Addition of sirolimus to cyclosporine in long-term kidney transplant recipients to withdraw steroid.

The aim of this study was to evaluate the feasibility of a steroid-free maintenance immunosuppression regimen in long-term renal transplant (KTx) recipients after addition of sirolimus (SRL) to cyclosporine (CsA)-based immunosuppression. A multicenter, prospective pilot study of steroid withdrawal (SW) was initiated for KTx patients. SW was divided into three phases: (A) conversion to a SRL + CsA + steroid regimen; (B) steroid tapering and withdrawal; and (C) maintenance with SRL + CsA. Primary endpoints of the study were incidence of acute biopsy-proven rejection (AR) and safety. In the A and B phases of the study 42 KTx patients (132 +/- 75 months post-Tx) were entered into the study, 18 of 42 (43%) with severe, acute side effects due to the CsA + SRL combination. These side effects were reversible with reduction of CsA or with suspension of the SRL/CsA combination. An amendment was introduced in the protocol to drastically reduce the CsA exposure to <50 ng/mL (trough) at the time of SRL addition. After this amendment, 39 other KTx patients entered the study and only 3 of 39 (8%) were discontinued because of toxic side effects. In the overall cohort of 81 KTx patients, the incidence of AR after SW was low (n = 5, 6.1%), all occurring within the first 3 months after SW. These findings indicate: (1) addition of SRL to very low-maintenance CyA exposure allows safe SW in KTx; (2) with the SRL + CsA combination, the incidence of AR after SW is low in long-term KTx patients; and (3) in the first 3 months after SW strict monitoring for early diagnosis and treatment of AR is mandatory.

Platelet thromboxane formation and BTG levels after intensive charcoal HP in uremics or regular hemodialytic treatment (RHT).

Vascular tissues from uremic patients show increased prostaglandin synthesizing capacity while uremic platelets have decreased thromboxane synthesis. It has been suggested that the platelet defects in uremia are partially corrected by hemodialysis and a correlation with the levels of guanidinsuccinic acid, phenolic acid, creatinine or urea has been demonstrated. In our study 6 patients with end-stage renal disease on RHT, underwent, daily and for ten days, two-hours hemoperfusion, in order to obtain lower levels of toxic metabolites such as creatinine (less than 6 mg/dl.). Before and after this intensive treatment we have evaluated BTG plasmatic levels and thromboxane formation by platelets after thrombin and arachidonic acid stimulation. The thromboxane formation was not increased following this treatment, whereas BTG plasmatic levels were significantly diminished.

Clinical effectiveness of apheresis in the treatment of progressive systemic sclerosis.

Scleroderma is a chronic disease of unknown origin characterized by diffuse sclerosis of the connective tissue of the integument and other organs. As in systemic lupus erythematosus (SLE), rheumatoid arthritis and dermatomyositis, a variety of antibodies may be found in the serum, suggesting that immune mechanisms may be involved. In two uremic patients with scleroderma, the effects were studied of the removal, by pheresis, of antinuclear antibodies, immune complexes, and immunoglobulin factors perpetuating the inflammatory response. We used a membrane plasmapheresis with a hollow-fiber type plasmafilter (Plasmaflo, Asahi) connected online with a hemofilter for conventional dialysis. The aim of this preliminary study was to induce a remission of the edematous inflammatory phase. The correlation of a improvement in clinical response and a decrease in the levels of immune complexes or other factors of inflammation was observed. In our view membrane-plasmapheresis is a process safely carried out by the hemodialysis staff and it may be of clinical effectiveness, especially, in patients with life-threatening complications of progressive systemic sclerosis.