[Early kidney-pancreas transplantation in type 1 diabetics prevents hemodialysis]. / Il trapianto precoce di rene-pancreas previene l'ingresso in dialisi dei diabetici tipo 1.

BACKGROUND: The life-expectancy of type 1 diabetics (T1D) on dialysis is still shorter than that of non-diabetics. Pancreas transplantation (PT) in its different modalities should be considered as a life-saving procedure. METHODS: We analyzed our referral activity of T1D to PT from 1992. Since 2002, we have created a kidney and diabetes out-patient clinic devoted to the prevention of diabetic nephropathy and to the early referral of suitable T1D to combined kidney- pancreas transplantation (KPT) and isolated pancreas (PTA). RESULTS: In the last 14 yrs, 25 T1D underwent KP in our district (620000 inhabitants). At the beginning, KPT was performed abroad, but then the borders were closed. After stopping in the mid 1990s, KP activity restarted addressing preemptive KPT and PTA. Currently, only one patient is on dialysis while awaiting KPT. Four T1D were evaluated and excluded from the list on medical grounds; two patients are on the list and a further two patients are currently under evaluation. CONCLUSIONS: The implementation of a cooperative network among dialysis and transplant centers, supported by devoted out-patient clinics allowed the effective prevention of the dialysis requirement in T1D. Out-patient clinics devoted to diabetic nephropathy should play a pro-active role in preemptive KP, including the 'new' option of islet transplantation according to the Edmonton protocol.

Clinical evaluation of internal hemodiafiltration (iHDF): a diffusive-convective technique performed with internal filtration enhanced high-flux dialyzers.

AIM: Efficiency in removing middle molecules such as beta2-microglobulin (beta2-MG) is one of the main purposes of modern dialytic therapy. In order to achieve this, techniques requiring complex machines and substitution fluid have been developed over recent years. Alternatively, the internal filtration/back filtration phenomenon can be used. The recent development of a so-called "internal filtration enhanced dialyser" prompted us to compare the removal of beta2-MG together with other small molecules when the dialyser was used either in standard hemodiafiltration (HDF) or internal hemodiafiltration (iHDF). METHODS: Ten stable, anuric, hemodialysis (HD) patients treated by thrice weekly standard bicarbonate HD using low-flux synthetic membrane entered the study. A new high-flux polysulfone dialyser designed with the specific aim of enhancing internal filtration (BS-1.6 UL, 1.6 m2, Toray Industries) was used. Post dilution HDF (2.5 l/hour of substitution fluid, dialysate flow 500 ml/min) was compared with iHDF (dialysate flow 750 ml/min), with blood flow at 300 ml/min. Samples were obtained at the start and at the end of the session in order to measure the % removal of urea, creatinine, uric acid, phosphate and beta2-MG (corrected for total protein concentration). In addition, after 20 min of dialysis the clearances of the same molecules were measured. A mathematical model has been developed for the description of the hydrodynamic phenomena taking place within the dialyser and of fluid filtration across the membrane. RESULTS: No significant differences have been observed in removal rate switching from HDF to iHDF except for beta2-MG removal, which was slightly higher in HDF than in iHDF Phosphate clearance is significantly higher than those obtained with creatinine in both HDF (p<0.005) and iHDF (p<0.01) modalities. The total convection calculated with the model is reduced with respect to HDF only by 24% (4100 ml/h vs. 5400 ml/h on the average). CONCLUSIONS: iHDF is a high flux dialysis method, which, if performed with a dialyser designed to enhance internal filtration, obtains a much higher removal rate in comparison with dialysers in traditional high flux dialysis, as previously reported in the literature. Provided that the dialyser is used on a dialysis machine working with ultra pure dialysate and UF control, this dialyser line can perform reliable internal HDF without the need for replacement solution. Considering the narrow difference in performance observed between iHDF and HDF, and the increasing number (and age) of patients leading to higher dialysis costs, iHDF represents a cost-effective alternative to other diffusive-convective techniques.

Receptor binding at two different temperatures to discriminate agonist and antagonist behaviour of adenosine A1 receptor ligands in rat brain.

The inhibitory binding constants, Ki, at the adenosine A1 receptor in rat brain have been measured at 0 and 25 degrees C for 25 typical ligands. The Ki ratios at the two temperatures are greater and smaller than unity for adenosine agonists and xanthine antagonists, respectively. These results suggest that two-temperature measurements of in-vitro Ki constants represent a simple method of discriminating between in-vivo agonistic and antagonistic behaviour of A1 adenosine receptor ligands.