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.

Stability of human lymphocyte differentiation antigens when stored at room temperature.

The development of monoclonal antibodies to human differentiation antigens and cytofluorographs have added a new dimension to immune monitoring. However, the technology is such that regionalization will most likely occur. We have demonstrated that human lymphocyte antigens OKT3, OKT4, OKT8 and OKT11 are stable in blood samples stored in ACD at room temperature for less than 72 h. This will allow samples to be analyzed in regional centers.

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.

Humoral immunity in renal transplantation Detection of cytotoxic antibodies to lymphocyte antigens other than HLA-A,B,C and Ia-like antigens in patients with vascular graft rejection.

By using a Fab2 fragment blocking assay with cultured human B lymphoid cells and peripheral lymphocytes as targets, cytotoxic antibodies to Ia-like antigens, to HLA-A,B,C antigens, and to lymphocyte structures other than these two types of histocompatibility antigens were identified in serial post-transplant sera from 18 renal allograft recipients. Multiple combinations of these three types of antibodies were seen in 78% of the sera. A higher reactivity as well as higher titers of antibodies were found in patients with graft failure from rejection. The occurrence of anti HLA-A,B,C or anti Ia-like antibodies did not show any relationship to graft outcome. However, cytotoxic antibodies to other antigens (referred to as non-HLA antibodies) were detected in five of the six patients with graft failure and in only one patient with graft survival. In this latter patient, non-HLA antibodies occurred with a chronic rejection episode and were no longer detectable when the rejection ceased. This study shows that the Fab2 fragment blocking assay is a useful method to identify antibodies to multiple specificities in sera from kidney graft recipients, and suggests that non-HLA cytotoxic antibodies may be associated with graft rejection.

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.

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.

Effectiveness of a second course of OKT3 monoclonal anti-T cell antibody for treatment of renal allograft rejection.

A second course of OKT3 monoclonal anti-T cell antibody was given to 21 recipients of kidney transplants. Rejections reversed in 43% of patients in whom 95% of rejections had reversed with their initial OKT3 course. Reversal was highly dependent upon the timing of rejection, anti-OKT3 antibody production, and T cell CD3 modulation. Rejections treated greater than 90 days after transplantation were resistant to OKT3 reversal. High-titer anti-OKT3 antibodies prevented OKT3 reversal of rejection, and effective CD3 (the cell surface target of OKT3) modulation was necessary for successful OKT3 reversal of rejection. Reexposure to OKT3 further stimulated anti-OKT3 antibody production and broadened the specificity of the antibodies produced. OKT3 can effectively and safely be used a second time for treatment of early T cell-mediated renal allograft rejections if high-titer anti-OKT3 antibodies have not been made.

Successful transplantation of blood group A2 kidneys into non-A recipients.

The ABO subgroup A2 has been reported to be less reactive with the anti-A1 antibody naturally occurring in the serum of group O and B recipients and to occur in approximately 20% of group A individuals. Between March 1986 and February 1987, the Midwest Organ Bank (MOB) in Kansas City, screened all group A renal donors for the A2 subgroup. A total of 190 cadaverdonor kidneys were retrieved during this time, of which 68 were subgroup A1 and 16 were subgroup A2 (incidence of A2 = 19% of As and 8.5% of all donors). Of the subgroup A2 kidneys, 13 were transplanted into 9 group O and 4 group B recipients. One group O recipient received an HLA-identical A2 living-related graft. Recipients were not preselected or modified by splenectomy, plasmapheresis, or other means, and were treated with cyclosporine, steroids--and, in most cases, azathioprine, after transplantation. There was one hyperacute rejection and there were 5 acute cellular rejection episodes, 3 of which were reversed. One additional patient died at 2.5 months with a functioning graft. Including the successful living-related graft, 10 of 14 patients (71%) have functioning grafts, with a follow-up of 5 to 14 months, and a mean creatinine of 1.7 mg/dl. We find that the A2 subgroup represents a small but important minority of A donors, and that transplantation into non-A recipients can generally, but not universally, be safely accomplished. We recommend the screening of A donors for the A2 subgroup in both the cadaver-donor and living-related groups, and suggest that the utilization of A2 donors in non-A patients may contribute to the transplantation of group O and highly sensitized patients--and, in some cases, improve the degree of HLA matching.

OKT3 monoclonal antibody plasma levels during therapy and the subsequent development of host antibodies to OKT3.

OKT3 levels and the presence of human antibodies to OKT3 were determined in the plasma of 66 patients receiving OKT3 monoclonal antibody (5 mg i.v. daily) for the treatment of acute renal allograft rejection. Plasma 24-hr trough levels of OKT3 rose over the first three days and then remained in a steady state over the remainder of the 14-day period of OKT3 therapy, with a mean level of 902 +/- 71 ng/ml (mean + SEM). On termination of OKT3 therapy plasma levels of OKT3 dropped to very low levels after 3 days. Host antibodies, usually of low titer, developed in a number of patients, usually 2-3 weeks after the start of OKT3 therapy. 37/43 patients (86%) who received OKT3 alone developed IgG anti-OKT3 antibodies; 9/23 patients (39%) who received Cytoxan in addition to OKT3 developed IgG anti-OKT3 antibodies, a significantly lower (P = 0.0002) incidence. The present regimens permitted maintenance of adequate levels of circulating OKT3 for 2 weeks, a sufficient time to reverse acute renal allograft rejection in most patients.

The effects of intraoperative administration of OKT3 during renal transplantation.

The use of the monoclonal antibody OKT3 for induction immunosuppression in renal transplantation is increasing--however, the safety of intraoperative administration continues to be questioned because of first-dose effects. The current study was designed to examine the effects of intraoperative administration of OKT3 on the cardiovascular and pulmonary systems in 161 consecutive renal transplant recipients. Patients receiving OKT3 intraoperatively during renal transplant (99 cadaver recipients) were compared with 62 patients not administered the drug (31 cadaver, 25 living-related-donor, 6 living-nonrelated donor). Intraoperative airway pressure (highest, average), O2 saturation (SaO2), temperature, blood pressure changes, cardiac rhythm, and bronchospasm were compared in these two groups. Significant physiologic changes noted in the group receiving OKT3 included increased temperature (both intraoperative and postoperative), decreased SaO2 (postoperative), and increased FiO2 (postoperative). Despite these differences, no clinically significant changes were noted in the group receiving OKT3. OKT3 induction given at the time of surgery was associated with a significantly increased one- and three-year graft function. This study demonstrates that first-dose administration of OKT3 intraoperatively during renal transplantation is safe and effective.

Cold ischemia time: an independent predictor of increased HLA class I antibody production after rejection of a primary cadaveric renal allograft.

BACKGROUND: Cadaveric kidneys experiencing longer cold ischemia time (CIT) are associated with higher levels of delayed graft function, acute rejection, and early graft loss. One mechanism to explain these results is that ischemia/reperfusion (I/R) injury makes the allograft more immunogenic by upregulating molecules involved in the immune response (e.g., HLA Class I/II). METHODS: We evaluated the influence of CIT on the production of HLA Class I antibody level, measured by an antihuman globulin panel reactive antibody (AHG PRA) level, in 90 unsensitized recipients of primary cadaveric renal transplants (from a total of 1442 between 1985 and 1997) who rejected their kidneys. RESULTS: By multivariate analysis, a CIT of 15 hr or more (vs. < 15 hr) independently increased the risk of the AHG Class I PRA level being > or = 20% after unsensitized patients rejected their first kidneys (relative risk=3.57; 95% confidence interval=1.26 to 10.14; P=0.01), despite the same degree of Class I/II mismatch between the two CIT groups. The overall mean peak PRA level after primary kidney rejection was significantly lower for the CIT < 15 hr group (25.9%+/-33.9; n=24) compared with the CIT > or = 15 hr group (46.3%+/-36.5; n=66) (P<0.001). CONCLUSION: Longer CIT induces a humorally more immunogenic kidney.

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.

Identification of alpha3, alpha4, and alpha5 chains of type IV collagen as alloantigens for Alport posttransplant anti-glomerular basement membrane antibodies.

BACKGROUND: Alport syndrome is a hereditary disorder of basement membranes especially affecting the kidneys, ears, and eyes. Some patients who undergo renal transplantation lose their kidneys as a result of posttransplant anti-glomerular basement membrane (anti-GBM) disease. METHODS: In the present study, we analyzed serum from 21 unselected Alport patients who underwent renal transplantation. Eleven samples were from patients without posttransplant anti-GBM nephritis, and 10 were from patients with this disease. RESULTS: Thirteen serum samples [10 alport posttransplant nephritis serum (APTN) and three Alport posttransplant serum (APT)] revealed linear binding to the GBM by indirect immunofluorescence. By using direct ELISA and immunoblotting with GBM constituents and type IV collagen NC1 domains from bovine, human, and recombinant sources, we detected anti-GBM antibodies in all Alport patients in varying titers. Five samples showed specific reactivity to the alpha3 chain, four to the alpha5 chain, six to both alpha3 and alpha5 chains, one to the alpha3 and alpha4 chains, and two to the alpha3, alpha4, and alpha5 chains of type IV collagen. The varied spectrum of reactivities was present equally in nephritic and non-nephritic sera. Ten control samples from non-Alport transplant patients did not exhibit specific binding to the GBM. CONCLUSIONS: These results suggest that the absence of alpha3, alpha4, and alpha5 chains of type IV collagen in the Alport kidney leads to alloantibodies in all Alport patients who receive transplants, irrespective of whether they develop nephritis or not. Although all Alport transplant patients develop this humoral response, only a select few develop anti-GBM disease. We suggest that this difference could be attributable to a genotypic effect on the ability of some individuals to launch a cell-mediated immune response.

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.

A randomized clinical trial of induction therapy with OKT3 in kidney transplantation.

A randomized, prospective multicenter trial was conducted to compare the safety and efficacy of OKT3 as an induction therapy with that of conventional immunosuppressive therapy administered to cadaveric renal allograft recipients. Two hundred fifteen patients were treated either with OKT3 plus azathioprine and steroids for 14 days with the delayed addition of cyclosporine on day 11, or with conventional immunosuppression (steroids, azathioprine, and cyclosporine). OKT3 patients had significantly fewer rejection episodes (51% vs. 66%, P = 0.032), a longer time to initial rejection (46 days vs. 8 days, P = 0.001), and fewer rejection episodes per patient (0.82 vs. 1.14, P = 0.014) than conventionally treated patients. Kaplan-Meier estimates of two-year graft and patient survival rates were 84% and 95%, respectively, for the OKT3-treated group, and 75% and 94%, respectively, for the conventionally treated group. Following a subsequent first rejection episode, OKT3 reversed 93% of the rejections in patients receiving OKT3 induction therapy and 94% in patients receiving conventional therapy. Adverse experiences reported during OKT3 induction therapy were similar to those seen when the drug was used for rejection. Following initial exposure, 40.3% of the patients tested were positive for anti-OKT3 antibody, only 6.7% of which were of high titer (1:1000). In the presence of low titer (1:100 or less) antibody, OKT3 was successful in reversing rejection in five of six retreated patients tested. In conclusion, treatment with OKT3 (in combination with azathioprine, steroids, and the delayed addition of cyclosporine) is an effective approach for renal allograft maintenance.

Long-term graft survival is improved in cadaveric renal retransplantation by flow cytometric crossmatching.

BACKGROUND: Cadaveric renal retransplantation is associated with a higher risk of early graft failure than primary grafts. A large proportion of those graft losses is likely attributable to donor-directed HLA class I antibodies, detectable by flow cytometry cross-matching but not by conventional crossmatching techniques. METHODS: Long-term graft survival in a group of 106 recipients of consecutive cadaveric renal regrafts between 1990 and 1997, in whom a negative flow T-cell IgG crossmatch was required for transplantation, was compared with two other groups of cadaveric transplant recipients. The first group consisted of 174 cadaveric regrafts transplanted between 1985 and 1995 using only a negative anti-human globulin (AHG) T-cell IgG crossmatch. The second group was primary cadaveric transplants done concurrently with the flow group (1990 to 1997) using only the AHG T-cell IgG crossmatch. RESULTS: The long-term (7 year) graft survival rate of flow crossmatch-selected regraft recipients (68%; n= 106) was significantly improved over that of regraft recipients who were selected for transplantation by only the AHG crossmatch technique (45%; n=174; log-rank=0.001; censored for patients dying with a functioning graft). Graft outcome for the flow cross-matched regraft recipients was not significantly different from that of primary cadaveric patients (72%; n=889; log-rank=0.2; censored for patients dying with a functioning graft). Finally, a positive B-cell IgG flow cytometric crossmatch had no influence on long-term regraft outcome. CONCLUSIONS: The use of the flow T-cell IgG cross-match as the exclusion criterion for cadaveric renal retransplantation yields an improved long-term graft outcome over that obtained when only the AHG cross-match is used and has improved survival of regraft recipients to the level of our primary cadaveric renal transplant population.

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.

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.

Transplantation rate of the blood group B waiting list is increased by using A2 and A2B kidneys.

BACKGROUND: We have increased the transplantation rate for blood group B cadaveric waiting list candidates by transplanting them with A2 and A2B kidneys. METHODS: Since 1991, five of the seven renal transplant programs in our organ procurement organization service area have preferentially transplanted blood group A2 and A2B cadaveric kidneys to B blood group waiting list candidates with histories of low anti-A isoagglutinin titers. RESULTS: Between 1991 and 1997, these five centers performed transplantations on 71 patients from the B cadaveric waiting list. Of those 71 patients, 29% (21 of 71) underwent transplantation with either A2 (n=18) or A2B (n=3) cadaveric kidneys. In 1997 alone, 48% (11 of 23) of the B patient transplant recipients received A2 or A2B kidneys. CONCLUSIONS: Transplantation of A2 and A2B kidneys into B waiting list patients has successfully increased access of B patients to kidneys. Such an allocation algorithm implemented nationally may similarly increase the transplantation rate of B waiting list candidates.

Determinants of waiting time for heart transplants in the United States.

BACKGROUND: Reports have been published on factors affecting the variations in waiting times for kidney and liver transplant candidates who have been registered on the United Network for Organ Sharing's waiting list. This study reports on determinants of waiting time differences that occur in the eleven UNOS regions for heart transplant candidates. METHODS: Retrospective analysis of 11,345 primary heart waiting-list registrations and 15,868 cadaveric donors, from whom 7,043 hearts were recovered and transplanted for the years 1994-96. Because estimated populations in the eleven UNOS regions vary from 10.8 to 43.2 million, analyses utilized Registrations/million population and Transplants/million population to obtain an R/T ratio. The relationship of the R/T ratio to the median waiting time was then examined for different demographic variables. RESULTS: The numbers of new heart candidate registrations, heart transplants performed, and waiting list deaths have undergone little change from 1991 through 1996. National median waiting times varied by basic demographic variables such as ABO blood type, race, age group, and UNOS medical urgency status. In the eleven UNOS regions, registrations per million ranged from 11.5 to 33.0 and transplants per million from 5.3 to 10.7. Registration/Transplant ratios correlated with median waiting times for urgency Status 1 and 2 as well as for blood group O recipients. Correlation with blood type AB recipients was less consistent, in part, due to the small number of AB recipients. CONCLUSIONS: There are wide variations in the number of heart transplant candidate registrations and in the number of heart transplants performed in the eleven UNOS regions. The registration to transplantation ratio correlated with median waiting times in these regions. Factors possibly contributing to the observed variations were examined.