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Background: Perioperative antibiotic prophylaxis may prevent infection following renal transplantation but it also contributes to development of resistant microorganisms. With refined surgical techniques, improved graft preservation, and immunosuppressive monitoring during recent decades one can question the present use of perioperative antibiotic prophylaxis. We retrospectively evaluated the incidence of infection in our renal transplant centre where antibiotic prophylaxis is not routinely used in renal recipients. Concurrently we performed a survey of perioperative antibiotic use to establish the current world-wide practice. [ABSTRACT FROM PUBLISHER]

Thrombotic microangiopathy (TMA) and hemolytic uremic syndrome (HUS) represent serious threats to kidney allograft recipients. During a 4-year period, among 850 kidney transplantations, seven recipients with primary HUS and seven recipients (eight transplants) with previous or de novo TMA/HUS were identified and given calcineurin inhibitor (CNI)-free immunosuppression by sirolimus (SRL), mycophenolate mofetil and steroids. Thirteen out of 15 transplantations were successful in the long term; resulting in a mean creatinine of 101 mumol/L (16.4 months follow-up). In patients maintained on CNI-free regimen, no TMA/HUS recurrences were observed. A high rate of acute rejections (53%) may indicate insufficient immunosuppressive power and/or a causative relationship between TMA/HUS and rejection. Wound-related complications were abundant (60%), and call for surgical/immunosuppressive countermeasures. Our experience supports the idea that CNI's are major offenders in TMA/HUS induction. Total CNI elimination seems essential, as the nephrotoxic combination CNI + SRL may promote TMA. Features of TMA/HUS should be carefully explored in recurrent 'high responders'.

This study was undertaken to compare the efficacy and safety of tacrolimus (Tac) with cyclosporin microemulsion (CyA) in pediatric renal recipients. A 6-month, randomized, prospective, open, parallel group study with an open extension phase was conducted in 18 centers from nine European countries. In total, 196 pediatric patients (<18 yr) were randomly assigned (1:1) to receive either Tac (n = 103) or CyA (n = 93) administered concomitantly with azathioprine and corticosteroids. The primary endpoint was incidence and time to first acute rejection (intent-to-treat). Baseline characteristics were comparable between treatment groups. Excluding deceased patients (n = 9) and patients lost to follow-up (n = 31, mostly transferred to adult care), 95% of 2-yr data (159 of 167 possible patients), 87% of 3-yr data (142 of 163) and 73% of 4-yr data (114 of 156) were retrieved. At 1 yr Tac therapy resulted in a significantly lower incidence of acute rejection (36.9%) compared with CyA (59.1%, p = 0.003). The incidence of corticosteroid-resistant rejection was also significantly lower with Tac (7.8% vs. 25.8%, p = 0.001). At 4 yr, patient survival was similar (94% vs. 92%, p = 0.86) but graft survival significantly favored Tac (86% vs. 69%; p = 0.025, log-rank test), respectively. At 1 yr, the mean glomerular filtration rate (GFR) (Schwartz formula, ml/min/1.73 m(2)) was 64.9 +/- 20.7 (n = 84) vs. 57.8 +/- 21.9 (n = 77, p = 0.0355), at 2 yr 64.9 +/- 19.8 (n = 71) vs. 51.7 +/- 20.3 (n = 66, p = 0.0002), at 3 yr 66.7 +/- 26.4 (n = 81) vs. 53.0 +/- 23.3 (n = 55, p = 0.0022), and at 4 yr 71.5 +/- 22.9 (n = 51) vs. 53.0 +/- 21.6 (n = 44, p = 0.0001) for Tac vs. CyA, respectively. Cholesterol remained significantly higher with CyA throughout follow-up. Three patients in each arm developed post-transplant lymphoproliferative disease. Incidence of insulin-dependent diabetes mellitus was not different. Tac was significantly more effective than CyA in preventing acute rejection in pediatric renal recipients. Renal function and graft survival were also superior with Tac. Glomerular filtration rate appears to be an useful surrogate marker for long-term outcome.

Background: Adrenocortical carcinoma is a highly malignant tumour with a poor prognosis. Surgery is the treatment of choice, with repeated procedures if necessary., Material and Methods: A 39-year-old woman presented with a pronounced Cushing's syndrome with virilizsation. Investigations showed an adrenocortical carcinoma with a diameter of 12 cm and two large metastases in the liver. She was admitted for palliative surgery. The primary tumour and one liver metastasis were resected. Three months later a right hepatectomy was performed, with excision of the remaining liver metastasis. Mitotane tablets were given all the time., Results: After the first operation the patient's clinical condition improved radically. Two years later she was clinically healthy without any tumours and normal hormone levels. After 27 months a relapse in the liver was found by computed tomography, and after 33 months steroid hormone precursors again increased. Radiotherapy to the liver metastasis was given, and at 48 months the patient is still healthy and has no relapse., Interpretation: Patients with adrenocortical carcinoma should be treated with extensive surgery, if necessary with repeated resections. Additional chemotherapy should be considered. This case confirms that surgical therapy has effect on metastasizing and hormone producing adrenal carcinoma and we consider that intensive surgery has improved this patient's prognosis.

Background: Though the great majority of hepatic and perihepatic neoplasms may very well be treated by conventional surgical techniques, a few patients will have lesions seemingly inaccessible by traditional in situ surgical procedures., Material and Method: We present two patients with retrohepatic sarcoma and liver haemangioma respectively, treated by hepatectomy, ex situ resection and hepatic autotransplantation., Results: The first patient, a 64-year-old man, had a completely uneventful postoperative course and had no indication of recurrent sarcoma two years later. The second patient, a 29-year-old female with a giant hepatic haemangioma developed postoperative hepatic artery thrombosis. Following thrombectomy her further course was satisfactory and the patient was discharged with normal liver function three weeks postoperatively., Interpretation: Ex situ liver surgery (bench surgery) with liver autotransplantation should be considered when traditional in situ surgery on the liver or adjacent structures is not applicable.

The treatment of a 64-year-old man with a retrohepatic neoplasm deemed not accessible by conventional in situ surgical techniques is presented to illustrate the potential benefit offered by techniques adapted from liver transplantation and vascular surgery. A computed tomography scan performed for uncharacteristic abdominal discomfort revealed a hepatic or retrohepatic tumor compressing the inferior vena cava. Biopsies were interpreted as probably leiomyoma or malignant schwannoma. The liver with neoplasm and retrohepatic inferior vena cava was removed en bloc and taken to the back table where the neoplasm invading the inferior vena cava wall was removed together with the inferior vena cava. The inferior vena cava was then replaced by a 22-mm polytetrafluoroethylene graft and the 3 hepatic veins were reconstructed with anastomoses to this graft. The liver was then autotransplanted by standard transplantation technique. The postoperative course was uneventful and the patient is in good health more than 2 years after surgery.

Background: Statin therapy has been reported to reduce the acute rejection rate following renal transplantation in a pilot study. The present study is the first randomized, double-blind and adequately powered study to examine the effect of statins on acute rejection of renal allografts., Methods: A total of 364 patients were randomly assigned to receive either fluvastatin 40 mg or placebo in combination with conventional cyclosporine-based immunosuppressive therapy. The primary end point was treated first acute rejection. Secondary end points included biopsy-proven rejection, histological severity of rejection, occurrence of steroid-resistant rejection, and serum creatinine at three months following transplantation., Results: Fluvastatin was well tolerated; no patients developed myositis or rhabdomyolysis. There was no difference in the acute rejection rate [86 (47.3%) fluvastatin vs. 87 (47.8%) placebo] and no significant difference in the severity of rejection, steroid resistant rejection or mean serum creatinine at three months (160 micromol/L vs. 160 micromol/L). Total cholesterol, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol and triglyceride levels increased following renal transplantation. With the exception of the increase in HDL-C, which was augmented, the increases in lipid parameters were significantly reduced by fluvastatin (total cholesterol +17.5% vs. 35.7%; LDL-C +6.3% vs. 46.7%; HDL-C +43.3% vs. 38.1%; triglyceride +52.2% vs 77.6%)., Conclusions: Contrary to the reported effects of statins, fluvastatin had no effect on the incidence or severity of acute rejection following renal transplantation. There were no increases in adverse events. A significant and potentially beneficial alteration in the lipid profile was observed in the early post transplant period. We conclude that fluvastatin may be used safely to correct dyslipidemia in patients with end-stage renal failure through the peri-transplant period.

We present a 50-year-old female who experienced generalized convulsion 3 months after a successful cadaveric renal transplantation. The first cerebral CT scan indicated cerebral frontal infarction. Repeat CT some days later revealed progressive lesions, and a highly malignant tumor or abscess was suspected. Antifungal and broad-spectrum antibacterial therapy was initiated. Cerebral MRI could not differentiate between these conditions, but a neutrophil granulocyte scan strongly suggested an infectious process. A stereotactic puncture of the frontal lobe was followed by temporary improvement. A severe progressive left-sided hemiparalysis gave indication for a craniotomy with evacuation of the abscess 9 days later. Culture of aspirated pus yielded growth of a gram-positive, rod-shaped bacterium, later identified as Nocardia otitidiscaviarum by sequencing the 16S rRNA. The patient was treated with meropenem plus rifampicin intravenously for 6 weeks followed by oral ciprofloxacin and rifampicin for 2 months. Due to pharmacokinetic interaction with rifampicin, the prednisolone dose was doubled, and the dose of tacrolimus had to be tripled for maintenance of adequate trough concentrations. Five months following cessation of antibiotic treatment, the patient has regained normal strength and function in her left-sided extremities and has a serum creatinine level of about 160 micromol/l (1.8 mg/dl)., (Copyright 2000 S. Karger AG, Basel)

Increasing shortage of organs for transplantation is a global phenomenon. In spite of a high kidney transplantation rate (45 per million population), the waiting list for kidney transplantation in Norway increased by 22% from 1996 to 1998. The waiting list for lung transplantation increased by 129% in the same period. The average annual number of cadaveric organ donors was 15.8 per million, with significant differences in donation rate between the health regions. Investigators have established the incidence of potential organ donors to be around 50 per million population per year. Failure to identify or support a potential donor and refusal of permission from relatives are important reasons why organ donation does not occur. We give a brief overview of programmes implemented in various European countries to increase organ donation. Improvement of donor hospitals organisation in order to support potential donor detection as well as training and motivation of hospital staff are considered important steps for increasing the organ donation rate.

According to the International Pancreas Transplant Registry, more than 1,000 pancreas transplantations are now performed annually. When performed simultaneously with a kidney transplant, pancreas transplantation is a generally accepted treatment for type 1 diabetic patients with end stage renal disease, and the pancreas graft survival in this setting is equivalent to that of the kidney graft. The reported results of solitary pancreatic transplantation in non-uraemic diabetic patients have been less favourable due to a high rejection rate in combination with difficulties in rejection diagnosis and treatment. However, the introduction of new immunosuppressive drugs over the last few years has drastically improved the survival of solitary pancreatic grafts and allows for a rising enthusiasm. The majority of the 122 transplantations performed in Oslo so far were simultaneous kidney and pancreas transplantations. Duct occluded segmental grafts were used until 1988 when the pancreatico-duodenal technique with bladder drainage was introduced. In March 1998 we changed to enteric drainage of the exocrine pancreas due to a high percentage of lower urinary tract problems and bicarbonate loss associated with the bladder drainage technique. The positive impact of a functioning pancreas transplant on the recipient's quality of life is well recognised, whereas long-term beneficial effects on the secondary complications of diabetes are not well documented. A short overview of various aspects of pancreas transplantation is given, including experience with the 122 transplantations performed at the National Hospital, Oslo, Norway.

The influence of serology-based HLA matching on the risk of acute rejection episodes and of graft loss was analyzed in a material of 678 living donor (LD) and 997 cadaveric donor (CD) renal transplantations performed in our center in the period 1989-97. In LD transplantation, recipients of HLA-identical sibling grafts had the lowest rejection risk and the best graft survival, with a half-life estimate of 30 years. One-HLA-haplotype mismatched grafts did better than two-haplotype mismatched related or unrelated donor grafts. Matching for HLA-DR significantly reduced the rejection risk of one-haplotype mismatched grafts. In CD first transplants, HLA-DR matched grafts had a lower incidence of rejection and better survival than HLA-DR mismatched grafts. Expected half-life for HLA-DR matched grafts was 12 years compared to less than 7 years for HLA-DR mismatched grafts. The effects of matching for HLA-A and -B did not reach statistical significance. In CD regrafts, a two-antigen mismatch for HLA-A or -DR led to a significantly poorer graft survival, but the panel-reactive antibody (PRA) status of the recipient was the most influential factor. In CD renal transplantation, we conclude that organ allocation based on matching for HLA-DR 1-14 is effective and not too difficult to obtain even in centers with a short patient waiting list.

Background: A single-center study of 655 nonsensitized recipients of primary cadaveric kidney grafts is presented., Results: Graft survival in serologically HLA-DR 1-10 antigen-matched grafts to nonsensitized recipients at 1 year was 90%, compared with 82% (P=0.004) and 73% (P=0.001) in one and two DR antigen-mismatched grafts. The corresponding figures at 5 years were 76%, 62%, and 56%, respectively. Matching for the DR antigens 11-14, or for some DR alleles only detectable by genomic typing, further improved graft survival, but the differences did not reach statistical significance. Matching also for the serologically defined HLA-A and -B antigens did not significantly further improve overall graft survival, but some effects for grafts surviving at least 1 year were observed. Among recipients of grafts mismatched for zero, one, or two HLA-DR antigens, acute rejection episodes were experienced in 48%, 64% (P<0.001), and 82% (P<0.001), respectively, within the first 3 months. HLA-A and -B mismatches showed no significant correlation to acute rejection episodes., Conclusion: Matching for the DR antigens 1-10 significantly secures and prolongs the survival of first cadaveric renal grafts. Our results also show that DR 1-10 antigen-matched combinations can often be obtained even in rather small recipient pools, when actively sought for.

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.

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.

The Nordic organ exchange organization, Scandiatransplant was established in 1969. The organization, which covers a population of 23.9 million inhabitants, includes all 11 organ transplant centers in the 5 Nordic countries Denmark, Finland, Iceland, Norway and Sweden. The economy is solely based on transplant center fees. All Nordic patients waiting for an organ transplant are registered on one common waiting list. Rules for the exchange of organs are settled by unanimous decision, and the compliance to the rules is excellent. Kidney exchange is based on HLA matching, whereas the exchange of livers and hearts is based on clinical urgency. In 1997, 43% of the liver transplantations in Scandiatransplant were performed with an exchanged organ and the exchange rate for kidneys was 20%. Currently, the Scandiatransplant waiting list includes 1,538 patients waiting for a kidney transplant, 20 patients are waiting for a liver, 37 for a heart, and 156 patients are waiting for a lung transplant. The organ donation rate in Scandiatransplant has declined in recent years, from 16.0 per million population (PMP) in 1993 to a level of 13.5 PMP in 1997. The number of kidney transplants has varied between 800-900 per year during the past 10 years, corresponding to 33-38 transplants PMP. Approximately 30% of the renal transplants were performed with kidneys from living donors. The liver transplantation activity was approximately 7 PMP per year. Heart transplantation was performed at a rate of 4-5 PMP per year, and lung transplants at 4 PMP per year.

The Nordic collaboration in organ transplantation was initiated nearly 30 years ago in the frame of Scandiatransplant. With a recent formalization of its structure, Scandiatransplant has become a modern organ exchange organization. The increasing activities of Scandiatransplant clearly reflect the continuously growing need for a close and firm Nordic collaboration in the transplantation field, for the benefit of the numerous patients waiting for an organ transplant.

Scandiatransplant is an organ exchange organisation founded in 1969. It serves a population of 23 million inhabitants in the five Nordic countries; Iceland, Norway, Sweden, Finland and Denmark. Scandiatransplant maintains a common central waiting list for all Nordic patients waiting for necro-organ transplantation. The waiting lists are maintained on a central computer by each of the eleven transplant centres in the organisation. The number of necro-organ donors in Scandiatransplant is about 340-375 yearly, corresponding to 15-16 donors per million population (PMP) per year. Since the foundation, a total of 14,500 necro-kidney transplants have been performed, and the number of transplants with extrarenal organs is steadily increasing. Presently, about 7-8 liver transplants PMP are being performed, and the heart transplant activity amounts to about 5 PMP. The supreme authority of Scandiatransplant is the Council of Representatives, in which each transplant centre is represented by one or more professionals who are clinically active in organ transplantation. The responsibility for day-to-day operations lies with the Board which has one member appointed by each of the five Nordic countries and a chairman elected by the Council. The activities of Scandiatransplant are financed exclusively by the participating centres.

Severe hypertension prior to renal transplantation has traditionally been an indication for bilateral nephrectomy. The reasons for hypertension after successful renal transplantation are however many, and the impact of simultaneous bilateral nephrectomy (BN) in this setting has not been well documented. We retrospectively evaluated 158 living-donor renal graft recipients. BN had been performed in 76 patients at the time of the transplantation and 82 were not nephrectomized (controls). All received a triple immunosuppressive drug regimen. Before transplantation, patients in the BN group used 1.8 +/- 0.9 (mean +/- SD) antihypertensive drugs/day, significantly more than in the control group (1.3 +/- 0.8; P < 0.05). Three months after renal transplantation no difference was found (0.9 +/- 1.0 drugs/day in the BN group vs 1.0 +/- 0.8 drugs/day in the control group). No difference was found with respect to serum creatinine, whole blood cyclosporin A (CsA) concentration or blood pressure between the groups. The number of blood transfusions during the first week after transplantation was significantly increased in the BN group (66 SAG units vs 4 SAG units). The median hospitalization length was also longer in the BN group (21 days vs 16 days). In order to circumscribe the pre-transplant difference in use of antihypertensive medication we studied a subgroup of 62 hypertensive recipients (BN/control = 31/31) matched for number of antihypertensive drugs at the time of transplantation (2.3 +/- 0.5 drugs/day in the BN group, 2.1 +/- 0.3 drugs/day in the control group). Three months after transplantation the use of antihypertensive drugs remained the same in the two groups (1.3 +/- 1.0 drugs/day in the BN group vs 1.3 +/- 0.9 drugs/day in the control group). At 3 months no difference was found between the two hypertensive subgroups regarding serum creatinine, whole blood CsA and haemoglobin concentration or systolic blood pressure. However, the BN patients were younger than the control group (38 +/- 10 years vs 49 +/- 11 years, P < 0.05) and this may explain the marginally lower diastolic blood pressure observed in the BN group (82 +/- 10 mmHg vs 87 +/- 7 mmHg, P < 0.05). It is concluded that, in recipients of living-donor grafts, bilateral nephrectomy performed at the time of transplantation did not influence the number of antihypertensive drugs used 3 months after a successful transplantation. Bilateral nephrectomy did however increase the need of blood transfusions during the first week after transplantation and also the hospitalization length.

Background: Pancreas transplantation has been reported to prevent development and progression of diabetic glomerulopathy., Study Design: Kidneys transplanted to type 1 diabetic patients were investigated for signs of diabetic glomerulopathy. Biopsies were obtained from 11 patients 2-4 years after simultaneous pancreas and kidney transplantation and from six patients 2-6 years after kidney transplantation alone. During follow-up, glycaemic control was monitored as glycated haemoglobin and, in the pancreas transplant patients, as i.v. glucose tolerance., Results: Measures of glycaemic control were consistently normal in only two pancreas transplant patients. Four had mean k values <1.0. In kidney biopsies from the pancreas transplant patients, thickness of the glomerular basement membrane was 395 (0.13) nm (mean, coefficient of variation), which is higher than normal (324 (0.13) nm, P=0.01) and not different from diabetic patients with kidney transplants alone, 418 (0.15) nm. The mean calculated annual increase in thickness did not differ between patients with and without a pancreas transplant, 26 (0.77) versus 29 (0.54) nm/year. Estimates of the mesangium and mesangial matrix were in the normal range in both groups while the interstitial volume fraction was increased and to a similar extent., Conclusion: The increase in thickness of the glomerular basement membrane in kidneys transplanted simultaneously with a segmental pancreas is probably an expression of diabetic glomerulopathy caused by the modest impairment in glucose metabolism present in most patients.