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The recognition of antibody-mediated rejection as an important factor in the reduction of long-term renal graft survival represents a new challenge to the immunosuppressive strategies of recent years, which have been quite successful in reducing the acute rejection rates as well as the side effects of pharmacological immunosuppression. The search for an effective treatment of chronic anti-donor antibody disease has been pursued mostly through limited single-center experiences and therefore in a dispersed fashion, without leading to the definition of a consolidated approach. The most frequently used pharmacological approaches stem from the experience of antibody-mediated acute rejection. In this review we will critically analyze the results reported so far of various intervention strategies and we will discuss future pharmacological novelties targeting the humoral immune response.

The incidence of lymphomas, especially non-Hodgkin's lymphoma (NHL), has shown a steady increase over the last decades. At the same time, the prognosis has improved. Given the longer survival of lymphoma patients, pathological manifestations related to malignancy might become more frequent. In this setting, the kidney is one of the most important solid organs affected by direct or indirect lymphomatous involvement. Kidney involvement can be related to obstruction or treatment-induced toxicity, but more intriguing are 1) direct infiltration (NHL); 2) renal malignancies in patients affected by Hodgkin's disease or NHL; 3) associated glomerular diseases. Primary infiltration is rarely seen, while secondary infiltration is described most frequently in autopsy series, even in the absence of renal failure. These alterations may mimic glomerular and/or interstitial disease. The association with kidney malignancies, mostly renal cell carcinoma but also urothelial tumors in Hodgkin''s disease, is higher in lymphoma patients than in the general population: the relative risk at 10 years is about 1.5. Glomerulonephritis is described in patients with Hodgkin's disease or NHL; in the former minimal change disease is most frequent, in the latter the glomerular pattern varies widely. Glomerulonephritis can precede, be concurrent with, or follow lymphoma manifestations. Renal biopsy is often needed in this setting.

Preemptive kidney transplantation is currently considered the optimal initial form of renal replacement therapy not only in terms of clinical outcome (recipient and graft survival) but also in terms of quality of life and social rehabilitation. The benefit of preemptive transplantation is clearly documented by an increasing number of studies based on many single-center experiences and also on the data of international registries. The advantages of receiving a transplant before dialysis (or at least within a few months of its initiation) are statistically evident both in patients receiving cadaver donor grafts and in those receiving living donor grafts. Among the factors that are considered responsible for these favorable results, the avoidance of dialysis-associated morbidity, the lower risk of acute and chronic rejection, the reduced frequency of delayed graft function, and the reduced frequency of cardiovascular mortality seem to play an important role. In the development of a preemptive transplantation program, however, some ethical issues must be carefully considered. At the moment, at least in most Italian regions, there is a persistent discrepancy between the number of kidney patients transplanted yearly and those still on the waiting list. How and when to allocate kidneys harvested from deceased donors to recipients not yet on dialysis remains a matter of debate. Preemptive allocation limited to elderly candidates who accept a double kidney transplant from marginal deceased donors is the most feasible choice at the moment. If a living donor is available, however, preemptive transplantation is mandatory and its implementation mainly depends on the efficacy of nephrologic counseling before the initiation of dialysis.

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.

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.

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.

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.

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.

Background: Post-transplant lymphoproliferative disorders (PTLD), ranging from lymphoid hyperplasia to clonal malignancy, are severe complications arising in solid organ transplant patients; their reported incidence ranges from 1 to 20%, according to factors such as type of transplanted organ and age of recipients. A strong correlation between Epstein-Barrvirus (EBV) infection, the grade and type of immunosuppression and the development of PTLD has been recognized. The detection and quantification of EBV-DNA load in peripheral blood have been utilized as prognostic markers for the development of PTLD, showing a correlation between high levels of EBV-DNA in the blood and the development of PTLD. In this study, we monthly monitored EBV viral load in 15 renal transplant recipients for six months. The number of EBV-DNA copies was measured in peripheral blood mononuclear cells (PBMC) and serum samples by a quantitative PCR protocol developed in our laboratory., Methods: Our EBV-DNA quantification protocol employs a previous screening of samples containing a significant number of viral DNA copies (>=1000 copies/105 PBMC or 100 mL serum) by semi-quantitative PCR followed by a precise quantification of the only significant samples by quantitative-competitive (QC)-PCR., Results: Our 15 renal transplant patients neither developed PTLD nor had recurrent acute illnesses or acute graft rejections during the study. The results obtained in the monthly follow up of EB viral load in PBMC samples confirmed its fluctuation in asymptomatic patients reported in the literature. In particular, 5/14 (35.7%) of EBV seropositive patients had an EBV-DNA load equal to 1000 EBV copies /105 PBMC, and 1/14 (7.1%) reached 5000 EBV copies /105 PBMC at least once in our study. In the EBV seronegative patient, EBV-DNA in PBMC samples was always undetectable (less than 100 DNA copies/105 PBMC). EBV-DNA load in all serum samples was less than threshold value of our quantification protocol (<100 DNA copies/100 mL serum). With regard to the immunosuppressive treatment, it should be noted that 66.7% of the six patients in whom EBV load reached values equal to or higher than 1000 DNA copies/105 PBMC, were on FK506 whereas only 33.3% of them were on CyA., Conclusions: Since the high positive predictive value of EB viral load in peripheral blood for diagnosis of PTLD reported by several Authors, and the described absence of correlation between the serological evidence of EBV reactivation and EB viral load, EBV viral load measurement in PBMC and serum samples using quantitative PCR techniques is a powerful diagnostic tool to monitor transplanted patients at risk of developing PTLD.

Background: In Italy, dialysis reimbursement is regulated by the "Tariffario delle prestazioni ambulatoriali" (G.U. N 216, 14/9/1996), which does not take into account separately the dialysis sessions performed in hospitalised patients. In these cases the dialysis activity is considered within the final DRG (Diagnosis Related Group). Aim of the study was an analysis of production costs of dialysis performed in hospitalised patients, according to the setting in which dialysis is performed (Intensive Care Units (ICUs), other Units, hospital dialysis ward)., Methods: The direct production costs were assessed by the "bottom-up" technique logic (cost definition from the single elements needed for producing the treatment) referring to specific Cost Centres. The main items considered were health-care staff, dialysis supplies and hardware, blood tests, dialysis data recording and transmission., Results: During the year 2000, there were 4,450 treatments performed in 490 patients. They included 924 haemodialyses in ICUs; 2,531 in the nephrology hospital dialysis ward; 602 peritoneal dialysis treatments in ICUs-other wards, 393 in the nephrology ward. Direct cost per haemodialysis treatment ranged from 276.05 E (UF) to 413.46 E (HF) in ICU, from 170.47 E (Bicarbonate Haemodialysis) to 275.36 E (Slow Haemofiltration) in hospital dialysis ward; for peritoneal dialysis between 128.95 E (CAPD in dialysis ward) and 282.10 E (CAPD in ICU/other Units). During the year 2000, the global cost of production was 1,038,346.65 E., Conclusions: The cost of dialysis in hospitalised patients is high. A dedicated budget is needed to avoid deficits, particularly in highly specialised Units of large referral hospitals.

The rate of the clinical adoption of the so-called pre-emptive transplantation is widely different among countries. In North America it represents 25 % of the total living donor transplantations; in Norway and Sweden it is 15 % and 9 %, respectively, of all grafts performed; in Italy it is less than 1%, whilst in countries like Austria, Germany and Ireland pre-emptive transplantation is nonexistent. Some concern on this type of transplantation was raised in the Seventies and were mainly based on the evidence that uraemia has an immunosuppressive effect, which could be weaker in the pre-dialysis period. Several clinical observations in the pre- cyclosporin era supported this assumption. Starting from the Eighties, however, several studies have demonstrated that pre-emptive transplantation may yield better recipient and graft survival. Moreover, a recent retrospective study, based on higher than 8000 living donor grafts that included both treated and untreated by long-term dialysis before transplantation, showed in the pre-emptive cohort a 52 % reduction in graft losses after the first year and also a lower incidence of acute rejections. Among the advantages of pre-emptive transplantation we find better rehabilitation and especially a lower risk of job loss. The risk of poorer patient compliance, as initially pointed out, has no longer been reported and can be overcome by adequate psychological preparation of the patient. Most centres performing pre-emptive transplantation favour the use of living donor because of the general shortage of cadaver kidney vs. the increasing number of dialysed patients on the waiting list. Nevertheless, in special circumstances (national programs with short waiting lists, uremic type I diabetics, children, primary type I hyperoxaluria), some AA also recommend the use of the cadaver donor.