Audun Flatmark

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.

Fifteen years' experience with renal transplantation in systemic amyloidosis

Abstract. At our center 62 renal transplantations (31 living donor and 31 cadaveric donor grafts) have been performed in 58 patients with amyloid renal disease since 1974. The amyloidosis was secondary to rheumatic disease in 74 % of the patients. Predialytic transplantation was performed in 28% of the patients. Mean follow‐up time was 5.1 years (0.3–14.5 years). One‐year actuarial patient survival was 79%, decreasing to 65% after 5 years. First graft survival was 74 % at 1 year and 62 % at 5 years. Patient death with a functioning graft caused 16 out of 25 graft losses. Infections caused 11 out of 18 deaths (61 %), more than half of them within 3 months. Renal transplant amyloid was diagnosed in about 10% of the cases (6/ 62); however, only about 3% of the grafts (2/62) were lost. These long‐term results encourage transplantation in amyloid renal end‐stage disease.

Aortoiliac reconstruction in preparation for renal transplantation.

Aortoliac angiography has always been an integral part of the pretransplantation work-up of renal transplant candidates in Norway. The present study was undertaken to investigate the value of this routine. Based on the angiograms of approximately 1400 patients evaluated for renal transplantation during the 7-year period 1984–1991, 26 were found to have aortic and/or iliac atherosclerosis requiring pretransplant vascular reconstruction. Fifteen of the 26 patients had aneurysm of the abdominal aorta and 11 had extensive aortoiliac occlusive disease. A prosthetic graft was inserted in 25 patients and endarterectomy of the aortic bifurcation was performed in one. The cause of death was coronary heart disease in four of six patients who died before, and in one patient who died after, transplantation. Sixteen patients received a renal transplant while four patients are still on the waiting list. Fifteen of the recipients are alive, 14 with functioning renal transplants. The low yield of patients below 40 years of age requiring vascular reconstruction calls into question the routine use of angiographic investigation of renal transplant candidates below this age. However, we recommend this routine for the higher age groups because it often provides the surgeon performing the transplantation with valuable information. Aortoiliac reconstruction as preparation for renal transplantation is advocated when atherosclerosis of a degree that may preclude transplantation is found. Because of the high risk of myocardial infarction in these patients, one must be especially aware of coronary atherosclerosis when evaluating patients for this procedure.

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).

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.

SIGNIFICANCE OF HLA-D/DR MATCHING IN RENAL TRANSPLANTATION

A low mixed-lymphocyte-culture response, indicating matching for HLA-D, was associated with a relatively good chance of graft survival in 62 recipients of renal transplants from living relatives mismatched for one or two HLA A and/or B antigens. In 96 cadaveric transplants prospectively typed for HLA-DR antigens, compatibility for these antigens improved the prognosis, irrespective of matching for HLA A and B antigens. In cadaveric transplants, a positive B-cell cross-match test before transplantation tended to predict inferior graft survival.

Long-Term Endocrine Function of Duct-Ligated Pancreas Isotransplants in Rats

Duct-ligated pancreas transplants were used to study the long-term B cell function after total acinar atrophy. Vascularized whole-organ pancreas transplantation was performed in 47 streptozotocin-diabetic inbred Wistar rats. Of 31 recipients which survived the first week, 30 were permanently cured of the diabetic state with restoration of normal blood glucose levels within 24 h. Metabolic and morphologic studies were performed for up to 16 months after transplantation, i.e. for most of the normal life span of the rats. The recipients of duct-ligated, heterotopic transplants demonstrated plasma insulin (IRI) values slightly above normal. Median blood glucose values were significantly lower than in the normal controls. Basal and stimulated IRI as well as glucose tolerance tests failed to reveal any reduction in the endocrine capacity of the transplants as compared to nondiabetic control. Light-microscopic examinations of grafts showed total acinar atrophy after the first weeks of duct occlusion. No apparent reduction of islet tissue was noted. The results demonstrate that total occlusion of the exocrine ductal system does not impair B cell function of the rat pancreas. The duct-ligated pancreatic transplant permanently reverses induced diabetes when pancreatitis and immunologic reactions are avoided.

Renal failure in familial lecithin-cholesterol acyltransferase deficiency.

Familial lecithin-cholesterol acyltransferase deficiency is a hereditary disorder of lipid metabolism. Lipid material is deposited in the kidneys, the glomerular capillary basement membrane is irregularly thickened, detachment and even loss of endothelial cells are seen in the glomeruli. Proteinuria was present in 8 out of 9 cases studied, usually it has not been detected before the age of 15-20. After 15-30 years with symptomless proteinuria, terminal renal failure has developed in 6 of the patients. Possible pathogenetic mechanisms of the renal damage is discussed; a large-molecular-weight low-density lipoprotein is suggested to be an important factor.