Dagfinn Albrechtsen

Ischemic heart disease - major cause of death and graft loss after renal transplantation in Scandinavia.

Causes of graft loss and death were studied in 1347 recipients of primary renal transplants followed for 5 years after transplantation irrespective of graft function. Immunosuppression consisted of high or medium dose CsA and prednisolone or low dose CsA and prednisolone and azathioprine. In recipients of cadaver grafts, death with a functioning transplant was more common than graft rejection after the first posttransplant year, accounting for 49% and 41% of the graft losses, respectively. Of deaths with a functioning graft, 53% were due to ischemic heart disease (IHD) and 10% were due to other vascular disease. In the 55− to 64-year-old age group, the risk of death from IHD was 6.4 times higher in the transplanted nondiabetic patients, 8.6 times higher in the dialysis patients (European Dialysis and Transplant Association figures), and 20.8 times higher in the transplanted diabetic patients than in the general population (national figures). A multivariate Cox regression analysis showed that old age, diabetes mellitus, occurrence of acute rejection, pretransplant transfusions, delayed onset of graft function, and male gender were significant for death in IHD. We conclude that, in comparison to reports from other regions, Scandinavian renal transplant recipients are at high risk of dying of HID. Future advances in long-term renal graft survival will depend largely on the success of preventing myocardial infarction and death in this patient population.

The impact of acute rejection episodes on long-term graft function and outcome in 1347 primary renal transplants treated by 3 cyclosporine regimens.

To characterize factors of importance for the occurrence of acute rejection as well as study the impact of these episodes on long-term renal survival and function, a total of 819 acute rejection episodes were studied in 951 primary cadaveric donor kidney recipients (CD) and in 396 primary living donor kidney recipients (LD). The patients were treated by three immunosuppressive schedules, namely, CsA given in a high dose, a medium dose, or a low dose. Additionally, all patients received PRED and patients in the low-dose group received AZA. The incidence of acute rejection was higher and occurred earlier after transplantation in the CsA medium dose and low dose groups than in the CsA high dose group (P < 0.05 and P < 0.01, respectively). Although the incidence of first acute rejection was similar in CD and LD patients, 59.1% vs. 60.6%, it was successfully reversed by antirejection treatment in a higher percentage in LD patients. The estimated graft half-life was shorter in patients who had acute rejection episodes than those who did not, 6.6 years vs. 12.5 years in CD pa

Depletion of T lymphocytes from human bone marrow. Use of magnetic monosized polymer microspheres coated with T-lymphocyte-specific monoclonal antibodies.

A new technique for depletion of T cells from bone marrow is presented. Bone marrow cells (BMC) were rosetted with magnetic monosized polystyrene micro-spheres coated with monoclonal antibodies (MAbs) specific for T cell CD2 and CD3 antigens. Rosetted T cells were subsequently removed from non-T cells with the aid of a magnet. This immunomagnetic separation procedure was carried out in less than 40 min and reproducibly removed T cells, leaving a maximum of 0.025% sheep-red-blood-cell (SRBC) rosette-forming cells and less than 0.02% T cells as detected by a T cell limiting dilution assay. The efficacy of the depletion procedure was further shown by flow cytometry data, by effective removal of cells from a T cell line added to the BMC prior to immunomagnetic separation, and by abrogation of interleukin 2 (IL-2)-producing capacity in T-cell-depleted BMC (BMC-T). The T cell depletion procedure provided a 43–74% recovery of non-T cells present in the Isopaque-Ficoll-isolated bone marrow mononuclear cell fraction and did not disturb the growth potential of stem cells, as assayed by hematopoietic stem cell assays.

Unrelated living donors in 141 kidney transplantations: a one-center study.

BACKGROUND Kidney transplantation is the optimal treatment for the majority of patients with end-stage renal disease. However, the shortage of kidneys for transplantation is a global problem, and any attempt to improve the donor situation would be of benefit to the growing number of patients on transplant waiting lists. PATIENTS AND METHODS Since 1984, we have transplanted 141 kidneys from genetically unrelated living donors. Donors were most often spouses and were accepted regardless of HLA match grade. Preemptive transplantation was performed in 39% of the patients. Standard triple-drug immunosuppression with prednisolone, cyclosporine, and azathioprine was used. The patients were followed from 6 months to 13 years. RESULTS The incidence of acute rejection during the first 3 months after transplantation was higher in recipients of grafts from unrelated donors than in recipients of grafts from related living donors or cadaveric donors. However, unrelated living donor grafts survived significantly better than did cadaveric grafts (P < 0.02) and had a survival rate similar to that of living-related donor grafts mismatched for one or both HLA haplotypes. The perioperative complication rate for the donor was low. CONCLUSION We consider unrelated living donors an excellent source for alleviating the shortage of donor kidneys.

Individualized T cell monitored administration of ATG versus OKT3 in steroid‐resistant kidney graft rejection

Abstract: Acute steroid‐resistant rejection episodes are recommended to be treated with set doses of anti‐thymocyte globulin (ATG) or anti‐CD3 monoclonal antibody (OKT3). Individualized T cell monitoring has been proposed as a tool for dose finding. A randomized study comparing the efficacy and safety of ATG (n = 27) with OKT3 (n = 28) in the treatment of biopsy verified acute steroid‐resistant rejection (ASRR) when both drugs were administered on the basis of daily individualized T cell measurements. A drop to below 50 cells/mm3 CD2+ T cells was considered adequate and used to guide the dose of ATG/OKT3. Demographic, clinical and histopathological severities of rejections were equal in the two groups. During the 10 days of T cell monitoring and antibody treatment, 13 patients were in need of dialysis (ATG = 7/OKT3 = 6). Two grafts did not respond to antibody treatment and were lost due to rejection (ATG = 1/OKT3 = 1). There were 26 biopsy verified re‐rejections (ATG = 12/OKT3 = 14) within the first 3 months following antibody treatment. Mean serum creatinine (μmol/L) was similar in the two groups (ATG/OKT3: before rejection 157 ± 72/151 ± 88, at start of antibody treatment 308 ± 125/330 ± 94, end of antibody treatment 254 ± 122/246 ± 144 and at follow‐up after a mean of 32 months 166 ± 55 (n = 24)/164 ± 57(n = 23)). To keep the T cell count below 50 cells/mm3, average dose ATG given was 354 ± 151 mg (2.3 administrations, range 1–4) and average OKT3 was 32.5 ± 6.8 mg in 10 doses. In conclusion, individualized T cell monitored administration of ATG and OKT3 is safe and seems as effective as a standard set dose in treatment of ASRR. Tailoring the dose for each individual patient lowers the cost.

Importance of HLA-DR Matching in Cadaveric Renal Transplantation: A Prospective One-Center Study of 170 Transplants

To investigate the influence of matching for HLA-DR antigens in renal transplantation, we assessed the outcome of 170 prospectively HLA-typed cadaveric kidney transplantations performed since 1977 in one center. We found a beneficial effect on graft survival of HLA-DR compatibility between donor and recipient (P < 0.05). A possible effect of matching for the HLA-A and B antigens could be seen only in the HLA-DR-mismatched combinations. Pretransplantation blood transfusions were associated with increased graft survival only in patients receiving HLA-DR mismatched transplants (P < 0.02). We conclude that major emphasis should be placed on obtaining HLA-DR compatibility renal transplantation. (N Engl J Med. 1980; 303:850-4).

A randomized trial of cyclosporine and prednisolone versus cyclosporine, azathioprine, and prednisolone in primary cadaveric renal transplantation.

A randomized trial was performed with the aim to compare two immunosuppressive treatment schedules in adult recipients of first cadaveric renal transplants. A total of 229 patients were randomized to double therapy with cyclosporine and prednisolone and 234 patients were randomized to triple therapy with cyclosporine, azathioprine, and prednisolone. Minimum follow-up was 4 years. The actuarial 5-year patient survival was 79.8% in the double therapy group and 82.3% in the triple therapy group (n.s.). The corresponding graft survival figures were 54.4% and 59.6% in the two groups, respectively (n.s.). There were no differences between the groups regarding cause of death or cause of graft loss. Renal function as determined by serum creatinine did not differ between the groups and was stable throughout the observation period. Azathioprine was instituted in a total of 51 patients randomized to double therapy. This subgroup of patients

Pretransplant plasma exchange or immunoadsorption facilitates renal transplantation in immunized patients

Patients with preformed antibodies against HLA molecules accumulate on renal transplant waiting lists and have inferior graft survival compared with nonsensitized patients. One hundred patients were included in a program of pretransplant removal of antibodies by plasma exchange (n=90) or immunoadsorption (n=10) in addition to prednisolone and cyclophosphamide medication. After plasma exchange, the panel reactivity and the antibody titer were reduced in about half of the patients, and after immunoadsorption the panel reactivity fell in 6 of 10 patients. Of the 83 patients who received grafts, 17 received a graft from a living donor (LD) and 66 received a graft from a cadaver donor (CD). Patients with a positive crossmatch against their LD were included in the program and were thus grafted with a recent positive, current negative crossmatched organ. Fifteen CD graft recipients had a pretreatment positive crossmatch toward their donor. No episodes of hyperacute rejection were seen. One- and 4-year graft survival rates in LD transplants with a recent positive and current negative crossmatch were 77% and 64%, respectively. At 1 and 4 years, graft survival rates were 70% and 57% in pretreated first CD graft recipients (n=27) and 61% and 47% in pretreated regrafted patients (n=39), respectively. In this program, a high rate of transplantation among the sensitized patients was achieved. Graft survival was inferior to that seen in nonsensitized patients, but was comparable to graft survival in sensitized patients at other centers.

The use of elderly living donors in renal transplantation

Abstract. The safety and the results of using living donors above the age of 60 years were studied. In 235 consecutive donors the complications were not different in elderly (n= 70) compared to younger donors. Graft survival and function were studied in 232 consecutive 1‐HLA‐haplotype mismatched grafts. Graft survival at 1 year was equivalent (87% vs. 92%), but after 2–6 years graft survival was inferior in recipients of older grafts (n= 62). The recipients of older grafts were 10 years older, and patient death with functioning graft was a more frequent cause of graft loss. Up to 4 years serum creatinine levels were significantly higher, but stable, in recipients of older grafts; at 5 years the difference was not significant. It is concluded that the use of elderly living donors is safe. Taking recipient age into consideration, graft survival is not different in the two groups. Graft function in older grafts is some what inferior, but stable.

Renal replacement therapy in elderly patients

The results of renal replacement therapy (RRT) in elderly patients in Norway were evaluated. During the 5-year period between 1981 and 1985, 368 patients at least 60 years of age (mean, 66.7 years) at the start of RRT were included and followed until 15 February 1987. Transplantation was planned for 249 patients; of these 127 were not grafted. The actuarial survival in this group was 64%, 44%, and 7% at 6, 12, and 48 months, respectively. Survival in 122 grafted patients was 93%, 87%, and 62%, respectively, and the corresponding graft survival was 70%, 67%, and 48%. The remaining 119 patients were allocated to long-term dialysis, with a survival of 63%, 48%, and 13%, respectively. Our results describe the outcome of a treatment program available to the entire elderly population accepted for RRT. In two-thirds of the patients transplantation was planned, and one-third of all patients were actually grafted, with good patient and graft survival. The results suggest that transplantation is the treatment of choice for most elderly patients.