[Clinical results of the various replacement therapies for chronic renal failure: haemodialysis and renal transplantation]. / Risultati clinici delle diverse terapie sostitutive dell'insufficienza renale cronica: emodialisi e trapianto renale.

Results from recent studies have demonstrated that kidney-transplanted patients have better expectation and quality of life than dialysis patients on a waiting list for kidney transplant. Moreover, the scientific literature has conclusively shown that the survival of the patient and of the kidney graft are better in patients who received a kidney from a living donor, than in patients who received a cadaveric kidney. The main factors that may have a negative influence on the kidney transplant are: the recipient's age, diabetes mellitus, smoking and the time spent on dialysis before the transplant. The shortage of cadaveric kidneys and the small number of living kidney transplant are the main obstacles to a more widespread use of kidney transplantation. Kidney transplant from living donors needs to be implemented because it represents the best treatment for patients with kidney failure and it can decrease or even avoid the need for dialysis before kidney transplantation.

Which kind of vascular access for hemodialysis in pediatric patients?

The choice of vascular access in hemodialysis pediatric patients can be challenging, due to the small diameter of vessels. In the last 19 years, 38 arteriovenous fistulas (AVF) for hemodialysis have been created on 21 patients; 25 of them were radio-cephalic AVF. The evaluation of the vessels was, in the majority of cases, done by clinical criteria. A local anesthesia was used in all surgical procedures. The percentage of early AVF failure was 24%. Long-term AVF survival was 97%, 65% and 55% at respectively 1, 3 and 5 years. Our data indicate that even in pediatric patients the radio-cephalic fistula is the first choice surgical procedure.

[Temporary vascular access for haemodialysis: is infection still the most important complication?]. / L'accesso vascolare temporaneo per emodialisi: e' ancora l'infezione la complicanza da temere maggiormente?

BACKGROUND: Aging in the dialitic population currently shows the problem of vascular access for haemodialysis. The use of temporary catheters for haemodialysis has increased the risk of infections. DOQI guidelines underline this problem. We think that the thrombosis of central veins is a problem as important as infection. METHODS: In the last two years we studied prospectively 310 patients. 686 catheters for haemodialysis were placed. Infection, malfunctioning of catheters and thrombosis of central veins were studied. We compared femoral catheters with jugular catheters. Finally we studied by ultrasound the jugular vessels diameter and thrombi of jugular vein. RESULTS. Fever was present in 5.55% of patients with femoral catheters and in 5.84% of the patients with jugular catheters. The malfunctioning incidence in patients with femoral catheters was 22.75% and 8.76% in patients with jugular catheters with statistic difference. Ultrasound study of jugular veins showed thrombotic incidence of internal jugular vein in 20,8% of patients. CONCLUSIONS: We think that with correct management of catheters there is no difference in the incidence of fever in patients with jugular catheters versus femoral catheters. Probably jugular catheters have better performance than femoral catheters. We need controlled studies to better understand the problem of central vein thrombosis.

Internal jugular vein thrombosis after positioning CVC in dialysis patients: The most common ultrasound patterns.

Frequently patients are started on hemodialysis after the placement of a central venous catheter (temporary or tunneled) in the internal jugular vein (IJV). Currenty this procedure is facilitated by ultrasound probes that improve the rate of success of catheter placement in vessels and diminishes the possible complications, minimizing the gap between nephrologists with wide surgical expertise and those with limited surgical experience. Stenosis and thrombosis of the subclavia vein are well documented complications derived from the placement of the venous catheter. Internal jugular vein thrombosis is not seen very often due to scarce clinical evidence. In our paper we have been able to systematically document various extrinsic thrombotic complications outside the central venous catheter, by use of ultrasound (periluminar or related to the vessel).

[Perspectives of immunosuppressive therapy in kidney transplantation]. / Prospettive di terapia immunosoppressiva nel trapianto renale.

Within recent years important progress has been made in the field of renal transplantation, both in terms of surgery and immunosuppression. At the present time renal transplantation offers a better expectation and quality of life to patients with end stage renal disease, compared with patients in dialysis. The survival of renal transplantation depends on many immunological and non immunological factors. The widespread use of calcineurine inhibitors (cyclosporine and tacrolimus) has improved the actuarial survival of transplanted kidneys at one year, decreasing the number and the severity of acute rejection episodes, but the calcineurine inhibitors did not improve the chronic rejection. The use of the new immunosuppressant drugs (mycophenolate mofetil, rapamicine and RAD, anti CD25 humanized antibodies) has contributed both to a further reduction of the number of rejection episodes and of side-effects of the immunosuppressant drugs, which have been possible thanks to the various combinations of these drugs. moreover these drugs allow the reduction or withdraw of steroids. Further studies will be necessary to ascertain that these new drugs improve the long term survival of transplanted kidneys and to define more precisely problems relating to the immunosuppressive therapy with respect to renal function, rejection, and patients' quality of life.

The side effect profile of sirolimus: a phase I study in quiescent cyclosporine-prednisone-treated renal transplant patients.

A 14-day ascending dose course of sirolimus (rapamycin, RAPA) was administered to quiescent renal transplant patients receiving a double-drug cyclosporine (CsA)/corticosteroid regimen in a double-blinded randomized study. Oral sirolimus or placebo was delivered twice daily in divided doses for 13 days and a final dose was administered on the morning of study day 14. In addition, patients in the sirolimus- and placebo-treated groups were compared with a demographically matched, concurrently treated control cohort of 30 patients who received the same concentration-controlled CsA/corticosteroid regimen. The study cohort was partitioned into four sirolimus dose level groups: placebo (0 mg/m2/day, N = 10), low dose (1 to 3 mg/m2/day, N = 9), medium dose (5 to 6 mg/m2/day, N = 9), and high dose (7 to 13 mg/m2/day, N = 12). the primary side effect of sirolimus was a reversible decrease in platelet (PLT) and white blood cell (WBC) counts. Cholesterol values increased statistically significantly in the sirolimus-treated patients when compared with those of the placebo patients, but not when compared with those of the control group patients. There were no statistically significant differences in the steady-state average concentrations of CsA among sirolimus dose groups (including placebo). No differences were observed between the pre- and post-sirolimus treatment values of systolic and diastolic blood pressure values, glomerular filtration rates (GFR), serum creatinine values (SCr), and serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT) or triglyceride levels. Because the principal side effects of sirolimus are distinct from the principal nephrotoxic properties of CsA, this drug combination may display potent immunosuppression without exacerbated toxicity.

Potential applications of therapeutic drug monitoring of sirolimus immunosuppression in clinical renal transplantation.

Sirolimus is a potent immunosuppressive agent with a novel mechanism of action. It inhibits the transduction of cytokine signals necessary for the proliferation and maturation of T cells. Because sirolimus blocks a broad spectrum of cytokine signals, it seems logical to use it as an adjunct to CsA-based immunosuppression. The high degree of synergy between these two agents, as suggested by the rigorous median-effect analysis, has been confirmed by a reduced rate of rejection episodes among human renal allograft recipients. However, Phase I studies document wide interindividual variation in the pharmacokinetic parameters of 26 stable renal transplant patients, thereby suggesting that optimal therapy may require monitoring of drug concentrations, which is a task that has been somewhat simplified by the good correlation of trough level to AUC. Development of a monoclonal antibody assay system may simplify the monitoring of drug concentrations further. Additional studies of sirolimus will be required to determine the therapeutic concentrations and ratios of sirolimus to CsA that provide optimal immunosuppression, and to assess the possibility of a steroid-free regimen.