bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of 1‐280α‐h atrial natriuretic peptide on acute renal failure in cadaveric renal transplantation
Authors: Gianello Pierre , Carlier Marianne , Jamart Jacques , Hulhoven Réginald , Bernheim Jan , Bernard Alfred , Ketelslegers Jean Marie , Squifflet Jean Paul
Published: September 2024

The efficacy and safety of (1‐28) α‐human ANP in preventing acute tubular necrosis (ATN) in cadaveric renal transplantation was tested by comparing ANP infusion with a maximal hydration (MH) regimen. which we previously reported as effective in lowering the incidence of ATN (1, 2). Since the production of endogenous ANP increases with volume overloading (3), we hypothesized that increased endogenous ANP production may contribute to the beneficial effects of MH in renal transplant recipients. We thus conducted an open randomized study comparing the effect on early renal allograft function of MH (control group) versus moderate hydration plus ANP infusion (ANP group). Forty patients were blindly paired in two groups of 20 according to the duration of cold ischemia time (mean ±2 h). The demographic characteristics of donors and recipients were similar. Using a Swan‐Ganz catheter, hemodynamic parameters were monitored for 4 h after transplantation. The group receiving ANP and moderate hydration was perfused to a mean pulmonary arterial pressure (PAP) of ≤20 mmHg. The PAP in patients receiving MH was driven to ≥25 mmHg. In the ANP group, a bolus of 100 μg of ANP was infused into the graft's renal artery at the time of unclamping, followed by 24 h of continuous intravenous infusion at 0.03 μg/kg/min. Thereafter, the patients received ANP at a rate of 0.01 μg/kg/min until the serum creatinine reached <2 mg/dl. As a consequence of the hydration regimen, the PAP at unclamping was lower in the ANP group than in the control group: 20±3 and 26±4 mmHg, respectively (p<0.05). The ANP plasma levels were significantly higher during the first 3 d in the ANP group (p<0.001). The median recovery rate of renal function was similar in both. groups. No patients in the ANP group experienced ATN while 4 patients (20%) in the control group did (p=0.125). The need for hemodialysis was markedly reduced in the ANP group compared to the control group (1 ANP‐treated patient required dialysis once whereas 5 patients from the control group underwent dialysis a total of 26 times; p= 0.068). ANP administration was well‐tolerated and no hypotensive episodes were reported. This preliminary study suggests that ANP infusion is at least as effective as maximal hydration in preventing ATN and represents an efficient alternative for transplantation centers which do not use maximal hydration as a standard regimen in managing kidney allograft recipients.
Evidence for an increased rate of bacterial infections in liver transplant patients with cytomegalovirus infection
Authors: van den Berg A. P. , Klompmaker I. J. , Haagsma E. B. , Peeters P. M. J. G. , Meerman L. , Verwer R. , The T. H. , Sloof M. J. H.
Published: September 2024

It has been reported that cytomegalovirus (CMV) infections increase the susceptibility of transplant patients for other opportunistic infections. Most of these studies date back from a time when CMV infection was difficult to diagnose and antiviral treatment not available. We therefore analyzed CMV‐related morbidity after OLT in 111 consecutive patients. CMV monitoring was done weekly using the antigenemia assay, a quantitative marker of the viral load, in addition to serology. CMV infection occurred in 66/95 (69%) evaluable patients. Antigenemia was detected in 94% of them. The number of CMV antigen‐positive cells was helpful to monitor the course of infection and differentiate CMV disease from other complications. CMV infection was symptomatic in 48/66 (73%) patients. Mild disease occurred in 30 patients, and severe constitutional symptoms or organ involvement in 18. No patient died as a direct result of CMV infection, but mortality between day 30 and 180 tended to be higher in CMV‐infected patients (15 vs. 0%, p<0.1). CMV infection was associated with a 2.45‐fold higher incidence of major infections between day 30 and 180 after OLT (p<0.05). Most of these infections were caused by gram‐positive cocci. We conclude that CMV not only causes substantial morbidity, but also increases the risk of bacterial infections.
Antilymphocyte induction immunosuppression in the post‐Minnesota antilymphocyte globulin era: incidence of renal dysfunction and delayed graft function. A single center experience
Authors: Malinow Louis , Walker Jennifer , Klassen David , Oldach David , Schweitzer Eugene , Bartlett Stephen T. , Weir Matthew R.
Published: September 2024

Between 4/91 and 12/93, 262 patients received cadaveric (CRT) (n=205) or living donor (LRT) (non‐HLA identical) renal transplants. All patients were treated with the same sequential induction immunosuppression protocol, with the exception of different forms of antilymphocyte sera: either Minnesota antilymphocyte globulin (MALG), antithymocyte globulin (ATG), orthoclone antibody (OKT3), d 1 postoperatively, or OKT3 intraoperatively. With the withdrawal of MALG from the market, we wished to prospectively analyze the influence of these other antilymphocyte therapies on the incidence of delayed graft function (DGF) (the requirement for hemodialysis within the first week postoperatively) and renal function during the first 3 d postoperatively and during the subsequent 6 months post‐transplantation and compare that with our MALG experience. Of the 205 CRT, 76 received MALG with a DGF rate of 18.4%, 50 received ATGAM with a DGF rate of 22.0%, 38 received OKT3 postoperatively with a DGF rate of 39.5%, and 41 received OKT3 intraoperatively with a DGF rate of 39%. Of the 57 LRT, only two patients, one receiving intraoperatively OKT3 (secondary to graft thrombosis). and one MALG patient, suffered DGF. Serum creatinine values were obtained from postoperative d 1 through postoperative d 4 for 185 patients. Each of the four groups showed similar mean decrements in serum creatinine. The number of grafts functioning at 1, 2, 3 and 6 months postoperatively and serum creatinine values were not statistically different between the groups. We conclude that induction immunosuppression with MALG and ATGAM is associated with a lower DGF rate than OKT3 given either intraoperatively or postoperatively. However, with 6 months of follow‐up, we do not observe any difference in the incidence of rejection or graft function between the therapies. Consequently, we have chosen ATGAM as our preferred inductive therapy in the absence of MALG owing to its lower associated DGF rate.
Zinc deficiency and its repletion following liver transplantation in humans
Authors: Pescovitz Mark D. , Mehta Patricia L. , Jindal Rahul M. , Milgrom Martin L. , Leapman Stephen B. , Filo Ronald S.
Published: September 2024

Zinc deficiency is common in patients with end‐stage liver disease but its prevalence and resolution in liver transplant recipients has not been reported. We hypothesized that with normalization of liver function after transplant, zinc levels should rapidly return to normal, obviating the need for oral supplementation. Serum zinc levels were obtained as part of routine laboratory studies just prior to liver transplantation in 34 patients. Of these, 22 had at least one additional zinc level obtained post‐transplant. The charts of these 34 patients were retrospectively reviewed for preand post‐transplant zinc, albumin, protein, and cholesterol levels, prothrombin times, use of oral zinc supplementation, and patient demographics including age, gender, cause of liver failure, UNOS status at the time of transplant, and the use of a pre‐transplant trans‐jugular intrahepatic portosystemic shunt (TIPS). Post‐transplant, the patients received standard enteral formula for nutrition. The overall zinc level for the group was 37.4±9.0 μg/dl (mean±s.d., normal = 60‐150 μg/dl). Thirty‐two of the 34 patients (94%) had a zinc level in the subnormal range. There were no differences in zinc levels between patients with alcoholic and non‐alcoholic liver failure, males versus females, UNOS status (low = status 1 and 2, high = 3 and 4), pre‐transplant use of TIPS nor correlation between age and zinc level. All 22 patients who had a post‐transplant zinc level demonstrated an increase from 40.1±9.7 μg/dl to 68.5±14.1 μg/dl (p≤0.0001, paired t‐test). Our findings indicate that zinc deficiency, generally profound, should be assumed to be present in every patient with end‐stage liver disease awaiting transplant. During the waiting period oral supplementation with zinc should be provided. The degree of deficiency is not effected by cause of liver failure, UNOS status, or the presence of TIPS. Following transplantation, zinc levels rapidly recover, obviating the need for checking levels and oral supplementation.
Improved results with a simplified technique for pancreaticoduodenal transplantation with enteric exocrine drainage
Authors: Tydén G. , Tibell A. , Sandberg J. , Brattström C. , Groth C. G.
Published: September 2024

A simplified technique for pancreaticoduodenal transplantation with enteric exocrine drainage is described. The whole‐organ pancreaticoduodenal transplant is placed intraperitoneally with vascular anastomosis to the right common iliac artery and the caval vein, respectively. The graft duodenum is anastomosed side‐to‐side to the most proximal part of the donor jejunum. No Roux‐en‐Y loop or pancreatic duct catheter is used to protect the anastomosis with this technique. Nevertheless, excellent results have been obtained, with no graft losses occuring due to leakage or infection. With this technique, the 1‐yr patient and graft survival rates in uremic recipients of simultaneous renal and pancreas transplants are 100% and 87%, respectively.
Anatomical and physiological problems of Segment IV: liver transplants using left lobes from living related donors
Authors: Shinohara Hisashi , Tanaka Akira , Hatano Etsuro , Satoh Seiji , Kitai Toshiyuki , Inomoto Takuya , Tokuka Atsuo , Nishizawa Fumio , Kanazawa Akiyoshi , Uemoto Shinji , Inomata Yukihiro , Tanaka Koichi , Yamaoka Yoshio
Published: September 2024

We reviewed the problem of Segment IV in using left lobes from living related donors, in 18 left‐lobe transplants performed on pediatric patients who ranged in age from 6.0 to 17.3 yr, and in body weight from 19.8 to 58.0 kg. The separate monitoring of oxygen saturation of hemoglobin in the liver sinusoid of segments, using a spectrophotometric technique, demonstrated a delay in re‐oxygenation of Segment IV after the portal reflow, and revealed its return to comparable oxygenation with Segments II and III by the re‐arterialization. Hemoglobin content, which was determined by the same technique, occasionally increased in Segment IV during the operation, implying sluggish microcirculation caused by inadequate hepatic venous drainage. These characteristic profiles on tissue oxygenation and hemodynamics in Segment IV should be considered when using left lobes as living related liver grafts.
Preoperative application of glucocorticosteroids efficaciously reduces the primary immunological response in kidney transplantation
Authors: Fricke Lutz , Klüter Harald , Feddersen Andreas , Doehn Christian , Steinhoff Jürgen , Hoyer Jochem , Sack Klaus
Published: September 2024

Early acute rejection episodes have a considerable influence on long‐term prognosis of renal transplants. Therefore the aim of primary immunosuppressive therapy must be effective suppression of the immunological response following antigen recognition. Owing to their pharmacological properties, intravenously given glucocorticosteroids are suitable for the alteration of the primary immunological response. However, even after intravenous administration, glucocorticosteroids have a latency of hours prior to reaching maximum activity. In a prospective clinical study, 111 patients undergoing renal transplantation were preoperatively treated with 500 mg methylprednisolone for immunosuppressive induction. A historical group of 40 patients who had received the same dose as intraoperative bolus, was used for comparison. Postoperative immunosuppression did not substantially differ between the two groups. The incidence of acute rejections within 30 d after transplantation was a clinical parameter of the study. The mitogenic cytokine induction. was measured in blood samples which were collected intraoperatively and on days 1, 2, and 5 after transplantation. Cytokine release served as an in vitro parameter for the immunological responsiveness of the transplant recipient. In the group under study, the incidence of acute rejections was 21% (23/111) and, in contrast, 43% (17/30) in the historical group (p<0.05). 89% of the patients in the group being studied showed normal renal function after lyr, compared to 78% in the reference group (n.s.). Following preoperative (mean 5.09 h) administration of glucocorticosteroids, mitogenic cytokine induction (IL‐ 1β, IL‐2, SIL‐2R and IFN‐y) was almost completely blocked at the time of transplantation. A prospective, randomized study has just been started to evaluate the effect of preoperative administered glucocorticosteroids on the incidence of acute rejections and long‐term allograft survival.
Rupture of splenic artery aneurysm after liver transplantation
Authors: Jovine Elio , Mazziotti Alighieri , Grazi Gian Luca , Ercolani Giorgio , Gruttadauria Salvatore , Masetti Michele , Cavallari Antonio
Published: September 2024

Two patients with splenic artery aneurysm (SAA) ruptured following liver transplantation are reported.
Association between long‐term kidney graft survival and the presence of pre‐transplant cytotoxic anti‐HLA and/or non‐MHC ‘FcγRII blocking’ (anti‐TLX) alloantibody
Authors: Padányi Ágnes , Gyódi Éva , Rajczy Katalin , Perner Ferenc , Petrányi Gyözö G.
Published: September 2024

One hundred kidney graft recipients were analysed retrospectively with regard to the presence of FcγRII (EAI) blocking or cytotoxic HLA antibody induced by pretransplant transfusion. Previous studies suggested that transfusion induces the production of EAI blocking antibody which may have specificity to TLX/CD46/MCP alloantigens. A superior graft survival (65%/9 yr) was found in the presence of EAI alloantibody compared to graft survival in the absence of this antibody (40%/ 9 yr). Further analysis showed the following survival rates in relation to the combined appearance of HLA cytotoxic and EAI antibody (EAI positive, HLA negative 67%/9 yr; EAI positive, HLA positive 60%/9 yr; EAI negative, HLA positive 0%/ 9 yr; EAI negative, HLA negative 40%/ 9 yr). There was striking low graft failure in the first 6 months in patients with EAI antibody. Taking into consideration that the HLA B/DR mismatching grade in all various groups were the same and no considerable difference was found in association to graft survival, the presence or absence of EAI (anti‐TLX) antibody solely seems to have superior or additional effect on graft survival as compared to HLA matching.
Cancer incidence in 854 kidney transplant recipients from a single institution: comparison with normal population and with patients under dialytic treatment
Authors: Montagnino G. , Lorca E. , Tarantino A. , Bencini P. , Aroldi A. , Cesana B. , Braga M. , Lonati F. , Ponticelli C.
Published: September 2024

In this retrospective historical study, we compared the incidences of malignancies observed among 854 renal transplant recipients (RT) with at least 1 yr of follow‐up, with the incidences of neoplasias among patients under regular dialytic treatment (RDT) and a control population from Northern Italy. Cox's proportional hazard model was used in RT recipients in order to evaluate the prognostic factors related to the development of neoplasia. Seventy six out of 854 RT patients (8.9%) developed some malignant neoplasia: 46% of these 76 were cutaneous neoplasias including melanomas, and the remaining 54% non cutaneous cancers: 33% miscellaneous tumors (MT), mostly adenocarcinomas, 17% Kaposi's sarcomas (KS), 4% non‐Hodgkin's lymphomas (NHL). Malignancies had a higher incidence (p<0.01) among RT recipients than among control and RDT patients. However, MT were equally frequent among the three groups. RDT patients on the contrary, had similar incidence of neoplasias when compared to the control population, but showed at lower incidence of squamous cell carcinomas (SCC). The risk ratios (RR) for the most frequent neoplasias among RT recipients vs. control population were: 224.7 for KS, 7.4 for NHL, 6.2 for SCC, 5.7 for basal cell carcinomas (BCC), 4.0 for MT. The risk of developing ade novoneoplasia was of about 13% at 10 yr and of 34% at 20 yr.

In RT recipients, Cox's proportional analysis showed that age >40 at transplantation and male sex were the only risk factors associated with an increased incidence of neoplasias, while no difference was observed between conventional (azathioprine+methylprednisolone: Aza+MP) and CSA therapy or in CSA monotherapy vs. double or triple therapy. However, KS occurrence correlated both with CSA dose (RR 15.2 for monotherapy; 12.5 for double therapy; 2.98 for triple therapy) and with 10 or more i.v. methylprednisolone pulses for treatment of rejection (RR 5.2).

We conclude that in our series CSA does not increase the risk for development of neoplasias, when compared to conventional immunosuppression.
Role of granulocyte colony stimulating factor (G‐CSF) in reversing neutropenia in renal allograft recipients
Authors: Peddi V. R. , Hariharan S. , Schroeder T. J. , First M. R.
Published: September 2024

Neutropenia in solid organ transplant recipients may be caused by immunosuppressive therapy, antimicrobial therapy, as well as bacterial and viral infections. Filgrastim, a human granulocyte colony stimulating factor (G‐CSF) is used for the reversal of neutropenia. Although its influence is principally restricted to neutrophil progenitors, the safety of G‐CSF in terms of percipitating or aggravating allograft rejection and its efficacy in reversing neutropenia in kidney and combined kidney and pancreas transplant patients has not been studied or reported. In this study we retrospectively analyzed the use of G‐CSF between March 1992 and May 1994 at the University of Cincinnati Medical Center, in patients who received either a kidney or a combined kidney and pancreas transplant. A total of 25 patients developed 35 episodes of neutropenia and received an average of 2.9 doses of G‐CSF per episode. The mean WBC nadir was 2.6×103/cu mm with an average peak WBC count of 15.5×103/cu mm following treatment (p=<0.00001). The average number of days to peak WBC after initiation of treatment was 4.6 days. The mean pre‐treatment serum creatinine level was 2.3 mg/dl and the peak serum creatinine in the week following tratment remained the same. We conclude that G‐CSF is an effective treatment in reversing neutropenia in renal transplant recipients and does not precipitate or aggravate allograft rejection.
Cimetidine or ranitidine in renal transplant patients receiving cyclosporine
Authors: Barri Yousri M. , Ramos Eleanor L. , Balagtas Raul S. , Peterson John C. , Karlix Janet L.
Published: September 2024

While H2‐receptor antagonists are commonly used in renal transplant patients to prevent peptic ulcer disease, they have been associated with immunostimulation, interference with cyclosporine (CSA) metabolism, and inhibition of tubular secretion of creatinine. In renal transplant patients, cimetidine in high doses has been shown to cause a sustained rise in serum creatinine (Scr) and to reduce creatinine clearance (CrCl) with no change in inulin clearance. In this short‐term prospective study, we evaluated the effects of single daily doses of cimetidine or ranitidine on renal function, and CSA serum concentration. Fourteen renal transplant patients with stable renal function were assigned to receive either cimetidine 400 mg daily or ranitidine 150 mg daily for 7 days. In patients who received cimetidine, a slight rise in Scr was observed at days 2 and 5 which was not statistically significant, but no significant change in CSA trough level was noted. No changes in Sc, or CSA level were noted in the patients who received ranitidine. No changes in GFR were observed in either cimetidineor ranitidine‐treated patients. We conclude that, in our short‐term study, cimetidine or ranitidine in the doses used in this study did not affect the GFR or CSA level, or Scr.
Serial monitoring of soluble interleukin‐2 receptor as a rapid marker of cytomegalovirus infection and response to antiviral therapy1
Authors: Rossi Stephen , Schroeder Timothy , Muth Karen , Hanto Douglas , Munda Rino , Hariharan Sundaram , First M. Roy , Ryckman Frederick , Balistreri William
Published: September 2024

Serial sIL‐2R serum levels were evaluated as an indicator of cytomegalovirus infection and response to antiviral therapy. All cases of post‐transplant CMV infection or disease were studied over a 2.5‐year period with serial sIL‐2R serum levels monitored daily post‐transplant until discharge, during each inpatient admission and with each outpatient laboratory analysis. Mean sIL‐2 levels±S.E.M. rose from a baseline level of 3662+321 U/ml to 11657±3311 U/ml at the time of diagnosis. Serum SIL‐2R concentrations were significantly elevated from baseline as early as 14 days prior to diagnosis of CMV. Mean peak sIL‐2R levels occurred an average of 4 days after the initiation of ganciclovir therapy and remained significantly elevated for an average of 20 days of treatment. Serum sIL‐ 2R levels in patients with resolved CMV returned to within 20% of baseline after 20 days of therapy. These data support the idea that serial monitoring of SIL‐2R serum levels may be useful adjunctively in the diagnosis of CMV as well as determining the response to and duration of antiviral therapy.
Ketanserin: a new perspective in posttransplant erythrocytosis?
Authors: Borawski Jacek , Mazerska Maria , Rydzewski Andrzej , Pawlak Krystyna , Rowinski Miroslaw , Mysliwiec Michal
Published: September 2024

We have recently shown that ketanserin, an antagonist of peripheral serotonin 5‐HT2 receptors lowers blood erythropoietin (Epo) levels in some chronic hemodialysis patients. Based on this finding, a preliminary study was undertaken to investigate the effect of a 3‐week oral ketanserin administration on serum Epo concentration and relevant hematological parameters in 4 renal allograft recipients with posttransplant erythrocytosis (PTE). We found a marked decrease in Epo concentrations following ketanserin administration, from 48% to 76% of the abnormally elevated pretreatment values with subsequent increases at 3 weeks after discontinuation of the drug in all patients studied. In 3 of them a corresponding decrease or no rise in the erythrocyte count were noted. During the 6‐week study period, the need for monthly phlebotomies was eliminated in these patients. It is hypothesized that ketanserin diminishes erythropoietin synthesis and may become a new drug in the treatment of posttransplant erythrocytosis.
New concepts in tolerance
Authors: Wood Kathryn J.
Published: September 2024

Increasing the immunologic specificity of immunosuppressive therapies used to prevent graft rejection is one of the fundamental aims of research designed to develop new approaches for immunosuppression. The objective of work in this area is to identify both strategies and the mechanisms responsible for the induction of tolerance to alloantigens in vivo. Three topics in this area of transplantation immunobiology are considered: (i) The tools available for investigating the induction of tolerance to alloantigens, including T‐cell clones, transgenic mice, and neonatal and adult models of tolerance induction. (ii) Strategies for tolerance induction that are being explored in experimental models and in clinical transplantation. These strategies can be divided into two categories: those that aim to induce tolerance in the long term after transplantation and those that aim to induce unresponsiveness at the time of grafting. (iii) The mechanisms responsible for the induction of tolerance to alloantigens. Five nonmutually exclusive hypotheses have been proposed to explain the induction of peripheral tolerance. These are, in broad terms, deletion, anergy, ignorance or helplessness, exhaustion and suppression. The immune status of the recipient may influence which of these mechanisms operates in any particular situation. What is apparent from all studies is that tolerance induction is a dynamic process, and any or all of these mechanisms may be operating at different stages of the induction and maintenance process.
Molecular mechanisms of new immunosuppressants
Authors: Halloran Philip F.
Published: September 2024

Maintenance immunosuppressive drugs act by partially blocking rate‐limiting steps in the immune response. The new maintenance immunosuppressive drugs are either inhibitors of de novo synthesis of nucleotides (purines or pyrimidines), or are immunophilin‐binding drugs that inhibit signal transduction in lymphocytes. The new inhibitors of de novo nucleotide synthesis include mycophenolate mofetil (MMF), mizoribine (MZ), brequinar (BQR), and leflunomide (LEF). MMF and MZ act to inhibit de novo purine synthesis, by inhibition of inosine monophosphate dehydrogenase (IMPDH). They create a selective immunodeficiency in T and B lymphocytes. MMF is hydrolyzed to mycophenolic acid (MPA), an uncompetitive inhibitor of IMPDH. MPA reduces the pools of guanine nucleotides, and increases some adenine nucleotides, inhibiting the cell cycle. Thus the number of specific effector T and B lymphocytes is reduced by limiting clonal expansion. MZ is a competitive inhibitor of IMPDH, which creates a similar defect. The relative clinical effectiveness of MMF versus MZ is not known. MMF has been approved in a number of countries; MZ has been approved in Japan. The inhibitors of de novo pyrimidine synthesis (BQR, LEF) act on the enzyme dehydroorotate dehydrogenase. Neither is currently in clinical trials in transplantation. The new immunophilin‐binding drugs inhibit either the calcium‐dependent phosphatase calcineurin (CN) [tacrolimus (or FK‐506) and the microcmulsion form of cyclosporine (CSA)] or signaling from growth factor receptors [rapamycin (sirolimus)]. Tacrolimus binds to FK binding protein‐12 (FKBP‐12) to create a complex that inhibits CN. CSA binds to cyclophilin to create a complex that inhibits CN. Inhibition of CN prevents activation of cytokine genes in T cells. The relative clinical effectiveness of tacrolimus versus microemulsion CSA is unknown. Rapamycin inhibits signaling from growth factor receptors, such as IL‐2R. Rapamycin binds to FKBP to create a complex that engages proteins called TOR (target of rapamycin), or RAFT (rapamycin and FKBP target), which may be kinases. The result is a block in the ability of cytokine receptors to activate cell cycling, interfering with clonal expression. Deoxyspergualin, a parenteral drug in development for induction or antirejection therapy, may inhibit intracellular chaperoning by Hsc70, a member of the heat shock protein family. It may have its principal effect by inhibiting the activation. of transcription factor NF‐κB in antigen‐presenting cells and monocytes.
Heart transplantation for patients over age 60
Authors: Everett Jeffrey E. , Djalilian Ali R. , Kubo Spencer H. , Kroshus Timothy J. , Shumway Sara J.
Published: September 2024

As the proportion of people over age 60 in our society continues to rise, so does the number of potential heart transplant candidates. Advanced recipient age, however, has long been used as an exclusion criterion for transplantation, though the upper age limit remains poorly defined. The purpose of our study was to analyze the outcomes of 31 heart transplant recipients over age 60 at our institution. They were followed with regard to early and late morbidity and mortality. Mean follow‐up time was 50 months. The 1‐ and 5‐ yr survival rates were 90% and 85%. These rates were not significantly different compared with younger (age 18 to 59) recipients transplanted in the same time period. The older recipients more frequently developed osteoporotic changes as well as cutaneous and visceral malignancies, but had infrequent rejection episodes. Overall, heart transplantation is safe and effective for patients over age 60 with end‐stage congestive heart failure. Both 1‐ and 5‐yr survival rates are well within the acceptable range and do not differ significantly from younger recipients. Individualized immunosuppression might help reduce the incidence of malignancy in older recipients, but further studies are needed. Matching donor and recipient age would make the best use of available organs.
The importance of early cyclosporine levels in pediatric kidney transplantation
Authors: Matas Arthur J. , Gillingham Kristen J. , Chavers Blanche M. , Nevins Tom , Kashtan Cliff , Mauer S. Michael , Payne William D. , Gruessner Rainer , Najarian John S.
Published: September 2024

We studied the impact of early cyclosporine (CSA) levels on the incidence of rejection in pediatric transplant recipients. Between 1 January 1984 and 31 December 1994, a total of 234 pediatric patients underwent kidney transplants and received CSA immunosuppression. We analyzed the impact of CSA levels (at 1 wk, 2 wk, 1 month, 2 months, and 3 months) on the incidence of rejection in the first 3 and the first 6 months post‐transplant. We found that CSA levels at all timepoints correlated; i.e. recipients with low levels in the early post‐transplant period tended to have low levels throughout the first 12 months. Multivariate analysis for risk factors for biopsy‐proven rejection in the first 3 months revealed that the CSA trough level was the critical factor (p<0.05). Recipients with CSA trough levels <100 ng/ml had 2.24 times the risk of rejection vs. those with blood levels >100 ng/ml. Similarly, the CSA trough level at 1 month was the critical risk factor for biopsy‐proven rejection within the first 6 months (p<0.05). The major risk factor for graft loss within the first 12 months was a biopsy‐proven rejection episode. We conclude that in pediatric kidney transplant recipients, early CSA trough levels <100 ng/ml are associated with a significantly increased incidence of rejection in the first 6 months post‐transplant.
Cytomegalovirus infection associated accelerated heart allograft arteriosclerosis may impair the late function of the graft
Authors: Koskinen Petri , Lemstrøm Karl , Mattila Severi , Häyry Pekka , Nieminen Markku S.
Published: September 2024

Cardiac allograft arteriosclerosis is the most important limiting factor of long‐term survival of heart transplant recipients. Several clinical studies have suggested the association between CMV infection and heart allograft arteriosclerosis, chronic rejection. To determine the temporal impact of CMV infection on the development of heart allograft arteriosclerosis we quantitated coronary angiograms obtained from 72 heart transplant recipients followed for 1‐6 yr post‐transplantation. To examine the graft function, echocardiography was evaluated. CMV infection was associated with early development of allograft arteriosclerosis manifested by intense diffuse pruning of the coronary arteries including their smallest branches already after the second post‐transplant year. Even 6 yr post‐transplantation the magnitude of arteriosclerotic changes was significantly higher in recipients with CMV infection compared with patients without infection (P<0.02). No difference in echocardiographic parameters including ejection fraction (EF), left ventricular end diastolic diameter (LVEDD) and left ventricular mass (LVM) between recipients with and without CMV infection was recorded early after transplantation. However, when compared to recipients without CMV, the CMV accelerated chronic rejection seen in coronary angiography associated with impaired late graft function as judged by decreased EF in patients with CMV infection 6 yr post‐transplantation (P<0.02). No differences in LVEDD or LVM between the patient groups occurred. Taken together, these results suggest that CMV infection is associated with intense cardiac allograft arteriosclerosis affecting the whole coronary tree soon after transplantation. The intensity and magnitude of these chronic vascular wall changes increase and persist during subsequent years, indicating that the risk for graft loss and death due to chronic rejection is especially high during the first 5 post‐transplant years in CMV‐infected patients. Echocardiography may not be a sensitive method to distinguish patients with early CMV‐accelerated allograft arteriosclerosis but coronary angiography must be performed.
VCAM‐1 and E‐selectin expression during cytomegalovirus infection in post‐transplant myocardial biopsies
Authors: Allen Margaret D. , King Christine , MacDonald Thomas O. , Himes Victoria
Published: September 2024

Adhesion molecule expression may become useful in monitoring cardiac graft rejection, but first the question of whether expression is upregulated by cytomegalovirus (CMV), a common post‐transplant infection, must be answered. To study this, all cardiac biopsies (n=201) on 12 cardiac transplant recipients were examined for rejection grade and VCAM‐1, ICAM‐1, and E‐selectin expression over the first 6‐15 months post‐transplant. Adhesion molecule expression in biopsies taken during documented CMV infections were compared to those taken in the absence of infection, both overall and sorted as to rejection grade.

There were 17 CMV infections in this patient group. VCAM‐1 was expressed in 82% of biopsies coincident with CMV infections, compared to 43% of biopsies unrelated to CMV infection, a significant difference (p<0.01). E‐selectin was expressed in 65% of biopsies with CMV infection, compared to 30% of biopsies unrelated to CMV infection, also statistically significant (p=0.01). Both VCAM‐1 and E‐selectin were expressed in 80% of biopsies without rejection taken during CMV infections, significantly greater than the 24% incidence of VCAM‐1 and 14% incidence of E‐selectin expression in biopsies without rejection that were not concomitant with CMV infection. In the absence of CMV infection, both VCAM‐1 and E‐selectin expression correlated significantly with rejection grade, but this relationship became invalid in the presence of CMV infection. ICAM‐1 expression bore no relation to CMV infection.

VCAM‐1 and E‐selectin expression in cardiac biopsies can be upregulated with CMV infection in the absence of graft rejection.
Disparate changes in plasma and tissue pentosidine levels after kidney and kidney‐pancreas transplantation
Authors: Hricik Donald E. , Wu Yu Ching , Schulak James A. , Friedlander Miriam A.
Published: September 2024

The advanced glycation end‐product, pentosidine, was measured in plasma proteins and skin collagen before and after kidney and kidney‐pancreas transplantation in order to determine the relationship between plasma and tissue levels and to characterize the pattern of change in pentosidine levels after correction of hyperglycemia and/or renal failure. The content of pentosidine in skin collagen was higher than that in plasma proteins both before and after transplantation. However, there was no correlation between plasma and skin pentosidine levels. Prior to transplantation, the content of pentosidine in skin collagen was related to the duration of dialytic therapy, presence of diabetes mellitus, age, and female gender. Following transplantation, plasma pentosidine levels were inversely correlated with glomerular filtration rate (r=‐0.64; p<0.01). While plasma pentosidine levels consistently decreased after transplantation, levels in skin collagen increased in 10 of 13 patients, including 5 of 6 recipients of kidney‐pancreas transplants. Our results indicate that tissue levels of pentosidine persist for long periods of time after kidney or kidney‐pancreas transplantation, despite consistent decreases in levels measured in plasma proteins. The observed increase in tissue pentosidine levels in a majority of patients suggests that formation of advanced glycation end‐products may continue after otherwise successful kidney or kidney‐pancreas transplantation.
CREG matching for first cadaveric kidney transplants (TNX) performed by SEOPF centers between October 1987 and September 1995
Authors: Thompson John S. , Thacker Leroy R.
Published: September 2024

The Southeastern Organ Procurement Foundation (SEOPF) data base from October 1987 to September 1995 includes 12 536 first cadaveric kidney transplants, of which 39.5% were placed into non‐white recipients (N‐WR). Consequently, the SEOPF data offered an excellent sample in which to examine the effect of a number of conventional HLAA, B versus public (crossreactive group, CREG) matching schemes on access and graft survival (GS). The standard applied was that 3‐yr GS had to be greater than that of the mean GS of the racial group. Because of the excellent 1‐ and 3‐yr GS of 0 A,B,DR mismatched kidneys in both white recipients (WR)=87.9% and 82.8% and N‐WR‐86.9% and 80.9%, these transplants were excluded from further analysis. Thereafter, the mean 1‐ and 3‐yr GS of the remaining 7011 WR and 4862 N‐WR transplants used for all subsequent comparisons were 82.5% and 72.4% for WR versus 80.9% and 63.0% for N‐WR. Four different matching schemes were compared: 1) Class I A, B versus CREG hierarchical effect disregarding DR; 2) 0, 1, 2B, DR versus 0‐2 CREG, DR mismatching; 3) DR mismatching disregarding Class I A, B or CREG mismatching and 4) Class I A, B versus CREG mismatching stratified for DR. Two and possibly three CREG, DR mismatched groups were identified in which improved access and GS occurred in comparison with the 0, 1, and 2B, DR mismatched transplants currently receiving 7, 3 and 1 point in the UNOS sharing algorithm. The 1‐ and 3‐yr GS in WR and N‐WR of these groups were as follows: 0 CREG, 0 DR mismatches: 85.7% and 78.3% in WR (n=385); 83.0% and 69.4% in N‐WR (n=157). 1‐3 CREG, 0 DR mismatches: 84.5% and 74% in WR (n=1550); 82.7% and 65.7% in N‐WR (n=1083). Based on this analysis, there may be a significant potential advantage of prospective Class I CREG over A, B matching for first cadaver kidney transplantation.
OKT3 induction therapy: influence of duration on rejections and infections
Authors: Zibari G. B. , Boykin K. N. , Thomas J. P. , Aultman D. F. , Aradhye S. A. , McMillan R. W. , McDonald J. C.
Published: September 2024

Anti‐lymphocyte induction therapy in renal transplants remains controversial relative to efficacy and cost benefit. It has been suggested that shortening the duration of induction therapy from 14 to 7 d would provide adequate efficacy at less cost. Our objective was to compare the efficacy and complications of short (7 d or less, group A) versus standard (14 d or more, group B) duration of OKT3 induction therapy in renal allograft recipients. We performed a retrospective review of all renal allografts performed between July 1989 and September 1994. Two groups were identified based on the duration of OKT3 induction therapy. There were no significant differences between group A or B in the distribution of age, sex, race, degree of HLA matching, and etiology of renal failure. Patients in group B experienced fewer rejections at 3 and 12 months (p=0.0236 and p=0.0065, respectively) as well as fewer viral infections during the first year of follow‐up (p=0.0435). No difference on the mean number of bacterial or fungal infections existed between the two groups. There were no statistically significant differences in patient or graft survival, although patients in group B had a tendency towards increased 1‐yr graft survival.
Alloimmunization against platelet antigens in renal transplant patients with acute vascular rejection
Authors: Kekomäki S. , Salmela K. , Partanen J. , Koskimies S. , Kekomäki R.
Published: September 2024

Acute vascular rejection (AVR) of a kidney graft, in which the graft vascular endothelium is main target for the injury, is considered antibody‐mediated. Integrins of vascular endothelium and platelets have several alloantigenic epitopes in common, e.g. human platelet alloantigen (HPA) 1 on β3, integrin of glycoprotein (GP) IIbIIIa and HPA‐5 on α2of GP lalla. The clinical significance of HPA expression by vascular endothelial cells is unknown. Platelet antibodies in serum samples from 26 renal allograft recipients with AVR and 30 patients without AVR were studied. Also the HPA‐types of the patients and their respective graft donors were determined. Strong platelet alloantibodies were observed in seven of the 26 AVR patients (27%). In five of these cases the antibodies had HPA‐specificity. No reference patient without AVR had strong platelet antibodies. In two AVR patients strong HPA‐5b antibodies coexisted with an HPA‐5b‐positive graft. Despite acute rejection episodes, neither of the grafts was lost. It seems likely that, with current immunosuppressive treatment, anti‐HPA‐5b does not necessarily cause permanent dysfunction of a graft originating from HPA‐5b‐positive donor.
Value of endothelin in cellular rejection after liver transplantation
Authors: Fábrega Emilio , Figols Javier , Dueñas Carmen , Crespo Javier , Casafont Fernando , Sanchez‐Antolín Gloria , de las Heras Gonzalo , Amado Jose Antonio , Pons‐Romero Fernando
Published: September 2024

Endothelin‐1 is a vasoconstrictor peptide released by the vascular endothelium by various chemical and mechanical factors. Cellular rejection is one of the most common complications following orthotopic liver transplantation, endotheliitis being its most specific and consistent histological feature. To assess the role of endothelin in cellular hepatic rejection, we studied 21 cirrhotic patients undergoing elective liver transplantation. These patients were divided in two groups: Group I comprised 10 patients without cellular rejection, and Group II comprised 11 patients with cellular rejection. Endothelin was measured on day 7 after transplantation, on the day of liver biopsy, and after treatment for rejection. We found a significant increase in the plasma endothelin levels in the early postoperative period in the patients with moderate or severe cellular rejection compared with the non‐rejection group. It remained significantly elevated until the clinical diagnosis of rejection was made. This value returned to baseline with successful treatment. So, the monitorization of this peptide may be of help in the diagnosis of rejection, its severity, and the evaluation of its resolution.
Isoniazid hepatotoxicity in renal transplant recipients
Authors: Antony Suresh J. , Ynares Christina , Dummer J. Stephen
Published: September 2024

Tuberculosis occurs at higher rates in renal transplant recipients than in the general population. It would be desirable to use isoniazid prophylaxis in renal transplant recipients at risk for reactivation of tuberculosis; yet many transplant centers do not routinely employ INH prophylaxis because they perceive transplant recipients to be at an enhanced risk of hepatotoxicity from isoniazid. Data on the risk of isoniazid in renal transplant patients receiving cyclosporine‐based immunosuppression are limited. We retrospectively studied 83 renal transplant recipients (mean age 39.1±11.7 yr) who had received INH prophylaxis between 1985 and 1994. Eight patients had laboratory evidence of chronic hepatitis B or chronic hepatitis C infection. The mean duration of INH therapy was 344±163 d. The mean serum glutamate oxalacetic transferase (SGOT) at the start of INH therapy was 24.1±10.9 I.U., and 10% of patients had mildly elevated SGOTS. Mean peak SGOT during therapy was 36.4±15.3 I.U. (p<0.001 compared to start SGOT). In follow up, 31% of patients had an abnormal SGOT (>40 I.U.); however, the elevations were small (the highest SGOT was 88 I.U.) and never necessitated discontinuation of INH. No patient had jaundice or other evidence of clinical hepatotoxicity. The 95% confidence interval for the observed frequency of clinical hepatitis was 0% to 4.3%. At the end of INH therapy the mean SGOT was 22.7±6.2 I.U. (p>0.2, compared with start SGOT) and only one patient had an abnormal SGOT. In conclusion, it appears that the risk of renal transplant recipients developing serious hepatotoxicity with the administration of INH is low and not different from normal individuals.
Ethical and policy issues in altruistic living and cadaveric organ donation
Authors: Spital Aaron
Published: September 2024

Organs for transplantation are usually obtained from living genetic relatives or from heart‐beating cadavers. Unfortunately, these sources have so far been unable to keep up with demand. As a result, there is a large and steadily increasing number of potential recipients awaiting transplantation, some of whom will die before an organ can be found. In an attempt to rectify this tragic situation, several solutions have been proposed. This review will consider proposals designed to increase the availability of human organs without resorting to commercialism. These include expanding the use of living donors by: 1) encouraging donations by genetic relatives; 2) allowing volunteers a greater voice in determining their own suitability; 3) encouraging the use of emotionally related individuals and accepting altruistic strangers; and 4) considering motivated identical twin minors and older adolescents as donors. Suggestions for increasing the pool of cadaveric donors include: 1) overcoming the family consent barrier by presuming consent, mandating completion of binding advanced directives, or by eliminating the need for consent entirely; 2) reconsidering non‐heart‐beating donors; 3) elective ventilation for organ donation; and 4) accepting organs from anencephalic infants before brain death occurs. All of these proposals raise concerns which are discussed. Those approaches considered to be ethically acceptable and to hold promise for success should be vigorously pursued, beginning with carefully designed pilot studies. Hopefully, such an approach will eventually increase the number of organs available for patients sufferung from end‐stage organ disease.
Significance of tubulitis in chronic allograft nephropathy: a clinicopathologic study
Authors: Tsamandas A.C. , Shapiro R. , Jordan M. , Demetris A.J. , Randhawa P.S.
Published: September 2024

Tubulitis is the principal lesion used for the diagnosis of acute rejection (AR) in the Banff schema for renal allograft pathology. It is considered to be reliable for assessing AR early after transplantation. However, its significance in biopsies with concurrent changes of chronic allograft nephropathy (CAN) is less well understood. To address this issue we studied seventeen allograft biopsies taken 9‐108 (median 39) months post‐transplant from 17 patients. All specimens were scored for AR and CAN using Banff criteria. Medical records were reviewed to determine the clinical course of the patients. Five biopsies showed t1 changes, whereas nine biopsies graded as t2, and three biopsies as t3. The CAN scores varied from cg0, cil, ctl, cvl, to cgl, ci3, ct3, cv3. A response to increased immunosuppression, defined as a fall in the serum creatinine of at least 20% compared to the peak value, was observed in 7/17 (41%) cases. The responsive cases included 2/5, 4/9, and 1/3 cases respectively with t1, t2, and 13 tubulitis. The mean ± SD CAN scores in these three groups were 8.4 ±1.8, 6.5±1.4. and 7.0±1.4, respectively.

We conclude that the presence of coexisting tubulitis and CAN in renal allograft biopsies may indicate reversible acute rejection. In this study, clinical response was observed in 7/17 (41%) patients. Patients with therapeutically responsive rejection could not be differentiated from refractory cases by serum creatinine, tubulitis grade, per cent glomerulosclerosis and sum scores for AR or CAN. Hence a trial of anti‐rejection therapy may be warranted pre‐emptively in all such cases.