Rejection Episodes In Patients Research Articles

The Effects of Donor Age on the Outcome of Penetrating Keratoplasty in Adults

The purpose of the study is to determine whether there is a higher incidence of complications in adult patients receiving corneas from pediatric donors compared to those receiving corneas from adult donors. The design is a follow-up of two matched cohorts. The outcome of penetrating keratoplasty in 29 adult patients (age 20 years of age and older) receiving pediatric donor corneas (range, 0-5 years) was compared to that of 29 control patients matched for recipient age and diagnosis who received adult donor corneas (range, 40-70 years). Chart review was performed. Graft rejection, postoperative keratometry, postoperative refractive cylinder, postoperative intraocular pressure, and graft failure due to rejection were measured. One or more allograft reactions occurred in 11 (37.9%) of 29 patients who received pediatric donor corneas compared to 2 (6.9%) of 29 patients who received adult donor corneas (P = 0.005, chi-square). There were a total of 20 rejection episodes in patients receiving pediatric donor corneas compared to a total of 5 rejection episodes in patients receiving adult donor corneas. The average postoperative keratometry was 46.1 diopters for the pediatric donor group and 44.0 diopters for the adult donor group (P = 0.03). There was no statistically significant difference in average refractive cylinder (P = 1.0), intraocular pressure (P = 0.26), or the incidence of graft failure due to rejection (P = 1.0) between the two groups. The average follow-up time for clear grafts was 58.3 months in the pediatric donor group and 59.9 months in the adult donor group. The incidence of allograft reactions and the postoperative corneal curvature is greater in adult eyes undergoing penetrating keratoplasty with young donor corneas compared to those undergoing penetrating keratoplasty with older donor corneas. There was no difference in the incidence of graft failure due to rejection between the two groups.

Microchimerism and rejection in clinical transplantation

Haemopoietic microchimerism has been identified in recipients of solid-organ transplants and is thought by some to be critical for the development and maintenance of immunological tolerance. The aim of this study was to correlate prospectively the persistence of donor cells with clinical outcome in recipients of kidney, kidney and pancreas, and liver transplants. Persistence of donor cells in recipient peripheral blood was assessed at 3 days, and at 1, 3, 6, and 12 months after transplantation by a two-stage nested PCR technique to detect donor MHC HLA DR gene specifically. A pretransplant blood sample was collected from each patient to serve as an individual negative control. Seven liver, six kidney and pancreas, and 17 kidney patients were enrolled. 12 of the 17 kidney patients and all of the kidney and pancreas, and liver recipients were suitable for analysis. Exact matches for donors and recipients at the HLA DR loci (n = 1) or inability to obain primer pair specificity among similar HLA DR types (n = 4), meant that we were unable to analyse five patients. Donor DNA was detected in 20 (80%) of 25, ten (40%) of 25, seven (30%) of 23, five (22%) of 23, and six (32%) of 19 recipients at 3 days, and 1, 3, 6 and 12 months post-transplant, respectively. Within individuals, the detection of donor DNA varied over time; only two patients had detectable donor DNA at all times. Analysis of the whole group of transplant patients showed a similar frequency and severity of rejection episodes in patients with and without microchimerism as defined by detectable donor DR genes. These data suggest that a significant percentage of the recipients had persistent donor class II DNA in the peripheral circulation for at least 1 year after transplantation. We showed that a pretransplant blood sample is critical to avoid a false-positive result, and suggest that detectable chimerism may vary over time in individual patients. Therefore, analysis of microchimerism with a single, post-transplant analysis may not help in making clinical decisions for individual patients.

OKT3 for primary therapy of the first rejection episode in kidney transplants.

The improvement in one-year graft survival has allowed transplant centers to focus on long-term graft survival. A study of 665 primary cadaveric kidney transplants from a single center treated with cyclosporine demonstrated that patients did not develop chronic rejection if there was not an episode of acute rejection. This study is a retrospective review of 314 consecutive kidney transplants from a single center to determine if early, aggressive treatment of the first episode of acute rejection will improve graft survival without increasing recipient morbidity. The course of 314 consecutive kidney transplants performed during a 27-month period (245 CAD and 68 living-related) was studied. Demographic characteristics were equivalent between the two groups, and all patients received sequential quadruple immunosuppression using ALG and CsA. Patient and graft survivals at 2 years were 89.7% and 84%, respectively. At least one rejection episode occurred in 41% of the patients, one-half within 30 days of transplant. Rejection episodes were treated by oral prednisone taper, primary ALG or OKT3, or "rescue" therapy with ALG or OKT3. Graft survival in the 52 recipients treated with OKT3 for primary treatment of first rejection episode was 20% better than the 50 patients treated with PRED (P = 0.0847). Comparing the 39 recipients of primary CAD kidneys treated with primary OKT3 vs. 38 treated with PRED demonstrated a 32% improvement in 2-year graft survival (P = 0.033). There was no increase in second rejection episodes in patients treated with OKT3. Renal function was equivalent in patients with rejection regardless of type of antirejection therapy used. Of patients treated for rejection, 22% had symptomatic CMV infections, which were divided equally between the two groups. Eighty-two patients received a single course of OKT3, 28 received two courses, and 2 patients received OKT3 three times. Only two patients developed antimurine antibodies that required abandoning OKT3 for the treatment of rejection. This study clearly demonstrates that the early use of OKT3 as primary treatment of rejection results in significant improvement of 2-year graft survival in recipients of first CAD kidney transplants. There is no increase in episodes in CMV in patients treated with OKT3 as primary therapy and no increase in patient mortality. Early use of OKT3 does not prevent or decrease incidence of subsequent rejection episodes. Renal function in surviving grafts is not improved in patients treated with OKT3 vs. PRED.(ABSTRACT TRUNCATED AT 400 WORDS)

FREQUENCY OF KIDNEY REJECTION IN DIABETIC PATIENTS UNDERGOING SIMULTANEOUS KIDNEY AND PANCREATIC ISLET CELL TRANSPLANTATION

An increased frequency of kidney rejection has been reported in diabetic patients who have simultaneous pancreas and kidney transplantation compared with patients who have a kidney transplant alone. Kidney graft outcome is similar in the two groups. The mechanism for increased kidney graft rejection with a simultaneous pancreas graft is not clear. It is ascribed to the immunogenicity of the exocrine pancreas that initiates migration of activated cells from the peripheral blood that are entrapped in the kidney. Since the volume of the transplanted tissue is less in islet transplantation (usually < 2 ml) than in pancreas transplantation, one might not expect an increased frequency of kidney rejection in islet cell recipients. We looked at biopsy-proven kidney rejection episodes in patients who had combined kidney and islet transplants and compared this with the frequency of rejection in diabetic and nondiabetic patients who underwent a kidney transplant alone under the same immunosuppression. Diabetic patients who had kidney islet transplants (n = 9) had a higher frequency of rejection (100%) compared with diabetic patients (n = 107, 55.1%) and nondiabetic patients (n = 327, 65%) who had a kidney transplant alone. The 1-year graft and patient survival rates were not different among the groups. Although the number of patients is small, it would appear that transplantation of a low volume of islet cells with high purity can lead to an increased frequency of kidney rejection. This is unlikely to be explained solely on the basis of fewer antigen matches in these recipients but may reflect the inherent immunogenicity of the purified islet preparations. Alternatively, there may be an effect of their direct infusion into the portal vein.

Outcome of cardiac transplant recipients with a positive donor-specific crossmatch--preliminary results with plasmapheresis.

To assess the influence of a positive T or B cell IgG crossmatch on the development of rejection and mortality following cardiac transplantation, we reviewed all cardiac transplants performed in Utah between March 1985 and October 1990. Of the 328 cardiac allograft recipients, 11 (3.4%) had an IgG positive crossmatch. Actuarial survival at 24 months in the positive crossmatch group was 57.3% +/- 0.02 while that of the controls was 86.1% +/- 2.1 (P < 0.05). Allograft rejection occurred earlier in recipients with a positive crossmatch (10.0 +/- 5.8 days versus 34.0 +/- 2.3 days, P < 0.001). The first allograft rejection episode in patients with a positive crossmatch was characterized by immunoglobulin and complement deposition in small blood vessels and interstitial edema and endothelial cell activation in the absence of a lymphocytic infiltrate. Furthermore, the allograft rejection in the positive crossmatch group was accompanied by hemodynamic compromise in a large proportion of the patients (73%). In addition to augmentation of immunosuppression, plasma exchange therapy was performed within the first week following transplantation in 8 of the 11 positive crossmatch patients. Survival in the patients treated with plasma exchange (75%) appears to be better than in those not receiving plasma exchange (33%) within one week of transplantation. While immunosuppressive therapy aimed at the humoral arm of the immune system and plasma exchange therapy may improve survival in recipients with a positive donor-specific crossmatch, survival is worse in patients with a positive crossmatch than in patients with a negative crossmatch. Thus, it would appear prudent to prospectively crossmatch cardiac transplant candidates with a greater risk of developing a positive crossmatch, such as those potential recipients with an elevated level of panel-reactive antibodies.

Monoclonal antibody specificity: Orthoclone OKT3 T-cell blocker.

Orthoclone OKT3, a murine monoclonal antibody of the IgG2a class, was initially developed as a pan-T cell monoclonal antibody for use as a marker to differentiate between cell subsets. Only later did its potential role in treating allograft rejection become apparent. At first, its mechanism of action in such cases was not understood. Subsequent investigations demonstrated that OKT3 not only removed all T cells, but also specifically interacted with the T3 antigen recognition complex found on late thymocytes and mature T cells, consequently blocking the immunologic function of these cells. When injected into a patient, OKT3 can act in three ways to reverse allograft rejection. It initially coats, or opsonizes, the circulating T cells, which are then removed by the reticuloendothelial cells in the liver and spleen. OKT3 also modulates the T3 antigen recognition complex of circulating T cells, producing cells with all their phenotypic characteristics, except for the T3 molecules and the antigen recognition complex. The key mechanism of action of OKT3 in treating allograft rejection may be its ability to block the killer function of sessile T cells. In contrast to polyclonal antiserums, each molecule of OKT3 monoclonal antibody is virtually identical and has an identical specificity, thereby producing consistent reactivity to human T cells with a defined and relatively low degree of toxicity. Although derived from a hybridoma and grown in mouse ascites, OKT3 undergoes numerous purification steps to ensure that the final product is sterile, biochemically pure, homogeneous IgG2a. Furthermore, each batch is checked to make sure that its functional activity is the same as the standard.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of warm ischemia time and HLA (A and B) matching on renal cadaveric graft survival and rejection episodes.

In a retrospective single-center study the influence of warm ischemia time and simultaneous influence of HLA (A and B) matching on one-year renal graft survival was analyzed in 170 adult recipients of primary cadaveric renal grafts. One-year survival of grafts with warm ischemia times longer than 50 min was only 40% (n = 10). When warm ischemia time was shorter than 50 min, a 1-min increase of warm ischemia time correlated with 1% decrease in one-year graft survival as a result of rejection. This detrimental effect of warm ischemia time on graft survival was not yet significant one month after transplantation, but became more evident as follow-up time was lengthened. Warm ischemia time also correlated with the number of reversible rejection episodes in patients with a graft functioning for longer than one year (P less than 0.04). The beneficial influence of HLA (A and B) matching on one-year graft survival was significant (P less than 0.05 log linear test). This influence was even more evident with longer warm ischemia times. It is concluded that warm ischemia has a detrimental influence on graft survival that is mediated by rejection, and it is suggested that this might be due in part to altered presentation or expression of HLA-antigens of ischemically damaged kidney tissues.

Development of a radioimmunoassay for a high molecular mass tubular antigen in urine — Its application for early detection of tubular damage

In order to isolate urinary kidney antigens, the gammaglobulin fraction of an antiserum against human kidney cortex plasma membranes was coupled to Sepharose 4B. By immun ospecific affinity chromatography an antigen fraction was obtained from the urine of a patient suffering from severe kidney disease. After gel filtration, the main fraction, eluted with the exclusion volume of a Sephadex G-200 column and enriched 16 000-fold, was labelled with 131I and used in a radioimmunoassay system. Soluble kidney antigens, presumably of proximal tubular origin, could be detected and quantified by the assay system in urine samples of patients with various diseases. The samples did not need to be treated, either concentrated or dialyzed, before application. The results of our experiments show a correlation between antigen excretion and kidney damage. Rejection episodes in patients with kidney transplants could be recognized early by enhanced antigen excretion. Potentially nephrotoxic drugs caused antigen excretion as well. In normal, healthy subjects output of the antigen was very low. The assay system might be of value for monitoring renal diseases.

Radiation reversal of acute rejection in patients with life-threatening infections.

Four patients with established life-threatening infections suffered rejection episodes on postrenal transplant days 17, 25, 228, and 351 associated with markedly reduced immunosuppressive therapy. In three patients, azathioprine had been discontinued and the fourth was receiving 25 mg daily. Prednisone was reduced to 10 to 15 mg/day in three patients and the fourth held constant at 30 mg/day. Antilymphocyte globulin was discontinued in all patients. Radiation was administered to prolong the interval before nephrectomy in two critically ill patients. However, in all patients, rejection was completely reversed with external cobalt radiation alone, 150 roentgens per treatment and a total of 300 to 900 R per rejection. Each patient recovered and has normal renal function. Our experience indicates that radiation alone may be used successfully to treat rejection episodes in patients with life-threatening infections when other immunosuppressive measures have been discontinued or markedly reduced.

Hyperchloremic acidosis in early diagnosis of renal allograft rejection.

Hyperchloremic renal tubular acidosis has been observed to occur in a surprisingly high percentage of episodes of rejection in patients who have had cadaver renal allografts. Impairment of hydrogen ion excretion is the commonest defect, although multiple defects in tubular function have also been encountered. In those rejection episodes that were not associated with the development of hyperchloremia, the pattern of acid excretion resembled that associated with simple loss of functioning nephrons. In over half of the cases hyperchloremia became evident before rejection became definable by conventional criteria (sometimes even 1 to 2 weeks before). Elevation in serum chloride in patients who have had cadaver renal allografts is a valuable and reliable early sign of rejection. Furthermore, it may indicate smouldering rejection activity even when serum creatinine has come back to prerejection levels during reversal of the episode. Reestablishment of normochloremia may be a good prognostic guide to the efficacy of treatment of a rejection episode, provided allowance is made for the effect of exogenous sodium bicarbonate, which may also have been deemed necessary.