[The concept of ultrapure solution online production]. / Il concetto di produzione online di liquido ultrapuro.

Online preparation of dialysis fluid, i.e., continuous mixing and immediate use, was introduced in 1964 and has contributed significantly to the expansion of dialysis therapy through simplified handling, improved microbiology, and enhanced efficiency. Online prepared replacement solution for hemofiltration was shown to be clinically safe as early as 1978, but the implementation was delayed for 20 years because of regulatory conservatism. Online preparation of sterile and pyrogen-free solutions for infusion is based on the use of water and concentrates that are mixed and distributed in a hygienically designed and maintained flow path. Ultrafilters with known retention capacity are placed in strategic positions to remove bacteria and endotoxins, which gives a sterility assurance level of at least six magnitudes, as required by the pharmacopoeia for sterile products. Microbiologic testing of the fluid should be applied when designing, validating, and troubleshooting online systems but not for routine quality control, because it only gives retrospective information. Quality assurance has to be built into a system and the way it is operated. The use of ultrapure dialysate must be considered as a suitable option for all hemodialysis modalities. To achieve this goal, one must keep in mind that ultrapure dialysate and infusate result from a complex chain of production where ultra-purity and/or sterility of the final solution relies on the weakest or worst component of the chain. Online fluid preparation, when properly performed, is safe, simple, and cost-effective and enhances the efficiency as well as the biocompatibility of dialysis therapy.

The catheter as Ariadne's thread to follow the path of Peritoneal Dialysis (PD) through the long-term experience of a Center.

In our institution, the first patient was treated by HD in 1955. In the middle of the '60s, the PD technique, revised by Maxwell (1), was implemented. The access to peritoneum was obtained by repeated puncturing of the abdomen, the catheter being removed after each session. In 1966, our first results on one year of PD were published (20 patients treated, 13 affected by ARF and 7 by CRF, for a total number of 150 sessions). Since 1967, the procedure of the repeated punturing was improved by the Seldinger technique. The efficiency of the PD intermittent treatment was increased with the "fast shift" schedule and PD automation was pursued with the project of a cycler (1968). The first CRF patients were treated by fast shift PD. In the late intermittent PD phase, the adoption of permanent catheters, destined to endure in our practice, the rigid and the soft indwelling for long-term treatments, allowed us to launch programs of home and nocturnal PD. With the incoming CAPD age, the greatest care was directed to the role of the catheter. The adoption of the surgical insertion by paramedian approach through rectus muscle, minimized, in our experience, the early complications. With the reduction of peritonitis rate, the later catheter complications increased in terms of patient discomfort, hospitalization and technique survival. On those grounds, in our institution a prospective trial on a ten year period was undertaken to compare, in terms of late complications rate, new versions of the classic Tenckhoff straight catheter (ST). The surgical insertion method was adopted for all the types, for a total of 196 catheters in 163 CRF patients. The tip displacement rate (12.2% with ST) decreased, albeit non significantly, with Swan Neck (7.9%), but was markedly and significantly reduced (1.0%) with the Self-Locating (SL) catheter experience. The surgical insertion of SL was comparable to that of ST. For those reasons, in recent years, in our institution the SL catheter became the first choice catheters for CRF patients.

EPO or not-EPO? An evidence based informed consent.

BACKGROUND: Informed consent is crucial in therapeutic choices; however, the forms presented to patients are often locally developed and information may not be homogeneous. OBJECTIVE: To prepare an evidence-based model for informed consent, applied in the case of erythropoietin therapy (EPO) as a teaching tool for medical students. METHODS: Methodological tools of Evidence-Based Medicine (EBM) were developed within the EBM Course in the Medical School of Torino, Italy, as problem solving and patient information tools (5th year students work in small groups under the supervision of statisticians, epidemiologists and experts of internal medicine--nephrology in this case). RESULTS: Methodological and ethical problems were identified: in the pre-dialysis field, evidence from randomized clinical trials (RCT) is scant; how to use evidence gathered in dialysis? How to deal with implementation? How with the mass media? Do we need to discuss the drug choice with the patients? How to deal with rare and severe side effects?). The "evidence" was searched for on Medline/Embase, by using key-words and free terms. About 680 papers were retrieved and screened. Forms available on the Internet were retrieved and a general scheme was drawn: it included 5 areas: title, aim and targets (patients and family physicians); search strategies and updating; pros and cons of therapy; alternative options; open questions. CONCLUSIONS: EBM may offer valuable tools for systematically approaching patient information; the inclusion of this kind of exercise in the Medical School EBM courses may help enhance the awareness of future physicians of the correct communication with patients.

Twenty years of renal replacement therapy in a type 1 diabetic patient: advantages of a multiple choice dialysis system.

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.

[Costs of dialysis in hospitalised patients with acute or chronic renal failure, according to area of treatment]. / Costi dei trattamenti dialitici condotti in aree operative differenziate in pazienti ospedalizzati, acuti e cronici.

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.

Patient knowledge and interest on dialysis efficiency: a survey.

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.

[Daily dialysis: evaluation of the first year of experience at home and in a limited care center]. / La dialisi quotidiana: valutazione del primo anno di esperienza a domicilio ed in un centro ad assistenza limitata.

BACKGROUND: Among self dialysis treatments, daily dialysis is encountering a growing interest. Aim of this study was to evaluate results of the first year of daily dialysis in our Center. METHODS: Since November 1998, twelve patients started daily dialysis. One patient started RRT on daily dialysis; one patient was in training; 8 were on home dialysis, 3 in the limited care center. Selection of patients was performed according to wide acceptance criteria as for age (range 33-61 years), dialysis follow-up (range 1-23 years), comorbidity (=/>1 comorbid factor present in 8). Dialysis schedule consisted of 6 sessions per week (2-3 hours), blood flow 250-320 ml/min, individualized dialysate. Occasional shift to 3-4 times per week were allowed for logistic or working reasons. RESULTS: Results were analyzed taking into account patient satisfaction and main clinical parameters. In 9/12 the choice of treatment resulted from both clinical reasons and patient preferences, while in 3 was due to clinical indications (1/3 dropped out). The main reasons of choice were logistic or research of the best treatment. The most common fears regarded fistula and needle puncturing. Despite the time unconvenience, the rapidly regained well being was the reason for choosing this treatment. Also in this relatively short follow-up the favorable results reported as for weight gain, blood pressure control and metabolic pattern are confirmed. The few side effects were multifactorial (fistula thrombosis after blood pressure normalization, 2 recurrences of atrial fibrillation). CONCLUSIONS: In conclusion, daily dialysis resulted also in our centre as a promising alternative even in difficult patients.

Limits of aortic stop flow infusion chemotherapy in the treatment of advanced cancer.

BACKGROUND: Advanced and relapsed tumors remain a challenging disease with a poor and dismal prognosis. Our choice for inoperable tumors consists in a percutaneous treatment strategy involving intra-arterial chemotherapy and hemofiltration, with previous blood stop-flow, which allows high doses of Cisplatin-cisplatinum, cis-diammine-dichloroplatinum (CDDP) and Mitomycin C (MMC) in the tumor-bearing area with minimal systemic toxicity. METHODS: We analyse the morbidity and mortality associated with stop-flow in 20 patients with unresectable and/or metastatic thoraco- abdominal tumors, non responders to prior systemic chemotherapy. RESULTS: In our experience, the rate of major side effects of the procedure was 31% with a mortality of 5%. The side effects were related to the radiological procedure and to the chemotherapic treatment. A 74-year-old patient died for acute kidney toxicity within 15 days after the procedure. The other transient toxicity symptoms recorded were: nausea, vomiting, increasing of creatinine levels, diplopia and appearance of necrotic ulcer associated to chemotherapic drugs. Concerning the complications related to the radiological technique, the main problem was the rupture of the balloon stop-flow catheter in four patients. CONCLUSIONS: Stop-flow is a new procedure that could develop in the future, thanks to the possibility of obtaining a higher dose intensity of chemotherapic drugs in districts or organs affected by advanced tumors, with less systemic side effects. Unfortunately, the uncertain results in terms of increasing survival and the default of effective devices are to be resolved for a wider application of the procedure.

Daily dialysis Kt/V and flexible schedules: is it possible to control efficiency, when and how?

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.

Modelling the "ideal" self care--limited care dialysis center.

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.

[Relationship between risk profiles, prognosis, and outcome of patients with acute renal failure treated with dialysis]. / Rapporto tra profili di rischio, prognosi ed "outcome" del paziente con insufficienza renale acuta (IRA) in dialisi (RRT).

BACKGROUND: The paradox of the increased mortality in the patients with acute renal failure (ARF) although submitted to better cares and newer renal replacement therapies (RRT) has recently prompted to the use of quantitative individual severity scores (ISS) calculating for each patient an individual death probability (DP) in correlation with the risk covariates found before the start of RRT; beside the clinical use, the ISS allow an evaluation of the effect of strategies and modalities of treatments as quantitative additive factors eventually added or subtracted to the base-line individual background of risk. The ideal index should be chosen on the basis of its precocity (origin just at the start of therapy), sensitivity (true positive against false positive results), universality (independence from the development set) and discriminative power (the capability to discern patients potentially treatable from those with an unchangeable prognosis). Indexes already validated in their development set should be used and studied into a different set ("evaluation set"). METHODS: The aim of this study has been: to evaluate a literature index (ATN-ISS, Liaño, developed prospectively in a remote set) in the local (A) environment on 340 patients with ARF successively treated with dialysis (mostly hemo-filtration) studied retrospectively along a 4 year period in our regional hospital and compare its performances with a local index (PDTOR) developed by logistic analysis in the same pool; the fitness of both tests to the real outcome has been evaluated by the Limeshow test and by ROC curves; to compare both indexes in a remote environment (B) of a dialytic pool of 345 patients extracted by a group of 25721 patients treated by 25 Italian ICU (Archidia Study group). The responses of the two indexes have been compared even with the index (SAPSII) prospectively generated at the admittance in the ICU by the Archidia Group. RESULTS: In the local set (A) TOR-ISS fits well with the outcomes (Limeshow test C2 = N.S.) as expected being evaluated in its own "development" set, while ATN-ISS significantly underestimates deaths, perhaps working on a retrospectively built data-base, that could contain fewer risk elements than necessary. (B) In the remote set, ATN-ISS fits very well, while TOR-ISS significantly overestimates expected deaths, for its retrospective origin or for a real lower death incidence compared to that of its development set. SAPSII shows no correlation at all with the outcome because its calculation is often well before (10 days on average) than the actual start of dialytic treatment. CONCLUSIONS: In conclusion ATN-ISS, an index built prospectively on a large cohort of patients, fits correctly in a remote prospectively built evaluation set. Retrospective built indexes or data-base don't allow a correct ISS evaluation while ICU indexes (SAPSII, APACHE), generated at the admittance in the ICU should not be used for ARF patients submitted to dialysis.

[Research potential of a regional registry]. / Potenzialità di ricerca di un registro regionale.

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.

[Quality of data or quality of care? Comparison of diverse standarization methods by clinical severity, based on the discharge form, in the analysis of hospital mortality]. / Qualità dei dati o qualità dell'assistenza? Confronto tra diversi metodi di standardizzazione per gravità clinica, basati sulla scheda di dimissione, nell'analisi della mortalità ospedaliera.

Using discharge abstract data, we analysed hospital mortality comparing four different methods of risk adjustment. All patients discharged from the S. Giovanni Battista (Molinette) hospital in Turin (Italy) between January 1996 and June 1999 (n = 169,746) were classified with All Patient Refined--Diagnosis Related Groups (APR-DRG). A first analysis evaluated the time trend of hospital mortality by semester. A second analysis compared hospital mortality during the last 12 months among eight units of internal medicine (n = 5592). All comparisons were made through logistic regression models. As the quality of discharge abstracts increased during time and showed variation among units with similar patients, all comparisons were repeated using four models, characterised by increasing predictivity and sensitivity to quality of data. In addition to crude comparisons (A), the other models included as risk factors: B) age and emergency admission; C) same as 'B' plus expected mortality by APR-DRG; D) same as 'B' plus expected mortality by APR-DRG and risk of death subclass. If no risk factors were considered (A), hospital mortality showed an increasing trend, with an odds ratio (OR) of 1.02 by semester, with a 95% confidence interval (CI) between 1.01 and 1.03. The association was weakened when age and mode of admission were taken into account (B) and disappeared when the APR-DRG expected mortality was also considered (C) (OR = 1.00; CI = 0.98-1.01). Finally, if the comparisons were adjusted also for the expected mortality by APR-DRG and risk of death subclass (D) a reversed trend appeared (OR = 0.95; CI = 0.94-0.97). The comparison among the units of internal medicine gave discordant results according to the method used to adjust for confounders. The most striking variations were detected for those units with the best and the worst clinical data. The unit with the poorer clinical data (average number of diagnoses per patient = 2.9) showed a crude OR of 1.38 (CI = 0.99-1.93) and an adjusted OR (D) of 1.71 (CI = 1.10-2.66); the unit with the best quality of data (average number of diagnoses per patient = 4.4) changed the OR from 1.55 (CI = 1.06-2.26) (A) to 0.66 (CI = 0.37-1.17) (D). In conclusion, these results confirm the high sensitivity of the APR-DRG classification to the quality of data and, more in general, suggest to be prudent when using powerful instruments like this to assess quality of care, especially if the quality of data among the units compared is less than optimal or not homogeneous.

[Complex vascular access]. / Gli accessi vascolari complicati.

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.

Elderly patients on dialysis: epidemiology of an epidemic.

The increase in the incidence of elderly patients starting dialysis has been as sharp, during the 1980s-1990s, as an epidemic (+70%, +150% in different settings). According to this study, performed in Piemonte, northern Italy, the process is still ongoing. During the period 1981-93, according to the Regional Registry of Dialysis and Transplantation (RPDT: data on 100% of centres and patients), the cohort on treatment increased by 79.5% and the annual incidence by 48.3%; the increase is limited to older people and is greater in males. Nephroangiosclerosis/ischaemic renal disease and diabetes mellitus are the main diagnoses. Since the increase of elderly patients is still ongoing, forecasts are difficult; according to a computer simulation, a plateau of patients on treatment is reached only if incidence is stabilized, While it is impossible to exclude a decrease in hidden selection or an increase in referral, complex modifications at the overall population level are presumably at the basis or the increase of elderly patients on dialysis. Despite the increase in average age, however, survival improved throughout the period; this confirms the interest towards the open dialysis system adopted in Piemonte, which is characterized by easy shifts among treatments and by the widespread use of high tolerance techniques.

Prescription and surveillance of the acetate-free biofiltration sessions: the bicarbonate cycle.

A computerized system, structured by 4 different models concerning urea depuration, and bicarbonate and sodium handling in acetate-free hemodiafiltration has been conceived for integrated use covering each step of the therapeutic cycle, from a) the prescription of the session to b) its delivery, up to c) the dose-response analysis: the system, now fully developed for the bicarbonate cycle, covers both working areas; the medical one, with a program implemented on a Personal Computer, called Skipper which deals with steps a) and c), and the nursing area, with a program built into the dialytic equipment software. The Skipper program supports the prescription step (a) testing the session schedule by bicarbonate, sodium and urea kinetics. The dialytic equipment, (step(b)) using a different program, on the basis of the scheduled parameters memorizes the end-session plasma bicarbonate level and reacts to any modifications of the parameters regarding blood flow and fluid reinfusion flow suggesting opposite changes in order to reach the scheduled results. Finally (step (c)), the Skipper system statistically evaluates the observed end session bicarbonate plasma level with an expected value with upper and lower confidence bounds obtained by a multiple regression analysis performed on a large population of patients.

Cyclo-oxygenase blockade abrogates the endotoxin-induced increase in Na(+)-dependent hepatic amino acid transport.

BACKGROUND: Endotoxemia is characterized by a marked increase in the uptake of amino acids by the liver, but the regulation of this response has not been fully elucidated. In the current study, we investigated the potential role of prostaglandins as mediators of this response. We examined the in vivo effects of the anti-inflammatory agent ketorolac, a cyclo-oxygenase inhibitor that blocks prostaglandin synthesis, on hepatic amino acid transport activity in endotoxin-treated rats. METHODS: We assayed the activities of the Na(+)-dependent transport systems A and N in hepatic plasma membrane vesicles prepared from endotoxemic rats that were pretreated with ketorolac or vehicle. Hepatic plasma membrane vesicles were prepared by differential centrifugation, and the transport of [3H]glutamine (system N) and [3H]2-methylamino-isobutyric acid (system A) was assayed. Hepatic plasma membrane vesicles were also prepared from normal rats that received prostaglandin E2, and glutamine and MeAIB transport were measured. RESULTS: Endotoxin treatment resulted in a twofold to threefold increase in Na(+)-dependent amino acid transport activity in hepatic plasma membrane vesicles secondary to an increase in the transport Vmax, which was consistent with the appearance of increased numbers of corresponding transporter proteins in the hepatocyte plasma membrane. Pretreatment with ketorolac almost completely abrogated the endotoxin-induced increase in hepatic amino acid transport. Administration of prostaglandin E2 to normal rats resulted in a statistically significant increase in glutamine and alanine transport by hepatic plasma membrane vesicles prepared from these animals. CONCLUSIONS: Prostaglandins play a key role in mediating the accelerated hepatic amino acid transport that occurs during endotoxemia.