Endothelial progenitor cell-derived microvesicles improve neovascularization in a murine model of hindlimb ischemia.

Paracrine mediators released from endothelial progenitor cells (EPCs) have been implicated in neoangiogenesis following ischemia. Recently, we demonstrated that microvesicles (MVs) derived from EPCs are able to activate an angiogenic program in quiescent endothelial cells by a horizontal transfer of RNA. In this study we aim to investigate whether EPC-derived MVs are able to induce neoangiogenesis and to enhance recovery in a murine model of hindlimb ischemia. Hindlimb ischemia was induced in severe combined immunodeficient (SCID) mice by ligation and resection of the left femoral artery and mice were treated with EPC-derived MVs (MVs), RNase-inactivated MVs (RnaseMVs), fibroblast-derived MVs or vehicle alone as control (CTL). Since MVs contained the angiogenic miR-126 and miR-296, we evaluated whether microRNAs may account for the angiogenic activities by treating mice with MVs obtained from DICER-knock-down EPC (DICER-MVs). The limb perfusion evaluated by laserdoppler analysis demonstrated that MVs significantly enhanced perfusion in respect to CTL (0.50±0.08 vs 0.39±0.03, p<0.05). After 7 days, immunohistochemical analyses on the gastrocnemius muscle of the ischemic hindlimb showed that MVs but not fibroblast-MVs significantly increased the capillary density in respect to CTL (MVs vs CTL: 24.7±10.3 vs 13.5±6, p<0.0001) and (fibroblast-MVs vs CTL: 10.2±3.4 vs 13.5±6, ns); RNaseMVs and DICER-MVs significantly reduced the effect of MVs (RNaseMVs vs CTL: 15.7±4.1 vs 13.5±6, ns) (MVs vs DICER-MVs 24.7±10.3 vs 18.1±5.8, p <0.05), suggesting a role of RNAs shuttled by MVs. Morphometric analysis confirmed that MVs enhanced limb perfusion and reduced injury. The results of the present study indicate that treatment with EPC-derived MVs improves neovascularization and favors regeneration in severe hindlimb ischemia induced in SCID mice. This suggests a possible use of EPCs-derived MVs for treatment of peripheral arterial disease.

Loss of nephrin expression in glomeruli of kidney-transplanted patients under m-TOR inhibitor 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.

Assessment of cardiovascular risk in waiting-listed renal transplant patients: a single center experience in 558 cases.

Cardiac screening is recommended to prevent cardiovascular death after renal transplantation. This retrospective observational study illustrates the results of application of a cardiac assessment algorithm in a series of 558 renal transplant candidates at a single center in Turin, Italy. A dipyridamole-stress sestamibi myocardial scintiscan (DMS) performed in 302/558 (54.1%) cases was positive in 52 (17.2%), negative in 200 (66.2%), borderline in 16 (5.3%), and with signs of previous necrosis in 34 (11.4%). Coronary lesions detected by angiography in 48.1% of the 52 positives were treated medically (13.5%) or by percutaneous/surgical procedure (34.6%). Coronary lesions were detected in 14.1% of asymptomatic population subgroup. The minor and major cardiovascular event rates and the cardiovascular death rate were 1.9%, 0%, and 0%, respectively, in positive DMS group (high-cardiological risk) vs. 10%, 4.5%, and 3.5% in the negatives (p > 0.5; n.s.). It is suggested that not increased cardiovascular event or deaths rates in the high-risk group reflect early coronary lesion detection and correction. Since 55.9% of cardiovascular events or deaths occurred in the negative group more than 24 months after the DMS, its mandatory repetition every two yr after a negative finding is recommended.

[The history of peritoneal dialysis at the Molinette Hospital in Turin, Italy]. / La storia della dialisi peritoneale all'Ospedale Molinette di Torino.

In the Renal Unit of the Molinette Hospital of Turin, peritoneal dialysis (PD) was introduced in the mid 1960s to treat patients suffering from acute renal failure. The peritoneal catheter, which was then a stiff catheter, was inserted by a surgeon at each dialysis session. Between 1966 and 1970 there were a series of improvements, such as the first cycler for intermittent PD, fast-shift DP, and a homemade machine for automatic PD. During the early 1970s, a new type of stiff peritoneal catheter was introduced, which was used also for patients suffering from chronic renal failure. Towards the end of the 1970s the soft Tenckhoff peritoneal catheter started to be used, as well as continuous ambulatory peritoneal dialysis (CAPD), which made it possible to treat a large number of patients at home. The 1980s brought a new surgical technique for the insertion of the catheter, and in the 1990s new peritoneal catheters were introduced which reduced the number of early and late complications. Around the turn of the century, the PD service was reorganized and improved, with dedicated personnel and facilities. Moreover, automated PD was introduced and the treatment of peritonitis was standardized according to international guidelines.

[Kidney retransplantation: indications and limits]. / Il ritrapianto renale: indicazioni e limiti.

Whether or not to consider a uremic patient for retransplantation remains a matter of debate. Donor shortage and putative poor outcomes are the main cons, improved results in the last decade and a better survival (HR 0.50) with retransplantation than dialysis stand as pros. The percentage of patients waitlisted for retransplantation or already having been retransplanted is increasing (up to 20-30%) and the absolute contraindications are limited to rare conditions (loss of previous transplant due to anti-glomerular basement antibodies in Alport's syndrome, early recurrence of GNF or hemolytic uremic syndrome). When retransplantation is considered, however, careful screening for risk factors is mandatory, whether they are related to the previous graft or to the recipient's clinical features or the donor's demographics and immunological status. In the last decade the clinical outcomes of retransplantation have significantly improved. No difference in patient survival at the fifth year has been reported between first, second and third grafts. The kidney survival at the same interval is above 70% for the second graft and 65% for the third graft. Nephrectomy of a previous graft is not necessary if not for clinical reasons. As far as the maximum number of retransplants is concerned, most transplant centers (69%) set no clear-cut limit. In conclusion, also taking into account that many patients after graft failure ask for readmission to the waiting list (75% in our experience), we think the retransplantation option should always be evaluated.

Severe crescentic BK virus nephropathy with favourable outcome in a transplanted patient treated with Leflunomide.

Herein reported is a severe case of BK virus nephropathy, probably caused by an intense/overimmunosuppression and identified 17 months after transplantation. The diagnostic biopsy showed extracapillary proliferation and typical cytopathic lesions, both in tubular epithelial cells and in those of the glomerular crescents. Severe inflammatory infiltrates, tubulitis, tubular atrophy and fibrosis were also observed. Immunohistochemistry and molecular biology disclosed the presence of an AS variant of the BK virus with a high viral load, both in renal tissue and urine. Immunosuppression was reduced and Leflunomide therapy administered for a month. Although this led to an improvement in the renal function, the therapy had to be suspended due to the onset of a skin rash. A second biopsy was performed 7 months later. The cellular crescents were no longer present and there was no evidence of either histologic or immunohistochemical findings consistent with an active BK virus infection. Tubular atrophy and interstitial fibrosis were still present. In addition, fibrotic crescents, which may be interpreted as late scarring changes of previous epithelial proliferation, were found. Although molecular investigation still showed the presence of the BK virus, the viral load in renal tissue, urine and serum was greatly reduced. Indeed, serum and urine viral load was still low at the last control, five months after the second biopsy. The morphologic and clinical evolution are reported and the possible role of the therapy is discussed.

Monitoring of human Cytomegalovirus infection by antigenemia and viremia in the first 100 days following renal transplantation and relation to antiviral strategies.

AIM: Human Cytomegalovirus (HCMV) is a relevant pathogen in transplant recipients, particularly in the first three months post-transplantation. The use of antiviral prophylaxis and pre-emptive therapy is able to reduce incidence of HCMV infection and disease. The incidence of HCMV infection and disease in renal transplant recipients in the first 100 days post-transplantation was investigated, in relation with HCMV serological matching and therapeutic management. METHODS: Incidence of HCMV infection in the first 100 days post-transplantation was evaluated by pp65-antigenemia in 165 patients on a total number of 1241 clinical samples. Patients were divided in four groups according to donor/recipient serological matching: D(-)/R(-) (low risk of HCMV disease), D(-)/R+ and D+/R+ (intermediate risk) and D+/R(-) (high risk). Antiviral strategy (prophylaxis in high risk group; pre-emptive therapy in intermediate risk group, no therapy in low risk group) and immunosuppressive protocol were recorded. RESULTS: Incidence of antigenemia-positivity was as follows: 0/3 D(-)/R(-) patients; 59/130 (45.4%) D+/R+; 5/16 (31.3%) D(-)/R+; 4/16 D+/R(-). No significative difference was found between the four groups in terms of incidence of antigenemia-positivity in the first 100 days following transplantation. Antigenemia values >50 pp65-positive/2x10(5) peripheral blood leukocytes (used to start pre-emptive therapy) were present in 18/130 (13.8%) D+/R+; 1/16 (6.2%) D+/R(-); 0/16 D(-)/R+. Viral kinetics in patients with HCMV infection was described. CONCLUSION: No significative difference was found in terms of incidence of HCMV infection in the first 100 days post-transplantation in relation to immunosuppressive protocol and serological matching, suggesting the appropriateness of antiviral strategies and viral monitoring adopted in this setting.

[Preventive renal transplantation: considerations and future plans]. / Il trapianto di rene preventivo: riflessioni e progetti.

A kidney transplant before the start of dialysis or after only a short period of dialysis is acknowledged as the best therapeutic option for the uremic patient. However, the number of patients in Italy waiting for a kidney is stable (around 6,400 at the latest report) and the annual number of transplants is not increasing (a slight decrease is forecast for 2007). Opening the deceased-donor waiting list to patients who are not yet on dialysis remains a matter of debate and has been possible only in Tuscany thanks to the high rate of kidney procurement in this region. As far as the Piedmont region is concerned, the balance between performed transplants and new candidates for transplantation is stable, with a mean waiting time of nearly 2 years. Taking into account also the current decline in donations, the possibility of placing pre-dialytic patients on the waiting list requires further evaluation. Nevertheless, some strategies may be within reach. Above all, the use of kidneys from living donors, which represents the ideal condition for preventive transplantation, should be extended. For patients lacking a suitable living donor, a program of earlier admission to waiting lists should be activated.

Development of a quantitative-competitive PCR for quantification of human cytomegalovirus load and comparison with antigenaemia, viraemia and pp67 RNA detection by nucleic acid sequence-based amplification.

AIM: The human cytomegalovirus (HCMV) is an important pathogen in immunocompromised patients, such as transplant recipients. The use of sensitive and rapid diagnostic assays can have a great impact on antiviral prophylaxis and therapy monitoring and diagnosing active disease. Quantification of HCMV DNA may additionally have prognostic value and guide routine management. The aim of this study was to develop a reliable internally-controlled quantitative-competitive PCR (QC-PCR) for the detection and quantification of HCMV DNA viral load in peripheral blood and compare it with other methods: the HCMV pp65 antigenaemia assay in leukocyte fraction, the HCMV viraemia, both routinely employed in our laboratory, and the nucleic acid sequence-based amplification (NASBA) for detection of HCMV pp67-mRNA. METHODS: Quantitative-competitive PCR is a procedure for nucleic acid quantification based on co-amplification of competitive templates, the target DNA and a competitor functioning as internal standard. In particular, a standard curve is generated by amplifying 10(2) to 10(5) copies of target pCMV-435 plasmid with 10(4) copies of competitor pCMV-C plasmid. Clinical samples derived from 40 kidney transplant patients were tested by spiking 10(4) copies of pCMV-C into the PCR mix as internal control, and comparing results with the standard curve. RESULTS: Of the 40 patients studied, 39 (97.5%) were positive for HCMV DNA by QC-PCR. While the correlation between the number of pp65-positive cells and the number of HCMV DNA genome copies/mL and the former and the pp67mRNA-positivity were statistically significant, there was no significant correlation between HCMV DNA viral load assayed by QC-PCR and HCMV viraemia. CONCLUSIONS: The QC-PCR assay could detect from 10(2) to over 10(7) copies of HCMV DNA with a range of linearity between 10(2) and 10(5) genomes.

[The Italian Society of Nephrology Guidelines (3rd Edition): principles and methods]. / I principi ed i metodi della III edizione delle Linee Guida della Società Italiana di Nefrologia (2005-2006).

Scientific Societies at both a local and international level are making big effort to prepare their clinical practice guidelines. The Italian Society of Nephrology has already published in two previous editions a series of guidelines relating to various aspects of management and diagnosis of different renal diseases. In this review we present the criteria of the 3(rd) edition of the Italian Society of Nephrology guidelines. This 3(rd) edition of guidelines will be based on the availability of scientific evidence in different areas of nephrology, dialysis and transplantation. Ten key intervention questions have been identified, based on the availability of systematic reviews of randomized trials or individual randomized address them. Systematic reviews and randomized trials are the optimal study design to address intervention questions. These have been summarized based upon rigid methodological criteria and strictly reflect the evidence basis. The different phases of development and publication of the 3(rd) edition of the Italian Society of Nephrology guidelines are presented.

Clinical impact of bacterial contamination of perfusion fluid in kidney transplantation.

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.

"Decoy cells" in urine.

BK virus-associated nephropathy is an emerging cause of kidney transplant loss. Tapering immunosuppressive drugs and antiviral agents are the only therapy. The diagnosis is based on immunohistochemical findings or polymerase chain reaction on renal biopsy. Phase-contrast microscopy without staining is a simple test to screen the urine of transplant recipients for BK nephritis. Any kidney transplant unit should have the ability to detect decoy cells by phase-contrast microscopy on a spot urine.

Renal transplantation in patients over 65 years of age: no more a contraindication but a growing indication.

INTRODUCTION: Worldwide organ shortage and the increasing age of end-stage renal disease patients demanding a graft have prompted extensive use of marginal donors. The "old-for-old" allocation has been proposed for the elderly. The aim of this study was to evaluate the results of a policy of free acceptance into the waiting list of recipients older than 65 years. METHODS: From 1987 to 2004 70 patients whose mean age was 67.4 +/- 2.8 years, underwent an extensive pretransplant evaluation including cardiac studies. Immunosuppression was based upon low-dose steroids, and cyclosporine (50%) or tacrolimus (44%). RESULTS: Patient and graft survival at 1, 3, 5, and 10 years were 85%, 78.5%, 75%, 50%, and 80%, 74%, 70%, 36%, respectively. Death occurred in 17/70 (24%), 14 of whom had a functioning graft. The causes of death were 30% cancer, 23% cardiovascular, 23% sepsis, 12% cerebrovascular hemorrhage, 12% meningitis. The acute rejection (AR) rate was 18.6%. The causes of graft loss were: 71% patient death, 4% irreversible AR, 4% vascular thrombosis, and 21% chronic allograft dysfunction. The main complications were: 52% prostatic hypertrophy, 40% urinary tract infections, 8.6% diabetes, 11% pneumonia, 10% cardiovascular diseases, 7% urological complications, 8% abdominal pathology, 6% acute pyelonephritis, 8% non-skin cancer. CONCLUSIONS: Despite the increased vulnerability of the elderly, they should not be excluded a priori from renal transplantation. Extensive pretransplant screening, mainly cardiovascular, and a tailored immunosuppression are two crucial issues. The moderate rate of AR suggests that these patients do not have an impaired immunocompetence as far as acute rejection is concerned.

Addition of sirolimus to cyclosporine in long-term kidney transplant recipients to withdraw steroid.

The aim of this study was to evaluate the feasibility of a steroid-free maintenance immunosuppression regimen in long-term renal transplant (KTx) recipients after addition of sirolimus (SRL) to cyclosporine (CsA)-based immunosuppression. A multicenter, prospective pilot study of steroid withdrawal (SW) was initiated for KTx patients. SW was divided into three phases: (A) conversion to a SRL + CsA + steroid regimen; (B) steroid tapering and withdrawal; and (C) maintenance with SRL + CsA. Primary endpoints of the study were incidence of acute biopsy-proven rejection (AR) and safety. In the A and B phases of the study 42 KTx patients (132 +/- 75 months post-Tx) were entered into the study, 18 of 42 (43%) with severe, acute side effects due to the CsA + SRL combination. These side effects were reversible with reduction of CsA or with suspension of the SRL/CsA combination. An amendment was introduced in the protocol to drastically reduce the CsA exposure to <50 ng/mL (trough) at the time of SRL addition. After this amendment, 39 other KTx patients entered the study and only 3 of 39 (8%) were discontinued because of toxic side effects. In the overall cohort of 81 KTx patients, the incidence of AR after SW was low (n = 5, 6.1%), all occurring within the first 3 months after SW. These findings indicate: (1) addition of SRL to very low-maintenance CyA exposure allows safe SW in KTx; (2) with the SRL + CsA combination, the incidence of AR after SW is low in long-term KTx patients; and (3) in the first 3 months after SW strict monitoring for early diagnosis and treatment of AR is mandatory.

Play-back theatre, theatre laboratory, and role-playing: new tools in investigating the patient-physician relationship in the context of continuing medical education courses.

AIM: The aim of this study was to report on the validation of a role-playing approach, using play-back and theatre laboratory in the context of a continuing medical education (CME) course on predialysis and transplantation, to discuss the patient-physician relationship. METHODS: The course was developed with the help of a theatre director. The role-playing 2-day course was designed to be highly interactive for a small group (15-20 participants), based on a core of case reports (dialysis, transplantation, and return to dialysis after graft failure). Two stages were included: play-back theatre in which experiences told by the participants were mimed by a group of actors, and theatre laboratory in which different aspects of voice and touch were explored. Opinions were gathered by an anonymous semistructured questionnaire completed by all participants. RESULTS: The course obtained a high score from The Ministry of Health (14 credits, 1 per teaching hour). The opinions of the 18 participants were highly positive; all liked the courses. Sixteen of 18 asked to repeat the experience. The strong emotional involvement was an advantage for 15 of 18, sharing emotional aspects of the profession for 10 of 18, and usefulness in clarifying opinions on "dark sides" of our profession for 10 of 18. CONCLUSION: The positive opinions recorded during this experience, the first experiment with a "psycho-theatrical approach" developed in a CME course in our country, suggest the benefit of implementing nonconventional, educational approaches in a multidisciplinary discussion of the patient-physician relationship in transplantation medicine.

Diffuse vascular damage in a transplanted kidney: an indication for nuclear magnetic resonance?

Vascular lesions are an increasing challenge after renal transplantation due to the wider indications for recipients and acceptance criteria for donors. Diagnostic approach and prognostic interpretation are still matter of controversy. The case reported herein may summarize some of the issues in this regard. A 54-year-old woman, on renal replacement therapy since 1974, and a kidney graft recipient from 1975 to 1999, received a second graft in 2001. The donor age was 65 years (cold ischemia 22 hours; two mismatches). The early posttransplant follow-up was characterized by delayed graft function, hypertension, and diabetes. During the initial hypertension workup, renal graft ultrasound (US) Doppler demonstrated increased vascular resistances, stable over time (resistance index 0.74 to 0.77); renal scintiscan displayed homogeneously parenchymoa and angio-magnetic resonance imaging (MRI), an homogeneous parenchymal vascularization. Initial immunosuppression with tacrolimus and steroids was modulated by adding mycophenolate mofetil to taper tacrolimus (to reduce nephrotoxicity and hypertension). Despite this, kidney function slowly deteriorated; serum creatinine reached 3 to 3.5 mg/dL by the second year. After a severe hypertensive crisis with unchanged scintiscan and US doppler examinations, angio-MRI revealed the almost complete disappearance of parenchymal enhancement beyond the lobar arteries. A renal biopsy confirmed the severe vascular damage. The patient was switched to rapamycine and a low-dose of an angiotension converting enzyme (ACE) inhibitor. She did relatively well (serum creatinine 2.2 to 3 mg/dL) for 6 months, when rapid functional impairment forced her to restart hemodialysis. This case, almost paradigmatic of the problems occurring when the rigid vasculature of long-term dialysis patients is matched with "marginal kidneys," suggests that MRI may be a sensible good to define vascular damage in the grafted kidney.

CKD patients and erythropoietin: do we need evidence-based informed consent?

BACKGROUND: Consent to therapy is increasingly requested in the form of ''informed consent''. OBJECTIVE: To validate an evidence-based informed consent form for erythropoietin (EPO) therapy and to evaluate patient opinions about the informed consent approach. METHODS: An evidence-based informed consent form was developed as part of the Evidence-Based-Medicine course at the Medical School of Turin, Italy. It was validated by anonymous questionnaires (0-10 analogical scales and open answers) administered to patients at different stages of CKD (19 pre-ESRD, 26 hemodialysis, 12 transplant patients) attending an outpatient unit of the University of Turin, to 8 nurses, and to 26 medical students. RESULTS: All individuals filled in the questionnaire. Interest in a detailed explanation of the therapy was high (median 9), as was comprehension (median 9), with no differences between patients with regard to disease stage (pre-ESRD vs. RRT) or educational level. Prior knowledge of the therapy was affected by the educational level (p=0.013 for the advantages and p=0.004 for the side effects) and the professional role (patients vs caregivers: p=0.009 for the advantages and p<0.001 for side affects); patient knowledge of the advantages (median 6) tended to increase as the disease progressed (p=0.015). The most common response by patients was that informed consent was necessary for all drugs (35.1%); 73.1% of the caregivers considered it necessary only for severe side effects. The preferred modality of consent was discussion with the caregiver during the clinical controls (42% of all cases). CONCLUSIONS: Patient interest in and comprehension of an informed consent form with a detailed explanation of the therapy was high; the caregiver's opinion was still the most valued teaching tool.

[New immunodepressant drugs for the prevention and control of kidney transplant rejection]. / I nuovi farmaci immunodepressivi per la prevenzione ed il controllo del rigetto nel trapianto di rene.

The increasing number of kidney transplantations performed yearly in Italy should prompt nephrologists to improve their knowledge in these patients that fall "by default" in the nephrologists' province. In taking on of this task in addition to a skilled clinical and organizational capacity, it demands experience and an updated knowledge of the immunosuppressive drug machinery currently available. Calcineurin inhibitors (cyclosporine and tacrolimus) are well-defined milestones, currently used. Less well known are some recent drugs such as rapamycin and its analogues, mycophenolate mofetil and mycophenolic acid, anti-CD 25 monoclonal antibodies, chimeric and humanized. These drugs are, or they have become, available commercially in the last few years or they are going to be registered in the near future. However, their registration is due to years of usage in the large majority of current immunosuppressive regimens where they can play the role of a primary or an ancillary drug. Other drugs such as FH778, FTY720, anti-CD 20 (rituximab) and anti-CD 52 (alentuzimab) monoclonal antibodies are still undergoing trials in many collaborative phase 2 and 3, studies. Finally, a third group of drugs is targeted at the co-stimulator molecule network and it is an interesting and challenging opportunity for the near future. A detailed knowledge of the overall therapeutic armamentarium is useful in the kidney transplantation field where all drugs, from the beginning to date, must always be kept in mind. The new drugs do not supplant the old drugs. Knowing the pros and cons of each immunosuppressive drug used in the therapeutic management of kidney transplantation is crucial in improving the clinical results in general, and in tailoring the best regimens in different clinical settings pro-posed by kidney recipients today.

Renal transplantation in a case of mannosidosis.

Mannosidosis is an inherited autosomal recessive mucopolysaccharidosis. Patients affected accumulate mannose-rich compounds in various tissues and excrete an increased quantity of oligosaccharides with mannose as a component. A case of type II mannosidosis with end-stage renal failure is reported. The patient, after 6 years of regular hemodialysis treatment, received a kidney transplant. At the time this article was written, the graft was functioning well and thesaurismotic renal deposits had not been observed. The clinical course of mannosidosis was silent and the patient's quality of life was good. Although the risk of recurrence could not be excluded, it seems that renal transplantation can be safely offered to patients affected with mannosidosis type II, in the rare setting of chronic renal failure.

B19 virus infection in renal transplant recipients.

BACKGROUND: B19 virus infection with persistent anaemia has been reported in organ transplant recipients. Detection of B19 virus DNA in serum is the best direct marker of active infection. OBJECTIVE: The present study evaluated the incidence and clinical role of active B19 virus infection in renal transplant recipients presenting with anaemia. STUDY DESIGN: Forty-eight such recipients were investigated by nested PCR on serum samples. The controls were 21 recipients without anaemia. Active HCMV infection was also investigated as a marker of high immunosuppression. RESULTS AND CONCLUSIONS: In 11/48 (23%) patients B19 virus DNA was demonstrated in serum versus only 1/21 (5%) of the controls. Ten of these 11 patients had already been seropositive at transplantation and active infection occurred in eight of them during the first 3 months after transplantation. The remaining patient experienced a primary infection 9 months after transplantation. Eight (73%) of these 11 patients displayed a concomitant HCMV infection and four (36%) showed increasing serum creatinine levels but none developed glomerulopathy; 3/11 (27%) recovered spontaneously from anaemia whereas 8/11 (73%) needed therapy. In conclusion, the relatively high occurrence (23%) of B19 virus infection in patients presenting with anaemia, suggests that it should be considered in the differential diagnosis of persistent anaemia in renal transplant recipients. Presence of the viral DNA should be assessed early from transplantation and the viral load should be monitored to follow persistent infection and better understand the relation between active infection and occurrence of anaemia, and to assess the efficacy of IVIG therapy and/or immunosuppression reduction in clearing the virus.