Culturally competent methods to promote organ donation rates among African-Americans using venues of the Bureau of Motor Vehicles.

BACKGROUND: The diversity of the nation is one of society's greatest assets, but this feature is overshadowed by the disproportionate burden of disease that exists among America's minorities. Evidence of the disparate health status has been documented in low life expectancy, cancer, diabetes, cardiovascular, and kidney disease as well as a plethora of disorders that necessitate organ transplantation. Many minorities have been reluctant to register to become organ donors. This circumstance can be alleviated by educating the public regarding the necessity of organ transplantation. We have developed a "unique" collaborative outreach program designed to promote acceptance of organ donation in African-Americans (AAs). Our outreach curriculum at Bureau of Motor Vehicles (BMV) has resulted in increased registrations and awareness regarding the need and positive perceptions toward donation. METHODS: We developed a culturally sensitive outreach program: cultural sensitivity indicates how culture has the ability to influence communication between patients and health providers. An "Outreach Promotional Contest" was strategically targeted toward 28 Ohio BMVs to promote and assist in an outreach educational program regarding organ donation/registry. RESULTS: The consequence/results has been an increase of 3.4% in the BMV locations. The one BMV, with the highest increase was attended predominantly by AAs which moreover, won first place in the contest (6.425%; P < .05). CONCLUSION: To increase the number of people willing to register, we believe that both community education regarding the need and importance, as well as culturally sensitive promotion of organ donation, is the best way to increase organ donor registries particularly among minority populations.

Quantitative assessment of the first acute rejection as a predictor of renal transplant outcome.

BACKGROUND: Acute rejection (AR) of the transplanted kidney has been identified as the major risk factor for the development of chronic rejection and immunological graft loss. However, the clinical presentation and response to AR therapy can vary considerably between recipients. METHODS: We studied the first AR episode in 201 kidney-only recipients transplanted between January 1987 and June 1998 who were biopsied between April 1993 and June 1998 and were graded using the Banff schema. All patients received cyclosporine-based immunosuppression. There were 134 cadaver donor (66.7%) and 67 live donor (33.3%) recipients followed for a mean of 46.2 (range 4-128) months. All Banff grade 1-3 and 40/78 borderline (BL) cases were treated for rejection after biopsy. These patients were compared with a contemporaneous control population who did not experience AR. Demographic risk factors associated with graft loss were identified in both univariate and multivariate analysis. Daily (0-18) serum creatinine (SCr) values during and after the AR were plotted for each patient to generate curves and calculate area under the serum creatinine versus time curve (mg/dl/day). Four response patterns to treatment were identified according to the velocity of % increase (V1) and decrease (V2) of serum creatinine. These were identified as rapid rise and fall (n=62); rapid rise and slow fall (n=43); slow rise and fall (n=55); and slow rise and rapid fall (n=41). Kaplan-Meier graft survivals were compared between the groups. RESULTS: Any Banff grade was associated with increased risk for graft loss (P=0.0001). However, no significant differences were observed between the Banff BL and B1-3 groups, or among those BL patients who were treated or remained untreated for AR. Multivariate analysis identified a black recipient (P=0.03, risk ratio 2.0) and area under the serum creatinine versus time curve (P=0.0001, risk ratio 3.2) as significant risk factors for graft loss. The AR response pattern RS resulted in a significantly (P=0.0072) diminished 5-year graft survival (45%) compared with the other groups. Serum creatinine pattern, but not Banff grade, was also a significant (P=0.025) predictor of re-rejection. CONCLUSIONS: These data suggest that all Banff grades, including BL, carry a significant risk for graft loss, and the initial response to antirejection therapy can predict long-term graft outcome. They support the practice of treating AR promptly and definitively and suggest that the RS subgroup of rejecting grafts could be targeted for additional antirejection therapy. This subgroup can be identified by 10 days of AR therapy, and should be the subject of further study.

Determinants of chronic renal allograft rejection in cyclosporine-treated recipients.

We analyzed the development of chronic rejection in 511 kidney-only renal transplants in 507 patients between July 1987 and November 1994. A database was established for recipients > or = 18 years old who received cyclosporine-based immunosuppression and demonstrated graft survival for a minimum of 12 months. The 347 recipients of cadaver transplants (67.9%) and 164 recipients of live donor transplants (32.1%) were followed for 12 to 102 months (mean 51 months). Chronic rejection was diagnosed in 124 transplants (24%), with a mean time to diagnosis of 23+/-18 months (range 3-92). Risk factors were identified in a multivariate analysis using the Cox model. The impact of the timing and severity of rejection episodes was analyzed in a univariate model. The presence of chronic rejection resulted in decreased (P=0.0001) 5-year graft survival for both cadaver graft (83.7% vs. 58.2%) and live donor graft (93.2% vs. 53.1%) recipients. Significant variables for the development of chronic rejection included an acute rejection episode (P=0.0001), a black recipient (P=0.0006), donor age > or = 50 years (P=0.006), and a serum creatinine level >2.0 mg/dl by 6 months after transplantation. Severity of rejection measured by peak serum creatinine or posttreatment return to baseline was not related to chronic rejection. However, acute rejection episodes lasting for more that 5 days (P=0.03) or occurring after 6 months (P=0.001) did influence time to chronic rejection. In addition, mismatching for donor-recipient race was a significant (P=0.008) risk factor for recipients of cadaver grafts. We conclude that acute rejection is the most significant risk factor for chronic rejection, and the long-term fate of grafts may be determined as early as the first 6 months. Racial matching of donor-recipient pairs may be useful to minimize chronic rejection risk. Future advances that diminish the incidence and severity of acute rejection may have the greatest impact on long-term survival.

Should obese patients lose weight before receiving a kidney transplant?

BACKGROUND: The results of renal transplantation in obese recipients have been controversial, with some reports finding increased morbidity prohibitive and others finding increased morbidity acceptable. We attempted to determine whether obese patients in extreme excess of their ideal body weight should undergo transplantation. METHODS: The study population included 127 obese (body mass index >30 kg/m2) patients who were compared with a matched nonobese control group (body mass index <27 kg/m2) of 127 recipients with similar demographics. There were no significant differences between the groups according to donor source, recipient race or sex, retransplants, transplant percent reactive antibodies, cause of renal failure, or hypertension. However, significantly more obese patients had a pretransplant history of angina (11.2% vs. 3.2%, P=0.02) or a previous myocardial infarction (5.6% vs. 0.8%, P=0.04). RESULTS: The mean follow-up was 58.9+/-40 (range 3-170) months. Nonobese patients enjoyed a significantly (P=0.0002) greater patient survival (89% vs. 67%) at 5 years and suffered only about half the number of deaths (25 vs. 46) during the period of observation. Cardiac disease was the leading cause of death (39.1%) in the obese group. Patient death had a major impact on graft survival because there were no differences between the groups when death with graft function was censored from the analysis. There were no significant differences between the groups in delayed graft function, acute rejection, chronic rejection, length of hospital stay, operative blood loss, or mean serum creatinine up to 5 years. However, obese patients experienced significantly (P=0.0001) more complications per patient (3.3 vs. 2.2) and a greater incidence (P=0.0003) of posttransplant diabetes (12% vs. 2%). Similar cyclosporine blood levels were observed in obese recipients even though they were receiving 0.75-2 mg/kg/day less cyclosporine than the nonobese recipients. CONCLUSIONS: Outcome differences in obese renal transplant patients were primarily due to a higher mortality resulting from cardiac events. Obesity seems to have little effect on immunologic events, long-term graft function, or cyclosporine delivery. Aggressive pretransplant screening for ischemic heart disease is essential to identify an especially high-risk subgroup of obese patients. Although it would seem prudent to recommend weight reduction <30 kg/m2 to all patients before transplant, these data suggest that obese patients with a history of cardiac disease should not be transplanted until weight reduction has been accomplished.

A randomized prospective controlled trial of oral acyclovir versus oral ganciclovir for cytomegalovirus prophylaxis in high-risk kidney transplant recipients.

BACKGROUND: Posttransplantation cytomegalovirus (CMV) infection remains a significant cause of morbidity in kidney transplant recipients. We performed a randomized prospective controlled trial of oral acyclovir versus oral ganciclovir for CMV prophylaxis in a group of renal allograft recipients considered at high risk for CMV disease due to the use of OKT3 induction therapy. METHODS: A total of 101 recipients of cadaveric (83) and zero haplotype-matched live donor (18) kidney transplants were entered into the trial. A total of 22 D-R- patients received no prophylaxis. Twenty-seven D+R-, 29 D+R+, and 23 D-R+ patients were randomized to receive 3 months of either oral acyclovir (800 mg q.i.d.) or oral ganciclovir (1000 mg t.i.d.). Doses were adjusted according to the level of renal function. The D+R- patients were also given CMV immune globulin biweekly for 16 weeks. Surveillance blood cultures were obtained at transplantation, at months 1, 2, 3, and 6, and when clinically indicated. The primary study end points were time to CMV infection and disease the first 6 months after transplantation. RESULTS: The mean follow up was 14.4 months. Both agents were well tolerated, and no drug interruptions for toxicity occurred. CMV was isolated in 14 of 39 (35.9%) acyclovir-treated and 1 of 40 (2.5%) ganciclovir-treated recipients by 6 months (P=0.0001). Symptomatic CMV disease occurred in 9 of 14 (64%) of the acyclovir patients, two with tissue-invasive disease. Infection rates for acyclovir vs. ganciclovir, respectively, stratified by CMV serology were: D+R-, 54 vs. 0%, P=0.0008; D+R+, 43 vs. 6.6%, P=0.01; D-R+, 8.3 vs. 0%, P=NS. No patient developed CMV infection while taking oral ganciclovir, however three delayed infections occurred 2-7 months after finishing therapy. Each patient had been previously treated for acute rejection. CONCLUSIONS: Oral acyclovir provides effective CMV prophylaxis only for recipients of seronegative donor kidneys. Oral ganciclovir is a superior agent providing effective CMV prophylaxis for recipients of seropositive donor kidneys. Recipients who are treated for acute rejection are at risk for delayed CMV infection during the first posttransplantation year.

Transplantation of pediatric en bloc cadaver kidneys into adult recipients.

BACKGROUND: To maximize the renal donor pool, cadaveric pediatric en bloc kidneys have been transplanted as a dual unit by some transplant centers. We compared the short- and long-term outcomes of adult recipients of cadaveric pediatric en bloc renal transplants versus those of matched recipients of cadaveric adult kidneys. METHODS: Thirty-three adults who received pediatric en bloc kidney transplants between April 1990 and September 1997 were retrospectively identified and were compared with 33 matched adults who received adult cadaveric kidney transplants. The groups were identical for transplantation era, immunosuppression, recipient sex, race, cause of renal failure, mean weight, and follow-up duration (37.8 vs. 37.5 months). The mean recipient age study versus control was lower (36.3 vs. 48.9 years, P=0.0003). Results. There was no difference between the en bloc and adult donor groups in the 3-year patient survival rates (95% vs. 87%, P=0.16) or the 3-year graft survival rates (87.3% vs. 84.2%, P=0.35). Further, there was no difference in en bloc patient or en bloc graft survival time stratified by recipient age (14-44 vs. >45 years, P=0.11), en bloc donor age (<24 vs. >24 months, P=0.39), or recipient weight (<60, 61-75, >75 kg; P=0.60). Differences in serum creatinine (mg/dl) for the en bloc versus the control group at the time of discharge (3.0 vs. 7.8 mg/dl, P=0.06), at 1 year (1.4 vs. 2.0 mg/dl, P=0.06), and at 2 years (1.1 vs. 1.6 mg/dl, P=0.14) had dissipated by the time of the 5-year follow-up examination (1.1 vs. 1.6 mg/dl, P=0.14). Vascular complications were more prevalent in the en bloc group: renal vein thrombosis (one case), thrombosis of donor aorta (two cases), arterial thrombosis of one renal moiety (two cases), and renal artery stenosis (two cases). There were no differences between groups in delayed graft function, acute or chronic rejection, posttransplant hypertension, posttransplant protein-uria, or long-term graft function. CONCLUSIONS: Collectively, these data indicate that transplanting pediatric en bloc kidneys into adult recipients results in equivalent patient and graft survival compared with adult cadaveric kidneys. Further, the data also suggest that pediatric en bloc kidneys need not be strictly allocated based on recipient weight or age criteria.

A randomized prospective trial of low-dose OKT3 induction therapy to prevent rejection and minimize side effects in recipients of kidney transplants.

BACKGROUND: We attempted to minimize the undesired side effects and maximize the benefit of OKT3 induction therapy in renal transplantation. METHODS: One hundred and one recipients of kidney-only transplants were randomized to three groups. Each received low-dose 2.5-mg OKT3 induction for 7-14 days, but different premedication on days 0, 1, and 2. Group I was given 250 mg i.v. methylprednisolone at 1 and 6 hr, and group II received another 500 mg at 1 hr before initial OKT3. Group III received Atgam 15 mg/kg on day 0 and began OKT3 on day 1. A CD3+ T-cell cut-off of 50/mm3 was used to guide therapy. Maintenance therapy included cyclosporine and steroids for each patient. However, groups I and II were also given mycophenolate mofetil, and group III received azathioprine as a third agent. All rejections were biopsy confirmed and Banff scored. RESULTS: No differences in demographic or transplant characteristics were noted between groups I, II, and III, and mean follow-up was 25.7 (1-38) months. There was no significant difference in actuarial patient (90%, 91%, 94%) or graft survival (83%, 88%, 84%) at 3 years between the respective groups. Mean creatinine values and infectious complications were similar for each group. No patient experienced acute rejection during induction, and eight patients required dose escalation to sustain suppression of CD3 counts. The incidence of acute rejection at 6 and 12 months was significantly (P=0.004) greater in group III (38.2, 44.1%) than in either group I (15.1, 18.1%) or group II (14.7, 17.6%); relative risk 1.988 (95% CI 1.012-3.906). Formation of anti-OKT3 antibody was significantly (P=0.006) greater in group III (26.5%) than in group I (6%) or group II (2.9%). Group I recipients enjoyed significantly (P=0.001) fewer (2.17) OKT3 side effects on days 0, 1, and 2 than group II (3.03) or group III (2.49), and contained the largest number (61%) of recipients who experienced no side effects. Group I also exhibited the most suppressed profile of OKT3-induced release of tumor necrosis factor-alpha (P=0.006), interferon-gamma (P=NS), and interleukin-6 (P=0.01) on days 0 and 1. CONCLUSIONS: Low-dose 2.5-mg OKT3 with pretreatment of split-dose steroids on days 0, 1, and 2 provides the most effective method for OKT3 induction, which minimizes side effects for most patients. Subsequent maintenance therapy with cyclosporine, mycophenolate mofetil, and steroids provides effective rejection prophylaxis without increased complications for up to 3 years. Predepletion of T cells before exposure to OKT3 does not prevent cytokine release.

Cyclosporine disposition and long-term renal function in a 500-pound kidney transplant recipient.

Patient size has been suggested as a risk factor in kidney transplantation. We have followed a recipient of a cadaver kidney who became massively obese (232 kg, 511 lbs) 5 years posttransplantation. He has maintained stable renal function with no rejection episodes and at 5 years has a measured serum creatinine of 2.2 mg/dL, creatinine clearance 42 mL/min, and urinary protein excretion of 320 mg/24h. Both oral and intravenous cyclosporine (Sandimmune) pharmacokinetic studies were done on a steady-state dose of 150 mg, which represents 0.65 mg/kg per dose. The patient exhibited very high bioavailability, F = 95%, and an oral elimination T1/2 of over 21 hours. These data confirm that stable cyclosporine delivery in very obese recipients can be sustained by dosing normalized to the ideal body weight and trough level monitoring.

Testicular seminoma originating in an undescended testis in a renal allograft recipient.

Immunosuppressed transplant recipients are at significantly increased risk for developing neoplasms than are nonimmunosuppressed individuals. However, only six cases of pure testicular seminoma following renal transplantation have been reported in the English literature. This case report represents the first description of a seminoma arising in an undescended testis post-transplantation. We propose that it may be prudent to remove atrophic undescended testes when lifelong immunosuppressive therapy is anticipated, because accelerated tumor growth can occur.

The use of expanded criteria cadaver and live donor kidneys for transplantation.

The use of expanded criteria donors (non-traditional donors) can help lessen the current shortage of kidneys available for transplantation. The use of older donors has accounted for a large measure of the increase in the organ donation rate; however, the most significant factors found to impact on transplant success negatively traditionally have been shown to be extremes of donor age and last-hour urine output. Less significant variables affecting success rates are average systolic blood pressure, terminal serum creatinine, and days of hospitalization. With the appropriate selection of organs from expanded donors, acceptable outcomes can be obtained. When living donors are selected properly, kidneys with anatomic variants without pathologic significance can be used safely. Kidneys with a heightened potential for the development of progressive disease should not be transplanted. Efforts to decrease the cold ischemia time by increasing the use of kidneys from expanded criteria donors may improve the outcome of transplantation further. Advances in surgical techniques, preservation solutions, and methods for predicting eventual long-term renal function in kidneys from expanded donors will be critical in allowing precise selection criteria for kidneys for transplantation, resulting in the optimum use of a scarce and precious resource. Until options such as xenotransplantation become clinically feasible, the challenge will be to identify which donor organs previously considered suboptimal can be used safely to expand the organ donor pool.

Acute colonic pseudo-obstruction (Ogilvie's syndrome) after renal transplantation.

BACKGROUND: Acute colonic pseudo-obstruction (Ogilvie's syndrome) in the immunosuppressed patient is associated with increased morbidity and mortality. Renal transplant recipients possess several comorbidities that increase the risk of acute pseudo-obstruction of the colon. The aims of this study were to present our experience with this syndrome and to evaluate the potentiating factors in these patients. A review of the literature for pseudo-obstruction following renal transplantation is presented. METHODS: Seven patients who developed Ogilvie's syndrome were identified in a retrospective review of 550 kidney-only transplants. Pretransplant data, potential risk factors, presentation, management, and outcome details were retrieved. The medical literature was reviewed using Medline. RESULTS: Seventy-eight patients with Ogilvie's syndrome in the early posttransplant period have been reported. The associated morbidity and mortality was heightened in this immunocompromised population. Obese transplant recipients (body mass index >30 kg/m2) were at significantly increased risk for developing this syndrome. CONCLUSION: A broad armamentarium of treatment options is available, but the key to successful resolution lies in early recognition.

Transfer of endogenous retroviral superantigen from donor to recipient B cells following priming to induce peripheral T cell tolerance.

Endogenous retroviral superantigens such as vSAG-7 are highly stimulatory for T cells through interaction with the T cell receptor on the basis of V beta usage. Priming of adult MMTV 7-negative mice with vSAG-7-expressing cells has been shown to result in peripheral V beta 6/CD4+ T cell activation followed by tolerance to further interaction with the superantigen. The goal of the current study was to examine the cells presenting vSAG-7 during this initial burst of in vivo T cell activation. Priming of MMTV 7-negative BALB/c (H-2d) mice with DBA/2 (H-2d, MMTV 7+) spleen cells resulted in a 5- to 12-fold increase in the number of B cells in the lymph nodes. These B cells expressed increased levels of I-A and I-E class II MHC determinants. Use of MMTV 7-negative CB.17 (H-2d, Ighb) mice as recipients of DBA/2 (Igha) cells indicated that the increased number of B cells was of host, rather than donor, origin. The number of donor-derived (IgM/B220+) B cells observed during the course of vSAG-7-reactive V beta 6/CD4+ T cell activation was very low. Proliferation of unprimed T cells from MMTV 7-negative mice was induced during coculture with B cells from the lymph nodes of vSAG-7-primed recipients and was blocked by anti-class II MHC antibodies, as well as by an anti-vSAG-7 antibody. Highly purified host B cells from vSAG-7-primed recipients specifically stimulated the blastogenesis of V beta 6/CD4+ T cells in vitro. Collectively, the results indicate that following priming to induce peripheral tolerance, vSAG-7 is transferred from donor cells to class II MHC determinants on recipient B cells and is presented to the T cell repertoire by the autologous B cells.

Recipient polyclonal B cell activation and immunoglobulin production induced by priming with a retroviral superantigen.

The superantigen vSAG-7 (or MIs 1a) is a membrane glycoprotein encoded by the endogenous retrovirus mouse mammary tumor virus 7 (MMTV-7) and is highly stimulatory for V beta 6/CD4+ T cells. Priming of adult MMTV-7-negative mice with vSAG-7-expressing cells initially results in the activation of the peripheral V beta 6/CD4+ T cell compartment and is followed by T cell tolerance to the superantigen. During the course of tolerance induction the number of recipient B lymphocytes increases in the lymph nodes, but not the spleen, of vSAG-7-primed recipients. These B cells also express increased levels of class II MHC and present passively acquired superantigen. In this study we asked if these effects on the host B cell compartment are followed by the production of immunoglobulin. Priming of MMTV-7-negative BALB/c or CB.17 mice with vSAG-7-expressing cells from DBA/2 mice induced increases of both IgM and IgG2a in the serum. Use of Igh congenic CB.17 (IgMb) mice as recipients of the vSAG-7-presenting cells from DBA/2 (IgMa) donors indicated that the IgM and IgG produced were entirely of host origin. Priming with vSAG-7 also amplified (four- to fivefold) the antibody-producing cell response induced to a suboptimal dose of sheep RBC. Priming with purified B cells from vSAG-7 donors resulted in recipient V beta 6/CD4+ T cell activation and increased numbers of recipient B cells in the lymph nodes, but did not induce immunoglobulin production. In contrast, priming with purified CD8+ T cells resulted in increased quantities of serum IgM but not vSAG-7-reactive T cell activation or increased numbers of recipient B cells in the lymph nodes. These results indicate that the T cell activation and increased B cell number with upregulated class II MHC expression initially observed following vSAG-7 priming of adult MMTV-7-negative recipients are not linked to the induction of the recipient-derived immunoglobulin production.

U-stitch ureteroneocystostomy: a new renal transplantation ureteral reimplantation technique associated with reduced urologic complications.

Urologic complications represent the most frequent complications following renal transplantation and are associated with significant morbidity. We present the results of the first 105 patients who underwent ureteroneocystostomy at our institution using a new surgical ureteral reimplantation technique designed to reduce the incidence of urologic complications after renal transplantation.

The use of kidneys from living donors with renal vascular disease: expanding the donor pool.

PURPOSE: The disparity between the number of patients awaiting organ transplantation and the number of available donor organs continues to increase. We report the outcomes of transplantation using kidneys from living donors who had unilateral renovascular disease. MATERIALS AND METHODS: We identified 5 living donors who had unilateral renovascular disease, including saccular renal artery aneurysms, an arteriovenous malformation, localized atherosclerosis and fibromuscular renal artery stenosis. Each donor was normotensive and asymptomatic, and had otherwise normal renal function. RESULTS: In each case the abnormal kidney was removed, the lesion was repaired ex vivo and the kidney was successfully transplanted without complication in the donor or recipient. Each recipient had a serum creatinine of less than 2 mg./dl. and each donor remained normotensive with stable renal function at up to 3 years of followup. CONCLUSIONS: Kidneys from living donors with renovascular disease can be transplanted safely provided that careful selection, informed consent and a normal remaining kidney are ensured.