Everett K. Spees

The detrimental effects of delayed graft function in cadaver donor renal transplantation.

Data collected prospectively on over 3800 cadaveric renal transplants performed between June 1977 and July 1982 by the 41 member institutions of the South-Eastern Organ Procurement Foundation were analyzed to determine the influence of delayed graft function (DGF) on patient and graft outcome. Approximately 35% of first graft recipients and 47% of regrafted patients were found to have DGF, as determined by the necessity for dialysis at one week posttransplant. First-graft recipients with DGF tended to include more black recipients, patients with higher peak levels of panel reactive antibody (PRA), less use of antilymphocyte serum (ALS) posttransplant, slightly longer organ preservation times and the more frequent use of organs preserved by ice alone. Multivariate (Cox) regression analysis considering DGF simultaneously with ten other potentially confounding variables showed a highly significant association between DGF and overall graft loss from all causes (P<10−5), irreversible graft rejection (P<0.001) as well as patient death (P=0.012). The differences in graft survival between first graft recipients with DGF (n=961) versus those without DGF (n=1769) at one and four years posttransplant were 46%±2 vs. 60%±1 and 28%±3 vs. 40%±2, respectively. The detrimental effect of DGF was highly significant irrespective of the source of donor organs or the type of preservation used. For first transplant recipients who recovered good graft function by one month following DGF (n=564), there was a significant decrease in eventual graft survival, as compared with patients who had graft function at one month but no prior history of DGF (n=1407; P=0.008). However, patients with history of DGF who had good graft function at six months (n=361) showed no significant difference in longer-term graft survival when compared with similar patients with good graft function at six months but no history of DGF (n=912). Interestingly, first transplant recipients with DGF were found to have significantly better graft survival if they had received bilateral native nephrectomy at least one month prior to transplantation. These results indicate that delayed graft function following cadaver donor renal transplantation provides a significant risk for eventual graft and patient survival that is principally manifested during the first six months posttransplant. In addition, patients who recover graft function following DGF appear to also remain at higher risk for early graft loss, while pretransplant bilateral native nephrectomy may afford some protection against the detrimental effects of DGF.

Comparative effects of pregnancy, transfusion, and prior graft rejection on sensitization and renal transplant results.

An analysis of all 2879 cadaveric donor transplants performed during the Southeastern Organ Procurement Foundation (SEOPF) Prospective Study from June 1977 to October 1981 was performed to determine the relative effects of previous pregnancy, pretransplant transfusion, and previous grafting on patient sensitization and renal transplant results. Previous transplantation was found to have the greatest quantitative effect on sensitization as measured by percentage of reactive antibody (PRA). Pregnancy had an intermediate effect while transfusion resulted in a very low, but statistically highly significant, increase in PRA levels. The sensitizing effect of transfusion was greatest in previous transplant recipients and minimal in parous females. Actuarial graft survival in males stratified for transfusion, transplant number, and PRA level showed significant enhancement in first graft recipients associated with transfusion regardless of PRA level. However, the benefit of transfusion was lower in regrafted recipients with PRA of ≤60% and not present at all in those with PRA of >60%. Prior graft loss did not significantly affect graft survival in unsensitized (PRA = 0) patients, but was associated with decreased graft survival in sensitized patients. Primary graft survival in females stratified by PRA level, transfusion, and prior pregnancy revealed a mildly detrimental effect of pregnancy in untransfused females, and no beneficial effect of pretransplant transfusion in nonpregnant females. However, prior pregnancy appeared to be beneficial in transfused females and transfusion was beneficial in previously pregnant females. Untransfused females without prior pregnancy had significantly better graft survival than untransfused males, irrespective of PRA level. The effect of sensitization on graft survival stratified for transfusion, prior pregnancy, and previous transplantation was of significant detriment only in transfused, regrafted males and transfused, previously pregnant females. This study, while limited only to patients who received transplants, indicates that transfusion, prior pregnancy, and previous transplantation should be considered as associated variables when their effects on sensitization and graft outcome are analyzed.

The Urological Evaluation and Management of Patients with Congenital Lower Urinary Tract Anomalies Prior to Renal Transplantation

Previously, patients with chronic renal failure and major congenital anomalies of the lower urinary tract (often with urinary diversion) were thought to be poor candidates for renal transplantation. Pre-transplant evaluation and possible urinary reconstruction are essential in these patients to achieve successful renal transplantation. Ten patients, including 7 adults, presented with congenital anomalies of the lower urinary tract that were responsible for renal failure. Percutaneous suprapubic cystostomy aided in the assessment of bladder function. Undiagnosed posterior urethral valves were found in 2 adults. Patients with exstrophy, neurogenic bladder or a contracted bladder (with augmentation cystoplasty) had urinary drainage into the bladder at the time of renal transplantation. Sometimes an imperfect bladder can be used for urinary drainage with transplantation but, otherwise, intestinal conduits are still a viable alternative.

Identification of donor factors predisposing to high discard rates of cadaver kidneys and increased graft loss within one year posttransplantation ― SEOPF 1977-1982

From 1977 to 1982, the South-Eastern Organ Procurement Foundation (SEOPF) conducted a prospective study to determine the fate of all cadaver kidneys retrieved by member institutions. During the study period, 6152 kidneys were retrieved, 1264 being discarded. Donor factors predisposing to wastage included AB and A blood groups, donor age greater than 30, hospitalization greater than 3 days, serum creatinine greater than 2.0 mg%, average systolic blood pressure less than 80, last-hour urine output less than 100 ml, proteinuria, heart not beating at time of nephrectomy, and kidneys not removed en bloc. Donor factors affecting graft survival rate at one year include age, length of hospitalization, last-hour urine output, and changing serum creatinine. The data suggest that certain donor kidneys are less likely than others to be transplanted depending on donor characteristics and retrieval practices. Furthermore, some of these factors have a negative impact on long-term success when kidneys are transplanted.

Multivariate analysis of risk factors in cadaver donor kidney transplantation

Data collected prospectively on 3811 kidney transplants performed between June 1977 and July 1982 with follow-up to July 1984 by the 42 member institutions of the South-Eastern Organ Procurement foundation were analyzed to identify factors associated with graft and patient outcome in patients not receiving cyclosporine. Multivariate Cox regression analysis was used to examine the association and relative risk of 24 variables with three actuarial outcomes: overall graft failure, irreversible rejection, and patient death. Factors having no suggested association with any outcome included: recipient sex, history of pregnancy, blood group, and time on dialysis; organ preservation method, time and source; donor race; crossmatch test sensitivity; and annual center transplant rate. In decreasing order of relative risk, the factors most significantly associated with irreversible rejection were: loss of two or more prior grafts, low HLA-A,B match, lack of pretransplant blood transfusion, high (greater than 60%) pretransplant sensitization to leukocyte (HLA) antigens, and delayed graft function. Splenectomy, insulin-dependent diabetes, and antilymphocyte serum therapy provided the greatest risk of patient death. Factors such as recipient age, race, and native nephrectomy had suggested associations with outcome. By adding each center as a separate covariate in the analysis, other center-dependent factors were quantitated and found in some cases to have a highly significant association with graft and patient outcome. These results provide a basis for evaluating the potential risk of graft loss or patient death for those prospective cadaver kidney transplant recipients not being considered for cyclosporine therapy.

The effect of HLA–A, –B matching on cadaver renal allograft rejection comparing public and private specificities

Data collected prospectively on 3811 cadaver renal transplants performed between June 1977 and July 1982 by the 42 member institutions of the South-Eastern Organ Procurement Foundation (SEOPF) were analyzed to determine whether donor-recipient compatibility based on public rather than private HLA-A,-B specificities influenced the beneficial effect of HLA matching on outcome. HLA compatibility was calculated considering match and mismatch based on common private or various public (crossreactive group, [CREG]) specificities. Donor-recipient compatibility using certain CREG assignments provided an equivalent means of stratifying graft outcome by the degree of HLA-A,-B match or mismatch, and other CREGs assignments did not. Multivariate Cox regression analysis of donor-recipient compatibility based on certain public antigens showed as high an association (P < 10−5) between good matching and decreased graft rejection as did matching for private antigens alone. Patient stratification by HLA match provided a stronger association with graft outcome than by HLA mismatch, irrespective of whether private or public antigens were considered. The likelihood of finding a better match was significantly increased using CREG assignments, and patients with at least one matched private antigen had equivalent or better graft survival when additional public antigens were matched. These findings indicate that with conventional immunosuppressive therapy: (1) matching of private or public HLA-A,-B antigens plays a highly significant role in decreasing renal allograft rejection; (2) matching based on certain public antigens can provide the same or a better association with outcome as private antigens; and (3) the association (crossreactivity) of various HLA specificities can be defined on a functional basis in terms of graft survival.

Transplantation for polycystic kidney disease.

During the 4-year period from June 1977 to May 1981, a total of 108 patients with polycystic kidney disease and 2440 nonpolycystic patients received cadaver renal allografts in the Southeastern Organ Procurement Foundation (SEOPF) Prospective Study. There were no significant differences between the groups with and without polycystic disease in terms of recipient blood group, history of splenectomy, or preformed antibody status. As a group, transplanted polycystic patients underwent native nephrectomy more often, had a better HLA match, received less antilymphocyte serum (ALS), and were slightly older than nonpolycystic patients. Although proportionately fewer polycystic patients received pretransplant transfusions than nonpolycystic patients (P = .002), transfusion was associated with a significant increase in graft survival in the polycystic group (P less than .05), as well as in the nonpolycystic group (P less than .0001). Gene frequency analysis showed no HLA-A, or -B antigen linkage with polycystic disease. No significant differences existed between the polycystic and nonpolycystic groups in terms of overall graft and patient survival. However, transplanted polycystic patients died more frequently from bacterial sepsis (P less than .05), especially from gram-positive organisms (P = .01). Pretransplant bilateral nephrectomy did not affect the incidence of sepsis. However, following graft failure, patients with bilateral native nephrectomy had a greater incidence of severe anemia (50% versus 39%) and death (58% versus 25%; P less than .05) than those with unilateral nephrectomy or no nephrectomy. Treatment with ALS did not significantly improve graft survival in those with polycystic disease. A strong positive correlation was found between patient death and treatment with ALS only in the polycystic group (P less than .01). These findings indicate that the use of pretransplant bilateral native nephrectomy and posttransplant ALS should be judicious in the polycystic patient because they may be associated with increased morbidity and mortality.

A three year experience using modified bovine arterial heterografts for vascular access in patients requiring hemodialysis.

Between January 1974 and December 1976 28 arteriovenous fastulae were created in 25 uremic patients using modified bovine arterial heterografts. Bovine grafts were inserted only if the patients own vessels were deemed inadequate to permit. the development of a useable Brescia tistula. Graft patency by the life-table method was 92% at three months and 75% at one year. Complications leading to graft failure included late thrombosis, inadequate healing of skin flaps, and graft disruption secondary to faulty cannulation. Ten patients died; none of the deaths were graft-related. At the end of the period of observation all patients requiring hemodialysis had functioning bovine grafts, It is felt that for this purpose the modified bovine arterial heterograft is superior to any other currently available vascular conduit. The location of these grafts should be planned so as to make maximal use of distal vaseulature and allow multiple sequential access procedures in the same extremity. An idealized approach which encompasses these principles is presented.

The influence of pretransplant transfusions, using different blood products, on patient sensitization and renal allograft survival

An analysis of data collected during the South Eastern Organ Procurement Foundation (SEOPF) Prospective Study from 1977–1982 was performed to identify the relative effects of different blood products on patient sensitization and graft survival in cadaveric donor renal transplant recipients. More than 2700 primary and 800 regrafted patients from 40 transplant centers were included in this study. A significant increase in actuarial graft survival was seen in primary recipients who had pretransplant transfusions with only frozen blood (P < 0.003), washed blood (P < 0.0005), packed blood (P < 0.0001), or any combination of blood products (P < 0.002) as compared with those who received no transfusions. No blood product was found to provide a significantly greater increase in graft survival than any other blood product. Likewise, regrafted patients had significant and equivalent increases in graft survival associated with each type of blood product examined. The increased graft survival associated with each blood product was the result of decreased graft rejection, and not apparently related to other differences among patients receiving different types of blood. Furthermore, the type of blood used in pretransplant transfusions did not significantly influence the degree of patient sensitization for first-graft recipients, although regrafted recipients who received packed blood or a combination of blood products showed a slightly greater degree of sensitization than those who received only frozen or washed blood. First-graft recipients given packed or mixed blood had a small, statistically insignificant increase of hepatitis B virus (HBV) antigenemia, compared with those receiving frozen, washed, or no blood. Regrafted patients given any type of transfusion had a 3–4-fold increased incidence of HBV antigenemia as compared with nontransfused patients, but this difference also was statistically not significant. These findings suggest that the benefits of increased graft survival and the risks of sensitization or HBV infection associated with pretransplant transfusions are not significantly affected by the type of blood used.

Cadaver renal transplantation ignoring peak-reactive sera in patients with markedly decreasing pretransplant sensitization

A review of more than 3000 cadaver donor renal allograft recipients transplanted between June 1977 and July 1982 as part of the South-Eastern Organ Procurement Foundation (SEOPF) Prospective Study was performed to identify patients who received a transplant following a significnt decrease in pretransplant sensitization as measured by the percentage of panel-reactive antibody (PRA). Such patients were identified as having had a most reactive (historical peak sera) PRA level at least 40 percentage points higher than their last sample tested prior to transplant (current sera). Additional data were obtained on 157 of these Patients, who also had no history of pretransplant immunosuppression and had a negative pretransplant crossmatch with current sera. Data included the dates of pretransplant sera samples, the specific techniques used for each serum sample that was crossmatched or screened for PRA, and the serological results. The population studied included 17 of 87 first-transplant recipients and 17 of 70 regrafted recipients whose pretransplant crossmatches with peak sera were positive or not done. These subgroups showed no decrease in graft or patient survival compared with cohorts (70/87 first-transplant recipients and 53/70 regrafted recipients) for whom peak sera crossmatching was performed with negative results. Additional stratification for the techniques used in crossmatching and screening, as well as the interval between peak and current PRA levels, showed no significant associations with eventual graft or patient outcome. These results suggest that crossmatch testing using peak sera may not be important in predicting eventual graft or patient outcome for patients with a marked decrease in PRA prior to transplantation and a negative crossmatch with current sera.