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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.

Background: Restarting dialysis after kidney transplantation is a critical step with psychological and clinical implications. Maintenance of residual renal function a known factor affecting survival in chronic kidney disease, has so far not been investigated after a kidney transplantation., The Case: A 54-year-old woman who started dialysis in 1974 (first graft, 1975-1999) received a second "marginal" kidney graft in February 2001 (donor age, 65 years). Her chronic therapy was tacrolimus and steroids. She had a clinical history as follows: nadir creatinine level of 1.5 mg/dL, moderate-severe hypertension, progressive graft dysfunction, nonresponsiveness to addition of mycophenolate, tapering FK levels, and a rescue switch from tacrolimus to rapamycin. From October to December 2003, the creatinine level increased from 2-2.8 to 7 mg/dL. Biopsy specimen showed malignant and "benign" nephrosclerosis, posttransplantation glomerulopathy, and tacrolimus toxicity. Chronic dialysis was started (GFR <3 mL/min). Rapamycin was discontinued. Dialysis was tailored to reach an equivalent renal clearance of >15 mL/min (2 sessions/wk). Blood pressure control improved, nephrotoxic drugs were avoided, and fluid loss was minimized (maximum 500 mL/hr). By this policy, renal function progressively increased to GFR >10 mL/min in May 2004, allowing a once or twice weekly dialysis schedule, with good clinical balance, and obvious advantages for the quality of life., Conclusion: This long-term patient, who restarted dialysis with severely reduced renal function, regained sufficient renal function to allow once weekly dialysis. Thus, careful tailoring of dialysis sessions at the restart of dialysis may allow preservation of residual kidney function, at least in individuals for whom a subsequent graft is unlikely.

Maintenance of residual renal clearance is a clinical advantage, protecting against the long-term effects of uremia: although demonstrated in peritoneal dialysis, the strategies in hemodialysis are less clear. This case suggests that dialysis schedules individualized on the basis of renal clearances may help preserve residual function. SB is a 58 year-old male who started dialysis in emergency (creatinine 30.7 mg/dL) in 1993. He had a history of gout, small shrunken kidneys and moderate hypertension. The clinical diagnosis was vasculointerstitial nephropathy. Eighteen months after starting hemodialysis on a conventional thrice weekly schedule, the patient was switched to 2 sessions/week (creatinine clearance increased to 6 ml/min). Thereafter, clearances were checked in alternate months and treatment was tailored to an equivalent renal clearance > or =12 ml/min (1-2 sessions, 2-3.30 hours/week). Ten years after beginning dialysis, he is on a twice weekly schedule (3.30 hours), is normotensive, works full-time and does not want to go on a transplant waiting list.

The prognosis of diabetic patients on renal replacement therapy (RRT) is usually poor. We report on the type 1 diabetic woman with the longest RRT follow-up in our area: over 20 years, half on dialysis, half with a renal graft. CS started RRT at age 27 on peritoneal dialysis (3 years), continued until an underdialysis syndrome developed, was switched to acetate dialysis and, because of poor tolerance, to hemofiltration which with good clinical results, allowing her to become the first Italian patient on home hemofiltration, which continued for 5 years. A cadaver graft lasted for the subsequent decade, despite several complications; afterwards she resumed bicarbonate dialysis, choosing a frequent home hemodialysis schedule. Despite several vascular access problems, her clinical conditions were good enough to candidate her for a second renal transplant, performed 3 years ago. This history of active self-care may draw attention to the advantages of a multiple choice dialysis network.

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.

Background: Therapeutic compliance is fundamental on dialysis; however following a therapy requires a prior understanding of it. Aim of the study was to assess the need and interest for information on dialysis efficiency and to prepare a dedicated teaching tool., Methods: 72 patients, on hemodialysis in two limited-care satellite units, were given a questionnaire testing knowledge and interest on dialysis efficiency. In a subsequent second phase, following patients' suggestions, a cartoon book was prepared and opinions recorded., Results: 63 patients' returned the questionnaire. 79.4% had basic knowledge on routine blood tests, 30.1% were aware of their specific meaning. All patients asked for further information, preferring books to other media. The book "Kt/V as cartoon" was distributed; 71.2% read it, 93% scored it as good-very good. In the Unit employing flexible dialysis schedules, 22/42 patients increased dialysis time., Conclusions: Despite insufficient knowledge on dialysis efficiency, patient interest is high. An educational program is feasible and may also give practical results, such as self-increase in dialysis time.

Background: Daily hemodialysis is a promising treatment schedule but uniform criteria for defining efficiency are lacking., Methods: On our daily dialysis (DD) schedule, duration is flexible (2-3 hours, patients are free to add up to 30 min/session), Qb 250-350 mL/min; dialyser 1.6-1.8 m2. Study was performed on 12 pts on DD for > or = 2 months, with > or = 4 Kt/V on subsequent days, tested in the same laboratory., Goal: To evaluate variability and identify a simple method for weekly calculation, Kt/V was assessed for 133 sessions., Results: On flexible DD, variability of Kt/V-session is high (relative error 4.9%-22%). On flexible schedules, within the time range chosen (2-3 hours) variability of average hourly Kt/V is lower (standard deviation: min (0.014; max (0.052 hour, relative error 4.9%-10%) allowing calculation of weekly Kt/V (averaging 3 sessions: relative error < 6%) suitable for clinical practice., Conclusions: Flexible schedules, allowing patients to increase treatment time, are an interesting clinical option, but a challenge for Kt/V assessment.

Limited care dialysis is an interesting option, which has gained attention in several settings because of the aging of the uremic cohort. The aim of this study was to assess its potential in the Piedmont region in northern Italy, evaluating patients' and care-givers' preferences and testing them in a mathematical model of organisation. The study was conducted in the satellite unit of a university hospital (200-210 dialysis patients), following 35 patients (15 at home, 20 in the center, 10 on daily dialysis). Opinions were collected with a questionnaire and features identified were empirically tested through a simulation model. Most patients (34/35) preferred a small unit, with a stable caring team. Further options were flexibility of dialysis schedule, multiple treatment options, integrated center/home care. These needs could be met by a flexible organization including conventional dialysis (3/week) and daily dialysis (6/week). We employed a simulation model (ARENA software) to calculate the nurses required for each shift and the opening hours and best schedule for the unit. Addition of daily dialysis (2-3 hours) to two conventional 4-5 hour sessions to increased the number of patients followed or "spared" beds, ensuring flexibility. According to patients' best choice (7 dialysis stations), and to the recorded calls, the needs are for two nurses per shift, two shifts per day and six nurses for up to 30 patients in limited care. In conclusion, small centers with flexible schedules can tailor dialysis to patients' needs. A managerial approach is valuable for testing cost/benefit ratios in specific contexts.

Background: The need for data bank gathering information in dialysis patients is as old as dialysis. Dialysis Registries presently active are characterized by different policies of data gathering (large vs small number of information) and of use (research vs economical or clinical purposes). Aim of the work was a discussion on the use of a Regional Registry (RPDT, Regional Registry of Dialysis and Transplantation of Piedmont, Italy), gathering since 1981 a wide set of information (about 80 items) on all patients treated in a relatively small area (about 4,300,000 inhabitants)., Methods: Two researches were selected: the first includes patients treated for > or = 20 years by RRT. Cases were identified on the basis of RPDT data and an inquiry regarding all patients was performed, with specific interest on comorbidity. The second includes diabetic patients on regular RRT, a sample of which was further analyzed in high detail., Results and Conclusions: While a Regional Registry, even gathering a wide set of data is unable to answer to the most qualitative questions, such as quality of life, its archives are a powerful tool to identify cases. Furthermore, ad hoc inquiries may represent a way to control quality of data or to test new fields to be studied. In the case of patients with long RRT follow-up, comorbidity questions were tested before being included on RPDT. In the case of a sample of diabetic patients, type of diabetes and cause of ESRD were controlled. This biunivocal relationship between clinical work-up and epidemiological archives may often interest future perspectives.

Availability of a proper vascular access is a basic condition for a proper extracorporeal replacement in end-stage chronic renal failure. However, biological factors, management and other problems, may variously condition their middle-long term survival. Therefore, personal experience of over 25 years has been critically reviewed in order to obtain useful information. In particular "hard" situations necessitating complex procedures have been examined but, if possible, preserving the peripherical vascular features.

The systemic production of tumor necrosis factor (TNF)-alpha was evaluated in uremic patients before and after hemodiafiltration (HDF) and paired filtration dialysis (PFD) and in the interdialytic period. Both HDF and PFD were performed using polysulfone dialyzers with either standard or ultrapure dialysis fluid. TNF-alpha was quantitated by using a specific biological assay based on its cytotoxic effect on a TNF-sensitive human melanoma cell line SK-MEL-109. Postdialytic mean plasma TNF-alpha levels decreased, albeit not significantly, in regard to predialytic values. These results differ from those obtained in patients on HDF using other high-permeability membranes such as polymethylmethacrylate and polyacrylonitrile (AN 69) as recently described by us. Of interest, the adoption of ultrapure dialysis fluid resulted in a marked reduction in the interdialytic production of TNF-alpha. These results suggest that the enhanced production of TNF-alpha in patients dialyzed with high-permeability membranes is mainly dependent upon the bacteriological purity of dialysis fluid.

We studied 1,622 patients who started regular dialysis treatment between 1985 and 1989 in 19 centers from the Italian CAPD Study Group. There were 962 pts (59%) and on HD; 660 pts (41%) on CAPD. CAPD pts were older and had more risk factors at the start than HD pts (p < 0.0001). Overall patient survival was not statistically different between CAPD and HD at 6 years (42% CAPD; 54% HD). Multivariate analysis (Cox's model) on all population revealed that age and pretreatment risk factors had a statistically significant impact on patient survival (p < 0.0001), but not the type of dialytic treatment (CAPD or HD). When multivariate analysis was applied separately by treatment modalities, in HD group age and risk factors had the same negative influence on survival (p < 0.0001) while in CAPD group the influence of age on survival was less significant (p 0.025). This multicenter study carried out with appropriate statistical methods in a large number of pts demonstrates that patients' survival at 6 years is not different on CAPD and HD (despite the worse patient selection on CAPD) and can be even better on CAPD for aged patients.

The Authors review the mechanisms involved in the production of cytokines during substitutive extracorporeal treatment with particular reference to microbial contamination and possibility of backfiltration of bacterial constituents more likely to occur with high permeability membranes. Recent and on-going studies from our laboratory support the contention that patients treated with high permeability membranes may be chronically stimulated. Use of "ultrapure" solution indeed brings about a marked reduction in predialytic plasma levels of tumor necrosis factor (TNF) in regard to what observed when standard solutions are adopted.

Tumor necrosis factor (TNF-alpha) and interleukin-1 (IL-1 beta) are cytokines primarily produced by monocytes/macrophages when stimulated by endotoxin, complement-derived anaphylatoxins and the specific antigen. In the present study, the plasma levels of TNF-alpha and IL-1 beta were evaluated before and after hemodialysis with cuprophane membrane (in 9 patients) and hemodiafiltration (in 9 patients) using three high-permeability membranes such as polymethylmethacrylate, polyacrylonitrile (AN-69) and polysulfone. In vitro spontaneous production of TNF-alpha and IL-1 beta was evaluated in the supernatants from short-term cultured monocytes obtained before and after treatment. The predialytic levels of TNF-alpha and IL-1 beta were significantly higher (p less than 0.05) in the uremic population than in 21 healthy subjects taken as controls. The analysis of the uremic population regarding the mode of therapy indicated that in hemodialysis the predialytic plasma levels of TNF-alpha and IL-1 beta did not significantly differ from those of healthy subjects. In contrast, in hemodiafiltration with polymethylmethacrylate and AN-69, but not with polysulfone, the predialytic plasma levels of both cytokines were significantly (p less than 0.05) increased. No significant variation in plasma levels of both cytokines was observed after hemodialysis with cuprophane membranes. Hemodiafiltration with polymethylmethacrylate and AN-69, but not with polysulfone, brought about a consistent reduction in plasma levels of both cytokines. Detectable amounts of TNF-alpha and IL-1 beta were spontaneously produced by peripheral-blood monocytes 6 h after the end of hemodialysis but not of hemodiafiltration. These studies suggest a possible role of TNF-alpha and IL-1 beta in the biocompatibility of different extracorporeal treatments.

The outcome of renal transplantation in CAPD patients is still controversial since age and clinical differences often make comparison with hemodialysis patients difficult. The aim of this study was to analyse two homogeneous groups of patients, on CAPD and on hemodialysis. 18 CAPD (Group A) and 18 hemodialysis patients (Group B) were selected for a case-control analysis, matched for age, presence of acute tubular necrosis and Cyclosporine A regimen. Group A and B were not different for male/female ratio, donor age, HLA-Dr mismatches, arterial pressure, cold ischemia, or follow-up. Patient, graft survival and number of rejection episodes did not differ significantly at 1 year; serum creatinine at 6 and 12 months and CyA doses at 1 and 6 months were not different; hospitalization rates for first and subsequent admissions did not differ. Infection-free patients were 9/18 in Group A and 15/18 in Group B, with 12 episodes in Group A and 3 in Group B. Post transplant cholesterol levels showed a trend to increase in both groups and triglycerides levels to a decrease; differences in pre and post transplant in body weight were not significant at 12 months. In conclusion, the outcome of transplantation in CAPD patients is not significantly different from that in hemodialysis patients with similar clinical characteristics.

While the efficiency of treatment has been recently related to long-term clinical outcome, the relevance of tolerance on this subject, even on critically ill patients, has seldom been evaluated, for the limited size of single pools on high tolerance dialytic treatments (HTT) and the flux of pts. among treatments. Since 1981, on 2243 pts on files of the Dialytic Piedmont Regional Registry, 1399 treatments on acetate-hemodialysis (HD), 1153 on bicarbonate dialysis (BC) and 249 hemofiltration (HF) were compared by survival analysis (Mantel test) and yearly hospitalization rate (YH), according to age, factors of clinical high risk (HR) and presence of diabetes. BC and HF showed on HR pts. LTS comparable to HD (at 1 yr. 82, 78.3 vs 76.77%) despite the higher age, and the lower proportion of first choice (38.9%, 25% vs. 83.5%) testifying successful treatment of more critical cases. On non HR pts. HF, a less efficient treatment vs BD and AD, showed slightly reduced LTS (95.2% at 1 yr. vs. 98.1 and 97.9%). HY results higher on HF vs. BD on non HR pts. (10.4 vs. 5.3 and 2.1%) but improves on HR pts. (10.7 vs. 12.5%) and is lower than BC on diabetics (8.3 vs. 14.5%) (p less than 0.01).

Regenerated cellulosic membranes (CU) induced the aggregation of plasma-free human neutrophils when recirculated in a dynamic model of dialysis without the patient on the circuit. Neutrophil aggregation was linked to the production of PAF by these cells. In the absence of detectable PAF production, no neutrophil aggregation occurred, as observed during recirculation with polymethylmethacrylate (PMMA) membranes. With polycarbonate (PC), PAF production and aggregation of neutrophils were both almost half the values with CU. PAF production was studied in ten hemodialysis (HD) patients tested twice with CU and once with PC and PMMA membranes. PAF was extracted in the venous blood during filling of the dialyser for 9/20 of patients with CU (3.1 +/- 2.9 ng/ml, mean +/- 1 S.D.) a membrane that induced marked leukopenia (greater than 50% of basal values at 15 min), C3a des Arg generation (greater than 500% at 5 min), and plasma levels of the elastase-alpha 1-proteinase inhibitor complex (greater than 500% at the end of HD). Membranes such as PC and PMMA showing intermediate or low potential to induce leukopenia and C3a des Arg generation, respectively, did not trigger the production and release of PAF in detectable amounts at any interval. However, with PMMA, plasma neutrophil elastase was significantly higher than baseline at the end of dialysis. These levels were not significantly different (p less than 0.05) from those observed with CU and PC membranes.

A review of the literature is followed by the presentation of data obtained during a study of white blood cell kinetics in patients undergoing regular dialysis treatment. It was found that contact between white blood cells and the dialyzer results in a very prompt 'neutropenia-neutrophilia' stage and the deposition of billions of white blood cells on the membranes at the end of each treatment. A comparison of intradialytic leukocyte behaviour and the mean baseline white blood cell values was made in a total of 49 patients subdivided in four groups: 1. patients using coil and parallel flow dialyzers; 2. patients using dialyzers of different surface area; 3. patients of different dialytic age; 4. patients employing monoused or re-usable filters. No differences were noted in groups 1 and 4. In contrast, employing large dialyzers and the increasing dialytic age led to a variety of white blood cell patterns. Contrary to the information in the literature on leukocyte adhesion, it was observed that the cell deposits on the membranes and on the bubble trap filters, while predominantly composed of neutrophils, also contained monocytes and lymphocytes in proportions similar to those of the normal differential blood count.

The technical features of dialysis facilitate the transmission of hepatitis B virus and the outbreak of possibly serious epidemics among patients and hospital staffs. Statistical, epidemiological and clinical data have been collected on many occasions. They serve to emphasise the problem and the need for quarantined centres. The establishment of such a centre for HBsAg-positive patients is discussed in the light of personal experience in the design and setting up of quarantined rooms. The underlying technical and structural requirements are also examined. Reference is also made to two years' experience in the running of a room of this kind. Stress is laid on the importance of having a room for these patients, not only from the clinical standpoint (lessening of contagion), but also from teh social and exonomic standpoint (reduced costs and length of hospital stay, greater rehabilitation).

Urokinase treatment, previously employed with success in the declotting of deep venous thrombosis and arteriovenous shunts in patients undergoing regular dialytic treatment (RDT), was used in 23 cases of arteriovenous fistula thrombotic occlusion in 18 RDT patients. The treatment was successful in 65.2% of the cases without any negative side effects, except 1 case which may have developed a pulmonary embolism. Patients with severe hypofibrinolysis may need larger doses or may have a recurrence of the thrombotic episode. All therapeutic failures correlated with the presence of fibrosis or sclerosis.

Polymethylmethacrylate (PMMA) membranes with different net electric charges and percentage water contents (anionic 71%, neutral 70%, cationic 75%) were evaluated for their ability to stimulate plasma-free human polymorphonuclear neutrophils (PMN), and compared for potency to cuprophan (Cu), already described as being a potent trigger of PMN. The release of lysozyme, beta-glucuronidase, lactic dehydrogenase (LDH), and the generation of a platelet aggregating activity were studied in the supernatants from plasma-free human PMN incubated with different membranes. The PMN intracellular content of neutrophil cationic proteins (NCP), elastase, and cathepsin G were also studied by immunofluorescence using specific antisera on smears of PMN before and after incubation with each membrane. Only cationic, but not anionic or neutral PMMA induced a marked release of lysozyme (range 20-25% of the sonicated control, assumed as 100%), and beta-glucuronidase (40-43%), and marked depletion of the intracellular content of NCP, elastase, and cathepsin G, suggesting a degranulation process. Platelet aggregating activity was generated and referred to the release of platelet activating factor (PAF) only in the supernatants from PMN incubated with cationic, but not with anionic, or neutral PMMA membranes. These results indicate that modification of the net electric charge can per se turn PMMA, commonly recognized as inert, into a material with marked PMN activating effects, comparable to those of Cu, a highly reactive polymer.

The tasks required of a modern dialysis monitor are explained and the parameters that it supervises are described. Ways in which the maximum degree of safety can be assured are discussed and the criteria applicable the choice of equipment for routine hospital, home and research use are indicated.