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.

[Cadaver organ donation in Norway 1993-96]. / Organdonasjon fra avdøde givere i Norge 1993-96.

The annual number of cadaveric organ donors increased from 13.1 per million inhabitants in the period 1989-92 to 15.8 in the period 1993-96. Multiple organ harvesting was performed in 68% of the donors. There are significant differences in donation rate between health regions. An increase to 20 organ donors per year per million inhabitants is required to meet the anticipated need for organs. Strategies to increase organ donation are discussed.

The national kidney transplant program in Norway still results in unchanged waiting lists.

1. Of 2,670 patients starting renal replacement therapy for end-stage renal disease in Norway from 1989-1997, 76% were candidates for transplantation. The annual need for transplantations increased from 47 to 64 grafts PMP as the number of elderly patients increased. The national waiting list has remained almost stable during the period from 1989-1997 at levels of 25-30 PMP, but the dialysis population has increased from 57-105 PMP. 2. A total of 1,681 transplants was performed at an annual rate varying between 38 and 46 grafts PMP. The grafts were procured from LDs in 41% and CDs in 59% of cases. Totally 69% of all patients in need were transplanted and 54% of all patients requiring replacement therapy for end-stage renal disease received a transplant. 3. Graft survival rates in recipients of first LD grafts (n = 641) were 91% and 77% at one and 5 years, respectively. One-year graft survival was 97% in HLA-identical grafts (n = 71), 92% in haploidentical grafts (n = 419), 88% in 2 haplotype-mismatched related grafts (n = 43), and 87% in spousal donor grafts (n = 108). 4. Graft survival rates in recipients of first CD grafts (n = 801) were 84% and 65% at one and 5 years, respectively. The rates were 86% and 74% in younger (n = 557) versus 78% and 46% in older (> 65 years) (n = 244) patients. Death with a functioning graft caused approximately 45% and 75% of all graft losses in younger and older patients, respectively. Cardiovascular disease was the major cause of death. 5. A significant beneficial effect of HLA-DR matching was observed in CD grafts performed after 1989, in particular in patients older than age 65.

Alterations in lymphocyte subsets in blood may predict resectability in carcinoma of cardia or oesophagus.

Impaired immune responses in patients with carcinoma of cardia or oesophagus have previously been reported. However, we do not know whether resectability correlates with specific immunological variables. Immunological assessment was performed in 35 such cancer patients including measurement of total T cells (CD3+) and T cell subsets (CD4+ and CD8+), NK cells (CD16+) and B cells (CD19+) in blood. In vitro lymphocyte responses to phytohemagglutinin (PHA) separated from peripheral blood were quantitated. The numbers in peripheral blood of both total T cells (CD3+) and B lymphocytes (CD19+) were significantly lower in the inoperable patients compared to resected patients (P < 0.01). The number of NK cells (CD16+) was, however, not significantly lower in the inoperable patients compared to the patients operated for cure. Lymphocyte responses to PHA in vitro were similar in resectable and non-resectable patients, but significantly lower in inoperable patients compared to the controls (P < 0.01). In conclusion, resectability in carcinoma of cardia or oesophagus is associated with changes in both T (CD3+) and B (CD19+) cell subsets.

[Liver transplantation in Norway. Results after 10 years and 114 transplantations]. / Levertransplantasjon i Norge. Resultater etter ti års aktivitet og 114 transplantasjoner.

A total of 114 liver transplantations were performed in 106 patients in Norway during 1984-1994. Survival after one year was 65% and after three years 57%. The most frequent causes of death were infections and rejections. The survival rate improved considerably during the period, and after 1990 the 1 year survival was 70%. Approximately 2/3 of the patients return to work or education. Very few patients die later than 12 months after the transplantation. The most frequent indications were primary biliary cirrhosis, metabolic liver disease, primary sclerosing cholangitis, autoimmune cirrhosis and fulminant liver failure. The number of liver transplantations (approximately 4 per million inhabitants) is lower in Norway than in the other Nordic countries. The number should be increased to 7-8 per million inhabitants.

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.

Long-term low-dose calcitriol treatment in predialysis chronic renal failure: can it prevent hyperparathyroid bone disease?

In an uncontrolled open study 13 patients with moderate to preterminal renal failure were treated with low doses (average 0.36 micrograms/day) of calcitriol up to the time of renal transplantation, which was performed before dialysis had been initiated. A transiliac bone biopsy was obtained both at the start and at the end of the treatment period, the latter coinciding with renal transplantation. All patients who started calcitriol treatment at a creatinine clearance (Ccr) above 30 ml/min had normal bone histology at the time of transplantation, but this was not observed when calcitriol treatment was started at Ccr below 30 ml/min. The study suggests that full benefit of calcitriol at the bone level is obtained only if prophylactic administration is started early in the course of renal failure.

A randomized multicenter trial of cyclosporin and prednisolone versus cyclosporin, azathioprine, and prednisolone following primary living donor renal transplantation.

A total of 195 consecutive recipients of primary living donor renal transplants were randomized to receive either cyclosporin (CyA) and prednisolone (double therapy) or CyA, prednisolone, and azathioprine (triple therapy). There was no significant difference in patient or graft survival, incidence of acute rejection episodes, or major complications between the groups. The graft survival at 5 years was 71.5% in patients receiving double therapy and 71.6% in patients receiving triple therapy. In a Cox regression analysis, recipient age and occurrence of acute rejection were the only independently significant variables affecting graft survival, whereas treatment schedule did not. Renal function was stable throughout the observation period and did not differ between the double and triple therapy groups. A linear regression analysis showed that recipient age, donor age, gender, and occurrence of acute rejection significantly influenced the serum creatinine level. This and previous similar prospective studies in cadaveric renal transplantation indicate that there is no advantage of routinely adding azathioprine to a double drug regimen.

[Cadaver organ donation in Norway 1989-92]. / Organdonasjon fra avdøde givere i Norge 1989-92.

The annual number of cadaveric organ donors in Norway increased from an average of 12.4 per million inhabitants per year in the period 1985-88 to 13.1 in the period 1989-92. An increase to 20 organ donors per million per year is required to meet the anticipated need for organs. The donation rates differ greatly between health regions. Possible strategies to increase the organ donation rate are discussed.

A Scandinavian two-center study of BMA 031 in steroid-resistant rejection of renal grafts.

BMA 031 (Behring Monoclonal Antibody) was given to 25 renal graft recipients with biopsy-proven steroid-resistant rejections. A dose of 50 mg of BMA 031 was given i.v. on 7 consecutive days concomitantly with a standard triple-drug regimen. No premedication was administered before the first BMA 031 dose. After the first dose, 7 patients experienced moderate fever (< 39 degrees C), 5 patients had high fever (> 39 degrees C), 4 patients had nausea/vomiting, 3 diarrhea, 1 headache, and 1 hypertension. These reactions were seen only after the first dose except for 1 patient who developed urticaria on days 3-4. All the rejection episodes were reversed or partially reversed. Twenty-one patients experienced re-rejections 3-46 days after the last BMA 031 dose, and were treated with methylprednisolone and/or rabbit antihuman thymocyte globulin. Seven patients lost their grafts within 1 year (28%), including 2 patients who died of infection with a functioning graft. BMA 031 seems to be a safe drug with only few mild side effects, and it effectively reverses steroid-resistant rejections. Re-rejections were frequent, but mostly reversible.

Aortoiliac reconstruction in preparation for renal transplantation.

Aortoiliac 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.

Quality of life in Norwegian kidney donors.

The Norwegian kidney transplant programme is based on more extensive use of living donors than in other countries. Re-examination of the physical health of kidney donors has in the majority of studies revealed no long-term medical risk. The quality of life after donation has only been described in very few studies, and with a small number of donors. This report concerns a cross-sectional study of 494 donors with a mean observation time from donation of 6.7 years. A standardized questionnaire containing 19 items related to quality of life was used. The donors were compared to the general adult population in a county in mid-Norway. Out of the 19 quality of life items, the donors scored significantly better in 13. Donors who had experienced that the corresponding recipient had died have been tested separately. The results in this subgroup were equal to the population, but inferior compared to the rest of the donors. We conclude that the quality of life of Norwegian kidney donors is better than the general population. We will continue our policy of an extensive use of living kidney donors.

Fibro-muscular renal artery disease treated by extracorporeal vascular reconstruction and renal autotransplantation: short- and long-term results.

Over a 16-year period (1973-1989), 63 renal autotransplants were performed in 59 patients for fibro-muscular dysplasia (FMD) with renal artery stenoses (42 kidneys) or aneurysms (21 kidneys). About two-thirds of the autotransplants were performed before percutaneous transluminal angioplasty (PTA) was established for clinical use. However, vascular disease at a site or type not suitable for PTA was present in 57 (90%) of the kidneys. Hypertension was the leading symptom in 56 patients, including four in whom renal autotransplantation was performed as an emergency for acute renal artery occlusion or malignant hypertension. Blood pressure returned to normal or improved in 51 (91%) and remained unchanged in five patients (9%) following autotransplantation. Three patients with renal artery aneurysm in whom haematuria and loin pain were the indications for treatment, became asymptomatic following surgical intervention. Bilateral renal autotransplantation was performed synchronously in one and sequentially in three patients. There were no operative deaths, but two kidneys were lost postoperatively in two 2-year-old children owing to renal vascular thrombosis. In the follow-up period (mean 4.3 years), one additional kidney was lost at 3 months owing to progressive FMD. Blood pressure and renal function remained stable in all other patients. Based on the excellent results achieved in this series, it is concluded that extracorporeal vascular repair and renal autotransplantation is a safe procedure for the patient as well as the kidney affected by FMD. The procedure is advocated as an alternative to in situ reconstruction in patients with renal artery disease not accessible to PTA, such as aneurysms and complex branch renal artery stenoses.

Renal microvascular perfusion evaluated by single fibre laser Doppler flowmetry.

The single fibre laser Doppler flowmetry technique has been designed to perform continuous quantification of microvascular perfusion deep in tissue. In this study we have evaluated the use of the technique in renal tissue. A total number of 164 recordings were analyzed. Fluctuations in perfusion related to heart rate and respiration were observed. The possible nature of the low-frequency flow motion waves (10-12 min-1) is discussed. No significant difference in perfusion level could be detected between the upper, the middle and the lower parts of the kidneys (p greater than 0.69), or between the cortex and the medulla (p = 0.77). The spatial variation, expressed as the difference between two consecutive measurements, was large. The median and mean values of groups of data are however reproducible. When the renal artery is reopened after 30 sec of occlusion, the pre-occlusive flux levels are regained after approximately 1.5 sec. The single fibre laser Doppler flowmetry technique can be used for renal microcirculatory studies, but comparative studies with other methods have to be performed.

Raw soybeans stimulate human pancreatic proteinase secretion.

Intraduodenal instillation of raw soybeans stimulated pancreatic proteinase secretion in humans. Raw soybeans almost abolished the activity of chymotrypsin and severely reduced (50%) the tryptic activity. Immunoreactive tryptic and chymotryptic material simultaneously appeared in amounts 2 to 4 times basal concentrations. This increase, demonstrated with rocket immunoelectrophoresis, was begun within the first 10 min of soybean instillation. The enhanced secretion also persisted throughout the succeeding saline instillation, and it is suggested that the presence of Kunitz trypsin inhibitor contributed to this postprandial stimulation. An amidase that hydrolyzes low-molecular-weight substrates (i.e., benzoyl-arginine p-nitroanilide) was found in raw soybeans. Its low activity was not assumed to substantially bias standard trypsin assays. The increased proteinase secretion was, as previously published, not preceded by an elevated plasma cholecystokinin concentration. The raw soybeans also caused a nonparallel secretion of amylase and proteinases. Nervous, perhaps cholinergic, regulation mediates the inhibitor-stimulated proteinase secretion in humans. This stimulation yields both a general increase of proteinases and also a specific inhibitor-resistant trypsin. This is consistent with the physiologic need for proenzyme-activation in the presence of inhibitors and for restoration of the proteolytic capacity of the duodenal juice.

Aluminum metabolism and bone histology after kidney transplantation: a one-year follow-up study.

Parathyroid activity, bone aluminum (Al) metabolism, bone histology, and clinical bone disease were studied in 55 successfully grafted kidney recipients at transplantation (Tx) and after 1 yr of immunosuppression with a low dose corticosteroid and a high dose cyclosporin-A regimen. Symptoms of Al-related bone disease disappeared after Tx. Serum Al and stainable bone Al decreased. The rate of Al removal from the bone surfaces was independent of graft function (creatinine range, 62-415 mumol/L) and bone turnover. Osteoblast activity and bone formation rate increased, while mineralization lag time normalized. Indices of bone resorption remained elevated, indicating persisting hyperparathyroidism. Eighteen percent of the recipients had posttransplant hypercalcemia, most likely caused by incomplete involution of hyperplastic parathyroid glands, while 53% had normocalcemic hyperparathyroidism related to impaired graft function. Cortical thickness decreased, while cancellous bone volume remained stable after Tx; both indices correlated significantly at follow-up with their respective values at Tx. None of 46 radiologically examined recipients had aseptic bone necrosis 1 yr after Tx.

Fifteen years' experience with renal transplantation in systemic amyloidosis.

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.