatment itself accelerates arterial damage is poor. After transplantation, however, many patients are restored to a state not of normal renal function but of chronic renal impairment and have drug-induced hypertension and dyslipidemia, resulting in a vastly increased risk of atherosclerosis. Further research is required on optimal strategies to prevent or ameliorate cardiovascular disease, to establish the roles of lipid-lowering and antihypertensive therapies after transplantation and to define immunosuppressive ad hoc treatments for each kind of patient.

[Renal neoplasms and renal transplantation: current problems and future perspectives]. / Neoplasie renali e trapianto di rene: problematiche attuali e prospettive future.

Primary carcinomas of the kidney can develop in renal transplantation in four sets of circumstances: (1) detected in the donor, (2) detected as a pre-existing neoplasm in the recipient prior to transplantation, (3) as de novo malignancies arising post-transplantation in the native kidneys of the recipient, (4) or in the graft. In Italy, any renal mass detected during harvesting does not allow the use of any organs for transplantation; however, several reports from other countries have already shown the safety and efficacy of transplanting kidneys with small (<4 cm), unifocal, subcapsular tumors, after resecting the lesion at the back table and verifying the negativity of the surgical margins; this strategy could also be evaluated in Italy to expand the donor pool. Acquired cystic kidney disease (ACKD) is commonly observed in uremic patients undergoing chronic hemodialysis (HD); numerous studies have reported an increased prevalence of renal cell carcinoma (RCC) in association with this nephropathy. The use of ultrasound, computerized axial tomography (CAT) and magnetic resonance imaging (MRI) has greatly improved the ability to detect renal tumors at earlier stages associated with ACKD and the morbidity and mortality rate, in either uremic or transplant patients. RCC in the transplanted kidney is rare and, when recognized, requires nephrectomy. However, a conservative approach with nephron sparing surgery has been reported for selected cases as a useful strategy to treat renal carcinoma in the allograft.

[Correlation between the onset of early proteinuria and the outcome of renal transplantation. Experience of a single centre]. / Correlazione tra insorgenza di proteinuria precoce e decorso clinico del rene trapiantato. Esperienza di un singolo centro.

BACKGROUND: Proteinuria is associated with an increased risk of renal failure. In chronic kidney transplant failure it is associated with poorer graft outcome. MATERIALS AND METHODS: In our Unit 405 renal transplants were performed between April 1992 and December 2001. We analysed 1) the main causes of post-transplant proteinuria and 2) the prognostic significance for graft outcome in patients with a minimum follow-up of 6 months. RESULTS: Early proteinuria was associated with a higher incidence of chronic allograft nephropathy (CAN) and de novo/recurrent nephropathies. Graft outcome was poorer in patients with early persistent proteinuria. CONCLUSIONS: Proteinuria after renal transplantation increases the risk of graft failure. We can, therefore, hypothesize that a graft biopsy is the best way to reveal the causes of proteinuria so that therapeutic interventions, which have been shown to reduce proteinuria, can be applied immediately.