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Background: Intradialytic hypotension is mainly induced by the removal of extracellular sodium during dialysis, which impairs intravascular fluid refilling and reduces blood volume. To counter this complication we tested a new kind of profiled hemodialysis (PHD) consisting of the intradialytic modulation of dialysate sodium concentration according to individual profiles set up using a new mathematical model for intradialytic solutes and water kinetics. The clinical aim of this PHD is to stabilize blood pressure maintaining higher blood volume values than standard dialysis treatments. We clinically validated PHD in comparison with constant dialysate sodium dialysis (CHD)., Methods: Twenty hypotensive dialysis patients underwent one PHD and one CHD session maintaining the same dialysis length, sodium mass removal and body weight decrease. A new mathematical model was used to define both the dialysate sodium profiles for PHD and the constant dialysate sodium for CHD. Percent blood volume variation (Crit-line), mean blood pressure, heart rate, cardiac output (Doppler-echocardiography) were monitored intradialitically., Results: Cardiovascular stability improved on PHD as compared with CHD sessions; blood volume and cardiac output during PHD showed a lower decrease than on CHD, the differences statistically significant (from 30' and 60' respectively). Mean blood pressure was, at all time intervals, more stable on PHD than on CHD and was accompanied, on PHD, by a lower heart rate increase (differences statistically significant)., Conclusions: This study shows that PHD performed using dialysate sodium profiles elaborated by our mathematical model obtains, in hypotensive patients, a higher hemodynamic intradialytic stability than CHD, probably due to a higher stabilization of blood volume.

Profiled dialysis is a new conceptual approach to patient intradialytic vascular instability. It is based on the continuous modulation of dialysis operative parameters, such as dialysate sodium and UF rate, according to pre-established profiles. The points to be defined for profiled dialysis are: (a) the patient's individual sodium and masses already stated; (b) the patient's individual algorithms to fit the clinically effective intradialytic variations in plasma sodium and sodium mass; (c) a mathematical model from which sodium and UF profiles are automatically worked out at the beginning of each session. The basic concept of profiled dialysis should evolve towards an ongoing "profiling' programme. This is based on the continuous on-line intradialytic adjustment of profiles according to the patient's emerging clinical requirements.

The present comparative evaluation aims at establishing whether the basic structure of dialysis membrane is able to predict long-term clinical outcome. From a population of 1,256 patients on renal dialysis treatment, treated by the Institute of Nephrology and Dialysis of the St. Orsola University Hospital of Bologna from 1963 to 1993, 122 patients were retrospectively selected for the present study. Patients were divided into two different groups according to the kind of dialysis membrane used--cellulose-based (64 patients) and synthetic-based (58 patients) membranes. The parameters considered were: intradialytic biology, long-term biocompatibility, survival and morbidity, and cost/benefit. The results obtained demonstrate that cellulosic membranes can be said to cause a greater acute intradialytic biological response than synthetics, though not to a significant degree. There are, however, no significant differences in the biological changes from group to group. Nonsignificant differences were noted in long-term survival general morbidity. In terms of sheer cost, synthetic membrane treatment is anything up to 200% dearer than cellulosic.

A long-term retrospective evaluation (5 years) compares two groups of RDT patients (group 1 on continuous treatment with cellulosic membranes and group 2 with synthetic membranes) regarding survival, general clinical morbidity, and beta 2M-related morbidity. The results showed no significant long-term differences between the groups either for survival or general morbidity despite some differences in biocompatibility. The higher intradialytic removal of beta 2M by synthetic membranes did not lead to a reduction in either pre-dialysis beta 2M values or beta 2M related morbidity. The higher cost of synthetic over cellulosic membranes and the disappointing of many clinical expectations suggest that the use of such membranes, in association with alternative techniques, should take place only according to certain "elective" indications such as old age, diabetes, vascular instability or intradialytic disequilibrium syndrome.

Cellular immunity represents an interesting biological model for biocompatibility evaluation of artificial materials owing to its sensitivity to contact with the external environment and its capability of modulating response reactions to foreign agents. Advanced methodologies such as flow cytometry and the immunoenzyme techniques in particular have given new insights into lymphocyte structure and functions, enabling analysis of the in vivo modification of these cells. By means of these sophisticated techniques we investigated lymphocyte activation and proliferation during one single haemodialysis session. Findings clearly show that increases in HLA antigen density (class I and II), DNA synthesis, and interleukin-2 receptor serum concentration (Il-2R) take place during the dialysis procedure, and reach their maximum during the first hour of extracorporeal circulation. The relationship between dialysis procedure and cellular immunity appears noticeable and is of potential value in the evaluation and quantification of the biocompatibility of different dialysis membranes.

The results of a 1-7 years follow-up of multiple processed and recorded semiquantitative parameters in 148 cases of chronic uremia on regular dialysis treatment (RDT) are reported. Patients were grouped according to different levels of residual creatinine clearance (CCr) at the beginning of treatment (0-5, 5-15, and 15-21 ml/min). Regardless of a possible return to work and reasonable quality of life, patients on RDT with 0-5 ml/min CCr invariably present a worsening in various subclinical parameters semiquantitatively evaluated (bone biopsies; nerve conduction velocity; glucose A-V, etc.). In patients with 5-15 ml/min CCr better results are found. In patients with residual CCr above 15 ml/min, impairment in several parameters is hardly evident and even after several years of dialysis may still remain minimal. These results seem of importance as far as the effective and not the apparent dialysis rehabilitation is concerned.

A serial bone biopsy longitudinal study has been undertaken to asses the effects of Dialysis and Transplantation on uremic osteodystrophy. The clinical material consists of: normal (24 cases, 61 biopsies), patients with moderate renal failure on free diet (50 c., 61 b.), patients on Low Protein Diet (146 c., 251 b.), patients on Regular Dialysis Treatment (114 c., 256 b.), patients submitted to Transplantation (50 c., 84 b.). A significant correlation has been documented between duration of low protein diet and bone changes. In long-term dialysis patients remarkable differences have been found in "late" dialysis starting time (mean value of creatinine clearance at the beginning of treatment 2.04 +/- 1.7) in respect to "early" starting-time (mean value 13.1 +/- 3.9). In late group bone histomorphometry showed quite evident signs of secondary hyperparathyroidism and hyperosteoidism which remarkably worsened 3-4 years after dialysis. The aminoacids composition of the bone showed an increase in the total amount of aminoacids during dialysis, expecially for proline, hydroxyproline and glycine. In early group both basic values and progression rate of bone lesions were less severe. In transplanted patients with good renal function (serum creatinine less than 1.4 mg%) bone histomorphometric analysis showed a rather rapid disappearance of uremic bone lesions. A significant correlation was found between serum PTH, renal function and bone histology. On some occasions signs of secondary hyperparathyroidism were documented even after 16 months. A good correlation between inactive bone surfaces and immunosuppressive regimen was found.

Charcoal hemoperfusion has long been used in chronic uremia as an adjunct or substitute for conventional hemodialysis. In this study a regular combination of hemoperfusion and hemodialysis was used to cut down the weekly substitutive sessions from 3 to 2. Ten RDT patients were treated with the reduced-time schedule for 5-56 weeks. Clinical and metabolic conditions remained stable in all patients and no sign of inadequate treatment appeared. Long-term charcoal hemoperfusion was confirmed to be a safe and risk-free procedure. No change in platelets, white cells, red cells, fibrinogen and other hematochemical parameters were detected.

The use of charcoal hemoperfusion in the treatment of chronic renal failure has been proposed and applied by several authors. The availability of coating membranes of increased biocompatibility currently allows a safer and wider use of this purifying technique. It has been recently demonstrated that long-term treatment with combined hemodialysis/hemoperfusion yields an improvement of certain dialysis-resistant uremic signs in patients on regular dialysis treatment, while in selected patients it affords a marked reduction (up to one-third) in the overall time of treatment per week. The tolerance of long-term treatment is good. In line with these findings, a multicenter study has been carried out in Italy with two main aims: (1) to see whether long-term treatment with charcoal hemoperfusion is really safe and substantially free from side effects; (2) to verify in a larger and more varied population of patients whether such long-term treatment actually improves certain uremic signs persisting despite adequate dialysis treatment. A third phase of the multicentric study (reducing the weekly time of treatment) is currently being worked on. Five nephrology and dialysis departments took part in the study: in Bologna, Rome, Chieti, Ancona, and Lecce.