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Biomedical subjects

R H Kerman

Publications and source records attributed to R H Kerman.

At least 73 records · Page 4Linked to original sources
PubMed1988

The impact of HLA A, B, and DR blood transfusions and immune responder status on cardiac allograft recipients treated with cyclosporine.

From July 1982 to August 1986, 137 patients received heart allografts at our transplant (Tx) center. Recipients were treated postoperatively with cyclosporine (CsA) and prednisone (Pred), with a minority of patients receiving CsA, Pred, and azathioprine (Aza) as immunosuppression. The impact of pre-Tx immune factors on survival was evaluated, including HLA A, B, and DR mismatches (MM), blood transfusions (BT), immune responder status, crossmatch results, and donor and recipient AIDS-virus (human immunodeficiency virus, HIV-1) status. The overall patient survivals were 75%, 68%, and 62% at one, two, and three years respectively. Pre-Tx, 15/137 (11%) recipient sera and 5/137 (3.6%) donor sera were HIV-1 reactive in both enzyme immunoassay (EIA) and Western blot antibody assays. Two of the 5 recipients of HIV-1 (+) donor allografts are alive 11 and 29 months post-Tx, whereas the other 3 recipients died at 1, 31, and 36 months post-Tx from diseases unrelated to AIDS. All 5 were pre-Tx HIV-1 nonreactive. The survivals for the 15 recipients who tested pre-Tx HIV-1 (+) were 87%, 87%, and 69% at 1, 2, and 3 years, respectively, comparable to the overall group survivals. Pre-Tx strong and weak immune responders had comparable 12-month survivals of 73% and 80%, respectively. Six patients displayed a positive pre-Tx donor crossmatch, two were attributed to autoantibody, and 4 were attributed to donor T cell reactivity. Five of the six patients presently survive 14, 16, 30, 36, and 44 months post-Tx. Recipients treated pre-Tx with 1-4 BTs displayed significantly better 12-month survival (81% vs. 69%, P less than 0.05) and fewer rejections (1.3 +/- 0.9 vs. 1.9 +/- 1.0, P less than 0.05) than untransfused recipients. Recipients of a 0-1 vs. 2 DR donor antigen-mismatch experienced fewer rejections (1.3 +/- 1.0 vs. 1.8 +/- 1.1, P less than 0.05). Evaluation of the combined influence of HLA DR as well as pre-Tx BTs suggested a significantly improved survival (80% vs. 61%, P less than 0.05) and fewer rejection episodes (1.4 +/- 0.9 vs. 2.0 +/- 1.1, P less than 0.05) for 29 well-matched, transfused (0-1 DR MM and 1-4 BT) compared with 43 poorly matched, untransfused (2 DR MM and 0-BT) heart allograft recipients. Moreover, the benefit of DR matching was only observed in untransfused, but not transfused, cardiac recipients.

Adolescent↗
PubMed1988

The adverse impact of cytomegalovirus infection on clinical outcome in cyclosporine-prednisone treated renal allograft recipients.

Cytomegalovirus (CMV) infection was diagnosed in 28% (n = 144) of 516 renal allograft recipients treated with cyclosporine-prednisone (CsA-Pred) immunosuppressive therapy. The majority of infections produced either asymptomatic (n = 37) or mild-to-moderate (n = 75) clinical disease, while 10% were lethal (n = 14). Transplantation from a seropositive donor to a seronegative recipient was associated with an increased incidence of (CMV) infection but did not predispose to more severe clinical disease. Similarly, donor source (cadaver [CAD] vs. living-related donor [LRD]), age greater than or equal to 45 years, and antecedent pulse steroid therapy for the treatment of acute rejection were not correlated with clinically more severe disease. An increase in serum creatinine to greater than or equal to 25% of preinfection nadir values occurred in association with CMV infection in 106 patients, returning to nadir values or below in 74.5% of these individuals. CMV infection did not impact on actual patient survival among recipients of LRD or CAD allografts or on actual 1-year HLA-haploidentical or HLA-identical LRD graft survival. In contrast, actual 1-year cadaveric graft survival was significantly lower among CMV-infected (n = 95) vs. uninfected (n = 198) patients (75.8% vs. 87.8%, P = .01). In association with the finding of reduced actual 1-year CAD graft survival, CMV-infected patients were found to be more predisposed to develop acute rejection episodes. Of the CMV-infected CAD graft recipients, 48.4% developed greater than or equal to 1 acute rejection episode during the first year following transplantation vs. 25.3% of their uninfected counterparts (P less than .001). The impact of CMV infection in CsA-Pred treated renal transplant recipients does not differ substantially from that reported historically in association with prednisone-azathioprine immunosuppressive therapy.

Acute Disease↗
PubMed1988

Short-term and long-term function of cadaveric kidneys from pediatric donors in recipients treated with cyclosporine.

Short and long-term renal function of 67 cyclosporine-prednisone (CsA-Pred)-treated recipients of pediatric cadaveric donor kidneys followed for up to 68 months (mean 16 months) were compared with 67 recipients of adult kidneys (group 3), who were demographically matched for recipient age, sex, race, cause of disease, HLA compatibility, ABO blood type, and retransplant status. Thirty-seven of the pediatric kidneys came from donors less than or equal to 10 years old (group 1) and 30 from donors 11-16 years old (group 2). Group 1 displayed impaired short-term graft function: a significantly higher mean value of the nadir serum creatinine (SCr; 2.35 versus 1.63 mg/dl), a lower maximal creatinine clearance during the first 30 days (50.3 versus 65.7 ng/dl/1.73 m2), and a longer time to achieve the nadir creatinine (22.1 versus 17.2 days). Group 1 transplants also had a higher mean nadir creatinine at 3 months and a lower mean creatinine clearance (CCl) at 3 and 6 months. By 12 months the values in the group 1 pediatric kidneys were similar to those using the group 3 adult grafts. Therefore, CsA therapy did not preclude compensatory graft function. Group 2 grafts showed intermediate short-term function relative to groups 1 and 3. Mean SCr and CCl showed progressive improvement over time, significantly better than adult kidneys at two years. Graft loss was significantly greater at two years in pediatric compared with adult grafts, but significantly better than our historical controls using azathioprine-prednisone immunosuppression.

Adolescent↗
PubMed1988

Blood transfusion experience for cyclosporine/prednisone-treated renal allograft recipients at the University of Texas Medical School at Houston.

Our data indicate that CsA-P-treated primary recipients of cadaveric donor renal allografts as well as haploidentical living-related donor allograft recipients enjoy prolonged, successful patient and graft survivals whether conditioned with pretransplant transfusions or not. The data are important because they reflect clinical results from a single transplant center wherein the recipients have been immunosuppressed for approximately 7 years with little change in protocol. This is an important point since utilizing maximum therapeutic immunosuppressive efficacy will result in prolonged graft and patient survival.

Azathioprine↗
PubMed1988

Successful transplantation of 100 untransfused cyclosporine-treated primary recipients of cadaveric renal allografts.

This report examines the effect of pretransplant (pre-Tx) blood transfusions (BT) on the patient and graft survival results of 320 cyclosporine (CsA) and prednisone (Pred)-treated primary (1 degree) recipients of cadaveric (CAD) donor renal allografts. The 320 CsA-Pred treated 1 degree-CAD recipients included 100 pre-Tx untransfused (O-BT) and 220 transfused patients. The overall patient survival at 12, 24, and 36 months post-Tx were 94%, 94%, and 93%, respectively. There were no differences observed in graft survivals at 12, 24, or 36 months post-Tx whether patients received 0, 1-4, greater than or equal to 5-10 or greater than 10 pre-Tx BTs. A mean serum creatinine of 1.9 +/- 0.7 mg/dl was comparable among all BT groups at 12, 24, and 36 months post-Tx. The frequency of rejection episodes--namely, 37% for O-BT and 36% for greater than O-BT were identical. High-risk patients (greater than 45 years of age, diabetics, or blacks) were comparably distributed in O-BT and greater than O-BT groups and did not impact on the data. Similarly, increasing panel-reactive antibodies (PRA), associated with increasing numbers of pre-Tx BTs, did not influence the data. When HLA A, B, and DR matching results were combined with the BT groupings no differences were observed in patient or graft survivals. Poorly matched and untransfused recipients did as well as well-matched, transfused recipients. These findings suggest that CsA-Pred immunosuppressive therapy allows for successful 1 degree-CAD renal allograft transplantation without the need for pretransplant blood transfusion conditioning or matching of donor HLA A, B, and DR antigens to recipients.

Blood Transfusion↗
PubMed1987

Cyclosporine toxicity: the effect of combined therapy using cyclosporine, azathioprine, and prednisone.

Forty-nine patients among 360 who received renal transplants under cyclosporine (CsA)/prednisone (Pred) immunosuppression required alteration of the immunosuppressive regimen because of intractable nephrotoxicity. Twenty-five patients, converted totally to azathioprine (Aza)/Pred, suffered intractable nephrotoxicity with no associated evidence suggesting ongoing rejection. The results with Aza/Pred conversion were disappointing because of an unacceptably high incidence of rejection and allograft loss. Twenty-four patients with intractable CsA nephrotoxicity were, therefore, treated using an alternative approach combining Aza with aggressive CsA dose reduction, and continued Pred therapy. All patients tolerated initiation of Aza without complication; allograft rejection was not common. Renal function improved for 23 of the 24 (96%) CsA/Aza/Pred patients with mean serum creatinine levels falling from 3.5 +/- 0.5 mg/dL to 2.2 +/- 0.4 mg/dL after a mean follow-up of 14 months (P less than .001). Among 18 patients observed at least 12 months, seven (39%) enjoyed serum creatinine values less than or equal to 2 mg/dL. Nine CsA/Aza/Pred-treated patients (37.5%) required hospitalization because of infectious complications, all of which resolved with temporary reduction of immunosuppression and specific antimicrobial therapy when indicated. One patient sustained acute allograft rejection as a result of patient noncompliance, and one patient on a seemingly appropriate CsA/Aza/Pred dose responded initially to steroid pulse antirejection therapy; however, renal function again worsened. Two patients developed progressive renal dysfunction due to chronic rejection, and returned to dialysis 13 and 17 months, respectively, following initiation of CsA/Aza/Pred. Overall, the actuarial graft survival for CsA/Aza/Pred-treated patients was 100% at 1 year, and 84% at 2 years.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Multivariate analysis of risk factors impacting on immediate and eventual cadaver allograft survival in cyclosporine-treated recipients.

A multivariate analysis dissected the impact of donor procurement variables, immunologic risk factors, and alternate cyclosporine and prednisone induction immunosuppressive regimens on the early and eventual function of 303 consecutive cadaveric renal allografts. Primarily warm, but to a slight extent cold, ischemia time had an adverse impact on allograft function, as did the requirement for vasopressor or diuretic therapy. The occurrence of initial graft non-function adversely affected the probability of three-month graft survival, but did not alter either the longevity of organs, which subsequently recovered function, or patient mortality rate. The major immunologic risk factor was a second or multiple transplant, which was associated with an increased incidence of early graft failure, and impaired renal function in successful transplants. Correlations with HLA-B and DR matching were reflected in the quality of renal function, but not in graft survival rates. Cyclosporine (CsA) administration by continuous intravenous infusion, in order to avert initial elevated mean three-day, serum radioimmunoassay drug levels reduced the incidence of initial graft non-function. High levels were also associated with impaired early and eventual renal function. Rapid posttransplant taper of corticosteroids to 30 mg prednisone by day six was associated with a greater incidence of rejection episodes and early graft failure than a taper that achieved 30 mg prednisone at 60 days. Both the serum creatinine value and the degree of hypertension observed at one month afforded good prognostic indices of eventual graft survival. Therefore, renal allografts in CsA-treated patients were sensitive not only to adverse donor and immunologic risk factors, but also to excessive CsA drug levels in the early postoperative period. These findings suggest an induction immunosuppressive strategy utilizing slightly higher initial doses of steroids for CsA-sparing during the first three days, followed by increased, but judicious, administration of CsA to achieve steroid-sparing by virtue of effective rejection prophylaxis.

Cyclosporins↗
PubMed1987

Immunoregulatory mechanisms in cyclosporine-treated renal allograft recipients.

Cyclosporine (CsA)-treated recipients of a primary cadaveric (CAD) renal allograft were postoperatively evaluated for their donor and nonspecific immune responsiveness. Recipients with posttransplant (Tx) T helper (TH):T suppressor (TS) cell ratios less than 1.0 (averaged for the first 0-30 post-Tx days) had significantly better one-year serum creatinines (SCr) of 1.8 +/- 0.7 vs. 2.3 +/- 0.6 for recipients with TH:TS ratios greater than 1.0, P less than 0.05. Significantly fewer rejection episodes (30 vs. 57) and immune graft losses (10 vs. 19) were experienced by recipients with TH:TS ratios less than 1.0 vs. greater than 1.0, P less than 0.001 and 0.05, respectively. Recipients with TH:TS ratios less than 1.0 vs. greater than 1.0 displayed significantly lower post-Tx panel mixed lymphocyte culture (PMLC) stimulation indices (SI) of 24 +/- 11 vs. 38 +/- 6, P less than 0.05 and donor MLC SI of 15 +/- 6 vs. 31 +/- 8, P less than 0.05, respectively. Moreover, the post-Tx:pre-Tx donor MLC ratio of 0.58 +/- 0.2 vs. 1.1 +/- 0.32 was significantly lower in recipients with TH:TS ratios less than 1.0 vs. greater than 1.0, P less than 0.05. The suggested donor hyporesponsiveness in recipients with post-Tx TH:TS ratios less than 1.0 was further investigated by studying 46 CsA-treated allograft recipients for their ability to display regulatory T cell or adherent monocyte MLC suppressor activity. With a mean follow-up time of 5 +/- 4 months (range 0.5-14 months) we observed that 46% (21/46) of the patients displayed T cell suppressor activity, including 35% (16/46) with T-donor-specific and 46% (21/46) with T non-specific MLC suppressor activity. Additionally, 59% (27/46) of the patients also displayed nonspecific adherent monocyte MLC suppression. Recipients displaying either T cell or adherent monocyte suppression experienced significantly fewer rejection episodes than patients with no suppressor cell activity (P less than 0.05). Moreover, patients with T cell suppressor activity displayed a significantly lower panel and donor MLC vs. patients not displaying T suppressor activity (P less than 0.05. and 0.05, respectively). Finally, there was a significant correlation between the display of T cell suppressor activity in patients who were matched with their donors at the HLA-DR locus vs. no display of T suppressor activity in those patients unmatched with their donors at the HLA-DR locus.

Cyclosporins↗
PubMed1987

Investigation of HTLV-3 serology in a renal transplant population.

From June 1977 to March 1985, 572 renal transplants were performed at The University of Texas Medical School at Houston. This represented 220 patients (151 cadaveric [CAD] and 69 living-related donor [LRD] recipients) treated with azathioprine and prednisone (Aza-Pred) and 352 patients (250 CAD and 102 LRD) treated with cyclosporine (CsA) and Pred. Sera from each recipient before and after transplant (Tx) as well as from each of their 436 donors (265 CAD and 171 LRD) were retrospectively tested for the presence of antibody to the human T cell lymphotrophic virus type III (HTLV-3) by enzyme immunoassay (EIA) and Western Blot analysis. Of the 436 donors tested, only 1/265 (0.38%) CAD donors were both EIA repeatedly reactive and Western Blot positive, whereas none of the 171 LRD were reactive. Pre-Tx, 4/401 (1.0%) CAD and 1/171 (0.6%) LRD recipient sera were EIA repeatedly reactive, however, all 5 were to be Western Blot negative. Post-Tx, 4.2% of the sera (24/572, 4 LRD and 20 CAD recipients) were EIA-reactive. All 20 CAD recipient sera were subsequently found to be negative with Western Blot testing. However, 2 LRD sera (2/572, 0.35%) displayed EIA reactivity as well as Western Blot positivity. One LRD, Western-Blot-positive recipient is alive and well with a functioning allograft 39 months post-Tx, whereas the second LRD, Western Blot positive recipient died of septic complications 16 months post-Tx. Finally, the recipient of the Western-Blot-positive CAD allograft is alive with a well-functioning graft and remains EIA and Western-Blot-negative 36 months post-Tx.

Antibodies, Viral↗