bluuebunny/crossref_metadata_2025 huggingface dataset:
Metabolic problems in recipients of liver transplants
Authors: Jindal Rahul M. , Sidner Richard A. , Hughes Dianna , Pescovitz Mark D. , Leapman Stephen B. , Milgrom Martin L. , Lumeng Lawrence , Filo Ronald S.
Published: September 2024

We analyzed the metabolic problems in recipients of liver transplants. Immunosuppression consisted of cyclosporine, steroids and azathioprine. With a mean follow up of 3.5 yr, 37% of 71 recipients were rendered permanently diabetic and hyperlipidemic. Recipients who developed posttransplant diabetes had higher cholesterol levels and proteinuria, but decreased creatinine clearance. Transplant recipients who developed posttransplant hyperlipidemia had greater proteinuria, but their sugars and creatinine clearance were comparable to those who did not have hyperlipidemia. The most significant factor responsible for these metabolic complications was the total dosage of prednisone and cyclosporine. There was no effect of risk antigens on the development of diabetes.
Incidence of post‐transplant malignancy among 674 solid‐organ‐transplant recipients at a single center
Authors: Mihalov M. L. , Gattuso P. , Abraham K. , Holmes E. W. , Reddy V.
Published: September 2024

We evaluated the post‐transplant course of the entire solid‐organtransplant population at our institution to determine the frequency, incidence and specific type of post‐transplant malignancies which occured at a single center. Of 674 solid‐organ‐transplant recipients (305 renal, 307 heart, 54 lung, 8 heart/lung), we detected 79 malignancies (48 heart, 28 renal, 2 lung, 1 heart/lung), representing an overall cancer frequency of 11.7%, 15.6% for heart and 9.2% for renal transplant recipients. The frequency in both transplant groups was higher than that reported previously in the multicenter data in the literature (about 6%); we also noted a shorter interval to malignancy (27 vs. 61 months). The most common malignancies overall were skin/lip carcinomas and post‐transplant lymphoproliferative disorder (PTLD). The frequency of PTLD was higher in non‐renal (6.5%) than renal (0.7%) transplant recipients and statistical analysis confirmed a significant higher incidence of all malignancies (p=0.0032) and of PTLD (p=0.0001) in heart and lung recipients as opposed to renal transplant recipients. The frequency of total skin/lip carcinomas was essentially equal in the heart and renal transplant groups (6%), and statistical analysis showed no significant difference in incidence of this general type of malignancy; however, there was a marked disparity in interval to squamous cell carcinoma (SCC) between renal and heart transplant recipients (27 versus 59 months). This was associated with an apparent increase in the rate of occurence of SCC after 60 months in heart transplant recipients, a finding not previously reported in the multicenter data in the literature. We did not demonstrate a significant effect of the withdrawal of prophylactic OKT3 from the immunosuppression regimen of heart transplant recipients on the incidence of all tumors, PTLD or skin/lip tumors.
Treatment of acute glomerular rejection with FK 506
Authors: Woodle E. Steve , Spargo Benjamin , Ruebe Margaret , charette jane
Published: September 2024

Acute glomerular rejection is a distinct pathologic subtype of rejection that is often refractory to standard therapy and is associated with significant risk of graft loss. Both cellular and humoral mechanisms have been shown to be involved in the pathophysiology of acute glomerular rejection. FK506, because of its ability to inhibit both cellular and humoral mechanisms of rejection, provides a theoretically attractive approach for treating acute glomerular rejection. This initial experience with FK 506 treatment of acute glomerular rejection occurred in a 58‐yr‐old woman who received a 0 AB, 2 DR‐match cadaveric renal transplant. A renal allograft biopsy performed on post‐transplant day 77 for renal dysfunction (serum creatine 1.3→1.8 mg/dl) revealed moderate cellular and vascular rejection. Corticosteroid therapy provided a transient improvement in renal function; however, a repeat biopsy 7 d later revealed acute glomerular rejection with immunohistologic evidence of antibody‐mediated rejection (immunoglobulin and complement deposition in glomerular capillaries). FK 506 therapy was instituted and provided prompt reversal of the acute glomerular rejection as determined by serial renal allograft biopsies. One year later, recurrent rejection has not been observed, and good renal function is present. (Current serum creatine 1.7 mg/dl, creatine clearance 35 ml/min/m2, and 24 h urinary protein 230 mg.) Successful corticosteroid withdrawal has been achieved, and current immunosuppressive therapy consists only of FK 606 and azathioprine. This experience indicates that FK 506 can provide effective therapy for acute glomerular rejection, and that simultaneous treatment with plasmapheresis and an antilymphocyte antibody preparation may not be necessary. This experience also provides further evidence of the ability of FK 506 to inhibit antibody‐mediated rejection processes.
Renal allograft failure after simultaneous pancreas‐kidney transplantation: univariate and multivariate analyses of donor and recipient risk factors
Authors: Douzdjian Viken , Rice James C. , Carson Richard W. , Gugliuzza Kristene G. , Fish Jay C.
Published: September 2024

Although donor and recipient risk factors for renal allograft failure are well known after kidney transplantation, they are less well defined after simultaneous pancreas‐kidney transplantation. The purpose of this study is to evaluate the impact of donor and recipient risk factors on the outcome of the renal allograft in simultaneous pancreas‐kidney recipients. Simultaneous pancreas‐kidney transplant performed between 4/88 and 6/94 were reviewed (n=61) and univariate (Kaplan‐Meier) and multivariate (Cox regression) analyses of factors which affect kidney graft survival were performed. Twelve donor and eleven preand post‐transplant recipient risk factors were evaluated. Overall kidney allograft survival rates at 1, 2 and 5 yr were 81%, 76% and 66%. Donor age ≥40 yr (RR=2.3), donor female gender (RR=3.5), donor admission to pronouncement of brain death ≥48 h (RR=3), the occurrence of surgical complications (RR=2.1), and serum ≥2 mg/dl on post‐transplant day (RR=1.9) were independently associated with an increased hazard of graft failure. With the exception of length of donor admission, all of these factors were also shown to predict the risk of renal graft failure by univariate analysis. In conclusion, we have identified donor and recipient risk factors which independently predict the risk of renal graft failure after simultaneous pancreaskidney transplantation. Whether the differences between our center‐specific risk factors and those obtained from renal transplant registry data are true differences or simply reflect sampling error is unclear.
Treatment of renal allograft acute rejection with methylprednisolone: effect of fixed dose versus dose per body mass index
Authors: Douzdjian Viken , Rice James C. , Gugliuzza Kristene K. , Fisch Jay C. , Carson Richard W.
Published: September 2024

Considerable interpatient variability in steroid pharmacokinetics has been observed in renal transplant recipients. The purpose of this retrospective study is to evaluate the relationship between the dose of methylprednisolone (MP) used to treat acute rejection (AR) after renal transplantation and the response to treatment. 117 first AR episodes from 408 renal transplants were reviewed. The dose of MP used to treat AR was <45 mg/kg/2 in 60 patients and ≥45 mg/kg/2 in 57 patients. The correlation between fixed dose (<1.25 vs. 21.25 g) and dose based on BMI was evaluated by simple linear regression analysis (r2=0.78, p<0.0005). Response to treatment was as follows: MP successful (Group 1, n=80); MP failed, OKT3 successful (Group 2, n=17); MP and OKT3 failed (Group 3, n=3) and MP failed, no further treatment (n=17). No relationship was observed between the dose of MP, whether fixed or based on BMI, and (1) response to treatment of the first AR, (2) incidence of a second AR and (3) response to subsequent treatment with OKT3. Actuarial graft survival was higher in Group 1 compared to Group 2 (p<0.0005), lower in Black recipients (p=0.02) and higher when 245 mg/kg/2 of MP was used to treat AR (p=0.06). In conclusion, no relationship between the dose of MP, whether fixed or based on BMI, and the response to treatment of AR was observed. MP dosage based on BMI may be a reasonable alternative to a fixeddose regimen with the advantage of limiting steroid exposure and the consequent side‐effects.
Combined kidney and pancreas transplants through lower transverse abdominal incisions
Authors: Barone Gary W. , Sailors David M. , Ketel Beverley L.
Published: September 2024

Improvements in the surgical aspects of combined kidney and pancreas transplants have resulted in better overall graft and patient survival. Pancreas transplants were initially performed through lower transplant flank incisions opposite the kidney. However, because of high wound complication rate, most centers now perform pancreas transplants through lower midline incisions. We retrospectively reviewed our experience in 40 combined kidney and pancreas transplant recipients with an initial group of 6 midline incisions. and 34 later lower transverse abdominal incisions. The number of midline incisions was too small to make a direct comparison, but our series of patients with transverse incisions was compared with the reported literature using a midline incision. The overall infectious and hernia rates for the transverse incision were 12% and 6% respectively which are both very acceptable. The average operative time was 5.5 h. The transverse incision may be associated with less pain, shorter ileus, and fewer pulmonary complications. A lower transverse incision has the major advantage of excellent exposure directly over the iliac vessels and is our incision of choice.
Sequential coronary artery bypass grafting and orthotopic liver transplantation: A case report
Authors: Manas D. M. , Roberts D. R. D. , Heaviside D. W. , Chaudhry S. , Tocewicz K. , Hudson M. , Bayly P. , Thick M. , Dark J. , James O. F. W.
Published: September 2024

We report a case of combined coronary artery by‐pass grafting and orthotopic liver transplantation on cardiopulmonary bypass, in a 56‐yr‐old man with rapidly progressive ischaemic heart disease and end‐stage liver disease. Three months after surgery he is asymptomatic with normal liver function.
FK 506 therapy for refractory renal allograft rejection: lessons from liver transplantation
Authors: Woodle E. Steve , Bruce David S. , Josephson Michelle , Newell Kenneth A. , Piper James B. , Millis J. Michael , Cronin David , Whitman Greg , Ruebe Margaret , Thistlethwaite J. Richard
Published: September 2024

FK 506 has proven to be an effective immunosuppressive agent in liver transplantation, but its role in renal transplantation remains to be defined. Since the initial availability of FK 506 for treatment of refractory renal allograft rejection, we have applied an aggressive approach consisting of institution of rescue therapy at an early point in the rejection process combined with assiduous monitoring of FK 506 blood levels and the histologic response to therapy. A total of 17 adult patients were treated for refractory renal allograft rejection with this approach. Median follow‐up was 9 months post‐initiation of FK 506 therapy. Median time to first rejection was 26 d post‐transplant, and median time to FK 506 rescue therapy was 113 d post‐transplant. Sixteen of 17 patients received either ATGAM or OKT3 induction therapy. Prior to FK 506 rescue therapy, patients received the following antirejection therapy: corticosteroids 40+21 mg/kg (prednisone or Solumedrol), OKT3 (median 14 d), ATGAM (3 patients, 14 d each). FK 506 rescue therapy was successful in reversing the rejection process in all 17 patients. Fifteen patients (88%) demonstrated rapid reversal of rejection (i.e. reversal within 14 d), whereas three patients demonstrated delayed reversal. Nine month actuarial patient and graft survivals were 92% and 84%. When censored for documented noncompliance, nine month actuarial graft survival was 92%. Good long‐term renal function was observed (pre‐FK 506 baseline creatinine 2.1±0.5 mg/dl, current serum creatinine 2.1±0.6 mg/dl. Six recurrent rejection episodes occurred in 5 patients (29%) with a median time to recurrent rejection of 59 d post‐initiation of FK 506 rescue therapy. Each recurrent rejection episode was successfully treated by corticosteroids and/or increased FK 506 dose. CMV disease and lymphoma were not observed. Histologic evidence of FK 506 nephrotoxicity (hyaline necrosis in preglomerular arterioles) was observed in 6 patients 30% (median) time to diagnosis 49 d). FK 506 blood levels (whole blood TDX) between 10 and 20 ng/ml provided effective reversal in most patients. Current FK 506 dose and blood levels are 0.18±0.09 mg/kg/d and 7±2 ng/dl). FK 506 rescue therapy also allowed aggressive reductions in prednisone dose: (mean current prednisone dose 0.08±0.05 mg/kg/d). In conclusion, an aggressive approach toward FK 506 rescue: 1) provides prompt, effective reversal of refractory renal allograft rejection, 2) good long‐term renal allograft function, 3) balanced immunosuppression with respect to recurrent rejection, opportunistic infection and PTLD, 4) acceptable toxicity, and 5) aggressive reduction in corticosteroid dosing. Based on these findings, FK 506 rescue therapy is now the treatment of choice in our program for renal allograft rejection episodes that occur following antilymphocyte antibody therapy.
Simultaneous ureterocystoplasty and living related renal transplantation
Authors: Kim Charles O. , Gosalbez Rafael , III George W. Burke
Published: September 2024

Enterocystoplasty in preparation for renal transplantation in children with severely dysfunctional bladders is widely accepted by pediatric urologists and transplant surgeons alike. The risk for septic and other complications in this immunosuppressed population remains elevated however, since problems inherent to the use of bowel or stomach in the urinary tract become magnified in these patients. In addition, simultaneous enterocystoplasty and transplantation carry a significant risk, and we must therefore subject these children to two major operations within a short time span. We herein describe our experience with combining simultaneously ureterocystoplasty and renal transplantation in a child. We believe this procedure has major relevance, in particular in the group of patients with posterior urethral valves and chronic renal failure.
Captopril‐induced changes in effective renal plasma flow in hypertensive renal transplant recipients
Authors: Sud K. , Oomen R. , Jacob C. K. , Shastry J. C. M.
Published: September 2024

The role of converting enzyme inhibitor enhanced radionuclide investigations in post‐transplant hypertension is not clearly defined. Presence of renal failure, chronic rejection and use of cyclosporin A complicates the results. Captopril‐induced changes in effective renal plasma flow (ERPF) were studied in 10 patients with severe post‐transplant hypertension and no evidence of rejection. Angiographic correlation was available in all. Six patients had a significant increase in ERPF after captopril, and all had a negative angiogram. One patient on CsA with a negative angiogram had no change in ERPF. Three patients had a fall in ERPF, and all 3 had transplant renal artery stenosis. Captopril‐induced changes in ERPF can differentiate patients with native‐kidney‐induced hypertension from those with hypertension secondary to transplant renal artery stenosis in patients without evidence of rejection.
Interferon‐alpha therapy for hepatitis C virus recurrence after liver transplantation: long‐term response with maintenance therapy
Authors: Singh Nina , Gayowski Timothy , Wannstedt Cheryl F. , Marino Ignazio R. , Wagener Marilyn M.
Published: September 2024

Interferon‐alpha is currently the only available treatment for HCV hepatitis. We assessed the safety and efficacy of 6 month course of interferon therapy in 18 consecutive liver transplant recipients with recurrent HCV hepatitis and report the long‐term response with maintenance interferon. Median follow‐up after the institution of interferon was 24 months. Complete response was defined as normalization of both aspartate and alanine aminotransferase. Complete response after 6 months of interferon was observed in 28% (5/18); an additional 33% (6/18) of the patients were late responders. Overall, 61% (11/18) of the patients had long‐term sustained normal response at a median follow‐up of 24 months. Long‐term sustained response was observed in 73% (8/11) of the patients who continued interferon beyond 6 months vs. 43% (3/7) in those who received 6 months of interferon. Fatigue, headache and cytopenia were the most commonly observed side‐effects occurring in 39%, 22% and 28% of the patients, respectively. Discontinuation of interferon, however, was not required in any of the patients. Rejection was documented in 6% (1/18) patients receiving interferon; this incidence was not higher than rejection episodes occurring >6 months post‐transplant in other recipients transplanted during the same period and who did not receive interferon. Responders had a trend towards later recurrence of HCV hepatitis after transplantation. In conclusion, maintenance interferon was well tolerated and appeared to improve the long‐term outcome in our patients; however, future studies should evaluate this in a controlled trial.
The quest for living‐related kidney donors for children with end‐stage renal disease
Authors: Etheredge Edward E. , Zarifian April , Frentz Gary D. , Boineau Frank G.
Published: September 2024

In a pediatric renal transplant program that actively seeks livingrelated kidney donors, we achieved a living donor rate of 55% in 119 children. This approximates the national average but is less than an idealized goal. For black children, the living‐donor transplant rate was 41%, a disconcertingly low rate. In an attempt to define factors that negatively affected living‐related donor availability, we analyzed our evaluation process by distinct phases (interview, histocompatibility testing and medical evaluation). We classified our families on the basis of locale (urban, suburban and rural), family unit (two or less parents, adult sibs or other relatives presenting at interview) and economic status (designating only economic‐disadvantaged and other). While histoincompatibility is predictably a negative factor, the negative impacts of medical illness in the donor pool, economic disadvantage and single parent family are striking and cumulative. Our data validate the relative success of an aggressive recruitment policy in a patient population that includes many economically disadvantaged families. For pediatric renal transplant programs with low living‐related donor rates, our data should encourage review and possible modification of the donor recruitment process.
Microemulsion technology in the reformulation of cyclosporine: the reason behind the pharmacokinetic properties of Neoral
Authors: Ritschel Wolfgang A.
Published: September 2024

Management of transplant patients receiving cyclosporine therapy is complicated by interpatient and intrapatient variability in pharmacokinetic parameters caused by the drug's unpredictable bioavailability. Cyclosporine, a highly lipophilic cyclic polypeptide, has recently been reformulated using a microemulsion delivery system to improve its bioavailability. This new orally administered formulation, Neoral® (cyclosporine capsules and oral solution for microemulsion), has self‐emulsifying properties and spontaneously forms a microemulsion (particle size <0.15 μm) in the aqueous fluids of the gastrointestinal tract. Clinical trials in renal transplant recipients, liver transplant recipients with external biliary diversion, and healthy volunteers have demonstrated enhanced bioavailability and greatly improved dose linearity with the cyclosporine microemulsion compared with the original cyclosporine formulation, Sandimmune® (cyclosporine). The rate and extent of absorption were greater with the cyclosporine microemulsion under both fasting and nonfasting conditions, and there was a more consistent relationship between the administered dose and area under the time‐concentration curve. Early clinical efficacy trials in renal and liver transplant recipients have shown no difference in the incidence or severity of drug‐related adverse events. Studies on the long‐term efficacy and safety of the new microemulsion formulation are ongoing.
Comparison of two antilymphocyte globulins replacing cyclosporin A after first kidney allotransplantation and prolonged graft ischemia
Authors: Gantenbein Hubert , Bachmann Peter , Huynh Uyen , Steinhäuslin Florence , Weinreich Thomas , Schlumpf Rolf , Largiadèr Felix , Binswanger Ulrich
Published: September 2024

ATG/Fresenius (5 mg/kgBW) and ATGAM (Upjohn, 12.5 mg/ kgBW) replacing cyclosporin A were given during 7 d after transplantation to 20 patients in 1992 and 30 patients in 1993, respectively. Numbers of mismatches, combined kidney‐pancreas transplantation and severe infections were not different for the two groups. However, prednisone pulse therapies and additional antilymphocyte globulin treatments were more frequent after ATGAM than after ATG induction (p<0.01, χ2‐test).
Anti‐CD4 monoclonal antibody therapy
Authors: Delmonico Francis L. , Cosimi A. Benedict
Published: September 2024

Because they can be selected to target only cells which are crucial for rejection, monoclonal antibodies (mAbs) offer enormous potential for specific manipulation of the immune response. Interest in the clinical potential of anti‐CD4 mAbs has been heightened by the demonstration, in experimental models, that such therapy can produce long‐term donor‐specific non‐responsiveness. Early clinical trials using two murine anti‐CD4 mAbs (BL4 and mT‐151) were discouraging, with over 50% of recipients suffering early rejection episodes. Another murine preparation, OKT4A, was initially found to prolong allograft survival in non‐human primates. Limited clinical trials revealed that this mAb was well tolerated, that most recipients produced an antimurine response, and that only 26% of patients suffered rejection episodes during the first 3 post‐operative months. Another murine preparation, Max. 16H5, has been reported to reverse late onset acute rejection episodes as effectively as, but more safely than, conventional immunosuppression. More recent interest has focused upon humanized recombinants of these earlier murine anti‐CD4 preparations. cMT‐412, has been studied in recipients of heart or heart‐lung allografts. These patients were observed to have less frequent and markedly delayed rejection episodes, fewer infectious complications, and better overall survival than that observed in an ATG‐treated control group. Further studies are thus being undertaken. A CDR grafted IgG4 preparation of OKT4A has also been studied. This molecule (OKTcdr4a) contains only 8% of the parent murine sequence while retaining the binding affinity of OKT4A for the human CD4 antigen. In a pilot trial, biopsy‐proven reversible rejection episodes were observed in 2/11 (18%) of renal allograft recipients. There were no allograft failures and no antibody response to the mAb. These and other trials emphasize the intense interest in immunosuppressive regimens incorporating anti‐CD4 mAbs as well as the difficulties encountered in defining optimal protocols. Nevertheless, the impressive results observed in rodent and non‐human primate models suggest that these agents are likely to play an important role in future immunosuppressive protocols, particularly those designed to induce tolerance.
Liver transplantation for fulminant hepatic failure in a Jehovah's Witness
Authors: Seu Philip , Neelankanta Gundappa , Csete Marie , Olthoff Kim M. , Rudich Steven , Kinkhabwala Milan , Imagawa David K. , Goldstein Leonard I. , Martin Paul , Shackleton Christopher R. , Busuttil Ronald W.
Published: September 2024

Jehovah's Witness patients who refuse transfusions have generally not been felt to be candidates for liver transplantation owing to the frequent requirement for blood transfusions during liver transplantation. This is the first report to our knowledge of successful emergent liver transplantation without the use of blood or blood products in a Jehovah's Witness. The surgical and anesthetic strategies employed in achieving a successful outcome are discussed.
Cardiac evaluation of liver transplant recipients: QT dispersion in electrocardiogram
Authors: Tallgren Minna , Höckerstedt Krister , Mäkinen Judit , Kirvelä Maija , Lindgren Leena
Published: September 2024

Increased QT dispersion, the interlead variability of the QT interval length in the 12‐lead electrocardiogram, reflects uneven ventricular repolarization as a sign of cardiomyopathy. We analyzed QT dispersion in the preoperative electrocardiogram of 100 adult liver transplant recipients and 20 healthy control subjects. In 12% of the liver recipients, QT dispersion was increased above 65 ms (mean + 3SD). Six of these patients had a liver storage disease (haemochromatosis, Wilson's disease or amyloidosis). Five had a history of cardiac disease. Severe intraoperative cardiac complications occurred in three patients with markedly increased QT dispersion (≥99 ms). In conclusion, in liver storage diseases the heart may be affected, leading to increased risk of cardiac complications, which might be predicted from increased QT dispersion. Analysis of QT dispersion, a noninvasive inexpensive technique, can be recommended to be included in the cardiac screening of liver transplant candidates.
Gastric bypass in morbidly obese kidney transplant recipients
Authors: Marterre W. F. , Hariharan Sundaram , First M. Roy , Alexander J. Wesley
Published: September 2024

Severe post‐transplant obesity has previously been shown to have a negative impact on graft survival following kidney transplantation. It also contributes to late patient mortality and is associated with hypertension, diabetes and hyperlipidemia. We undertook Roux‐en‐Y gastric bypass (GBP) in three morbidly obese (200‐260% ideal body weight) (IBW) patients 6‐8 yr following kidney transplantation. Roux‐en‐Y gastrojejunostomy to a 30 ml stapled gastric pouch was created with the jejunojejunostomy (both loops) 80‐120 cm from the ligament of Treitz. By 12 months post‐GBP, weight loss plateaued at 100‐150% IBW. Both patients that had developed post‐transplant diabetes mellitus (PTDM) had complete resolution within 9 months following GBP. On average the patients required 3 less hypertension (HTN) medications after GBP; 2 of the 3 patients are now normotensive off medication. Improvements in hyperlipidemia were also shown. The absolute cyclosporine (CSA) requirement (mg/d) increased by approximately 33% (p=NS), and there was also a significant increase in the weight adjusted CSA requirement from 1.8 to 3.5 mg/kg/d (p=0.02, ANOVA) following GBP in order to maintain similar TDX trough CsA levels. GBP offers significant reduction in weight, HTN, PTDM and hyperlipidemia in morbidly obese kidney transplant recipients. However, CSA dose requirements may increase after GBP as a consequence of the defunctionalized intestine.
Must living renal donors be hospitalized overnight prior to surgery?
Authors: Friedman Amy L. , Goker Onur , Dennis Martin J. , Basadonna Giacomo P. , Wiklund Richard A. , Kliger Alan , Bia Margaret J. , Lorber Marc I.
Published: September 2024

To determine whether preoperative intravenous hydration was an important determinant of perioperative safety for the kidney donor or of early allograft function, 21 consecutive living donor transplants were assessed retrospectively. Donors hospitalized overnight received 1008±169 mL of intravenous fluid during the 8 h prior to operation, compared to no preoperative hydration among a cohort of 15 patients. No differences between intraoperative blood pressures, fluid administration, urine output, or time in the operating room were identified between groups. Postoperative allograft function was not compromised by the lack of hydration. We conclude that living kidney donors can safely undergo elective nephrectomy without prior intravenous hydration.
Mothers of children evaluated for transplantation: stress, coping resources, and perceptions of family functioning
Authors: Rodrigue James R. , III Russell G. Hoffmann , MacNaughton Kathleen , Graham‐Pole John , Andres Joel M. , Novak Donald A. , Fennell Robert S.
Published: September 2024

The stress, coping resources, and family functioning of 36 mothers of children awaiting transplantation were evaluated. Using standardized assessment techniques, we found that, overall, 20% of mothers reported clinically elevated stress responses and that parenting stress was higher for mothers of children evaluated for solid organ transplantation (vs. bone marrow transplantation). Coping strategies characterized by maintenance of personal and family stability were strongly associated with lower levels of parenting stress. Findings also showed significant disruption in family planning and activities, as well as a strong association between lower socioeconomic status and higher parenting stress. There is a need for the longitudinal assessment of parental and family functioning throughout the transplantation process as well as for interventions designed to reduce parenting distress.
Mediators of fibrinolysis in orthotopic liver transplantation
Authors: Cheema Surinder P. S. , Webster Nigel R. , Dunn Fiona , Bellamy Mark C.
Published: September 2024

Activation of fibrinolysis remains a clinical problem in orthotopic liver transplantation. We have measured tissue plasminogen activator (t‐PA), plasmin and α‐2‐anti‐plasmin (α2AP) activities in plasma from 10 patients undergoing elective transplantation. t‐PA activity increased during the anhepatic phase and immediately after graft reperfusion (p>0.001). This inrease could not be attributed to t‐PA released by the donor liver. Overall transfusion requirements did not relate with either t‐ PA or α2AP activities individually, but were strongly correlated with the ratio t‐PA/ α2AP (p>0.02). These results suggest that routine prophylactic use of antifibrinolytic agents may be beneficial.
Transient suppression of pancreatic endocrine function in patients following brain death
Authors: Yoshida Hiroyoshi , Hiraide Atsushi , Yoshioka Toshiharu , Sugimoto Tsuyoshi
Published: September 2024

To investigate pancreatic endocrine function in brain‐dead patients, an intravenous glucose tolerance test (i.v. GTT) was performed in 8 brain‐dead subjects maintained using the combined administration of vasopressin (ADH) and catecholamines during the first 3 days following the onset of brain death. Ten healthy adults served as control subjects. Although plasma glucose concentrations markedly increased and exceeded 300 mg/dl in most subjects just after the onset of brain death, they decreased to less than 200 mg/dl in most subjects after 24 h. The early insulin release also was significantly lower in brain dead subjects compared to controls (p<0.01). The late insulin release was not decreased compared to controls but rather increased, which was accompanied by decreased glucose disappearance rate. The early insulin release recovered rapidly during the first 3 days following brain death without significant changes in the plasma hormone concentrations such as epinephrine, human growth hormone, thyroid‐stimulating hormone, triiodothyronine, thyroxine, cortisol, and glucagon. The early insulin release and the plasma glucose concentration just before i.v. GTT was negatively correlated (R= ‐0.55, p<0.05). We suggest awaiting recovery from hyperglycemia and early insulin release provides a reasonable approach to transplantation of the pancreas.
Increased incidence of renal allograft thrombosis after continuous ambulatory peritoneal dialysis
Authors: van der Vliet J. Adam , Barendregt Wouter B. , Hoitsma Andries J. , Buskens Frans G.M.
Published: September 2024

Allograft thrombosis occurred in 44 cases (4.8%) among 915 consecutive cadaveric renal transplantations performed in a single center over a 13‐year peirod. Multiple logistic regression analysis of risk factors revealed that continuous ambulatory peritoneal dialysis (CAPD) was the only independent variable associated with renal allograft thrombosis. When CAPD was used for prior renal replacement therapy graft thrombosis occurred in 7.3% (22/303), whereas hemodialysis was associated with 3.6% (22/612) of graft thromboses (p<0.02). No differences in transplant characteristics, including hemodynamics, hematological parameters, immunosuppressive therapy, graft anatomy and preservation, were observed between the cases with graft thrombosis and a matched control group (n=88). CAPD treatment appears to be a risk factor in the development of renal allograft thrombosis that requires further perioperative coagulation studies in order to design an effective prophylaxis.
From mice to man: the preclinical history of mycophenolate mofetil
Authors: Sollinger Hans W.
Published: September 2024

In vitro studies demonstrating that mycophenolic acid (MPA) held promise as a powerful immunosuppressant led to a series of in vivo studies to further evaluate this interesting new agent. Experiments in mice showed that MPA had powerful lymphocyte‐selective immunosuppressive effects. A prodrug of MPA, mycophenolate mofetil (MMF), was developed to improve bioavailability on oral administration. Numerous tests demonstrated that MMF, alone or in combination with other immunosuppressives, prolonged allograft survival of various organs in several species and may be useful for reversing ongoing rejection. MMF also was found to be useful in prolonging xenograft survival. These animal experiments indicated that MMF had the benefit of relatively low toxicity and a good safety profile and drove early clinical trials of MMF. These trials showed that MMF is relatively safe and well tolerated in man and is of potential use for the prevention and treatment of acute allograft rejection. This article describes the preclinical history of the development of MMF, concentrating on the animal experiments and phase I and II trials that preceded the large‐scale clinical testing of this new immunosuppressant.
Local cellular immunology of experimental transplant vascular sclerosis
Authors: Orosz Charles G.
Published: September 2024

We have observed that most C57BL/6 (H‐2b) recipients of DBA/2 (H‐2d) heterotopic cardiac allografts retain their grafts for more than 60 days following treatment with anti‐CD4 MAb (GK1.5), anti‐VCAM‐1 MAb (M/K‐2), or gallium nitrate (GN). Nevertheless, many ongoing alloimmune responses are detectable more than 60 d post‐transplant in these mice: (i) continuous inflammatory endothelial activation and low‐grade cellular infiltration in the graft, (ii) modest frequencies of donor‐reactive T cells in the graft and spleen, (iii) mRNA for various cytokines (IL‐1, IL‐2, IL‐4, IL‐6, IFNγ, TNFα, TGFβ) in the graft, (iv) high levels of donor‐reactive alloantibody in the circulation, (v) variable development of allogeneic chimerism in the recipient, and (vi) development of interstitial fibrosis and neointimal hyperplasia in the graft. Despite the widely differing targets of GK1.5, M/K‐2, and GN, their therapeutic outcomes appear to be identical. Taken together, these observations suggest that long‐term allograft survival in these experimental systems is not the result of immune acceptance, i.c. allogeneic tolerance. Although these therapies interrupt the destructive progression of acute rejection, they permit many related immune responses in the graft recipient in association with the development of chronic rejection‐like histopathology.
Costimulation and its role in organ transplantation
Authors: Bluestone Jeffrey A.
Published: September 2024

Antigen‐specific T‐cell activation depends initially on the interaction of the T‐cell receptor with peptide/major histocompatibility complex (MHC). In addition, a costimulatory signal, mediated by distinct cell surface accessory molecules such as CD28, is required for complete T‐cell activation. One essential element of the CD28 costimulatory system that makes it an attractive target for immunotherapy is the selective effect of CD28 antagonists on activated T cells. Only cells encountering antigen presenting cells (APCs) without the appropriate CD28 ligand will be rendered functionally inactive as desired for any next‐generation immunosuppressive drug. This brief review will focus on the role of CD28/B7 interactions in regulating organ graft rejection. In vitro and in vivo studies will describe the use of a soluble fusion protein antagonist of CD28/B7 (CTLA‐41g), anti‐B7 MAbs, and genetically altered CD28 “knockout” mice to study immune responses. The studies suggest that: 1) CTLA‐41g induces long‐term, antigen‐specific unresponsiveness in vivo; 2) two distinct ligands for CD28, B7‐1 and B7‐2, are differentially regulated during immune responses; and 3) both B7‐1 and B7‐2 costimulatory molecules are active, in vivo, although B7‐2 plays a clearly dominant role in murine. allograft rejection.
Genetic engineering of endothelial cells to ameliorate xenograft rejection
Authors: Bach Fritz H. , Robson Simon C. , Wrighton Christopher J. , Stuhlmeier Karl , Ferran Christiane , Winkler Hans
Published: September 2024

The prospect of clinical xenotransplantation using pigs as donors (a discordant combination) holds out a potential solution to the shortage of human organs, as well as potentially widening the spectrum of patients who might benefit from a transplant procedure. While generalized clinical trials of pig to human organ transplantation (of immediately vascularized organs, such as the heart or kidney) will probably not occur in the very near future, there are reasons for optimism that this approach, deemed impossible a few decades ago, may find its way to the bedside. This optimism is based on two factors: First, a great increase in our understanding of the probable underlying causes of rejection and, second, the development of a number of important therapeutic approaches, including genetic manipulation of the donor animal, to tackle the manifold problems inherent in rejection of such a transplanted organ.
Mycophenolate mofetil for maintenance therapy in kidney transplantation
Authors: Gonwa Thomas A.
Published: September 2024

Mycophenolate mofetil (MMF) is a new immunosuppressive drug that selectively inhibitsde novopurine synthesis. It has been tested in three large double‐blind controlled trials for the prevention of rejection in renal transplant patients. These studies indicate that the use of MMF dramatically decreases the incidence of biopsy‐proven rejection, the use of multiple courses of steroids for rejection, and the use of antilymphocyte preparations for treatment of rejection. The drug was well tolerated with an acceptable safety profile. The main side effects were gastrointestinal (nausea, vomiting, diarrhea), but seldom resulted in the cessation of drug therapy. Hematologic side effects similar to those with azathioprine occurred and were reversible. There was a slight increase in CMV‐invasive disease with the use of MMF, but no deaths. Rates of malignancy were within published ranges for transplant recipients. Mycophenolate mofetil is a safe and efficacious drug for prevention of rejection in kidney transplant recipients.
Factors on graft survival of living donor kidney transplantation in a single center
Authors: Jin Dong Chan , Yoon Young Suk , Kim Yong Soo , Yoon Sun Ae , Ahn Seog Ju , Kim Suk Young , Chang Yoon Sik , Bang Byung Kee , Koh Yong Bok
Published: September 2024

We analyzed the potential factors that could influence the survival of graft, focused on primary graft living‐donor kidney transplantation with cyclosporine (CSA) therapy. 680 cases were enrolled in this study. Patients and graft survival rates were calculated by a Kaplan‐Meier product limit estimate with a 1‐day time interval. The analyzed variables were donor relationship, HLA matching, recipient age and sex, donor age and sex, ABO blood type compatibility, diabetic status, hepatitis virus infection, donor specific or non‐specific blood transfusion and acute rejection episode. The results suggested that acute rejection episode was the worst prognostic factor in graft survival. An HLA‐matched donor and a young male donor, i.e. a greater donor nephron mass for less recipient body mass, will show better long‐term survival. Diabetes and hepatitis B infection have some negative effects on the long‐term survival of graft kidney, but age of recipient, donor‐specific transfusion and donor‐recipient relationship have little effect.
A third kidney transplant: cost‐effective treatment for end‐stage renal disease?
Authors: Matas Arthur J. , Gillingham Kristen J. , Payne William D. , Dunn David L. , Gruessner Rainer W. G. , Sutherland David E. R. , Schmidt Walter , Najarian John S.
Published: September 2024

Given the organ donor shortage, some question whether a third kidney transplant can be justified. We studied the outcome of 51 third transplants (mean age 28±2 yr) done between 1 January 1985 and 31 December 1994. We compared hospital stay (mean±S.E.), cost, readmissions, readmission days, and outcome of third (vs. first and second) transplants. We found that patient survival for third transplants was equivalent to first and second transplants; graft survival was not as good. However, when third transplant recipients with recurrent disease (specifically, hemolytic uremic syndrome and focal sclerosis) were excluded from our analysis, we found no difference in 5‐yr graft survival (vs. first or second transplant recipients).

Of the 51 third transplant recipients, 41 had a cadaver donor transplant. Third cadaver transplant recipients tended to have a longer hospital stay (p=NS) than first cadaver transplant recipients but had no more readmissions or readmission days than first or second cadaver transplant recipients.

Employment data are available for 28 third transplant recipients; 16 (57%) are currently working or going to school. Of the 21 recipients who responded to quality of life questionnaires, 17 (81%) reported being healthy and all 21 (100%) said transplantation was not a drawback to their health. We conclude that third transplants should be considered for selected patients with renal failure whose first or second transplants have failed. Such patients can often be successfully transplanted.
Volume‐mediated pulmonary responses in liver transplant candidates
Authors: Kuo Paul C. , Schroeder Rebecca A. , Vagelos Randall H. , Valantine Hannah , Garcia Gabriel , Alfrey Edward J. , Haddow Gordon , Dafoe Donald C.
Published: September 2024

Pulmonary hypertension, defined as mean pulmonary artery pressure (mPAP) greater than or equal to 25 mmHg, is a recognized complication of hepatic dysfunction with portal hypertension and is considered a relative contraindication to liver transplantation. To characterize pulmonary hemodynamic responses in OLT candidates without pre‐existing primary pulmonary hypertension, 22 consecutive patients referred for OLT at the Stanford University Hospital underwent prospective right heart catheterization with pressure determinations at baseline and following infusion of 1 1 of crystalloid over 10 min. In addition, EKG, chest X‐ray and transthoracic echocardiograms were performed as a part of the routine evaluation. Eleven non‐cirrhotic patients served as controls. At baseline, 1/22 (4.5%) OLT patients had pulmonary hypertension while 9/22 (41%) developed pulmonary hypertension following volume infusion (p<0.0001). In contrast, 0/11 controls manifested elevated pulmonary pressures at baseline or following volume challenge. OLT candidates were found to have significant increases in mean pulmonary pressure and capillary wedge pressure (PCWP) compared to controls, suggesting intravascular volume overload or left ventricular dysfunction as potential causes. OLT candidates who manifested volume‐dependent pulmonary hypertension (a) had a 2‐fold higher baseline PCWP, (b) currently smoked, and (c) had previously undergone portosystemic shunts. Aggregate analysis of EKG, echo and CXR for determination of volume‐mediated pulmonary hypertension revealed a sensitivity of 25%, specificity of 75% and a positive predictive value of 40%. Preoperative identification of patients with a predisposition to manifesting elevated pulmonary pressures in the context of rapid volume infusion offers the potential for improved risk stratification and optimized clinical management.
Impact of first acute rejection episode and severity of rejection on cadaveric renal allograft survival*
Authors: Hariharan S. , Alexander J. W. , Schroeder T. J. , First M. R.
Published: September 2024

A total of 504 renal transplants were performed between 1984 and 1993; 408 (81%) were cadaver grafts. This study evaluated the impact of a first acute rejection episode and the severity of the rejection on cadaveric allograft survival. Acute allograft rejection was based on clinical evaluation and confirmed by renal biopsy. Ten patients were excluded from this study due to early patient or graft loss. Patients were divided into Group I (n=179), who never experienced acute rejection, and Group II (n=219), who had an acute rejection episode. Group II patients were divided into IIA (n=140), who had a mild first acute rejection episode treated with methylprednisolone, and IIB (n=79), who had moderate or severe acute rejection treated with OKT3. The overall 1‐, 2‐, 3‐, and 5‐yr actuarial cadaveric renal allograft survival for Group I was 80%, 76%, 74%, and 68%. The corresponding graft survival for Groups IIA and IIB were 75%, 63%, 58%, and 50%; and 79%, 71%, 65%, and 53% [p=0.03 (I vs. IIA), p=NS (I vs. IIB and IIA vs. IIB)]. A similar pattern of survival was seen in primary kidney allograft recipients. In conclusion, longterm graft survival was superior in patients who never experienced acute rejection compared to those with rejection. Improvements in long‐term graft survival can be accomplished in patients with severe rejection with OKT3 treatment resulting in comparable survival to those with mild rejection.
Early ganciclovir therapy effectively controls viremia and avoids the need for cytomegalovirus (CMV) prophylaxis in renal transplant patients with cytomegalovirus antigenemia
Authors: Gotti Eliana , Suter Fredy , Baruzzo Sara , Perani Vincenza , Moioli Fausto , Remuzzi Giuseppe
Published: September 2024

Cytomegalovirus (CMV) infection is still a problem for organ transplant recipients despite studies that long‐term prophylaxis with high dose of acyclovir or ganciclovir given to all organ recipients may limit the consequences of infection and disease. In the present report of 160 consecutive renal transplant patients, we used a diagnostic assay for CMV antigenemia (detection of CMV antigen in peripheral blood leukocytes) and treated with ganciclovir only those patients who had a positive test. No patient in this series had routine prophylaxis. Out of the 160 patients, 71 had clinical and/or laboratory signs of infection, and were tested for early antigen in peripheral leukocytes. The test was positive in 35, all of whom received a course of 3 wk ganciclovir treatment which effectively cured CMV in 34 out of 35. One patient was ganciclovir‐resistant, but responded to foscarnet. None of the 36 patients who had no early antigenemia and did not receive specific treatment developed the disease. The treatment was extremely well tolerated in all our patients with no adverse events. Thus, even though this was not a controlled study, our present results may be taken to indicate that long‐term acyclovir or ganciclovir for all organ transplant recipients might be no longer totally justified. We conclude that detecting viral antigen in circulating leukocytes identifies patients who are indeed at increased risk of developing severe CMV disease. When these patients are treated early enough, CMV is eliminated with a relatively short course of ganciclovir, which has virtually no side effects.