Sven Arvid Birkeland

Cancer risk in patients on dialysis and after renal transplantation

The increased risk of cancer in patients who have had kidney transplants has mainly been attributed to immunosuppressive therapy; however, the prior period of uraemia and dialysis has also been postulated as a cofactor. We analysed cancer risk retrospectively in a cohort of 4178 patients undergoing renal replacement therapy, of whom 3592 were treated with dialysis alone and 1821 later had transplants. We found that excess cancer risk in such patients occurred after transplantation and not during dialysis.

Pediatric renal transplantation without steroids

Abstract. Pediatric renal transplant patients present a number of challenges and problems, especially the inhibited post-transplant growth seen in children receiving standard immunosuppressive triple therapy that includes steroids. We report the successful use of steroid-free immunosuppression since 1990 in 14 pediatric renal allograft recipients who received a 10-day initial course of antilymphocyte globulin and surface area-adjusted doses of cyclosporine, 7 of whom also received mycophenolate mofetil (MMF) as maintenance immunosuppression. Only 1 patient died (3 months after transplantation as a result of a primary Epstein-Barr virus infection-induced lymphoproliferative disorder), 1 patient’s graft never functioned, and another patient lost his graft after 3 years because of chronic rejection. Three patients experienced early acute cellular rejection, which resolved in 2 cases with OKT3, and in the 3rd with MMF. There were no late acute rejections. All patients evidenced growth and a growth spurt under this regimen. We conclude that all the pediatric patients benefited from our steroid-free protocol and that this protocol is superior to conventional triple therapies, which entail the eventual reduction and discontinuation of steroids, a procedure that not only inhibits growth but also carries an additional risk of acute rejection due to a steroid-adapted immune response.

Malignant tumors in renal transplant patients. The Scandia transplant material.

In Scandinavia, between 1956 and 1974, 2672 kidney transplantations were performed on 2272 patients. Until 1974, 39 de novo malignant tumors were diagnosed among the 1872 patients who received their first and only graft in the period, and among the entire group of patients an additional 58 tumors were diagnosed until 1978; over 1/4 of these tumors were of mesenchymal origin and of these, over one half were reticulosarcomata, and one half were cerebral. Among 566 Danish recipients who received their first and only graft in the period 1969–1974, there was a highly significantly (P < 0.00001) increased tumor incidence in relation to the background population. A significant (P < 0.0005) relationship was found between the occurrence of tumors and human leukocyte antigen (HLA) mismatch. In the entire material no correlation was found to the number of transplantations given to the individual patient; there were significantly (P < 0.01) more tumors in recipients of necrokidneys compared with related kidneys; and there was a significant (P < 0.006) overrepresentation of recipients with chronic interstitial nephritis.

PRE-ECLAMPSIA—A STATE OF MOTHER-FETUS IMMUNE IMBALANCE

Serial lymphocyte counts and function tests were done during and after pre-eclamptic pregnancies, and in the offspring. Compared with normal pregnancies, pre-eclamptic pregnancies were associated with lower B-lymphocyte counts in the fathers; lower T-lymphocyte count, lower B-lymphocyte count, and impaired T-lymphocyte function in mothers; a low response in mixed lymphocyte culture (MLC) tests between the mother and father; and an increased B-cell count in the children. Follow-up of one pre-eclamptic woman throughout pregnancy showed important immune changes at the beginning of the second trimester. These findings suggest that pre-eclampsia is caused by a combination of maternal and paternal hyporesponsiveness together with fetal hyperresponsiveness.

Chronic antigenic stimulation from the graft as a possible oncogenic factor after renal transplant.

In the period 1956-1976, 3 649 kidney transplantations were performed on 3 040 patients in Scandinavia. In the same period 67 primary malignant tumours were detected in these patients. In comparisons using age and sex-specific incidence in a background population, the observed tumour incidence was significantly higher than expected. Analyses were made in regard to a number of factors with potential influence on oncogenesis. The interval from transplantation to appearance of tumour was significantly longer in the recipients of grafts from living relatives than in cadaver kidney recipients. Significant correlation of tumour incidence was found with HLA mismatch in recipients of necrokidneys. Chronic interstitial nephritis as underlying kidney disease and blood transfusion showed correlation with tumour incidence. From these observations the hypothesis is proposed that a chronic antigen effect is a dominant factor among the numerous possible oncogenic mechanisms in patients with transplants.

INDICATIONS FOR AND TIMING OF REMOVAL OF NON-FUNCTIONING KIDNEY TRANSPLANT

The clinical indications for and the timing of removal of non-functioning cadaver kidney transplants were studied in 49 of 58 kidneys which had never functioned or which ceased to function in the period 1979-1982. The reason for graftectomy was rejection in 32 cases, rejection and graft infection in eight, surgical complications in eight cases and infection in one case. Nine of the 58 failed kidney grafts were not removed. Graftectomy was performed within a week after diagnosis of graft failure in 24 of the 49 cases. The clinical indications for graftectomy were compared with the morphologic observations in the grafts. Discrepancy was greatest in regard to diagnosis of rejection and primary renal artery thrombosis. Severe complications related to graft failure aggravated the condition in 17 patients and resulted in eight deaths. Based on the findings, a management schedule is proposed. It facilitates postponement or avoidance of graftectomy and minimizes the risk of complications relating to failure of graft function.

The relationship between disease activity, treatment response, and immunologic reactivity in immunoblastic lymphadenopathy: a longitudinal study of treatment with levamisole and cytostatics.

In a longitudinal study, several immunologic in vitro tests were performed on peripheral lymphocytes in four patients with immunoblastic lymphadenopathy during sequential therapy with Levamisole and polychemotherapy.

Bacterial Urinary Tract Infection in Cyclosporine-A Immunosuppressed Renal Transplant Recipients

Urinary tract infection and rejection in 48 renal transplant patients immunosuppressed with cyclosporine-A monotherapy were analysed. Urinary tract infection was diagnosed in 52% of the cases with Escherichia coli dominating. Urinary tract infection took a mild and relatively uncomplicated course as only one case of graft pyelonephritis caused graft nephrectomy and no influence on graft survival was observed (p greater than 0.05) in the infected cases in contrast to rejection episodes which caused a significantly reduced graft survival (p less than 0.01).

Recovery of kidney function after cessation of graft function or prolonged dialysis treatment.

The occurrence of recovery of kidney function after cessation of graft function or prolonged dialysis treatment has been studied retrospectively, and the frequency was found to be roughly 1%, inasmuch as 8 of approximately 750 patients could dispense with dialysis after 10-131 weeks of treatment. The causes of recovery of kidney function are discussed, as the importance of keeping this possibility in mind.

Development of Anti-OKT3 Antibodies After OKT3 Treatment

The development of IgG and IgM anti-OKT3 antibodies the first 90 days after start of OKT3 treatment for acute cellular rejection was determined by ELISA in 25 consecutive renal transplant patients. The ELISA positive sera were then tested for neutralizing OKT3 antibodies by immunofluorescence inhibition assay utilizing the FACScan. The number of IgM positive patients was highest, four (16%) after 10 days of treatment and then declined. The highest number of patients, thirteen (56%) with IgG antibodies was found after 60 days. Sera with only IgM antibodies or with low IgG titers (< 1:100) did not neutralize OKT3. Five patients (20%) developed neutralizing antibodies. All of these patients had received OKT3 during an earlier transplantation. In four of these patients, the ACR had been reversed successfully before the development of antibodies, and in the last patient the ACR was reversed by a second course of Minnesota-ALG and increasing the dose of Cyclosporine. Monitoring the development of neutralizing anti-OKT3 antibodies is valuable in patients who have previously received OKT3 treatment.