Bionic kidney.

Bionic Kidney is a project still in progress which aims at replacing all renal functions, which has been carried out in an ideal attempt to improve the overall results of Renal Replacement Therapy. It contains all the requisites for a complete rehabilitation from Uremia. As a futuristic mini-device implanted in the body, it should be a reliable support to Transplantation performance, considering the scarcity of kidney donors.

Priorities in renal replacement programs.

The various alternative programs in renal replacement therapy have precise meritocratic ranking which unfortunately is still largely ideal today. New directions and scientific plans (bioartificial kidney, new immunomodulators, gene therapy) have to be followed to make today's ideal ranking become reality.

Tacrolimus is highly effective in both dual and triple therapy regimens following renal transplantation. Spanish and Italian Tacrolimus Study Group.

This open, multicenter, randomized, parallel-group study evaluated the efficacy and safety of tacrolimus-based dual and triple therapy regimens. For this 3-month study (with 12-month follow up), 491 adult renal transplant patients were randomized and received either dual therapy (tacrolimus/corticosteroids; 246 patients) or triple therapy (tacrolimus/corticosteroids/azathioprine; 245 patients). Patient survival rates at months 3 and 12 were 99.2 (dual) vs 99.6% (triple) and 97.8 vs 98.7%, respectively. Graft survival rates at months 3 and 12 were 94.1 (dual) vs 95.4% (triple) and 92.8 vs 93.3%, respectively. After 3 months, the incidences of treated acute rejection were 28.8 (dual) and 29.7% (triple); and 7.6 (dual) and 5.4% (triple) for corticosteroid-resistant acute rejections. Between months 4 and 12, three new first rejections were reported, (dual: 2, triple: 1). For leukopenia (1.3 vs 11.7%; P < 0.001) and anemia (14.8 vs 23.0%, P = 0.026), significantly higher incidences were reported in the triple therapy group. The incidence of de novo insulin-dependent diabetes was 5.6 (dual) and 4.0% (triple) at month 3. In terms of efficacy, no difference between the treatment groups was observed.

Kidney, patient and new millennium nephrology.

The way nephrology develops in the new millennium is bound to be affected by changes in the nephrologist's clinical environment, as well as by the progress made in basic research which will need to find a clinical application. The nephrologist can expect to be more and more involved in renal substitution therapy, not just providing the treatment, but also managing the cost of the service. In the field of nephropathology, the highest expectations surround molecular biology and its application to both acquired and hereditary renal disease; the goal is to find an outlet for gene therapy in clinical practice. Artificial substitution therapy will focus chiefly on the project of 'intelligent dialysis', whereby biological and diagnostic components are combined according the specific needs of the individual patient. The ideal scenario for renal transplantation in the coming millennium would be one where donor supply matches the demand (xenotransplant?), where immunomodulation is perfected, and where diagnoses are based on precise biomolecular events observed in real time.

Immune response following fresh arterial homograft replacement for aortoiliac graft infection.

INTRODUCTION: this prospective study defines the immune response to fresh arterial homograft replacement for graft infection. MATERIALS AND METHODS: ten patients who underwent ABO-compatible homograft transplantation were studied for anti-HLA antibody production, and CD3-CD4-CD8-positive lymphocytes subset. Immunological studies were performed preoperatively, and at early (1, 3, 7 days) and late (1, 3, 6, 12, 18, 24 months) follow-up. All patients received immunosuppressive treatment with cyclosporine (1-3 mg/kg/day). Abdominal CT scans were performed postoperatively at the 1, 6, 12, 18, 24 months follow-up. RESULTS: preoperatively, antibodies could not be detected. Postoperatively, as from 1st month post-transplant, a progressive increase in % PRA was observed in all patients, up to the 12th month of follow-up. Subsequently, at 18 and 36 months, a progressive decrease in % PRA was detected. Data showed that the recipient antibodies were directed against donor-specific antigens. During the immediate postoperative period (1, 3, 7 days) CD3- and CD4-positive T lymphocytes slightly increased, whereas CD8 simultaneously decreased. Later, CD3 and CD4 progressively decreased and CD8 increased. Clinically, all patients were cured of infection at late follow-up. CT scans showed thickening of the aortic wall (range: 2.5-4.5 mm), with no signs of aneurysmal degeneration. CONCLUSIONS: fresh arterial homografts are immunogenic. Implanted homografts induce a strong anti-HLA antibody response, similar to chronic rejection, in spite of immunosuppressive treatment.

The Academy of Science of Bologna and the kidney.

The Academy of Science of Bologna, founded in 1711, played an important role in the development of medicine. Receiving the heritage of Malpighi's and Morgagni's researches, the academy encouraged nephrological studies, which produced articles published in its journal, the Commentarii. Since the Commentarii were widely distributed all over Europe, the nephrological research practiced in Bologna reached all the main academies of science, in a fruitful circulation of knowledge. The paper presents the nephrological contributions to the Commentarii in the 18th century, thus introducing physicians, like Domenico Galeazzi and Luigi Galvani, who were both professors at the University of Bologna and at the Academy of Science. In their work three main topics can be identified: uroscopy, anatomy of the kidney and renal pathologies.

Aorta transplantation in man: clinical and immunological studies.

Aortic transplantation has progressively gained interest over the last few years and it is becoming a first choice indication in the substitution of infected prostheses. The most frequent complication in long-term vascular outcome (wall thickening, aneurysmatic dilation, stenosis), may occur through an immunological mechanism. In this study we investigated nine recipients, aged 48 to 65 years, of aorta segment replacement for anti-HLA antibody production (specificity and Ig class), CD3-CD4-CD8 T cell subpopulation dynamics and aorta wall thickness. Mismatch-specific IgG antibodies to HLA class I and HLA class II antigens were detected 1, 3 and 6 months after transplantation and persisted at a high concentration for at least 1 year. Furthermore, the absolute number of CD3, CD4 and CD8 positive lymphocytes increased progressively after aorta allograft. Tomography scanning showed a progressive thickness of the aorta wall. We can speculate that these anti-HLA antibodies in the recipients have the potential to harm the implant; therefore, aorta allograft should involve the induction of immunological tolerance by appropriate immunosuppressants.

Clinical use of profiled hemodialysis.

The new population on dialysis today consists mainly of high risk patients (the elderly, diabetics, etc.) with high cardiovascular scores, and such vascular pathology is the most important predisposing factor for the occurrence of a frequent intradialytic clinical complication, vascular instability syndrome, which covers a range of clinical problems. Recently a new dialysis technique, profiled hemodialysis (PHD), has been set up and proposed for routine use. PHD consists of the clinical use of preestablished individual dialysis profiles aimed at antagonizing the changes in intradialytic plasma osmolarity by continuous modulation of dialysate sodium concentration throughout the whole extracorporeal session. In particular, PHD aims at reducing the fall of plasma osmolarity in the first half of the session (when it is higher) by reducing the sodium removal rate through increasing its dialysate concentration while taking into account the desired individual sodium balance to be reached at the end of the session. In this work, we report clinical experience with PHD compared to standard hemodialysis with constant sodium dialysate (SHD) in terms of its efficacy to maintain a more stable intradialytic blood volume (BV) and more stable hemodynamics. The PHD used in this work has been implemented by a mathematical model for computing the individual dialysate sodium profile which we have recently validated (Ursino M, Coli L, La Manna G, Grilli Cicilioni M, Dalmastri V, Guidicissi A, Masotti P, Avanzolini G, Stefani S, Bonomini V. A simple mathematical model of intradialytic sodium kinetics: "in vivo" validation during hemodialysis with constant or variable sodium. Int J Artif Organs 1996;19:393-403.). Eleven uremic patients affected by hypotension at the beginning of dialysis treatment were studied. Each patient first underwent an SHD treatment and 1 week later a PHD treatment. The 2 extracorporeal sessions (one on SHD and the other on PHD) were performed in each individual patient under identical operative conditions including the sodium mass removal by the end of the session and the ultrafiltration rate. The crit line and Doppler echocardiography were used to determine BV, cardiac output (CO), and stroke volume (SV) throughout the sessions. The mean blood pressure (MBP) and heart rate (HR) were simultaneously monitored. PHD was associated with a more stable intradialytic BV and more stable hemodynamics compared to SHD. The higher stability of BV and cardiac function (in terms of SV and CO maintenance) which was obtained above all in the first half of the PHD session was associated with a higher stability of the MBP and the HR. This resulted in an enhancement in cardiovascular tolerance to ultrafiltration throughout the session in all tested patients. In contrast, SHD in the same patients was characterized by early significant changes in BV and cardiovascular parameters resulting in a significant decrease of the MBP and a significant increase of the HR throughout the session and also 1 h after the end of dialysis. Our results indicate that PHD may represent an efficient approach for the treatment of patients suffering from intradialytic vascular instability. If long-term clinical practice confirms the efficacy of PHD in controlling dialysis intolerance symptoms, it will have great scope as a routine procedure.

Mismatch-specific anti-HLA antibody production following aorta transplants.

In this study, we have investigated the nature and magnitude of the immunological response after implantation of human aortic segments. Five recipients of aortic segment replacement were studied for anti-HLA antibody production (specificity and Ig class), CD3, CD4, and CD8 T cell subpopulation dynamics, and aortic wall thickness. Mismatch-specific IgG antibodies to HLA class I and HLA class II antigens were first detected 1-3 months after implantation and persisted in high concentrations for at least 1 year. Computer tomography scanning showed a progressive thickness of the aortic wall. Also the absolute number of CD3, CD4, and CD8 positive lymphocytes increased progressively after implantation. In conclusion, as was observed earlier for heart valve allografts, human implanted aortic segments induce a strong anti-HLA antibody response in recipients. We speculate that these antibodies have the potential to harm the implant, for example, by having an impact on luminal narrowing.

Mechanical effects of heart pulse propagation on a vessel-graft suture line stress.

The effects of vessel joint where the both sides have different wall properties on the heart pulse propagation are investigated. Such a local disturbance can influence post-transplantation pathology and evolution of the organ inconsistency. Using a mathematical model, developed in a previous article, we perform analytical analysis and present some qualitative and quantitative estimations. The effects of jointed vessels with different thicknesses and radii on the local concentration of the pressure, radial wall displacement, bending moment and shear force are analyzed in detail. In particular, it is obtained that the bending and shear stresses at a joint sharply and strongly increase in comparison with the uniform vessel ones.

A simple mathematical model applied to selection of the sodium profile during profiled haemodialysis.

BACKGROUND: Among dialysis patients in the last 10 years the incidence of intradialytic dysequilibrium syndrome and symptomatic hypotension has increased significantly. Profiled haemodialysis (PHD), a new dialysis technique based on intradialytic modulation of the dialysate sodium concentration according to pre-elaborated individual profiles, has been set up to reduce intradialytic imbalances and the incidence of dysequilibrium syndrome and symptomatic hypotension. The present paper illustrates a new mathematical model for solute kinetics, single-compartment for sodium and two-compartment for urea, aimed at improving the use of PHD. The model allows the sodium profile to be elaborated a priori, before each dialysis session, according to the patient's clinical needs and respecting the individual sodium mass removal and weight gain. METHOD: The mathematical model was first derived and then applied to determining a rational dialysate sodium profile. A procedure which allows the method to be tuned to individual clinical needs on the basis of routine measurements performed before each session is also presented. The proposed method was validated in vivo during seven dialysis sessions, each performed on a different patient. RESULTS: The comparison between data predicted by the model and those obtained in vivo shows a good correspondence in particular concerning the time pattern of blood urea and sodium. The comparison between the model prediction and in vivo determined sodium and urea plasma curves showed standard deviations (2.25 mEq/l for sodium and 0.87 mmol/l for urea) only slightly higher than those attributable to laboratory measurement errors. Moreover, in vivo implementation of PHD by our model enables one to remove an amount of sodium mass comparable with the a priori quantity predicted by the model.

Guilielmus de Saliceto and his contributions to renal medicine.

Guilielmus, one of the most outstanding physicians of the 13th century practised a bedside teaching method and gave guidelines for diagnosing and treating diseases. Written summaries of clinical case histories were his basic didactic instruments and his practise was characterized by a high awareness of doctor-patient relations.

The presence of posttransplant HLA-specific IgG antibodies detected by enzyme-linked immunosorbent assay correlates with specific rejection pathologies.

Posttransplant monitoring of anti-HLA antibodies with routine techniques gives unsatisfactory results due to a variety of technical limitations. We investigated how a new alternative technique correlates with posttransplant clinical events. A total of 313 nonselected serum samples from 136 patients were screened by an ELISA utilizing captured soluble HLA class I antigens. We observed the absence of anti-HLA antibody production in acute rejection cases responding to standard antirejection therapy. On the other hand, we showed a clear presence of these antibodies in acute rejection episodes not responding to standard therapy (P<0.0001) and in chronic rejection (P<0.001). We conclude that routine posttransplant monitoring by ELISA offers early risk assessment that is crucial for proper immunosuppression and for antirejection therapy choice.