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C F Shield

Publications and source records attributed to C F Shield.

At least 19 recordsLinked to original sources
PubMed1998

Center-specific graft and patient survival rates: 1997 United Network for Organ Sharing (UNOS) report.

CONTEXT: Multiple comprehensive, risk-adjusted studies evaluating short-term surgical mortality have been reported previously. This report analyzes short-term and long-term outcomes, both nationally and at each individual transplant program, for all solid organ transplantations performed in the United States. OBJECTIVES: To report graft and patient survival rates for all solid organ transplantations, both nationally and at each specific transplant program in the United States, and to compare the expected survival rate with the actual survival rate of each individual program. DESIGN AND SETTING: Multivariate regression analysis of donor and recipient factors affecting graft and patient survival of all kidney, liver, pancreas, heart, lung, and heart-lung transplants reported to the United Network for Organ Sharing from 742 separate transplant programs. PATIENTS: A cohort of 97587 solid organ transplantations performed on 92966 recipients in the United States from January 1988 through April 1994. MAIN OUTCOME MEASURES: Short-term and conditional 3-year national and individual transplant program graft and patient survival rates overall and from 2 separate eras (era 1, January 1988-April 1992; era 2, May 1992-April 1994); comparison of actual center-specific performance with risk-adjusted expected performance and identification of centers with better-than-expected or worse-than-expected survival rates. RESULTS: One-year graft follow-up exceeded 98% and conditional 3-year follow-up exceeded 91% for all organs. Graft and patient survival improved significantly in era 2 compared with era 1 for all cadaver organs except heart, which remained the same. One-year cadaveric graft survival ranged from 81.5% for heart to 61.9% for heart-lung and 3-year conditional graft survival ranged from 91.3% for pancreas to 74.7% for lung. The percentage of programs whose actual 1-year graft survival was not different from or was better than their risk-adjusted expected survival ranged from 98.3% for heart-lung to 75.7% for liver. Most kidney, liver, and heart programs whose actual survival was significantly less than expected performed small numbers (less than the national average) of transplantations per year. CONCLUSIONS: Graft and patient survival for solid organ transplantations showed improvement over time. Conditional 3-year graft and patient survival rates were approximately 90% for all organs except for lung and heart-lung. The conditional 3-year survival rates were better than 1-year survival rates, indicating the major risk after transplantation occurs in the first year. The majority of transplant programs achieved actual survival rates not significantly different from their expected survival rates. Center effects were most significant within the first year after transplantation and had much less influence on long-term survival outcomes.

Actuarial Analysis↗
PubMed1998

Influence of the Rh (D) blood group system on graft survival in renal transplantation.

BACKGROUND: The Rh (D) blood group system has not traditionally been considered to be a clinically relevant histocompatibility barrier in transplantation since conflicting results of its clinical importance have been reported. METHODS: We analyzed 786 consecutive primary cadaveric renal transplants performed by transplant centers in our Organ Procurement Organization (OPO) between 1990 and 1997. We also analyzed United Network for Organ Sharing (UNOS) data on 26,469 kidney transplants done from April 1994 to June 1996. RESULTS: Multivariate analysis revealed that Rh identity between the recipient and donor was significantly related to better graft outcome (risk ratio, 0.43; 95% confidence interval, 0.30 to 0.61; P=0.0001). Multivariate analysis of the UNOS data revealed that the Rh -/- group may have a positive influence on graft survival with a risk ratio of 0.43 (P=0.14). CONCLUSION: Multivariate analysis of primary cadaveric renal allografts performed within the Midwest Organ Bank OPO indicates that Rh (D) is a clinically relevant histocompatibility barrier that influences 7-year graft survival.

Blood Grouping and Crossmatching↗
PubMed1998

Ten-year experience in transplantation of A2 kidneys into B and O recipients.

BACKGROUND: This article summarizes our 10-year multicenter experience with transplantation of 50 blood group A2 and A2B kidneys into B and O patients. METHODS: Since 1986, we have transplanted kidneys from 46 cadaver donors and 4 living donors who were blood group A2 (47 donors) or A2B (3 donors) into 19 B and 31 O patients. In 1991, we began allocating these kidneys preferentially to B and O recipients who were selected based on a history of low (< or =4) anti-A IgG isoagglutinin titers. Immunosuppression was no different from that used in ABO-compatible grafts. RESULTS: The 1-month function rate before thus selecting the patients was 68% (19/28), but is now 94% (17/18). Two-year cadaver-donor graft survival with this selection method is 94%, compared with 88% for 640 concurrent and consecutive ABO-compatible transplants (log-rank, 0.15). All four living-related transplants are still functioning, with a mean follow-up of 71 months. Since we began allocating A2 kidneys preferentially to B and O recipients, the percentage of the B patients who received A2 or A2B kidneys has increased from 29% (8/28) to 55% (10/18). CONCLUSIONS: Transplantation of A2 or A2B kidneys into B and O patients is clinically equivalent to that of ABO-compatible transplantation when recipients are selected by low pretransplant anti-A titer histories. This approach increases access of blood group B recipients to kidneys.

ABO Blood-Group System↗
PubMed1997

Use of gadolinium-enhanced, ultrafast, three-dimensional, spoiled gradient-echo magnetic resonance angiography in the preoperative evaluation of living renal allograft donors.

BACKGROUND: Renal allograft retrieval from live donors requires an accurate determination of kidney anatomy including the renal arterial supply. Traditionally, conventional angiography has served as the gold standard for obtaining this information. More recently, magnetic resonance angiography (MRA) has been compared with conventional angiography. Although MRA has been shown to be more cost effective and to have none of the co-morbidity associated with the angiographic process, it still has been perceived to be less accurate than angiography. METHODS: We compared images obtained using a relatively new technique of gadolinium-enhanced, ultrafast, three-dimensional, spoiled gradient-echo MRA with surgical findings in 15 living renal donors. In addition, average patient charge for MRA was compared with that of conventional angiogram. RESULTS: Fourteen patients were evaluated with the gadolinium-enhanced, ultrafast, three-dimensional, spoiled gradient-echo modality and the findings confirmed at surgery. On one occasion, a discrepancy occurred in which an accessory renal artery was suggested on the MRA but was not detected by conventional angiography. The accessory renal artery was later encountered at surgery. MRA was also used to evaluate patient 15 but was unsuccessful due to technical error. This patient was later found to have a positive cross-match with the recipient and therefore did not undergo surgery. CONCLUSIONS: We have found the gadolinium-enhanced MRA technique to be 100% accurate and as reliable as conventional angiography in determining renal vascular anatomy in living kidney donors. Additionally, it shares none of the associated potential angiographic complications and allows a 31% cost savings over angiography.

Contrast Media↗
PubMed1997

Assessment of health-related quality of life in kidney transplant patients receiving tacrolimus (FK506)-based versus cyclosporine-based immunosuppression. FK506 Kidney Transplant Study Group.

BACKGROUND: We evaluated health-related quality of life (HQL) in kidney transplant patients participating in a multicenter, prospective, randomized, phase III trial comparing tacrolimus to cyclosporine. HQL data were available for 303 of 412 patients and assessed with the SF-36 Health Survey and six multi-item scales: Current Health, Health Outlook, Health Distress, Fleming Self-Esteem, Bergner Physical Appearance, and Sexual Functioning. METHODS: Patients completed surveys at baseline, week 6, and months 3, 6, and 12. The mean change in HQL was evaluated by rejection occurrence and number of hospitalizations. Analysis of covariance was used to model endpoint HQL scores as a function of treatment group and baseline HQL. RESULTS: All scales but two met psychometric standards for group-level comparisons. Baseline demographics and HQL scores were not different by treatment. The mean HQL change was lower for patients with rejection compared with no rejection in seven of eight SF-36 scales and three of four remaining supplemental scales. One year after transplantation, study patients were functioning at least as well as half of the general population in Vitality and Role-Emotional Functioning, moving from the 18th percentile of the U.S. population scores to the 50th percentile for Vitality and 54th percentile for Role-Emotional Functioning. Patients improved their percentile ranking by at least 20 points in five of eight SF-36 scales. CONCLUSIONS: Patients with kidney disease demonstrate substantial HQL burden before transplantation, and transplantation is associated with substantial HQL improvements. Rejection is associated with less HQL improvement. Endpoint HQL values were significantly different (P<0.05) by treatment, favoring tacrolimus, in the Bergner Physical Appearance scale, which was designed to measure the HQL impact of side effects such as gingival hyperplasia and facial hirsutism on physical appearance.

Adolescent↗
PubMed1997

Antilymphocyte induction therapy in cadaver renal transplantation: a retrospective, multicenter United Network for Organ Sharing Study.

Antilymphocyte induction therapy in cadaver renal transplantation is controversial. The effectiveness of antilymphocyte therapy in the current era of cyclosporine and tacrolimus use has been questioned. The United Network for Organ Sharing data set for the Center-Specific Outcomes Analysis, which has been verified by the transplant centers, was used for this study. At the time information in the database was confirmed, all transplant centers were queried on their use of an antilymphocyte preparation at the time of transplantation, and whether it was used within 24 hr of transplant surgery, the duration of the specific reagent. This allowed us to analyze 24,191 cadaver transplant procedures performed between the October 1, 1987, and the January 31, 1991. Using Cox regression analysis, as well as semiparametric logistic regression models, we demonstrated improved allograft outcomes in patients who received either Minnesota antilymphocyte globulin for 5 days or more or OKT3 for 7 days or more. The relative risk was 0.82 for Minnesota antilymphocyte globulin and 0.86 for OKT3 (for both, P<0.001). Semiparametric models were then used to compare the effectiveness of the antilymphocyte preparation in both a patient with at least a three-antigen mismatch and patients who had a zero-antigen mismatch. The improvement in graft survival was seen in both match grades. These data demonstrate the improved outcomes with the use of antilymphocyte preparations during the early posttransplant period in the modern cyclosporine era.

Antibodies, Monoclonal↗
PubMed1997

Isoform switching of type IV collagen is developmentally arrested in X-linked Alport syndrome leading to increased susceptibility of renal basement membranes to endoproteolysis.

Normal glomerular capillaries filter plasma through a basement membrane (GBM) rich in alpha3(IV), alpha4(IV), and alpha5(IV) chains of type IV collagen. We now show that these latter isoforms are absent biochemically from the glomeruli in patients with X-linked Alport syndrome (XAS). Their GBM instead retain a fetal distribution of alpha1(IV) and alpha2(IV) isoforms because they fail to developmentally switch their alpha-chain use. The anomalous persistence of these fetal isoforms of type IV collagen in the GBM in XAS also confers an unexpected increase in susceptibility to proteolytic attack by collagenases and cathepsins. The incorporation of cysteine-rich alpha3(IV), alpha4(IV), and alpha5(IV) chains into specialized basement membranes like the GBM may have normally evolved to protectively enhance their resistance to proteolytic degradation at the site of glomerular filtration. The relative absence of these potentially protective collagen IV isoforms in GBM from XAS may explain the progressive basement membrane splitting and increased damage as these kidneys deteriorate.

Basement Membrane↗
PubMed1997

Nonenzymatic glycation of type IV collagen and matrix metalloproteinase susceptibility.

The glomerular basement membrane (GBM) is damaged in diabetes through complex mechanisms that are not fully understood. Prominent among them is nonenzymatic protein glycation leading to the formation of so-called advanced glycation end products (AGEs). We examined the effects of in vitro glycation of intact collagen type IV in bovine lens capsule (LBM) and kidney glomerular (GBM) basement membranes on their susceptibility to matrix metalloproteinases, using stromelysin 1 (MMP-3) and gelatinase B (MMP-9). Sites of cleavage of unmodified LBM collagen were located in the triple helical region. In vitro glycation by glucose severely inhibited the release of soluble collagen cleavage peptides by MMP-3 and MMP-9. The distribution of AGEs within the three domains of collagen IV (7S, triple helical, and noncollagenous NC1) were compared for LBM glycation using AGE fluorescence, pentosidine quantitation, and immunoreactivity towards anti-AGE antibodies that recognize the AGE carboxymethyllysine (CML). Marked asymmetry was observed, with the flexible triple helical domain having the most pentosidine and fluorescent AGEs but the least CML. The in vivo relevance of these findings is supported by preliminary studies of AGE distribution in renal basement membrane (RBM) collagen IV domains from human kidneys of two insulin-dependent diabetics and one normal subject. Pentosidine and fluorescent AGE distributions of diabetic RBM were similar to LBM, but the CML AGE in diabetic kidney was less in the triple helical domain than in NC1. Our results support the hypothesis that nonenzymatic glycation of collagen IV contributes to the thickening of basement membranes, a hallmark of diabetic nephropathy.

Adult↗
PubMed1996

HLA-DR and DQ typing by polymerase chain reaction using sequence-specific primer mixes reduces the incidence of phenotypic homozygosity (blanks) over serology.

Because of the inherent difficulties in allele assignment with HLA-DR serological typing, in 1993 our organ procurement organization-based HLA laboratory replaced serology with the molecular method of polymerase chain reaction using sequence-specific primer mixes (PCR-SSP) to type for DR and DQ at a resolution level equivalent to that of serologically defined antigens. In this study, we compared the incidence of DR blanks, where allocative homozygosity occurred, and graft outcome during our serology epoch (1987-1993) with that of our molecular epoch (1993-1996). The incidence of DR blanks by PCR-SSP (17.0%; 138/1101) was significantly lower (P<0.005) than in the serology epoch (21.5%; 569/2647). Although DQ is not a component of the allocation algorithm, the incidence of blanks in the molecular era (21.9%; 196/895) was 46% lower (P<0.001) than in the serology epoch (40.8%; 931/2277). Graft survival in 163 cadaveric renal transplant recipients for whom molecular DR allocation occurred (patient and donor were molecularly typed) showed that PCR-SSP typing had no significant effect on 2.5-year graft survival for patients mismatched for 0 (97%), 1 (90%), or 2 (94%) HLA-DR antigens (P=0.4; log-rank). In conclusion, molecular typing lowered the rate of DR and DQ blanks, but molecular matching for HLA DR and DQ did not influence graft outcome at 2.5 years.

Blood Grouping and Crossmatching↗
PubMed1996

Improved graft survival in cadaveric renal retransplantation by flow crossmatching.

OBJECTIVE: To evaluate the role of flow cytometry cross-matching on graft survival in patients undergoing cadaveric renal retransplantation compared with our conventional antihuman globulin cytotoxic crossmatch. DESIGN: In 1990, 6 of 7 transplantation centers in 1 organ procurement organization service area began performing cadaveric renal retransplantation only if the flow T-cell IgG crossmatch was negative. During that period, 1 center continued to use only the antihuman globulin T-cell IgG crossmatch. Prior to 1990, all centers used only the antihuman globulin T-cell IgG crossmatch as their crossmatch selection criterion for retransplantation. Regraft survival was compared between those centers by crossmatch selection criteria. PATIENTS: Patient selection and immunosuppression decisions were made at the transplantation center. SETTING: All flow cytometry crossmatches for all 7 centers participating in the evaluation were performed at the Histocompatibility Laboratory of the Midwest Organ Bank Inc, Westwood, Kan. RESULTS: Graft survival is significantly better (P = .03 [logrank test]) in regrafts when the flow crossmatch is used to select patients for transplantation. CONCLUSION: Flow crossmatching improves graft survival in cadaveric renal retransplantation by identifying a subset of patients with donor-directed HLA class I antibodies that are not detectable by our conventional antihuman globulin crossmatch.

Cadaver↗
PubMed1996

A cost-effectiveness analysis of OKT3 induction therapy in cadaveric kidney transplantation.

We evaluated the cost-effectiveness of a standard immunosuppressive regimen versus an OKT3 induction regimen in cadaveric kidney transplant recipients. Cost estimates were based on results from a five-center randomized trial comparing the safety and efficacy of OKT3 induction with a conventional triple-drug regimen and financial data from the National Cooperative Transplantation Study, the Medicare Provider and Analysis Review database, and other sources. Patients received OKT3 (5 mg/day) by intravenous (IV) bolus injection for 10 to 14 consecutive days in conjunction with azathioprine, prednisone, and the delayed addition of cyclosporine (CsA) on day 11 (n = 105) or a conventional immunosuppressive regimen consisting of CsA, azathioprine, and prednisone (n = 102). The following measures were used to evaluate the two regimens: costs incurred between transplantation and graft failure; the effectiveness of the two regimens as defined by length of graft survival; and cost-effectiveness ratios through 5 years of observed follow-up and modeled through the expected duration of graft survival. Results showed that OKT3 induction uniformly adds $8,219 to the cost of the transplant hospitalization. However, most of this cost is offset by a reduction in the cost of treating rejection episodes in the OKT3 group (P = 0.002). A trend toward improved graft survival was detected in the OKT3 group (P = 0.158). Through 5 years of observed follow-up, costs per year of graft survival are $30,474 with OKT3 versus $32,687 with the conventional regimen. Modeled through the expected duration of graft survival, OKT3 induction costs $8,335 for each additional year of graft survival. Results are fairly insensitive to wide variations in baseline assumptions. We conclude that OKT3 induction improves the cost-effectiveness of kidney transplantation.

Anti-Infective Agents↗
PubMed1996

OKT3 prophylaxis in renal grafts with prolonged cold ischemia times: association with improvement in long-term survival.

The data on patients participating in two randomized, prospective studies with similar immunosuppressive regimens were updated and combined to evaluate the long-term effects of OKT3 according to cold ischemia time (< or = or > 24 hr). Among 159 patients in the OKT3 and 153 in the cyclosporine A (CsA) group, 8 and 12 deaths occurred, respectively (P = NS). In patients with cold ischemia > 24 hours, OKT3 prophylaxis resulted in a lower mean number of rejection episodes per patient than did CsA prophylaxis within one year (mean +/- SEM: 0.87 +/- 0.11 vs. 1.35 +/- 0.14, respectively; P = 0.008) and within five years (1.07 +/- 0.12 vs. 1.49 +/- 0.15, respectively; P = 0.032). In contrast, rejection incidences in patients with cold ischemia < or = 24 hours was not significantly different in the two groups. In all study patients, there was a trend towards higher graft survival rates in the OKT3 group versus the CsA group (at 5 years, 73% vs. 66%, respectively; P = 0.182). Among recipients of kidneys with cold ischemia times > 24 hours, OKT3 patients had significantly higher graft survival than CsA patients at two years (84% vs. 64%, respectively) and at five years (71% vs. 56%, respectively; P = 0.045). Significant differences were not observed in recipients of kidneys with cold ischemia times < or = 24 hours. In conclusion, patients receiving renal grafts with long cold ischemia times strongly benefit from OKT3 prophylaxis.

Adult↗
PubMed1995

Detection of HLA IgG antibodies by two enzyme-linked immunoassays, solubilized HLA class I and PRA-STAT. Comparison with the AHG PRA.

HLA class I-directed IgG antibodies have traditionally been detected with a complement-dependent lymphocytotoxicity (CDL) technique. We have evaluated two solid-phase enzyme-linked immunoassays (EIA) and compared them with the CDL antihuman globulin (AHG) dithiothreitol-treated (DTT) PRA in their ability to discriminate between the presence or absence of HLA class I-directed IgG antibodies in serum from patients awaiting transplantation. The EIA were: (1) an EIA that uses solubilized HLA class I antigens (sHLA-I) isolated from a 240-member platelet donor pool, and (2) the PRA-STAT ELISA kit. For the first comparison, we used 691 serum samples from 272 patients taken before they had been transplanted. The data show a significant (P < 0.0001) linear correlation (r = 0.77 between the AHG DTT PRA and the sHLA EIA. They also demonstrate that the mean sHLA-I EIA ratio significantly increases (P < 0.01) above background levels with each stepwise increase in AHG DTT PRA level. Discordant results were 1.0% (7/691) for sHLA-I EIA+ PRA- and 6.3% (44/691) for PRA+ sHLA-I EIA-. However, a lower correlation was noted between the AHG DTT PRA and the PRA-STAT (Nextran) PRA results (n = 230; r = 0.42). The sHLA-I EIA is able to determine whether or not HLA Class I IgG antibodies are present in serum from transplant candidates and is an appropriate adjunct to the traditional CDL PRA assay, whereas the PRA-STAT is not.

Enzyme-Linked Immunosorbent Assay↗
PubMed1995

The OKT3 Antibody Response Study: a multicentre study of human anti-mouse antibody (HAMA) production following OKT3 use in solid organ transplantation.

Human anti-murine antibody titres following patient exposure to the monoclonal antibody Orthoclone OKT3 (muromonab-CD3) are determined by laboratories using diverse analytical methods which are not standardized and whose concordance is not established. A multicentre study group therefore compared testing for IgG anti-OKT3 antibody among seven laboratories. A set of 270 sera was obtained from 30 heart, 30 kidney and 30 liver transplant recipients with no previous exposure to OKT3 who were receiving OKT3 for induction immunosuppression. Sera were collected from each patient prior to and at 24 +/- 2 days and 31 +/- 2 days following initial OKT3 exposure. Identical aliquots of all 270 sera were tested for IgG anti-OKT3 antibody by each laboratory. In addition, the limit of detection of each laboratory's method was estimated by titration of an affinity-purified IgG anti-OKT3 reference material of known concentration. Anti-OKT3 antibody formation differed greatly among the three organ groups. Cardiac patients demonstrated the least sensitization and almost exclusively lower titres, while kidney recipients had more frequent and higher titre antibody formation. Liver recipients yielded the highest sensitization rate and the most frequent high titre sera. Importantly, the seven laboratories differed widely in the number of pretreatment sera reported as positive (ranging from 0% to 41% among laboratories), the number of post-OKT3 sera reported as positive (17-63%), the number of post-OKT3 samples with titre > or = 1000 (2-31%), and the number of patients sensitized 19-69%). Concordance among laboratories was highly variable, with interlaboratory agreement ranging from 38% to 83% on the sample titres assigned to 180 post-OKT3 sera. Many of the discordant results were consistent with differences in the limit of detection of the analytical methods, which ranged from 0.19 microgram/ml to > or = 15 micrograms/ml, a nearly 100-fold difference among laboratories. This study demonstrated the presence of both good concordance and significant discordance among laboratories in determining human anti-mouse antibody titres, and demonstrated that common titre categories (100, 1000, 10,000) were not equivalent among laboratories. The level of concordance among methods should be considered when comparing anti-OKT3 antibody results from different centres and their correlation with clinical events. Universal comparative testing, patterned after proficiency testing programmes, is needed to assess differences among laboratories and to bring uniformity and a sound interpretative basis to this field of testing.

Adult↗