HLA-DR1, -DR5, and -DR8 antigen disparities are associated with acute steroid-resistant rejection and poor kidney graft survival.
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Biomedical subjects
Publications and source records attributed to H Isoniemi.
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Serum lipid and lipoprotein profiles were performed in order to investigate lipid abnormalities 2 years post-transplantation in first cadaveric renal allograft recipients immunosuppressed with cyclosporin (CyA), azathioprine (Aza), and methylprednisolone (MP), or with any combination of two drugs. CyA was used in low doses. Total serum cholesterol, triglyceride, LDL cholesterol, HDL cholesterol, HDL2 cholesterol, HDL3 cholesterol, apolipoprotein A1, and apolipoprotein B were determined in 88 prospectively randomized patients with functioning grafts. When considering only the patients who remained on the original randomized treatment, there were no significant differences between the four groups in any of the measured variables. Mean total cholesterol was highest in the group receiving Aza and MP (6.8 mmol/l) and lowest in the group receiving triple therapy (5.8 mmol/l; NS). Mean triglyceride level was highest in the group receiving Aza and MP (2.3 mmol/l) versus 1.8-2.2 mmol/l in the groups receiving triple therapy, Aza + CyA, and CyA + MP. For all patients mean triglyceride level was highest in the group receiving Aza and MP (2.7 mmol/l) and lowest in the group receiving triple therapy (1.7 mmol/l; P less than 0.05). Mean HDL cholesterol ranged from 1.5 to 1.6 mmol/l in all groups. Neither CyA concentration nor CyA or MP dose correlated with cholesterol or triglyceride concentration. However, the average MP dose was twice as high in the group receiving Aza and MP as in the other two groups employing steroids. Serum cholesterol and triglyceride concentrations were related to body mass index (r = 0.28, P = 0.045 and r = 0.30, P = 0.029, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
The long-term effects of different immunosuppressive drugs and regimens on renal allograft histology are virtually unknown. Therefore, in order to investigate the long-term effects of triple drug treatment versus different combinations of two immunosuppressive drugs on allograft histology, a prospective, randomized trial was performed. One group received triple therapy consisting of low-dose cyclosporin (CyA), azathioprine (Aza), and methylprednisolone (MP), and three groups received combinations of two drugs, i.e., Aza plus CyA, Aza plus MP, and CyA plus MP. At 2 years, there were no significant differences with regard to graft (80%) or patient (87%) survival, or to graft function between the four groups. After 2 years, a protocol core biopsy was taken of all 102 patients having a functioning graft. Of these patients, 61 (60%) were still following the original, randomized treatment protocol; in the remaining cases, changes had occurred in the original protocol and so these cases were considered drop-outs in this study. Histological specimens were examined blindly by two independent observers. Most of the 34 histological variables examined showed no changes. Diffuse fibrosis was most frequent in the CyA plus MP group (70%) and significantly more severe than in the triple therapy group. Mesangial matrix increase in glomeruli was significantly less common in the triple therapy group (8%) than in any one of the double drug combination groups (47%). Two other changes in glomeruli--Bowman capsular thickening and global glomerular sclerosis--were also less frequent in the triple therapy group.(ABSTRACT TRUNCATED AT 250 WORDS)
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The effect of intravesically applied antibiotic solution in the prevention of infectious complications of renal transplantation was evaluated in a prospective, randomized study. The bladder was filled preoperatively with saline solution containing cephalotin in the test group, and with saline solution only in the controls. Both groups of patients received IV doses of cephamandole during, and once after, surgery. Two hundred consecutive patients were randomly allocated to the study groups. The overall incidence of urinary tract infection was 10.4% during the first 4 postoperative weeks; that of wound infections was 1.6% and of septicemia 3.3%. The addition of cephalotin to the bladder irrigation fluid did not have any effect on the overall incidence of infectious complications.
Fine-needle aspiration biopsies were used for clinical monitoring of liver allografts; 21 patients with an inflammatory episode of acute rejection (12.0 +/- 3.3 CIU at the peak) were studied; all episodes were reversible. The inflammatory infiltrate consisted mainly of lymphoid cells, including lymphoid blasts, with increased numbers of class II and IL-2-receptor expressing lymphocytes. No lymphoid activation was seen in corresponding blood specimens. A rapid response to antirejection therapy with high-dose steroids was recorded by FNAB. Another group of 7 recipients without rejection developed a severe CMV disease. The CMV disease was associated with mild inflammation in the FNAB (3.2 +/- 0.9 CIU at the peak), but fewer blast cells and activated cell types were recorded in the graft, and blast cells and lymphocyte activation were seen in the blood specimens, as well. The inflammation disappeared from the FNABs during successful antiviral treatment. The cellular findings of rejection and CMV infection were significantly different, and the presence or absence of rejection could be firmly established by FNAB.
The outcome of 64 repeated renal retransplantations (50 third, 13 fourth, and 1 fifth) during a period of 25 years was retrospectively evaluated. The prognosis of third and subsequent grafting was greatly improved if cyclosporine was included in the induction immunosuppressive regimen (one-year graft survival 79.9%, compared with 32.4% if CsA was not used). The onset of graft function was not delayed by CsA and the proportion of never functioning grafts was significantly lower (5.3%) in patients treated with CsA than in those treated without it (43.2%). Survival of the previous grafts for longer than one year favorably influenced the outcome of the subsequent grafts.
Until December 1988, 38 patients with primary biliary cirrhosis (PBC) had been transplanted in the Nordic countries. The observed survival probability in accordance with Kaplan-Meier analysis was around 75% 2-3 months after surgery, with few deaths during the next 3 years. The observed survival curve was compared with the expected survival calculated from the experience of a recent English PBC transplant series; the patterns are very similar. Secondly, the observed survival was compared with the expected survival curve, calculated from the survival experience of an international trial of medical treatment--that is, the expected survival had the patients not been transplanted; after the first 2-3 months the observed survival stayed better than the expected survival. Finally, the merits of transplantation for each particular patient was evaluated by means of the ratio of probability of survival when transplanted to probability of survival when medically treated 3, 6, and 8 months after surgery. The ratio increased with time, indicating a relative increase in the benefit of transplantation with time after surgery.
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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 less than 0.01), the 1.7 episodes in patients on CyA monotherapy (P less than 0.001), or the 1.6 episodes in patients receiving CyA together with MP (P less than 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 less than 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 less than 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).(ABSTRACT TRUNCATED AT 250 WORDS)
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.(ABSTRACT TRUNCATED AT 250 WORDS)
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