Tapering immunosuppressive therapy significantly improves in vivo cutaneous delayed type hypersensitivity responses.

Immunosuppressive therapy affects cell-mediated immunity and thereby increases the frequency of infections and malignancies in transplanted patients. We questioned whether reducing the immunosuppressive dose in stable kidney transplant patients has an in vivo effect on cutaneous delayed type hypersensitivity responses (DTH) reflecting cell-mediated immunity. We measured DTH responses to recall antigens (Tetanus, Diphteria, Streptococcus, Tuberculin, Candida, Trychophyton, Proteus, glycerin control) on the volar surface of the forearm in patients before and after successful reduction (50%) of the dose of mycophenolate mofetil (MMF) or azathioprine (AZA).

Calcineurin inhibitor withdrawal in stable kidney transplant patients decreases the donor-specific cytotoxic T lymphocyte precursor frequency.

Background: In a prospective study, calcineurin inhibitors (CNI) were withdrawn in patients two years after kidney transplantation. We questioned whether stopping CNI had an effect on the donor-specific reactivity, as CNI might hinder immune responses leading to graft acceptance.

Methods: We measured the donor-specific cytotoxic T lymphocyte (CTL) precursor frequency (CTLpf) in 54 patients before and after withdrawal of CNI.

Reduction of immunosuppressive load in renal transplant recipients with a low donor-specific cytotoxic T-lymphocyte precursor frequency is safe.

Background: Tapering of immunosuppressive medication is indicated to prevent long-term side effects. Recently, we have shown that renal transplant recipients can safely be converted from calcineurin inhibitors to MMF or AZA when their donor-specific cytotoxic T-lymphocyte precursor frequencies (CTLpf) are below 10/10(6) PBMC. We wondered whether a low CTLpf also had predictive value when immunosuppressive medication was reduced in patients only on MMF or AZA and steroid medication.

Tapering immunosuppression in recipients of living donor kidney transplants.

We have previously suggested that the in vitro donor-specific cytotoxic T-lymphocyte precursor (CTLp) assay can guide us to identify patients in which the immunosuppressive load can be tapered. In a clinical trial we had observed that a low (<10/10(6) PBMC) frequency of these CTLp was predictive for an uneventful rejection-free clinical course in patients that were converted from calcineurin inhibitors to mycophenolate mofetil or azathiopine. In the present prospective study in 81 stable kidney transplant recipients, already converted from calcineurin inhibitors, we measured CTLp frequencies and reduced the immunosuppressive load on a routine basis when CTLp were <10/10(6) PBMC.

Proteinuria after renal transplantation affects not only graft survival but also patient survival.

Background: Proteinuria is associated with an increased risk of renal failure. Moreover, proteinuria is associated with an increased death risk in patients with diabetes mellitus or hypertension and even in the general population.

Methods: One year after renal transplantation, we studied the influence of the presence of proteinuria on the risk of either graft failure or death in all 722 recipients of a kidney graft in our center who survived at least 1 year with a functioning graft.

The influence of cholesterol on mortality after transplantation is age dependent.

There is still no consensus on the treatment of elevated serum cholesterol in patients with a renal transplant. In the general population treatment is age dependent. We studied the influence of serum cholesterol 1 year after transplantation in all 676 recipients of a kidney graft transplanted in Rotterdam that survived and functioned for at least 1 year.

Cholesterol as an independent predictor of outcome after renal transplantation.

Background: The debate on the role of high serum cholesterol levels in cardiovascular disease or chronic vascular rejection in kidney-transplanted patients has not yet been settled.

Methods: We studied the influence of serum cholesterol at 1 year after transplantation on the failure risk in all 676 kidney graft recipients who survived with a functioning graft. Other variables included in this analysis were donor/recipient age and gender, original disease, race, number of HLA-A and -B mismatches, previous transplants, postmortal or living-related transplantation, and transplantation year.

Renal graft survival in native and non-native European recipients.

Most studies on the influence of recipient race on kidney transplant survival have been performed in the United States. Generally, they show a lower survival in African-Americans than in Caucasians. Since Rotterdam has gradually become a multi-ethnic society, we were able to study the effect of origin on kidney survival.

The vanishing importance of age in renal transplantation.

Background: The growing number of patients awaiting a kidney transplant raises questions about allocation of kidneys to the elderly and about the use of elderly donors. In all reported studies analyzing the influence of age on the outcome after renal transplantation, age is investigated as a categorical variable.

Methods: We studied age both as a categorical (Kaplan-Meier) and as a continuous (Cox) variable in a total of 509 cyclosporine-treated recipients of a primary cadaveric kidney graft who underwent transplantation between July 1983 and July 1997.

Losartan, an angiotensin-II receptor antagonist, reduces hematocrits in kidney transplant recipients with posttransplant erythrocytosis.

Background: Posttransplant erythrocytosis (PTE) occurs in 10-15% of patients with a well-functioning kidney transplant and is associated with increased morbidity. Although the mechanism of PTE is unknown, PTE responds to inhibitors of ACE (ACE-i) in most cases. ACE converts angiotensin I to angiotensin II and is a metabolizer of a number of other peptides.

Conversion from cyclosporine A to azathioprine treatment improves LDL oxidation in kidney transplant recipients.

The use of the immuno-suppressant cyclosporine A (CsA) after transplantation has been associated with less favorable plasma lipid profiles, which may contribute to the high incidence of cardiovascular morbidity and mortality in transplant recipients. Recent studies have suggested that oxidative modification of LDL plays an important role in the initiation and progression of atherosclerosis. It has also been demonstrated that CsA may facilitate lipid peroxidation in vitro and in vivo.

Dietary fish oil in renal transplant recipients treated with cyclosporin-A: no beneficial effects shown.

This study aimed to determine whether dietary supplementation with fish oil has a beneficial effect on graft function and the incidence of rejection in renal allograft recipients treated with cyclosporin A (CsA). Renal function, blood pressure, the incidence of acute rejection episodes, graft survival, and renal histology and immunochemistry were investigated. In a randomized, placebo-controlled, double-blind trial, groups of 25 recipients of primary cadaveric renal allografts who had been treated with CsA took fish oil (30% C20:5 omega-3 and 20% C22:6 omega-3) or coconut oil (63% C8:0 and 36% C10:0) at 6 g/day for 3 months.

Low-density lipoprotein oxidation is increased in kidney transplant recipients.

Oxidative modification of low-density lipoproteins (LDL) plays an important role in the pathogenesis of atherosclerosis. In addition, there is evidence that chronic vascular allograft rejection may be mediated by oxidised LDL. Plasma lipoprotein concentrations and parameters of LDL oxidation were determined in 19 kidney transplant recipients and 19 healthy controls.

Randomized trial of misoprostol in patients with chronic renal transplant rejection.

Chronic vascular rejection is a major cause of long-term graft failure after renal transplantation. We investigated the effect of the addition of misoprostol (200 micrograms four times daily) to standard immunosuppressive therapy on the outcome of chronic rejection in a double-blind, placebo-controlled trial. Patients had to fulfill predefined histological and clinical criteria.

The incidence of cervical intraepithelial neoplasia among women with renal transplant in relation to cyclosporine.

Objective: To evaluate the policy of an annual smear to screen renal transplant recipients for cervical intraepithelial neoplasia and invasive carcinoma and to determine the incidence of abnormal smears and CIN before and after the introduction of cyclosporine (1983).

Design: A retrospective study over the period 1971 to 1992.

Subjects: Postmenarchial women who received renal transplants and who were on immunosuppressive treatment for at least one month.

Increased morbidity and mortality in patients with diabetes mellitus after kidney transplantation as compared with non-diabetic patients.

The results of renal transplantation in patients with juvenile-onset diabetes mellitus were compared to those of a well-matched control group of non-diabetic patients. All transplantations were performed between 1977 and 1988. In the diabetic group hypertension (72 versus 41%), coronary artery disease (17 versus 0%), and peripheral vascular disease (19 versus 0%) had been significantly more frequent pretransplantation.