South-Eastern Organ Procurement Foundation Research Articles

306.3: Transplantation legislations in Turkey.

Organ transplantation became the preferred procedure for treatment of end stage organ failure. The success of any transplantation organization depends on legal, ethical, medical, social, psychological, economical and religious factors. An effective system should be created with regard to these issues; especially legislation. If transplantation legislation is lacking then it is better to stop or abandon transplantation in this country. In an attempt to start a deceased-donor donation program in Turkey, our group contacted and worked in cooperation with international networks, including the South Eastern Organ Procurement Foundation (Richmond, VA, USA) and the Eurotransplant Foundation (Leiden, The Netherlands). Thus, we were able to perform the first deceased-donor kidney transplantation on October 10, 1978, using an organ supplied by the Eurotransplant Foundation. During the early periods of transplantation, the lack of legislation in governing organ donation was the main hurdle in Turkey. To overcome this problem, we made attempts to convince members of Parliament, officials of the Department of Religious Affairs and the Ministry of Health that transplantation was a life saving procedure and should be supported. Our efforts were successful and we structured a law on organ procurement, preservation and transplantation, which was used as a model by many countries. On June 3,1979 the law was enacted by Turkish Government, and later that month on June 27, we performed the first local deceased-donor kidney transplantation. We worked with the Turkish public to provide education about the benefits of and social responsibilities involved in organ donation. In addition, we founded The Turkish Organ Transplantation and Burn Treatment Foundation in 1980 and printed standardized organ donation cards. On January 21,1982 additional articles were added to Law 2238, with the enacted Law 2594, which allowed for deceased donation without consent from next-of-kin. In 2001, the Ministry of Health established the National Coordination Center as an umbrella organization to promote transplantation activities, especially for deceased donor organ procurement. This system increased deceased organ procurement from 0.9 pmp to 7 pmp in 18 years. Until now, we have performed 3007 kidney and since 1988, 629 liver transplants. In over 40 years of solid organ transplantation history in Turkey, 38477 kidney transplants (8278 deceased, 30199 living); 14185 livers (4187 deceased, 9998 living); 1048 hearts; and 195 pancreas transplants have been performed nationwide in 82 different centers. Transplantation activities are accelerating day by day throughout the country, but deceased donors are still far below the desired rates. Efforts to increase awareness continue through the media, schools, and many public and private institutions. Improvements in legislation, education and coordination are key factors for increasing the quality and the quantity of transplantation activities in Turkey.

Multivariate Analysis of the Influence of Donor and Recipient Cytomegalovirus Sero-Pairing on Outcomes in Simultaneous Kidney-Pancreas Transplantation: The South-Eastern Organ Procurement Foundation Experience

The purpose of this study was to determine if donor (D) and recipient (R) CMV sero-pairing at the time of simultaneous kidney-pancreas transplantation (SKPT) subsequently influenced outcomes in a large cohort of patients with long-term follow-up. Between January 1, 1997 and December 31, 1999 complete data were available on 723 primary SKPTs performed at South-Eastern Organ Procurement Foundation member institutions. For purposes of this study, four groups were defined: D+/R−, n = 203 (28%); D+/R+, n = 206 (28%); D−/R+, n = 156 (22%); and D−/R−, n = 158 (22%). Patient and graft survival rates for the study groups were computed by Kaplan-Meier estimates and tests of equality of survival curves were performed utilizing both the log-rank and Wilcoxon test statistics. A multivariate analysis was performed using a Cox proportional hazards model and logistic regression. A total of 56% of Ds were CMV+ and 50% of Rs were CMV−. D serostatus was not, but R serostatus was, a significant independent risk factor for patient and kidney, but not pancreas, graft survival rates in the uncensored analysis. When examining the CMV D/R groups in both univariate and multivariate fashion, CMV sero-pairing was not an independent risk factor for death, graft loss, or rejection. However, when considering CMV sero-pairing as a binary variable (D−/R− versus all other D/R groups), 6-year patient, kidney, and pancreas graft survival rates were significantly higher in the D−/R− group ( P < .05). In conclusion, CMV seronegativity is present in half of diabetic patients at the time of SKPT, and protective CMV seronegative matching confers a long-term survival advantage.

The Living Organ Donor Network: a model registry for living kidney donors.

The South-Eastern Organ Procurement Foundation presents the first report on a programme to track donors through questionnaires completed at the time of donation, 3 months, 6 months, and yearly thereafter. Donors at participating centres were eligible for an insurance policy with a total benefit of 250,000 US dollars, covering accidental death related to donation, surgery, medical expenses of complications, and disability income. The four participating centres have registered 104 donors. Response rate to the questionnaires was 90.91%. The majority of the donors come from the immediate family (81.62%), either by blood or marriage. The majority of donors are employed full time, with income ranges similar to the national census. Donors rely on employer-provided vacation time and sick leave to recuperate, but the average donor required 12 days of unpaid leave before returning to work. Donors also experienced costs of transportation, lodging, and childcare. Anti-depressants were prescribed to 10.58% of donors, and 4.8% of donors reported they are treated for hypertension. Complications were reported by 37.5% of the donors, but only 7.6% of the complications were serious enough to require hospitalization or surgery. Donors reported higher complication rates than reported by the centres and experience financial burdens afterwards.

Organ donation and transplantation trends in the USA, 2003

This summary provides an overview of solid organ transplantation in the USA, produced as part of the 2003 OPTN/SRTR Annual Report. The Annual Report is prepared by the Scientific Registry of Transplant Recipients (SRTR) in collaboration with the Organ Procurement and Transplantation Network (OPTN) under contract with the Health Resources and Services Administration (HRSA). A wide range of activities related to solid organ transplantation in the USA are thoughtfully addressed in this publication with the intention of providing useful information to patients, the transplant community, the public, and the Federal Government.

Human leukocyte antigens DR and AB and kidney retransplantation.

Although class II human leukocyte antigen (HLA) DR mismatching has been shown to demonstrate a significant effect on kidney regraft survival, it has not generally been clinically emphasized. We examined 2,574 kidney retransplants performed in Southeastern Organ Procurement Foundation centers between January 1988 and December 1997 in which there was ABDR typing on both donor and recipient and pretransplant panel reactive antibody (PRA) data. Cox regression of multiple variables demonstrated that the most important risk factors in descending order were DR mismatching, non-white recipient, female donor, PRA as a continuous variable, and cold ischemia time. Although DR mismatching demonstrated a significant effect in white recipients, the impact was much greater in non-white recipients. In both groups, zero to four AB mismatches demonstrated no significant effect on regraft survival if DR was matched and only a minimal effect when DR was mismatched. The discrepancy of these findings with reports that demonstrate a stepwise decrease in regraft survival on the basis of the total zero to six ABDR mismatches was explained by the fact that the zero to six ABDR mismatches are a combination of AB mismatches with little effect and DR mismatches with a major effect. Regraft survival decreased progressively in association with increasing PRA. DR matching is critically important in kidney retransplantation. There was no significant difference in survival of zero ABDR mismatched retransplants compared with one to four AB and zero DR mismatched retransplants. On the other hand, kidney graft survival of all one to four AB and zero DR mismatches exceeded that of one or two DR mismatched retransplants. We propose that the association of decreasing regraft survival with increasing PRA reflects undetected sensitization to class II, and possibly class I, antigens.

Evaluation of Freeze-Dried Dura Mater Allograft as a Collagen Based Barrier (an experimental animal study).

Freeze-dried dura mater allograft (FDDMA) was evaluated as a cost-effective collagenous barrier using an experimental animal model to determine its biocompatibility and 'cell-occlusivity' potential. The FDDMA was processed at the Civil Hospital Ahmedabad, in accordance with the guidelines provided by the South-Eastern Organ Procurement Foundation, U.S.A. Fifteen Charles Foster rats were selected for a study period of 9 weeks. The 1st set graft procedure was performed in an abdominal pouch and after 1 week bilateral mandibular defects were created. One defect was covered by the FDDMA barrier (2nd set graft procedure) and the other defect served as the control. The post operative autopsy and morphological and histological assessments were carried out at 2 and 4 weeks for the 1st set graft, and 3, 6 and 9 weeks for the 2nd set graft procedure. There was acceptance of the 2nd set graft in a pre-exposed animal and no significant inflammatory response. The processed FDDMA demonstrated optimal 'cell-occlusivity' potential for guided bone regeneration to take place in Charles Foster rats.

HLA phenotypes of ESRD patients are risk factors in the panel-reactive antibody (PRA) response.

To determine whether recipient HLA phenotypes are correlated with an increased or decreased risk of alloantibody sensitization in end-stage renal disease (ESRD) candidates for first or repeat kidney transplantation; we analyzed 19440 kidney allograft recipients consisting of 13,216 Caucasians and 6224 non-Caucasians transplanted between 10/87 and 11/98 at South-Eastern Organ Procurement Foundation (SEOPF) member institutions. Relative risk values and 95% confidence limits were obtained using Wolfe's method. Logistic regression was used to adjust for covariates that influence sensitization, i.e. ethnicity, gender, age, pregnancies, transfusions, primary/repeat transplant and living versus cadaver donor. Univariate analysis of the entire cohort indicated that nine HLA allelotypes (DR1,4,7; B8,12,40; A1,2,11) were associated with a significantly reduced risk of sensitization, and five allelotypes (B42,B53; A 10,19,36) were associated with an increased risk of PRA responses. Corrected for the number of statistical comparisons, recipients with DR1, DR4, A1 or A2 were 15% less likely to be sensitized per allelotype. Recipients with B42, B53 or A36 were at increased risk of preformed antibodies, after correction of the P value, for an average of 38% increased risk per allelotype. In the multivariate analysis, HLA phenotypes identified as independent risk factors associated with protection against sensitization were DR1,4,7; B12(44,45); and A1,2, with an average reduced risk of 9% per allelotype. The only independent susceptibility allelotype was A36 with an increased risk of 29%. The A10 (25,26,34,66) group reached borderline significance. We also looked for HLA-DR,-B,-A combinations that could potentially represent protective or at risk haplotypes/genotypes. Stepwise logistic regression identified five combinations associated with protection: DR1-B35-A3; DR1-B35-A2; DR1-B44-A2; DR4-B44-A2; DR7-B57-A1 (RR range 0.83-0.63) with 27% average reduced risk per combination. Phenotype combinations associated with an increased risk of sensitization were: DR2-B44-A2; DR2B53-A2; DR3-B8-A1: DR3-B42-A30; DR6-B42-A30; DR11-B53-A30 (RR range 2.76-1.48) with an average increased risk of 70% per combination. This study provides strong evidence that HLA-linked genes influence the anti-HLA PRA response. The magnitude of the altered PRA response risk in DR-B-A combinations was approximately twice that of the allelotypes at individual loci. HLA-DR genes seemed to contribute most of the altered risk. The correlations between DR types and PRA responsiveness are consistent with the DR types previously regarded as predictors of kidney graft survival. The magnitude of increased PRA risk attributable to an allelotype or combination was approximately twice that associated with a decreased risk. We conclude that some HLA class II-linked genes modulate the PRA response in a clinically significant manner. This immune response gene (Ir) regulation probably operates through polymorphic HLA molecules in their physiologic roles of antigen processing and presentation to helper T cells.

Media effect on organ donation and transplantation

OUR GROUP at Hacettepe University carried out extensive experimental studies using canine and porcine transplantation models in the early 1970s. We performed the first successful living-related (mother-to-son) kidney transplantation in Turkey nearly 2 decades later on November 3, 1975, marking the first successful kidney transplantation. While our living-related kidney transplantation program continued, we performed the first cadaverdonor kidney transplantation with an organ supplied by Eurotransplant on October 10, 1978. Until the early 1980s, alternatives to cadaveric transplantation did not exist for recipients who lacked living-related donors. Our team established more integral links with international organ networks such as the South Eastern Organ Procurement Foundation (SEOPF, Richmond, Virginia) and Eurotransplant, which were initially the only sources for cadaveric kidneys. In the face of limited cadaveric donors and the need to expand the cadaver donor pool, we intensified our efforts to educate the Turkish public about the benefits and need for organ transplantation and donation. The efforts of the Turkish Parliament, the media, and the Board of Religious Affairs boosted our progress and contributed to the enactment of laws 2238 and 2594, which legalized the harvesting, storage, grafting, and transplantation of cadaver-source organ and tissues in our country. Our workload skyrocketed to meet the needs of the donor-seeking Turkish public, and these efforts resulted in the first cadaver-donor kidney transplantation from a local source in July 1979, an operation performed by our team. A national organ sharing program was initiated by our team in 1989. This facilitated the distribution of organs nationwide and improved the communication among the transplantation centers, thereby increasing the number of cadaveric organ transplantations. More than 3750 kidney transplantations involving 18 centers have been reported to the Ministry of Health since the first transplantation in Turkey. Our team performed 1167 kidney transplantations from November 3, 1975 to January 1, 1998, the most recent 846 procedures having been carried out at our new center at Baskent University. The past year in Turkey has seen wider publicity and television news coverage of organ donation and transplantation issues, largely as a result of chronic liver disease in a patient who was a press member. At the present time in our country, only 25% of kidney transplants come from cadavers, and of these only 25% are local. In 1997 we performed 72 kidney transplantations, 18 using cadaver organs and 16 of these transplants being from local sources. To date, this is the best yearly record we have achieved for local cadaveric kidney transplantation. In 1993, we performed 20 cadaveric transplantations but only three organs were local; in 1991 only 1 of the 18 cadaveric transplants used was from a local source. In 1986 our average cold ischemia time was 63 hours; that year 12 of 13 cadaveric kidney transplants were shipped to Turkey from abroad. In what could be viewed as a measure of the progress made since then, the average cold ischemia time for cadaveric kidney transplantations in 1997 was 17 hours. In addition, the total number of renal transplantations performed last year outnumbered those done in each of the past 8 years (Table 1). In developing countries, educating the public and broadening awareness about organ donation and transplantation is critical to the progress of harvesting and transplantation programs. Our workload, especially in organ harvesting, has

Effect of histocompatibility, sensitization and other risk factors on the outcome of 14,535 cardiac transplants (TNX) reported to the unos scientific registry: J.S. Thompson and L Thacker, University of Kentucky, Lexington, KY and the Southeastern Organ Procurement Foundation, Richmond, VA

Effect of histocompatibility, sensitization and other risk factors on the outcome of 14,535 cardiac transplants (TNX) reported to the unos scientific registry: J.S. Thompson and L Thacker, University of Kentucky, Lexington, KY and the Southeastern Organ Procurement Foundation, Richmond, VA

Effect of race on outcome following kidney and kidney–pancreas transplantation in type I diabetics: the South‐Eastern Organ Procurement Foundation experience*

In this study we analyze the South‐Eastern Organ Procurement Foundation (SEOPF) experience with kidney and kidney‐pancreas transplantation in IDDM recipients and evaluate the impact of racial disparity on patient and graft outcome. Data obtained from 4413 kidney‐alone and 884 pancreas transplants performed in White and Black type I diabetics at member institutions of SEOPF between 10/1/87 and 7/25/96 were analyzed. Survival data from 15,827 transplants performed during the same period of time in non‐diabetics were available for comparison. A lesser proportion of pancreas recipients were Black compared to kidney‐alone (12% vs 23%, p&lt;0.0005). Recipient race had no effect on patient survival in any of the groups studied. Kidney graft survival, on the other hand, was adversely affected by Black race in both non‐diabetic and diabetic recipients of a kidney transplant but not in diabetics who received a combined pancreas‐kidney transplant. As was the case for patient survival in diabetics, recipient race had no effect on pancreas graft survival. Cox Regression analysis showed that kidney‐pancreas transplant (p=0.034, RR=0.49) and female recipient gender (p=0.046, RR=0.68) were associated with a lower risk of failure of the pancreas graft. The following factors were independent predictors of kidney graft outcome: Donor age (p=0.0001, RR=0.95), kidneypancreas transplant (p=0.0004, RR=0.58), AB match (p=0.001, RR=0.86), DR match (p=0.006, RR=0.82), preservation time (p=0.012, RR=1.01), Black recipient race (p=0.047, RR=1.23) and living donor (p=0.06, RR=0.73). Our findings suggest that the effect of race on graft outcome observed in non‐diabetic and, to a lesser extent, diabetic kidney‐alone transplant recipients, is not present after kidney‐pancreas transplantation.

Regional organ procurement (ROP) trays in renal allograft distribution and outcome

ROP trays containing patient serum samples and distributed by the South‐Eastern Organ Procurement Foundation (SEOPF) were instituted to increase the likelihood of transplanting potential renal recipients who are highly sensitized to HLA antigens. This study examines kidney distribution and transplant outcome to assess equitable placement and clinical function post transplant with and without the use of ROP trays. Data were collected over a 26‐month period on the distribution of kidneys from 328 consecutive SEOPF donors from whom at least 1 kidney was procured. Shared kidneys were placed via the UNOS and SEOPF‐variance computer match programs. Of 656 kidneys, 596 were placed into 582 recipients; 60 were not used. ROP trays were used in placement of 492 kidneys and were not used for placement of 104 kidneys. Outcome was determined for 435 kidneys transplanted into SEOPF recipients. Only 33 (6.9%) recipients with ROP tray use and 10 (9.8%) without were sensitized to HLA. A 10% increase in placement to the originally intended recipient was seen with ROP tray usage over kidneys placed without ROP tray use (p ≤ 0.025). Recipients matched using ROP tray data averaged 29 positions higher on the match printout. There was no difference in tray use regarding placement of kidneys within or outside the donor's local UNOS region, nor was there a difference in mean HLA match of transplant pairs with and without ROP tray use, 3.2 and 3.1 antigens, respectively. Cold ischemia time was similar, 22.9 and 23.6 h, respectively, for kidneys placed with and without ROP trays. At post‐transplant discharge, there were no differences in patient status, graft failure, rejection treatment, dialysis need, or urine output whether or not ROP trays were used. Significantly, however, plasma creatinine at discharge and at 12 months was lower for those placed with ROP trays (2.5 mg/dl and 1.7 mg/dl) vs (3.1 mg/dl and 1.9 mg/dl), respectively. During this time period, all kidneys transplanted with use of ROP trays functioned as well or better than those transplanted without ROP tray placement. Thus, the use of ROP trays appeared to have a beneficial effect in getting more recipients of higher priority transplanted with equivalent, if not better, graft function.

HLA‐DQ matching in cadaveric renal transplantation

The impact of matching for the human leukocyte antigen (HLA)‐ DQ phenotype in cadaveric renal transplantation is unclear. We analyzed the effect of matching serologically defined HLA‐DQ phenotypes on renal allograft survival in 12,050 first cadaveric renal transplants (recipients were 63.5% white and 36.5% African‐American). Recipients were entered into the South‐Eastern Organ Procurement Foundation (SEOPF) database between 1 October 1987 and 6 June 1995. A series of life table analyses were done to test the equality of survival curves for HLA‐DQ match, both alone and accommodating for differences in recipient race and HLA‐DR match. Cox regression models were then performed to detect differences in allograft survival based upon HLA‐DQ match. Initial adjustments were done by recipient race. Subsequent adjustments were done by recipient and donor race, age and sex, cold ischemia time (CIT), body mass index (BMI), cyclosporine A (CyA) use, peak panel reactive antibody (PRA) titer, year of transplant, presence of diabetes mellitus (DM), and degree of HLA‐A,B and HLA‐DR match as covariates. The effect of varying degrees of HLADQ match on graft survival were similar between the two races (p=0.87). In all recipients, an 8.3% reduction in graft failure was observed for each increase in HLA‐DQ match using the Cox regression model adjusted only for recipient race (p=0.004). A non‐significant 3.0% reduction in graft failure (p=0.38) was observed for each level of increasing HLA‐DQ match when using the Cox regression model adjusted for recipient and donor race, age and sex, CIT, BMI, CyA use, year of transplant, DM, HLA‐A,B and ‐DR match. In this model, superior HLA‐A,B match and HLA‐DR match, recipient and donor age, male donor sex, shorter CIT, white race of recipient, lower peak PRA, CyA use, and absence of DM significantly improved graft survival (all ≤0.004). We conclude that HLA‐DQ matching does not significantly affect cadaveric renal allograft survival once adjusted for other known predictors of graft outcome.

The high grade match kidney sharing algorithm of the South-Eastern Organ Procurement Foundation (SEOPF): altering recipient demographics through improved matching.

Studies of kidneys shared through the South-Eastern Organ Procurement Foundation (SEOPF) have shown that regional organ procurement (ROP) trays can predict negative crossmatch in highly sensitized patients when the HLA match is of a high grade. In an attempt to offer more well-matched kidneys to highly sensitized patients, SEOPF organized the High Grade Match (HGM) Program. This United Network for Organ Sharing (UNOS)-approved allocation variance requires mandatory sharing of all kidneys by participating centers after UNOS mandatory sharing requirements have been met. The HGM levels of sharing are: (1) 0 A,B mismatch (MM); panel-reactive antibody (PRA) > or = 40%; negative ROP crossmatch; (2) 0 B,DR MM with > or = 40% PRA; negative ROP crossmatch; (3) 0 B,DR MM with PRA < 40%. Non-HGM cadaveric transplants at the same participating centers--locally or distally procured--serve as the control group. During the first 18 months of this program, the 23 participating centers shared 124 kidneys of the 1592 that were available. Well-matched kidneys (two mismatches or less) accounted for 91.1% in the HGM group, but only 19% of the controls (P<0.0001). Highly sensitized patients (PRA > or = 40%) represented 13.8% of the HGM group, but only 3.3% of the non-HGM group (P<.0001). With HGM kidneys, there was a shift in recipient demographics. Patients with blood group O, female patients, older patients, and retransplanted patients all accounted for significantly larger percentages of the HGM group compared with the non-HGM control group. The racial composition of the recipients of high-grade matches was, however, no different than that of the control recipients at the same centers. The HGM Program resulted in longer ischemia times, but graft survival was not affected. The 1-year actuarial graft survival rate (Kaplan-Meier) for HGM kidneys was not different from the control cadaveric graft survival rate. By sharing kidneys based on improved HLA matches with consideration for high PRA, the HGM Program offered more transplant opportunities to women, blood group O recipients, retransplants, and older patients.

HLA Associations in End-Stage Renal Disease Due to Membranous Glomerulonephritis: HLA-DR3 Associations With Progressive Renal Injury

Membranous glomerulonephritis (MGN) is the most common cause of idiopathic glomerulonephritis in American adults. African-Americans develop end-stage renal disease (ESRD) due to chronic glomerulonephritis four times more often than whites. To determine whether HLA phenotype associations existed in the subset of MGN patients with ESRD we analyzed HLA frequencies, by race, in patients with MGN entered in the Southeastern Organ Procurement Foundation registry between 1982 and 1992. HLA frequencies from 250 renal transplant patients with MGN (190 whites and 60 African-Americans) were compared with 4,506 race-matched cadaveric kidney donor controls (4,039 whites and 467 African-Americans). Race-specific odds ratios (ORs) were calculated and fitted into a log-linear model to determine associations between MGN and HLA frequencies. The reported values were considered significant (P < 0.05) after Bonferroni correction for multiple comparisons. HLA-DR3 and HLA-DR5 frequencies were increased in cases of both races compared with race-matched controls (race-combined ORs, 2.22 and 1.61, respectively; all P < 0.02). Interracial analyses revealed that HLA-DR7 frequency was decreased solely in whites with MGN (OR, 0.53; P < 0.04). The results of this study indicate that HLA-DR3 and HLA-DR5 are positively associated with ESRD due to MGN in patients of both races and that HLA-DR7 is negatively associated with MGN in whites. These analyses confirm the published reports of HLA-DR3 association with MGN in Chinese, French, British, Chilean, and American white populations. The novel association of HLA-DR5 may reflect the fact that the MGN cases in this study all had ESRD.(ABSTRACT TRUNCATED AT 250 WORDS)

HLA Associations in IgA Nephropathy and Focal and Segmental Glomerulosclerosis

Twenty percent of patients initiating Medicare-supported end-stage renal disease (ESRD) therapy in the United States have chronic glomerulonephritis-induced ESRD. IgA nephropathy (IgAN) and focal and segmental glomerulosclerosis (FSGS) likely account for many of these incident dialysis cases, although patients presenting with advanced renal insufficiency may not receive renal biopsies. To determine whether HLA phenotype associations existed in the subset of IgAN and FSGS patients who develop ESRD, we analyzed HLA frequencies by race in patients with these etiologies of ESRD entered in the South Eastern Organ Procurement Foundation (SEOPF) database. Serologically determined HLA frequencies from 605 renal transplant recipients with ESRD due to FSGS and 196 renal transplant recipients with ESRD due to IgAN were compared with those of 4,506 race-matched cadaveric kidney-donor controls. Race-specific odds ratios (ORs) were calculated and fitted into a log-linear model to determine associations between the HLA system and ESRD due to IgAN and FSGS. Values reported were considered significant (P < 0.05) after Bonferroni correction for multiple comparisons. HLA-B27 and HLA-DR1 frequencies were increased and HLA-DR2 frequency was decreased in African-American and white IgAN-induced ESRD cases compared with race-matched controls (race-combined OR of 2.10, 1.89, and 0.57, respectively; all P < or = 0.004). HLA frequency differences were not observed in FSGS-induced ESRD patients compared with controls. The results of this study indicate that HLA-B27 and HLA-DR1 are positively associated and HLA-DR2 is negatively associated with IgAN-induced ESRD in patients of both races.(ABSTRACT TRUNCATED AT 250 WORDS)

A Race-Controlled Human Leukocyte Antigen Frequency Analysis in Lupus Nephritis

Systemic lupus erythematosus (SLE) has higher incidence and mortality rates in addition to a greater risk for nephropathy in African Americans (blacks), compared with whites. We analyzed the South-Eastern Organ Procurement Foundation (SEOPF) database from 1982 through 1986 to determine if variation in human leukocyte antigen (HLA) frequencies, beyond those normally present between the races, were associated with lupus nephritis (LN). HLA antigen frequencies in 271 black and 230 white renal transplant recipients with LN as the cause of end-stage renal disease (ESRD) were compared with 4,506 race-matched cadaveric kidney donor controls. Odds ratios (ORs) and chi-square values were computed to assess the prevalence of each HLA phenotype among the cases versus the controls separately for blacks and whites. HLA-B8 and -DR2 frequencies were increased, and HLA-DR4 frequency was decreased in cases of both races compared with race-matched controls (race-combined ORs, 1.68, 1.46, and 0.49, respectively; all P < 0.01). Race-specific analyses showed that HLA-DR6 was decreased in black cases versus black controls (OR, 0.48; P < 0.001) and HLA-DR3 was increased in white cases versus white controls (OR, 1.88; P < 0.001). HLA-B8 and DR2 are positively associated and HLA-DR4 is negatively associated with LN in patients of both races. HLA-DR3 and -DR6 demonstrate race-specificity in LN and place whites at a disadvantage relative to blacks. It is likely that non-HLA-mediated genetic factors and/or environmental factors contribute to the increased risk of nephritis observed in black patients with SLE.(ABSTRACT TRUNCATED AT 250 WORDS)

Organ Donation and Blacks

The past decade has witnessed an inexorable widening in the gap between the supply of organs for transplantation (i.e., the donors) and the need for organs on the part of desperately ill candidates for transplantation. As of June 1990, some 20,882 persons were waiting for organs to become available.1 Three patients on the waiting list die every day as a consequence of this shortage,1 and the scarcity of organs has become the chief limiting factor in clinical transplantation.2 In 1978 the Southeastern Organ Procurement Foundation asked us to identify obstacles to organ donation in the black population, and in particular . . .

Racial Differences in HLA Antigen Frequency and Hypertensive Renal Failure

Black patients with hypertension are six times more likely to develop end-stage renal disease than are their white counterparts. To determine if genetic differences associated with the Human Leukocyte Antigen (HLA) system account for racial variation in hypertensive renal failure, we examined antigenic frequencies from a large renal transplant registry. Human Leukocyte Antigen phenotypes from cadaveric renal transplant recipients and donors in the South Eastern Organ Procurement Foundation database from 1982 to 1986 were analyzed. One thousand six hundred four renal transplant recipients with hypertensive renal failure as the cause of end stage renal disease (cases) were compared with 4506 race-matched cadaveric kidney donors (controls). Log-linear models were used to assess the relationship between hypertensive renal failure and prevalence of each HLA phenotype. Bonferroni adjustments of P values were used to correct for multiple comparisons. Comparison of HLA frequencies between blacks and whites with hypertensive renal failure demonstrated that blacks had an increased frequency of HLA-DR3 beyond that normally known to exist between black and white populations. Black cases compared to black controls had an 8.6% increase in HLA-DR3 frequency contrasted with a 1.6% decrease in the frequency of this antigen between white cases and white controls. This absolute 10.2% difference between the races was significant (P = .02) because the control black and white populations had nearly identical frequencies for this antigen. White cases compared to white controls had lower HLA-A1 and B8 frequencies (21.2% v 30.6%, P = .0005 and 13.7% v 22.3%, P = .001, respectively) and a greater HLA-B35 frequency (20.7% v 14.2%, P = .02).(ABSTRACT TRUNCATED AT 250 WORDS)

BENEFICIAL EFFECT OF CYCLOSPORINE ON RENAL TRANSPLANTATION

Data were collected prospectively on 8581 cadaveric renal transplants performed by institutions of the South-Eastern Organ Procurement Foundation (SEOPF) during the period November 1, 1983 through December 31, 1987. Cyclosporine was the initial then always used immunosuppressant for 5742 of these patients while 1050 never received cyclosporine. The drug was started late in the course of 481 transplants and stopped early in 378 cases. This allowed for 7651 transplants to be analyzed regarding these four categories of cyclosporine use or non-use. Actuarial graft survival for the cyclosporine "ALWAYS" group was 75% at one year, 68% at two years, 62% at three years, and 59% at four years compared with 55%, 49%, 45%, and 43%, respectively for the cyclosporine "NEVER" group (P less than 0.0001). Inclusion of the 930 cases that could not be categorized regarding cyclosporine use or for which actuarial data was not complete allowed all 8581 transplants to be analyzed by multivariate methods. This analysis disclosed significant effects on graft survival due to delayed graft function, prior transplant, recipient race, HLA match, level of PRA, and cyclosporine use. Organ sharing had no effect on graft outcome. While cyclosporine improves outcome in renal transplantation, the importance of other biologic factors affecting graft survival is not diminished by its use.

LIVING-DONOR RENAL TRANSPLANTATION IN SEOPF

The impact of haplotype match (HM), pretransplant transfusions, and cyclosporine use were examined for living-donor renal transplants performed among 49 centers in the South-Eastern Organ Procurement Foundation (SEOPF) from November 1983 to June 1988 with follow-up through March 1989. During this period, 750 2-HM, 1246 1-HM, and 120 0-HM living-donor transplants were performed at 46, 47, and 27 centers, respectively. Demographic comparisons of the HM categories demonstrated the greatest use of cyclosporine and donor-specific transfusions in the 0-HM group, and the greatest use of random blood transfusions (RBT) or no blood transfusions (NBT) in the 2-HM group. By univariate and multivariate (Cox regression) analyses, actuarial graft survival was significantly associated with haplotype match, although excellent 3-year graft survival was seen for 0-HM as well as 1-HM and 2-HM first transplant recipients: 74 +/- 5%, 80 +/- 2%, and 85 +/- 2%, respectively. Comparisons were also made among patients receiving DST +/- CsA, RBT +/- CsA, and NBT +/- CsA for each HM group by univariate and multivariate analyses. For 0-HM recipients, DST + CsA was most frequently used and associated with the best long-term survival (86 +/- 5% at 3 years) by univariate analysis. For 1-HM recipients, there were no apparent differences in graft survival between DST and RBT groups +/- CsA by univariate analysis, but the absence of transfusion (NBT +/- CsA) was associated with the poorest 3-year survival (79 +/- 4%). This was confirmed by multivariate analysis, where DST (P less than 0.06) and RBT (P less than 0.02) were each significantly associated with graft survival, and provided relative benefits (vs. NBT) of 0.56 and 0.44, respectively; CsA use was not significantly associated with outcome or a significant benefit. For 2-HM recipients, the poorest results were seen with DST + CsA (78 +/- 6% at 3 years) by univariate analysis; multivariate analysis suggested no benefit with DST or RBT, and an increased risk of graft loss with CsA. These results indicate that the use of pretransplant transfusions and CsA therapy may have differential benefits depending upon HM in living-donor renal transplantation.