bluuebunny/crossref_metadata_2025 huggingface dataset:
Effective immunization against influenza in pediatric renal transplant recipients
Authors: Edvardsson Vidar O. , Flynn Joseph T. , Deforest Adamadia , Kaiser Bruce A. , Schulman Seth L. , Bradley Alicia , Palmer JoAnn , Polinsky Martin S. , Baluarte1 H. Jorge
Published: September 2024

Viral infections such as influenza are an important cause of morbidity following organ transplantation. We evaluated the immunogenicity of a commercially available influenza vaccine in pediatric renal transplant recipients in a two‐phase, prospective study. In phase one, 47 transplant patients and seven control subjects with bronchopulmonary dysplasia received influenza vaccine. Sera were collected at the time of vaccination and 6 wk later. In phase two, sera from 18 transplant recipients and 47 healthy adults who had received the same vaccine were collected 6‐12 months after vaccination. Antibody titers to the A/Taiwan/1/86 antigen were measured with a hemagglutination inhibition assay in both phases of the study. Vaccine was well tolerated in all subjects. No vaccinated patient required hospitalization for complications of influenza infection. Vaccination did not increase the frequency of acute allograft rejection. In phase one, 43 patients (91%) and 5 controls (71%) either seroconverted (developed a fourfold or greater rise in titer), or developed post‐vaccination titers ≥1:160 (p=NS). Among the transplant recipients, non‐seroconverters had a higher pre‐vaccination geometric mean antibody titer (GMT) than those who seroconverted. Seroconversion developed independently of whether patients received double or triple immunosuppression. In phase two, post‐vaccination GMT were similar for patients and control subjects at 11.5 and 8 months post‐vaccination, respectively. In our study, influenza vaccination produced equivalent humoral immunity in transplant recipients and normal subjects. Routine influenza vaccination should be performed annually in this high‐risk population.
Cutaneous squamous cell carcinoma metastatic to the parotid gland in a transplant patient
Authors: Christiansen Timothy N. , Freije James E. , Neuburg Marcelle , Roza Allan
Published: September 2024

Parotid metastases from cutaneous neoplasms are rare and have a relatively good prognosis if limited to the lymph nodes. When extension beyond the lymph nodes occurs, prognosis is grave. It has also been reported that transplant patients have a higher incidence of cutaneous carcinoma, which tends to be more aggressive. We report a case of an aggressive squamous cell carcinoma metastatic to the parotid gland in a liver transplant patient. The literature pertaining to parotid area metastasis and cancer in transplant recipients is reviewed. We conclude that clinicians should have a higher clinical index of suspicion for cutaneous lesions in transplant patients and that cutaneous lesions at risk for metastasis to the parotid should be treated more aggressively.
Repeated HLA mismatches and second renal graft survival in centers of the South‐Eastern Organ Procurement Foundation
Authors: Heise Eugene R. , Thacker Leroy R. , MacQueen J. Marilyn , Peters Thomas G.
Published: September 2024

To determine if repeated HLA mismatches and other putative risk factors were predictive of second graft failure in second grafts performed at Southeastern Organ Procurement Foundation (SEOPF) member centers, we identified a cohort of 753 retransplants in which one or more HLA antigens were mismatched in primary grafts. Of this group, 158 (21.1%) received second grafts with repeated mismatches of one or more HLA‐A, B, or DR antigens that were previously mismatched in the primary graft (RMMs). All regrafts were cadaveric kidneys transplanted between 1982 and 1995. Multivariate analysis of 19 covariates in 438 regrafts identified four independent factors that were predictive of graft survival frequency in second transplants. Three of the four factors were associated with a reduced risk for graft loss in retransplants: cyclosporin A (CSA) use in regrafts (p=0.0001, RR=0.26), peak PRA<50% (p= 0.008, RR 0.52) and white donor race (p=0.035, RR=0.63). One factor was associated with an increased risk of second graft failure, namely, blood transfusion prior to the first graft (p=0.026, RR=5.14). None of the other 15 factors exerted significant additional risk to regraft survival frequency in these SEOPF data. In multivariate analysis, RMMs were not associated with altered graft survival frequency in regrafts (p=0.944, RR=0.99). We then used univariate analyses to determine whether RMMS had adverse effects on GS in particular subsets of recipients that were thought to be at increased risk for the second transplant failure. Univariate analyses were performed with methods that are sensitive to early events (Wilcoxon) and late events (log‐rank). The variables tested were CSA use for the regraft, duration of primary graft function, panel reactive antibody levels (PRA), immunopathologic cause of first graft failure, and HLA mismatch of the second graft. These analyses indicated that repeated HLA mismatches were not an associated risk factor in any of these subgroups. These SEOPF data indicate that RMMs are not predictive of increased frequency of graft loss in cadaveric donor second transplants. We conclude that our results do not support a policy of routine avoidance of RMMs, which may result in increased waiting time for a second donor without providing an improved graft survival rate. The available literature suggests that HLA antibody identification, the use of sensitive flow cytometric and antiglobulin‐augmented cross‐match tests, together with appropriate donor selection, optimal immunosuppression and patient management may be sufficient to avoid the early loss of second grafts.
Flow cytometry crossmatching and primary cadaver kidney graft outcome: relevance of T and B cell targets, historic sera and autologous controls
Authors: LeFor William M. , Ackermann John R. W. , Alveranga Denise Y. , Bowers Victor D. , Heinrichs Dennis F. , Kahana Lawrence , Shires Dana L. , Weinstein Samuel S. , Wright Charles E.
Published: September 2024

There is limited information regarding the role of flow cytometry crossmatching (FCXM) in primary cadaver kidney allografting and even less about B cell reactivity and graft survival (GS). Furthermore, there is little or no published data concerning reaction strength (cutoff value), the effect of historic sera reactions, and the usefulness of performing autologous crossmatches (XMs) on GS. These factors were examined retrospectively on 214 primary transplants performed from August 1991 to January 1994 with follow‐up to July 1995. Three‐color FCXMs were done on a 1024‐channel BD‐FACScan, and the shift in median channel fluorescence (MCF) over the negative control was calculated. All patients had a negative T cell (AHG) and warm B cell (2 wash, extended incubation) cytotoxicity XM, and none was excluded in calculating GS. A quantitative effect was noted as stronger MCF shifts vs. T or B cells correlated with decreased GS (r=0.98 and 0.92, respectively). Significant differences were seen with cutoff values of T=50 and B=110 which were 1.7‐1.8 times the SD above the mean MCF of normal sera controls. T neg patients (n=198) had 1‐ and 3‐yr actuarial GS of 86% and 79% compared to T pos patients (n=16) of 75% and 49%, p=0.008. B neg patients (n=177) had 1‐ and 3‐yr GS of 86% and 81% compared to B pos patients (n=37) of 78% and 47%, p=0.005. Most informative was the analysis of combined T and B cell FCXM results. Three year GS for T neg B neg patients (n=171) was 81%, and for T pos‐ B neg patients (n= 6), it was 83%, p=0.98. The 27 T neg ‐ B pos group's GS was lower at 62% but did not reach significance. Poorest GS was seen for T pos‐ B pos patients (n=10) at 23%, p=0.0001. Reaction patterns showed that T cells detected only HLA Class I antibodies, whereas B cells detected both Class I and II. Historic sera (≥1 month old) reactivity influenced GS. Patients with ≥2 past sera positive but current serum negative reactions vs. T or T plus B cells (n=7) had a poor 29% GS, while those historically positive only vs. B cells (n=7) had 100% GS. On the other hand, patients positive only with the current serum (n=16) had 2‐yr GS of 100% (false positive test?), while patients whose current and historic sera reactions were positive (n=21) had a 25–50% GS (true positive test?). About 1 in 5 patients (19%) displayed positive autologous FCXM reactions. Subtraction of autologous MCF shift values from those vs. the donor converted 17 patients to the T neg B neg or T pos B neg group whose 2‐yr actual GS was not significantly different (p>0.8) from those initially testing T neg B neg vs. their donors.
Donor‐specific HLA antibodies after transplantation are associated with deterioration in cardiac function
Authors: Leech Stephen H. , Mather Paul J. , Eisen Howard J. , Pina Ileana L. , Margulies Kenneth B. , Bove Alfred A. , Jeevanandam Valluvan
Published: September 2024

Although there is increasing evidence that mismatched donor HLA antigens are associated with a lowering of survival of human cardiac allografts, the effect of antibodies that bind those antigens is less clear. The existence of lymphocytotoxic antibodies prior to cardiac transplantation has been associated with a poor outcome in the majority of reports of relevant studies, as has their appearance post‐transplantation. But how such antibodies, especially those with HLA specificity, cause poor outcomes has been poorly understood. The purpose of this study was to investigate the effect of anti‐HLA antibodies appearing in the circulation after human orthotopic heart transplantation. Such antibodies were identified by a standard microlymphocytotoxicity technique using panels of frozen lymphocytes from normal donors who had been tissue typed. Of 74 patients transplanted over a 12‐month period, 4 (5.4%) developed alloantibodies specific for mismatched donor HLA antigens. The first patient developed antibodies to HLA‐A23 and B44 together with poor ventricular function and vascular rejection requiring retransplantation within 4 months. The other patients (3) developed antibodies specific for HLA‐DQ antigens and experienced variable numbers of episodes of cellular rejection with no evidence of vascular rejection on endomyocardial biopsy. Two of these three patients died (8 and 11 months post‐transplant) after three and six rejection episodes, respectively. The one surviving patient had seven rejection episodes and continues to have poor ventricular function 18 months post‐transplant. We conclude that alloantibodies specific for mismatched donor HLA antigens may have a deleterious effect on the outcome of the human cardiac allograft and should be monitored closely post‐transplant. Furthermore, such antibodies may mediate effects on the transplanted heart which are not detectable in specimens obtained by endomyocardial biopsy.
A new approach for increasing the organ supply
Authors: Kowalski Anne E. , Light Jimmy A. , Ritchie William O. , Sasaki Truman M. , Callender Clive O. , Gage Fred
Published: September 2024

The donation of organs and tissues for the benefit of another person is an altruistic act and one that is a guaranteed option for the next‐of‐kin through various national Required Request legislations. At the Washington Hospital Center we have developed an approach that permits organ recovery from non‐heart beating donors. The focus is on victims of fatal trauma and assures that each family is empowered with the right to make a donation decision. In October 1993 a consensus conference was held on implementing a program to recover organs from fatal trauma victims. The participants recommended that safeguards be incorporated to assure ethical treatment of both the trauma victim and the nextof‐kin. An Office of Decedent Affairs (ODA) was then established and implemented in September 1994. The ODA is staffed by Family Advocates who are on duty continuously and respond to all trauma and death. events. Their mission is to consolidate all death events, provide support to decedent families, assure that required request mandates are fulfilled, interact with the local Organ Procurement Organization (OPO) in the consent process, and facilitate the implementation of the Rapid Organ Recovery Program (RORP). The RORP consists of two specific procedures: cannulation of the femoral arterial‐venous system for flushing the kidneys with a preservative solution, and intubation of the peritoneum for in situ cooling using an ice/lavage process. In the 1‐yr period since the ODA was established, organ and tissue donation has increased by more than 300%.
Prevention of hepatitis B recurrence with indefinite hepatitis B immune globulin (HBIG) prophylaxis after liver transplantation
Authors: Nymann Trine , Shokouh‐Amiri M. Hosein , Vera Santiago R. , Riely Caroline A. , Alloway Rita R. , Gaber A. Osama
Published: September 2024

Liver transplantation for hepatitis B is followed by a high rate of recurrence some time after transplantation, resulting in poor outcome compared to liver recipients transplanted for other indications. Passive immunoprophylaxis with HBIG has been shown to decrease the rate of recurrence to 25–50%, but the intensity and length of treatment is still controversial. We studied 17 HBsAg positive patients who were transplanted for hepatitis B. Four did not receive immunoprophylaxis and they all reoccurred within 3 months. The remaining 13 have received indefinite, high dose HBIG (10 000 u or 40 000 u/dose depending on HBV DNA status pretransplant). Ten of 13 patients (77%) remain HBsAg negative after a mean follow‐up of 16.7 months with six of these ten patients being HBV DNA positive pretransplant. Of the three who have experienced recurrence, two received extensive additional immunosuppression beyond that normally administered to transplant patients (chemotherapy, multiple antirejection treatment). The last patient received 110 000 u of HBIG during the first 3 months, which produced an anti‐HBs titer level of 225 IU/L, but the following month he was HBsAg positive with an anti‐HBs titer of 13 IU/L. We conclude that HBsAg positive patients can be safely transplanted using indefinite, high‐dose HBIG prophylaxis. and that with adequate HBIG it is possible to prevent recurrence in HBV DNA positive patients as well.
Liver transplantation for alcoholic liver disease
Authors: Zibari G. B. , Edwin D. , Wall L. , Diehl A. , Fair J. , Burdick J. , Klein A.
Published: September 2024

Orthotopic liver transplantation (OLT) for individuals with alcoholic liver disease (ALD) remains controversial. This review was designed to evaluate the survival, recidivism, and rehabilitation of the alcoholic liver transplant recipient in a single transplant center. Methods: Between 10/86 and 11/92 203 liver transplants were performed in 179 patients. In 42 patients (23%) the primary etiologic diagnosis was ALD (36 males, 6 females, median age 47 yr). All ALD patients were evaluated preoperatively by social service, psychiatry, and medical psychology, in addition to hepatology and transplant surgery. A minimum abstinence period of 3‐6 months was encouraged, although exceptions were made for cases of extreme medical urgency in which a good prognosis for abstinence was predicted. Results: In OLT recipients with ALD, actuarial survival at 1, 2, and 3 yr was 74%, 71%, and 71%, respectively, compared to 71%, 71%, and 69% for all OLT recipients. Oneand two‐year survival was 85% in the most recently transplanted 86 patients, 20 of whom (23%) had ALD with 1‐ and 2‐yr survival of 84% (N.S.). Recidivism was monitored postoperatively by interviews with the patient and family, supplemented by random urine and serum toxicology. Of the 29 survivors, 2 (7%) returned temporarily to alcohol use but are presently abstinent. Although none of the ALD patients in this study was able to work prior to OLT, 76% of the survivors at least 4 months post‐transplantation were employed. Conclusions: Although our experience is small, our results suggest that OLT is appropriate therapy for carefully selected patients with endstage liver failure due to ALD. The multi‐disciplinary approach to preoperative evaluation of the alcoholic liver transplant candidate is effective in determining those patients committed to abstinence after a successful transplant.
Is matching for sex and age beneficial to kidney graft survival?
Authors: Busson M. , Benoit G. ,   Société Française de Transplantation and Association France Transplant
Published: September 2024

A total of 6889 cadaver kidney grafts carried out in the French transplant network from 1 January 1989 to 31 December 1992 were analyzed using single and multifactorial methods in order to evaluate the impact on graft survival of matching for sex and age between donors and recipients. The mean graft survival rate was 75% at 3 yr with donors between 10 and 50 yr of age compared to 65% for donors under 10 yr of age. and 67% at 3 yr for donors over 50 yr of age (p <0.000001). For child recipients there were no significant differences in graft survival whatever the difference in age with the donor (± 10 yr). For young adults (17–49 yr of age) the prognosis at 3 yr was the same (75%) whether the donor was in the same age category or older than the recipient. For older adults (> 50 yr of age) a poorer prognosis was obtained when the donor was 10 yr or more older than the recipient (61% at 1 yr, p=10−4). The grafts performed with male donors had a better prognosis (76% at 3 yr) than those using female donors (71% at 3 yr, p <0.0002). The poorest results were obtained with female donors when the recipient was male (70% at 3 yr). The results of the multivariate analysis of seven parameters involved in graft survival show that the main parameters significantly controlling graft survival are preimmunization before the graft (p=10−6), HLA‐DR incompatibility (p=0.004), retransplantation (p=0.008), donor sex (p=0.003), and matching for age between donor and recipient (p=0.01). These results suggest that age and sex should be considered as criteria in the choice of donors and recipients in organ allocation.
Increased β2‐microglobulin (B2M) is useful in the detection of post‐transplant lymphoproliferative disease (PTLD)
Authors: Sasaki Truman M. , Pirsch John D. , D'Alessandro Anthony M. , Knechtle Stuart J. , Kalayoglu Munci , Hafez Gholam R. , Sollinger Hans W.
Published: September 2024

This study examines whether changes in β2‐microglobulin (B2M) serum levels are useful in the early detection of post‐transplant lymphoproliferative disease (PTLD). Serum B2M is monitored daily post‐transplant at our center as a marker of change in lymphocyte activation. We identified 16 cases (16/1359; 1.2%) of PTLD from among 1359 kidney and kidney‐pancreas transplants. Those with CNS lymphoma (two patients) and titer change only (one) were not included in this review. Thirteen patients had serum titer and clinical evidence of EBV activity; 12 of these patients had histological evidence of PTLD (lymph node 6, kidney 3, and generalized disease 3). Three patients died with disseminated PTLD infection. Nine are alive but only two have the original transplant kidney. All patients received quadruple immunosuppression for induction, and 11 were subsequently treated with OKT3 or ALG for rejection. The mean number of days of induction ALG therapy was 14.8 d (20 mg/kg/d). The mean number of days of OKT3 therapy for rejection was 14.4 d (5 mg/d). During rejection the highest mean creatinine level was 6.8 mg/dL, and the highest mean B2M level was 16.4. With PTLD, the highest mean creatinine level was 7.0 mg/dL and the highest mean BM level was 32.3 mg/L. The difference in creatinine levels was not significant, but the difference in B2M levels was significant (p<0.01). We conclude that B2M levels are useful markers in differentiating rejection from PTLD.
OKT3 therapy increases cyclosporine blood levels
Authors: Vasquez Eva M. , Pollak Raymond
Published: September 2024

Numerous drugs have been reported to alter cyclosporine (CSA) blood levels, most notably, those drugs that interfere with cytochrome P450 metabolism. Our clinical experience suggested that OKT3 therapy may alter CSA blood levels as well. The purpose of this study was to assess the effect of OKT3 therapy on CSA trough blood levels. We reviewed medical records of all CSA‐treated renal transplant recipients during a 3‐yr period to identify patients who received antilymphocyte induction therapy. Patients receiving drugs known to interact with CSA were excluded from analysis. The study population (n=33) was divided into two groups: the OKT3 group consisting of 17 patients who received OKT3 therapy for 7 d post‐transplant (OKT3 group) and the control group consisting of 16 patients who received ALG induction therapy for 7 d post‐transplant (ALG group). Oral CSA (14 mg/kg) was administered preoperatively. Postoperatively, oral CSA (4 mg/kg) was administered twice daily, in addition to corticosteroids. and azathioprine. We evaluated CSA through levels on days 1, 3, 5, and 7 of antilymphocyte therapy and 3 d following completion of antilymphocyte therapy. On days 1 and 3, CSA trough levels did not differ between the two groups. However, median CSA trough levels (HPLC) were significantly higher among OKT3‐treated patients on day 5 of therapy (265 ng/ml), as compared to ALG‐treated patients (136 ng/ml; p<0.0001; Mann‐Whitney U‐test). On days 7 and 10, CSA trough levels did not differ between the two groups. CSA doses, however, had been adjusted based on levels obtained on day 5. We conclude that OKT3 therapy causes a significant rise in CSA trough levels. Recognition of this potential drug interaction is essential in titrating CSA doses in the early post‐transplant period to minimize risks of CSA toxicity or early rejection following induction therapy.
Economic analysis of Neoral in de novo renal transplant patients in Canada
Authors: Kingma I. , Ludwin D. , Dandavino R. , Wolff J.‐L. , Loertscher R. , Beauregard‐Zollinger L. , Bacquet P. , Boucher S. , Rivière M.
Published: September 2024

This pilot economic evaluation was performed as part of the Canadian arm of an international randomized, controlled, double‐blind safety and tolerability trial (OLM‐105 / NOF‐2). The clinical study compared the safety and tolerability of a new microemulsion oral formulation of cyclosporine A (Neoral®) with the oral cyclosporine. A preparation currently in use (Sandimmune SGC®)/(SGC). To assess the economic impact of Neoral in newly grafted renal transplant patients, primary cost data were collected at the five participating Canadian centers and evaluated from the Ministry of Health (MOH) and hospital perspectives. The results of this cost analysis are presented in this paper. Since the new formulation has shown more consistent absorption and a more predictable pharmacokinetic profile, medical resource utilization and, consequently, cost of treatment could be expected to be lower for those renal transplant recipients treated with Neoral than for those receiving standard SGC. The findings of this study support this hypothesis. Robustness of the conclusion was confirmed with sensitivity analyses. Reduced health care costs for patients treated with Neoral were primarily a result of fewer hospitalization days and lower physician costs for inpatient and outpatient procedures.
Cardiovascular risk factors in long‐term followup after orthotopic liver transplantation
Authors: Guckelberger Olaf , Bechstein Wolf O. , Neuhaus Ruth , Luesebrink Rainer , Lemmens Hans P. , Kratschmer Bernd , Jonas Sven , Neuhaus Peter L.
Published: September 2024

In a retrospective study the records of 302 adult patients (167 male, 135 female) after orthotopic liver transplantation (OLT) with a minimum follow‐up of 6 months (median follow‐up 18 months, maximum 5 yr) were reviewed with regard to cardiovascular risk factors. In 197 patients data concerning the occurrence of arterial hypertension, hyperglycemia, or hypercholesterolemia prior to OLT were available. We found a highly significant increase of cardiovascular risk factors following OLT. Obesity was found in 17.4% of male and 22.2% of female recipients after OLT. Hypercholesterolemia was evident in 66.2% of liver graft recipients. Hypertriglyceridemia occurred in 49.7% of all male patients. In females there was a significantly different prevalence of hypertriglyceridemia comparing patients with a follow‐up period up to 2 yr and more than 2 yr (50% vs. 24.6%, p=0.018). Nearly 45% of all patients met the criteria for arterial hypertension, with a slight increase in male patients beyond the second year of survival (p=0.094). Hyperglycemia had a significantly higher frequency in male than in female patients (30.5% vs. 10.4%, p<0.005). Furthermore we observed a clear trend towards reduction of occurrence of hyperglycemia more than 24 months after OLT, but not reaching statistical significance.

No correlation was detected when serum levels of triglycerides, and cholesterol, body‐mass‐index, and arterial blood pressure were compared with applied dosages of immunosuppressive agents [cyclosporin A (CyA), tacrolimus, and prednisolone]. Only decreasing tacrolimus application was significantly correlated with decreasing glucosemia (p=0.041).

Patients receiving tacrolimus instead of CyA as primary immunosuppressant showed a significantly lower prevalence of hypercholesterolemia. Even hypertension, hyperglycemia, hypertriglyceridemia, and obesity had a lower occurrence in patients treated with tacrolimus although not reaching statistical significance.
Clinical spectrum of invasive cryptococcosis in liver transplant recipients receiving tacrolimus
Authors: Singh Nina , Gayowski Timothy , Wagener Marilyn M. , Marino Ignazio R.
Published: September 2024

Invasive cryptococcal infections have been reported in 0.3–1% of the patients undergoing liver transplantation in the previous reports. In contrast, invasive cryptococcosis developed in 6% of 102 consecutive liver transplants at our institution receiving tacrolimus as primary immunosuppression. Cutaneous and/or osteoarticular infections due to cryptococcus were detected in 67% of the patients with cryptococcosis, whereas meningitis was present only in 17%. One of the six patients with cryptococcosis presented with refractory shock and multiorgan system failure attributable solely to cryptococcosis. Patients with cryptococcal infections were significantly older than all other liver transplant recipients (p=0.017), suggesting reactivation as opposed to primary infection as pathogenesis of cryptococcosis. 100% of the patients with cryptococcosis resided on the Eastern coast of the United States as compared to 59% of the patients without cryptococcosis (p=0.08). There was no difference in the severity of underlying liver disease, degree of immunosuppression or CMV infection or disease between patients who did and did not develop cryptococcosis. Atypical manifestations, e.g. cutaneous diseases or sepsis syndrome, as opposed to subclinical meningitis, may be a clinical feature of cryptococcal infection in liver transplant recipients.
Colon perforation after renal transplantation: a single‐institution review
Authors: Pirenne J. , Lledo‐Garcia E. , Benedetti E. , West M. , Hakim N. S. , Sutherland D. E. R. , Gruessner R. W. G. , Najarian J. S. , Matas A. J.
Published: September 2024

Colon perforation (CP) is an uncommon but dramatic complication after renal transplantation. Of 1530 consecutive kidney transplants performed at our center, 8 recipients had an CP (incidence of 0.5%), either early (n=5, 2‐14 days) or late (n=3, 8‐48 months) post transplant. Clinical symptoms were generally vague. Biological findings were inconstant. Risk factors for CP included a cadaver graft (versus a living donor), high body weight, history of diverticulitis, and Kayexalate use. Crucial to outcome were: 1) immediate diagnosis and 2) aggressive surgical care consisting of resectional therapy, broad‐spectrum antibiotics, and reduced immunosuppression. Applying these principles, mortality in our patients (25%) was lower than in previously reported series (33–64%). All grafts were functioning at the time of diagnosis; graft function was preserved in recipients who recovered from CP. Patients with a documented history of diverticulitis should undergo prophylactic colonic resection. Constipation and colonic dilatation should be treated aggressively in the early post‐operative period.
Soluble fraction of class I human histocompatibility leukocyte antigens in the serum of liver transplant recipients
Authors: McMillan Robert W. , Gelder Frank B. , Zibari Gazi B. , Aultman Donnie F. , Adamashvili Irena , McDonald John C.
Published: September 2024

In previous studies we reported a solid‐phase, enzyme‐linked immunoassay (ELISA) that can be used to quantitate the soluble fraction of human histocompatibility leukocyte class I antigens (S‐HLA‐I) and study their relevance in transplantation. In this study we determined the concentration and distribution of S‐HLA‐I in patients with end‐stage liver disease (ESLD), as well as in liver transplant recipients. Sera were obtained from 51 patients with ESLD and 40 donor‐recipient pairs. We analyzed the SHLA‐I in sera obtained from liver donors, as well as from liver transplant recipients (patients with ESLD), with sera from the latter obtained before and at various intervals up to 3 yr after transplantation. The results of the analyses justify the following conclusions: 1) Patients with ESLD had mean values of S‐HLA‐I (909 ± 596 ng/ml) greater than those for the normal population (643 ng/ml) (P < 0.05); the S‐HLA‐I secretion decreased with increasing severity of liver disease. 2) Patients with tumors had mean S‐HLA‐I levels (399 ng/ml) significantly lower than those in patients with ESLD related to other causes. 3) In liver transplant recipients the S‐HLA‐I levels stabilized at approximately 1 month after transplant and remained relatively stable thereafter (mean level 950 ± 536 ng/ml). The observed levels were also greater than those for the normal population (P<0.05). 4) Preoperative and postoperative S‐HLA‐I values in liver transplant recipients demonstrated a biphasic distribution, dividing patients into highand low‐secretor groups. 5) During the post‐transplant observation period, of these selected liver transplant recipients there was no difference between highand low‐secretor groups in the incidence of rejection (high, 70%; low, 67%), graft survival (high, 95%; low, 94%), or patient survival (high, 95%; low, 94%). 6) Measurement of the total amount of S‐HLA‐I, containing yet undefined ratios of both donor and recipient S‐HLA‐I, cannot be used to predict a state of tolerance in liver transplant recipients.
Vesical calculus: an unusual complication of renal transplantation
Authors: Klein Frederick A. , Goldman Mitchell H.
Published: September 2024

Vesical calculus formation in renal transplant patients is rare. We describe seven patients who developed calcium oxylate or combination calcium oxylate‐magnesium ammonium phosphate stones on a polypropylene suture nidus at the site of a ureteroneocystostomy. The use of a nonabsorbable suture in the urinary tract should be avoided.
Intensive care unit management in liver transplant recipients: beneficial effect on survival and preservation of quality of life*
Authors: Singh Nina , Gayowski Timothy , Wagener Marilyn M.
Published: September 2024

Determinants of outcome of intensive care unit (ICU) stay and quality of life in survivors was prospectively assessed in 50 consecutive liver transplant recipients requiring intensive care unit (ICU) management. Variables assessed included demographic, clinical and laboratory characteristics, measures of severity of illness (Child‐Pugh, Apache II, and organ system failure scores) and quality of life measures (physical functioning, perceived quality of life, stress, depression, and adaptive coping). Overall ICU survival was 82% (41/50). Nonsurvivors had significantly higher acute physiology scores (p=0.03), Apache II score (p=0.03), Karnofsky score (p=0.01) and serum bilirubin (p=0.05) on admission than survivors. Nonalert mental status (p=0.0002), hypothermia (p=0.035) and hypotension (p=0.027) on admission were significantly associated with mortality. During the ICU stay, requirement of mechanical ventilation (p=0.02), duration of ventilation (p=0.01), requirement of dialysis (p=0.0005), development of pulmonary infiltrates (p=0.0001) and infections in the ICU (p=0.003) were significantly associated with mortality. Requirement of mechanical ventilation was an independently significant predictor of mortality (with mechanical ventilation, dialysis and infections in the logistic regression analysis model). There was no difference in post‐discharge quality of life (as assessed by the perceived quality of life, stress, depression, and coping scores) in survivors of ICU stay as compared with patients who never required ICU care. Our study suggests that the ICU management can have a positive impact on outcome for liver transplant recipients. If they survive (and 82% did in this study), their quality of life is unaffected and as good as those whose postoperative course was not complicated by a critical illness requiring ICU care.
The fate of renal transplants in patients with IgA nephropathy
Authors: Frohnert P. P. , Donadio J. V. , Velosa J. A. , Holley K. E. , Sterioff S.
Published: September 2024

Background

IgA Nephropathy (IgA N) is one of the most common glomerulopathies and may lead to renal failure in 10–20% of cases. After renal transplantation, IgA N has a strong tendency to recur in the graft. Initially considered a benign condition, graft losses from recurrent IgA N have been reported over the last 20 yr, casting doubt on the initial premise. Since large single‐center studies of the fate of renal allografts in IgA N are rare and the Mayo Clinic transplant experience for IgA N is extensive (dating back to 1970), a review of these issues appeared worthwhile.

Methods

A retrospective study was done of all renal transplant patients who had had biopsy‐proven IgA N as underlying disorder. We extracted data on the underlying disease, history leading to renal transplantation, factors affecting transplant outcome, and on the course after transplantation with special attention to rejection activity and recurrence of the primary disease. Standard statistical methods were employed.

Results

53 renal allografts were transplanted to 51 biopsy‐proven IgA N patients: 12 were cadaveric (CAD) grafts, 3 HLA‐mismatched living related donor (LRD) kidneys, 29 one haplotype‐matched LRD and 9 HLA‐identical LRD organs. Five‐year actuarial graft survival was 100% in HLA‐ identical LRD, 88% in one haplotype‐matched LRD, and 74% in CAD grafts. All three HLA‐mismatched LRD kidneys were functioning up to 1.6 yr (longest follow‐up). Only one patient died after acute rejection of the CAD graft. There were 3 early graft losses from acute rejection and 4 late losses. IgA N recurred in 26% of allografts and led to significant loss of graft function in 10 of the 14 patients (71%) over a long period of observation. Three of four late graft losses were in patients with recurrent IgA N. Recurrence was not related to the type of graft, i.e. CAD vs. LRD, nor to the extent of HLA‐matching in LRD transplantation.

Conclusion

Renal transplantation in patients with IgA N has excellent patient and graft survival. There is a high rate of recurrence of the primary glomerulopathy in the renal allograft, and this event is by no means inconsequential. Loss of renal function and even graft loss occur over prolonged periods of time. There is no disadvantage getting a well matched LRD in regard to incidence of recurrent IgA N. Thus, we encourage LRD transplantation in IgA N.
Exposure to Mycobacterium tuberculosis (MTB) in a renal transplant candidate: what further preoperative screening tests are available?
Authors: Felger Jason , Halff Glenn A. , Esterl Robert M.
Published: September 2024

Despite negative preoperative screening for MTB, a renal candidate demonstrated active tuberculous lymphadenitis (TL) in a deep iliac node intraoperatively during living related renal transplantation. With intraoperative discovery of TL, both donor nephrectomy and renal transplant were aborted. The authors present this case of TL to discuss whether additional preoperative screening tests are available to document previous exposure to MTB in a renal transplant candidate. The diagnosis and treatment of MTB in patients on routine hemodialysis are reviewed. The authors review the operative case to emphasize that critical intraoperative measures must be taken to minimize operative and postoperative morbidity in the donor and recipient. Finally, the literature for current antibiotic regimens in the treatment of TL is reviewed.
Sequential biological immunosuppression. Induction therapy with rabbit antithymocyte globulin
Authors: Guttmann R. D. , Flemming C.
Published: September 2024

This paper describes 108 consecutively treated patients receiving 109 cadaveric (CD) and living donor (LD) renal allografts using a protocol of quadruple sequential immunosuppression with a rabbit anti‐human thymocyte IgG (Thymoglobuline®), azathioprine, tapering corticosteroids, and delayed introduction of cyclosporine A. The average length of induction was 6.1 d with an average Thymoglobuline® dose of 2.0 mg/kg/d. The mean serum creatinine pre‐transplant of the cohort was 877 ± 263 (sd) μmol/L, 146 ± 44 μmol/L by 3 months post‐transplant, and 136 ± 40 μmol/L at 1 yr. The overall 4‐yr actuarial patient survival was 96.6%, and allograft survival was 88.6% at 2 yr and 83.6% at 4 yr. The incidence of acute rejection episodes defined by intention to treat was 32%. Additionally, eight patients in this series received retreatment with Thymoglobuline® for a first acute rejection, and only one of these had a second rejection. This was in contrast to 5/11 recurrent rejections following steroid treatment only, and 5/13 recurrences following OKT3 treatment for the first rejection episode. The side‐effect profile of Thymoglobuline® was largely benign, and the biological agent was well tolerated with initial fever in 75%, chills in 27%, and leucopenia in 22% of the patients. All other drug‐related adverse events had a prevalence of less than 3%, and clinical signs of meningismus were seen in only one patient. There were five associated episodes of CMV. We conclude that Thymoglobuline as part of a quadruple sequential immunosuppressive regimen for renal transplantation is well tolerated and can be associated with a good shortand long‐term outcome of renal transplantation.
Drainage of the exocrine pancreas in clinical transplantation: comparison of bladder versus enteric drainage in a consecutive series
Authors: Pearson Thomas C. , Santamaria Pablo J. , Routenberg Kristine L. , O'Brien David P. , Whelchel John D. , Neylan John F. , Larsen Christian P.
Published: September 2024

The purpose of this study was to define the incidence of urologic and metabolic complications after simultaneous kidney/pancreas transplantation (SKPT) with bladder drainage (BD). Review of 55 SKPT with BD performed between 1989 and 1995 demonstrated patient, kidney, and pancreas survival rates of 95%, 89%, and 78%, respectively, with a mean follow‐up of 41 months (range 12‐78 months). Over this follow‐up period 78% of these patients experienced a urinary tract infection, 27% had hematuria, and 38% had at least one hospital admission for dehydration. Recent experience with primary enteric drainage of the exocrine secretions of the transplanted pancreas (n=11) has demonstrated the total absence of these complications (follow‐up range 2‐12 months). These results suggest the value of continuous re‐evaluation of surgical techniques as the care of transplant patients evolve.
Causes of renal allograft loss in black vs. white transplant recipients in the cyclosporine era
Authors: Valente John F. , Hariharan Sundaram , Peddi V. Ram , Schroeder Timothy J. , Ogle Cora K. , Alexander J. Wesley , First M. Roy
Published: September 2024

Black renal transplant recipients have a higher rate of allograft loss than white recipients. From 1 January 1984 to 1 January 1995, 463 transplants were performed at a single center and followed for a mean duration of 71 months. The causes of graft loss for white and black recipients. their age, gender, retransplantation rate, organ source, and HLA matching were compared. In the 150 black and 313 white recipients, graft loss rates in the first year were 20% in both groups, while after 1 yr there were 42 (28%) graft losses in blacks vs. 62 (20%) in whites (log‐rank test p=0.04). All diagnoses deemed causative of allograft loss were confirmed by biopsy. Chronic rejection resulting in graft loss occured in 15% (n=23) of black recipients compared to only 7% (n=22) of white recipients (p=0.002). There were no significant differences in the rate of death with a functioning kidney or other causes of graft loss between the two groups. A significant increase in HLA mismatches was noted in black recipients of cadaveric grafts compared to whites, but there was no difference between races in the rate of graft loss due to acute rejection. While the rate of graft survival remains lower in black recipients in the cyclosporine era, this is due entirely to late graft loss after 1‐yr post‐transplant due to chronic rejection.
Post‐transplant lymphoproliferative disease in kidney transplant patients in the new immunosuppressive era
Authors: Ciancio Gaetano , Siquijor Alex P. , Burke George W. , Roth David , Cirocco Robert , Esquenazi Violet , Byrne Gerald E. , Miller Joshua
Published: September 2024

Although the kidney transplant program at this center has been active for the past 18 yr, five out of the seven cases of post‐transplant lymphoma in kidney transplant patients were observed over the past 2 yr. During this period, we have shifted from cyclosporine to tacrolimus (FK506 or prograf) for maintenance immunosuppression and for rescue therapy. We have also introduced mycophenolate (RS ‐ 61443) and have continued an antibody induction regimen in the immediate postoperative period. FK506 is 50‐100 times more potent than cyclosporine. We have reported a decreased incidence of rejection, improved graft survival, and a general optimalization of patient survival with these newer regimens. Nonetheless, five cases of post‐transplant lymphoma out of 233 kidney transplants (2.1%) performed during this time period (December 1993 to December 1995) occurred between 3 months to 1 yr after the transplant. Four of the five patients are still alive between 12 and 24 months after the diagnosis of lymphoma was made. All were without evidence of ongoing disease. Three of the five have grafts with excellent function for longer than 18 months after transplantation, while one is marginal and one patient expired on dialysis. The third and fourth patients had severe rejection before the diagnosis of PTLD was made. While the occurrence of five cases of post‐transplant lymphoma over a 2 yr period is alarming, this is still within the 2–4% incidence of post‐transplant lymphoma that has been reported in the literature in kidney transplant patients. Our results probably reflect the increasing potency of our immunosuppressive protocols but do not show any increase in the aggressiveness of this entity of post‐transplant lymphoma during the continued follow up.
Reversal of accelerated renal allograft rejection with FK 506
Authors: Woodle E. S. , Newell K. A. , Haas M. , Bartosh S. , Josephson M. A. , Millis J. M. , Bruce D. S. , Piper J. P. , Aronson A. J. , Thistlethwaite J. R.
Published: September 2024

Although FK 506 has been shown to effectively reverse refractory renal allograft rejection, its ability to reverse accelerated renal allograft rejection as a primary agent has not been specifically addressed. Herein evidence of the ability of FK 506 to reverse accelerated renal allograft rejection is presented. A 16‐yr‐old highly sensitized (PRA 75%) male underwent a second cadaveric renal transplant procedure. Despite induction immunosuppression with ATGAM, cyclosporine, azathioprine, and corticosteroids, a marked elevation in serum creatinine (1.6‐2.1 ng/dl) and reduction in urine output (4000 ml/d–1000 ml/d) were observed on the sixth post‐transplant day. Renal allograft biopsy performed at that time revealed typical features of accelerated rejection including neutrophil margination in glomerular and interstitial capillaries, and C3, IgG, and fibrin deposition in glomerular and interstitial capillaries (by immunofluorescence). FK 506 therapy was promptly instituted and ATGAM therapy discontinued. Serum creatinine peaked within 3 d of FK 506 therapy (2.5 mg/ dl) and subsequently progressively dropped to 1.2 mg/dl. Repeat biopsy on FK 506 treatment day 12 revealed marked histologic improvement. Renal function remains excellent (1.3 mg/dl) 18 months after initiation of FK 506 therapy, and recurrent rejection has not been observed. This experience provides evidence that FK 506 therapy may effectively reverse accelerated renal allograft rejection, and that it provides a means for treating antibodymediated mechanisms of allograft rejection.
Risk of renal cell carcinoma after kidney transplantation
Authors: Kliem V. , Kolditz M. , Behrend M. , Ehlerding G. , Pichlmayr R. , Koch K. M. , Brunkhorst R.
Published: September 2024

Between December 1968 and July 1995, 2372 renal transplant recipients were seen regularly in our outpatient clinic. 154 patients (6.5%) of these subsequently developed a malignant tumor. One of the most frequently observed malignancies was a renal cell carcinoma in the native kidneys, found in 12 patients (7.8%; i.e. 0.5% of the total population), two of them with analgesic nephropathy and one with adult polycystic kidney disease. So‐called acquired cystic kidney disease of the native kidneys was found in 73% of the patients with renal cell carcinoma. In the patients with renal cell carcinoma the median age at transplantation was 43.9 (39–55) yr. The median time from onset of end‐stage renal failure and from transplantation to the appearance of the tumor amounted to 117.3 (43–206) and 75.8 (5–164) months, respectively. Despite nephrectomy, four patients died of the cancer (6–57 months).

As a consequence we suggest a regular sonographic screening of the native kidneys twice a year in all renal transplant patients. As in dialysis patients, the main risk factors for the development of renal cell carcinoma seem to be so‐called acquired cystic disease of the native kidneys and the underlying renal disease, such as analgesic nephropathy, and obviously not the immunosuppressive regimen after transplantation.
Pure red cell aplasia due to parvovirus B19 infection in solid organ transplantation
Authors: Ahsan Nasimul , Holman Michael J. , Gocke Christopher D. , Groff James A. , Yang Harold C.
Published: September 2024

Human parvovirus B19 disease is an infrequent but recognized rare cause of anemia in immunocompromised patients. A few cases of parvovirus B19 infections have been reported in transplant recipients, of those only four patients underwent renal transplantation. The primary immunosuppressive therapy in these patients included prednisone with either cyclosporine or tacrolimus. In one patient the disease was self‐limiting, while in three others the hematocrit improved following 10‐15 d of treatment with commercial intravenous immunoglobulin (IVIG). Herein, we report the fifth case of pure red cell aplasia due to parvovirus B19 infection in a renal transplant recipient who responded to a 5‐d course of IVIG. To our knowledge, this is the first case of parvovirus B19 infection in a patient with solid‐organ transplantation whose immunosuppressive regimen included both mycophenolate mofetil and tacrolimus and in whom an excellent clinical response was achieved with a short course of IVIG infusion.