Cancer risk after renal transplantation in the Nordic countries, 1964-1986.

The theory that cancer may arise under conditions of reduced immune capacity is supported by observations of humans with immune deficiencies such as occur following organ transplants. However, no study on humans has been done in which the reference population was the same as that in which the cancer cases arose and in which there was a sufficiently long period of follow-up. Information on 5,692 Nordic recipients of renal transplants in 1964-1982 was linked with the national cancer registries (1964-1986) and population registries. Person-years at risk were calculated from the date of first transplantation until death or the end of the study period and were multiplied by the appropriate age- and calender-specific incidence rates to obtain the expected numbers of cancers. Standardized incidence ratios (SIR) were calculated after stratification by a number of recorded variables. Altogether, 32,392 person-years were accrued, and 471 cancers occurred, yielding overall SIR of 4.6 (95% CI, 4.0 to 5.2) for males and 4.5 (95% CI, 4.0 to 5.2) for females. Significant overall 2- to 5-fold excess risks in both sexes were seen for cancers of the colon, larynx, lung and bladder, and in men also for cancers of the prostate and testis. Notably high risks, 10-fold to 30-fold above expectation, were associated with cancers of the lip, skin (non-melanoma), kidney and endocrine glands, also with non-Hodgkin's lymphoma, and in women also with cancers of the cervix and vulva-vagina. Among a number of donor and recipient variables studied, including tissue types and compatibility (ABO, HLA, DR), age below 45 years at the time of transplantation was the most important determinant for increased risk at most sites. Kidney transplantation increases the risk of cancer in the short and in the long term, consistent with the theory that an impaired immune system allows carcinogenic factors to act. The tumor risk is small in comparison with the benefits of transplants, but patients should be followed up for signs of cancer.

Clinical applicability of the immunomagnetic beads technique for serological crossmatching in renal transplantation.

The aim of the present prospective study was to investigate the clinical applicability of the immunomagnetic (IM) beads technique for serological crossmatching (XM) in renal transplantation. The IM XM were read after various periods of incubation, and the results were compared with those obtained by the conventional Kissmeyer-Nielsen (KN) technique. A total of 132 sera from 96 potential recipients were tested against cells from 62 donors. Eight-nine KN T-cell XM-negative renal allograft transplantations were performed, and the IM XM results were related to clinical 3-month follow-up data (incidence of primary non-function, never functioning grafts, graft losses and rejection episodes). The IM technique was clearly more sensitive than KN, and sensitivity increased markedly with increasing duration of incubation. KN-, IM+ reactions were predominantly found among sera from patients with panel-reactive antibodies (PRA, 2p less than 0.01), and thus probably caused by HLA antibodies. However, positive IM XM, appearing after more than 35 min of incubation, did not influence the overall clinical outcome in the observation period. With reading after exactly 35 min of incubation, XM results obtained by IM and KN techniques correlated well. Thus, we believe, that the IM XM technique will be as safe and effective in avoidance of hyperacute rejections as the conventional assay. In the present material, the incidence of primary nonfunction was significantly (2p = 0.0023) higher among PRA+ recipients compared to PRA- patients. To conclude, we recommended the IM technique with reading after exactly 35 min of incubation for easy, fast (70 min) and reliable XM, that is always possible to perform using peripheral blood.

Portal hypertension without liver cirrhosis in renal transplant recipients.

A rare syndrome of portal hypertension with esophageal varices but without evidence of cirrhosis in the liver biopsy was seen in 3 patients in a series of 1000 renal allotransplant recipients immunosuppressed with azathioprine and prednisone. The liver disease began 3-6 years after transplantation with abnormal liver function tests and esophageal varices with bleeding episodes. One patient had also ascites. Liver biopsy at the beginning of liver disease showed in one patient normal structure which eventually developed to slight diffuse fibrosis and nodular hyperplasia. One patient had diffuse fibrosis, and the third patient had strong sinusoidal engorgement with nodular hyperplasia, later on developing to cirrhosis. One patient is still alive and well, the two others died from liver insufficiency. 39 cases of non-cirrhotic portal hypertension in renal transplant recipients and histologic evidence of peliosis, sinusoidal dilatation, nodular hyperplasia or hepatic veno-occlusive disease have been identified in the literature. The cause of this disease is presumably azathioprine, but its rarity shows that it must depend also on other factors.

Acquired haemolytic anaemia due to isohaemagglutinins of donor origin following ABO-minor-incompatible kidney transplantation.

Of 1041 renal allograft transplantations performed in our centre, 142 (13.6%) were carried out with ABO-minor-incompatible kidneys. Anti-recipient ABO antibodies were found in two of 34 patients treated with cyclosporin. These two cases of severe but self-limited haemolysis due to anti-A1 and anti-B, respectively, are reported in detail. Among 108 azathioprine-treated patients no evidence of the disorder was found. The condition should be suspected in any recipient with an unexpected reduction in haematrocrit or other signs of haemolysis after ABO-minor-incompatible organ transplantation.

Herpes simplex infection in relation to kidney allograft survival.

Active infection with one of the herpes viruses, Cytomegalovirus, clearly worsens renal allograft survival. In the present study serologic evidence of infection with another herpes virus, Herpes simplex, was compared with graft survival in 89 cadaveric renal graft recipients transplanted during a two-year period at the Aarhus Center. With respect to Herpes simplex complement-fixing serum antibody status post-transplant, three groups could be identified: 1) No change in antibody titer (25 patients); 2) Significant (4-fold) or more antibody rises (41 patients); 3) No demonstrable antibody (23 patients). Actuarial graft survival was not significantly different in the three groups and thus Herpes simplex infection, in contrast to Cytomegalovirus, does not appear to influence the outcome of renal allograft transplantation.

Morphological and functional characteristics of isolated resistance vessels in advanced uraemia.

In order to obtain direct information on the properties of the resistance vasculature of patients with advanced uraemia, a technique was developed to dissect out small arteries (internal diameter about 165 microns) from biopsies of subcutaneous fat. Such arteries responded in a concentration-dependent manner to noradrenaline and angiotensin II, and the maximal force developed suggested that the vessels were fully viable. Although the biopsies were normally taken during operations under general anaesthesia, biopsies taken under local anaesthesia also appeared to be fully viable, suggesting that this technique may prove useful as a general method for studying the intrinsic vascular properties of humans. Biopsies were taken from 20 patients with uraemia, all of whom were treated with chronic intermittent dialysis, and 11 control subjects; up to three vessels were examined per biopsy. The uraemic state was not associated with changes in vascular morphology, or in vascular reactivity or sensitivity to noradrenaline, angiotensin II, potassium or calcium. However, for the uraemic patients and for the controls there was a positive correlation between mean blood pressure and the ratio of vessel media thickness to lumen diameter, as well as a negative correlation between mean blood pressure and vessel active media stress. The results suggest that uraemia treated with dialysis may not be associated with altered properties of the resistance vasculature. However, it appears that uraemic hypertension is associated with both morphological and functional abnormalities of the resistance vasculature.

Renovascular hypertension. Ability to renal vein ratio to predict the blood pressure level 18-24 months after surgery.

Fourteen patients with severe hypertension and renal artery stenosis were treated surgically. One patient died 4 days after surgery due to a cerebral thrombosis. The other 13 patients were followed for 18-24 months. Five were considered cured since the diastolic blood pressure (DBP) was less than or equal to 90 mm Hg without therapy. Five were improved since DBP was less than or equal to 100 mm Hg during treatment with only one or two antihypertensive agents. There were unchanged. Renal vein renin ratio (RVRR) was greater than or equal to 1.5 either before or after furosemide in all patients who were cured or improved and less than or equal to 1.5 in 2 of 3 who were unchanged. It can be concluded that surgical treatment cured or improved 77% of the patients, and that a RVRR greater than or equal to 1.5 is a good predictor of the blood pressure lowering effect of surgery.

The impact of HLA-DR antigen matching on the survival of cadaveric renal allografts. A prospective one-center analysis.

The impact of HLA-DR antigen matching on the survival of cadaveric renal allografts was assessed in 158 consecutive transplants performed in our unit since early 1978. In 41 donor-recipient pairs with two shared HLA-DR antigens, the actuarial graft survival rate at 6 months was 73% as compared with 51% in 76 transplants with one HLA-DR antigen shared and 32% in 41 transplants with zero shared HLA-DR antigens. This finding is highly significant (P for heterogeneity [PH] = 0.0005 and P for trend, [PT] = 0.0001). Our data clearly indicate that HLA-DR antigen sharing is more beneficial than merely avoiding HLA-DR incompatibility. But, the frequent antigen HLA-DRw6 was not taken into account in this study due to difficulties in its identification. We found no evidence that the observed beneficial effect of HLA-DR matching could be explained by interaction of other prognostic factors, such as sex, age, previous transplantation, diabetes mellitus or pretransplant blood transfusion. Patients who did not receive blood transfusion prior to transplantation had a significantly lower graft survival rate than those who did (13% vs. 56% at 6 months). HLA-DR matching was found to have a powerful effect on graft survival even among pretransplant blood transfused recipients (PH = 0.002, PT = 0.0006). We conclude that selection of recipients for transplantation should attempt to achieve HLA-DR identical combinations.

Spontaneous dissecting aneurysm of the renal arteries. A case and a review of the literature.

A case of dissecting aneurysm of the renal arteries is presented. The patient suffered from an intractable subarachnoid bleeding and the kidneys had been selected for transplantation. One kidney was never transplanted, the other was transplanted and rejected after few days. Dissecting aneurysms were present in the main artery and its major ramifications in both kidneys. Many investigators have claimed that dissecting aneurysm and fibromuscular dysplasia of the renal artery are different stages of but one disease. A review of the accumulated literature on dissecting aneurysm of the renal artery reveals, however, that this disorder shows a preponderance of middle-aged men, whereas fibromuscular dysplasia of the renal artery affects adolescent girls. It is concluded that the two disorders of the renal artery most likely represent different vascular diseases.

Cytomegalovirus infection and kidney graft survival.

Among 123 cadaveric renal allograft recipients transplanted in the period 1971-79, there were 18 with no evidence of past or present cytomegalovirus infection, 34 with primary infection and 71 with reactivated infection. One-year actuarial graft survival was 68%, 32% and 54%, respectively. The reasons for the better graft prognosis in the group without CMV infection were less rejection and fewer infections.

Renal transplantation in polycystic renal disease--a joint Scandinavian report.

During the period 1965-1977, a total of 339 patients with polycystic renal disease received at least 1 renal transplant at one of 10 transplant centres in Scandinavia. Patient survival at one year was 67%. The one year graft survival of 319 cadaveric grafts was 40%. The average age of the patient was 56.7 years. Patients who were 60 years or older (93 patients) had a significantly poorer patient and graft survival at one year (50% and 29.5% respectively). Patients receiving kidneys with O incompatibilities did significantly better than other donor-recipient combinations. Previous blood transfusions were associated with better graft prognosis, though the difference was only significant for 2 years. The incidence of posttransplant urinary tract infection (present in 47% of all the patients) was twice as common in patients with a history of pretransplant urinary tract infection (seen in 41% of all the patients). There was no association between posttransplant septicaemia and either pre- or post-transplant urinary tract infection. Only 10.5% of the patients were nephrectomized at the time of transplantation, half of these had urinary tract infection. Twenty-four per cent of the patients were nephrectomized in the posttransplant period, half of these because of infection. There was no difference in the graft survival data of the patients with or without pretransplant urinary tract infection. These findings justify a restrictive practice with regard to pretransplant nephrectomy in patients with polycystic renal disease.