Renal allograft immunosuppression

We have investigated the impact of triple drug immunosuppression on the occurrence of early inflammatory episodes, as detected by fine needle aspiration biopsy, and of episodes of clinical rejection during the immediate postoperative period. The prospective component of this study includes 128 consecutive first cadaveric renal transplant recipients receiving triple drug treatment consisting of azathioprine (Aza), cyclosporin (CyA) and methylprednisolone (MP). For controls we have used three historical groups: one immunosuppressed with Aza and MP (group A), another with CyA monotherapy (group B), and the third with CyA together with MP (group C) in equivalent drug dosages. On the average, 0.8 episodes of inflammation per patient were recorded during the immediate postoperative period of 30 days with triple drug treatment. This was significantly less than the 1.3 episodes in patients receiving Aza and MP (P<0.01), the 1.7 episodes in patients on CyA monotherapy (P<0.001), or the 1.6 episodes in patients receiving CyA together with MP (P<0.001). Although the first episode of inflammation commenced concurrently in each group and the peak intensity of inflammation was the same, the mean duration of inflammation was significantly shorter-2.7 days-under triple drug treatment than the 7.8–11.7 days for controls (P<0.001). The frequency of rejection episodes under triple treatment was also significantly lower-0.2 per patient-than the 0.8 per patient in controls (P<0.001). The first rejection episode occurred later in the triple drug treatment group-on the average, on day 15.2-than in the historical controls (on days 7.7–11.7). There was, however, no difference in the duration of rejection. There were no differences in patient survival between the four groups. Graft survival was 97% at 10 weeks for triple drug-treated recipients and 79%, 68%, and 87% for first grafts in groups A, B, and C, respectively. Disregarding a minor demographic bias for the triple drugtreated group with respect to preformed antibodies and preoperative dialysis treatment, the study suggests that the triple drug protocol, in the short run, is superior to any conceivable double drug combination or CyA monotherapy.     

Renal allograft immunosuppression: II. A randomized trial of withdrawal of one drug in triple drug immunosuppression

Abstract. A prospective randomized study was conducted to evaluate the impact of four different conversion protocols on graft outcome in long-term follow-up. Between January 1986 and May 1987, 128 patients with first cadaveric kidney allografts were randomized at the time of transplantation to four treatment groups of 32 patients each, to be assigned 10 weeks post-transplantation. During the first 10 weeks, all patients received triple therapy with low-dose azathioprine (Aza), cyclosporin (CyA), and methylprednisolone (MP). After 10 weeks, one group continued with triple therapy (group A) while the three other groups received different combinations of two drugs, namely, Aza and CyA (group B), Aza and MP (group C), or CyA and MP (group D). Withdrawal of MP (group B) or especially of CyA (group C) was associated with 4/29 (14%) and 10/28 (36%) acute rejection episodes, respectively, for 60 days after conversion. All rejections were mild and reversible. There were no rejections after Aza withdrawal or in the group that continued on triple therapy during the corresponding time period. The most common reason for dropping out after withdrawal, for those patients who could not continue on the originally randomized medication, was azathioprine intolerance (n= 12). Five patients were switched back to triple therapy after CyA withdrawal due to rejection. Steroid intolerance was rare and CyA in low doses was very well tolerated. At 1 year there were no statistically significant differences in graft survival between groups A, B, C, and D-81 %, 88%, 88%, and 88%, respectively-or in patient survival-88%, 88%, 88%, and 97%, respectively. For those patients continuing with the originally randomized treatment protocol, there were no differences in patient or graft survival either, the means being 91% and 89%, respectively. The most common cause of death after withdrawal was cardiovascular in nature, and there were no more fatal infections under triple drug treatment than with double drug regimens. There were no statistically significant differences in mean serum creatinine values at 1 year. The median serum creatinine values for groups A, B, C, and D were 112, 132, 133, and 133 μmol/l, respectively. At 1 year the mean CyA dose in the groups that continued with CyA was 3. 5–4. 2 mg/kg per day and CyA concentrations were equal.     

Value of albumin dialysis therapy in severe liver insufficiency

Abstract A blood purification system, molecular adsorbents re-circulating system (MARS), is based on the removal of both protein-bound and water-soluble substances and toxins in the liver. We treated a total of 88 patients within 2 years. Of these patients, 45 had acute liver failure (ALF), 31 had acute decompensation of chronic liver disease, eight had graft failure and four had miscellaneous conditions. Of the patients with ALF, 80% survived; in 23 patients their own liver recovered and 13 patients underwent successful transplantation. Only 23% of patients with acute-on-chronic liver failure survived. Most of them were not considered for transplantation due to their having liver failure from alcoholism and from not abstaining from drinking. MARS is a promising therapy for ALF, allowing the patient's own liver to recover or allowing enough time to find a liver graft. Best results were achieved in patients who had been intoxicated with a lethal dose of toxin. On the other hand, we did not observe much benefit in patients with severe acute-on-chronic liver failure (AcoChr) who did not undergo liver transplantation.     

Liver-First Approach for Synchronous Colorectal Metastases: Analysis of 7360 Patients from the LiverMetSurvey Registry

Annals of Surgical Oncology - The liver-first approach in patients with synchronous colorectal liver metastases (CRLM) has gained wide consensus but its role is still to be clarified. We aimed to...     

Renal allograft immunosuppression III. Triple therapy versus three different combinations of double drug treatment: two year results in kidney transplant patients

A prospective randomized trial was carried out to compare the long-term effects of triple therapy based on low-dose cyclosporin A (CyA), low-dose methylprednisolone (MP) and azathioprine (Aza) with three different double drug immunosuppressive regimens. After initial triple drug immunosuppression for 10 weeks, 128 patients were randomized into four different immunosuppressive groups: one group continued with triple therapy (group A) and the three other groups were treated with different combinations of two drugs: Aza and CyA (group B), Aza and MP (group C) and CyA and MP (group D). This report presents the 2-year results. For groups A, B, C and D, graft survivals were 75%, 78%, 84% and 81%, respectively, and patient survivals were 84%, 84%, 84% and 94%, respectively. After 2 years no patient had returned to dialysis in group C compared with one to three patients in every CyA-using group. However, at the end of the 2nd year, group C included more patients with deteriorating graft function than the other groups. Median serum creatinine was 107, 120, 139 and 129 mol/l for groups A, B, C and D, respectively. For the patients who remained on the original randomized protocol, there were no significant differences in graft function tests between the four groups, the median creatinine being 115, 115, 118 and 113 mol/l for groups A, B, C and D, respectively. Thus, no graft deterioration had occurred during the 2 years for these patients following the original protocol. Our results suggest that after initial triple therapy, patients with a first cadaveric kidney allograft can either continue with triple therapy or be converted to any of the double drug regimens without detriment to graft function, graft survival or patient survival for the next 2 years. This will allow more flexible and individual immunosuppressive treatment.     

The Association of Time to Organ Procurement on Short- and Long-Term Outcomes in Kidney Transplantation

Open in a separate window