bluuebunny/crossref_metadata_2025 huggingface dataset:
High survival rate of kidney transplants in IgA nephropathy patients
Authors: Lim Eduardo C. , Terasaki Paul I.
Published: September 2024

Background

Patients with various diseases such as chronic glomerulonephritis (CGN), pyelonephritis (PN), polycystic kidney disease (PKD), etc., have had remarkably similar kidney graft survival rates. It was interesting to see if patients with IgA nephropathy (IgAN), who have associated immunologic dysfunctions, might have an unusual response to their kidney allografts.

Methods

The graft survival rates of 374 patients with IgAN were compared to those of patients with other diseases from data submitted the UCLA Transplant Registry by over 200 different centers.

Results

The 5‐year cadaver donor graft survival rate in patients with IgAN was 76%, compared to 60% for controls (PN, PKD and CGN). Matching IgAN for age, sex, and race at 4 yr still yielded significantly higher graft survival of 86% compared to 68% for controls. Functional graft survival, which counts death as lost‐to‐follow‐up, was also higher at 5 yr among IgAN patients (77%) compared to controls (66%). Grafts from HLA‐identical sibling donors and 1‐haplotype‐matched related donors also had higher survival in IgAN recipients than in patients with other diseases. Thirty‐four IgAN‐sensitized patients with preformed cytotoxic antibodies had a 97% 5‐year graft survival rate. Graft survival to 5 yr among 60 patients with IgAN who were not transfused was 90%. Transfusion reduced the graft survival to 84% at 1 yr and 73% at 5 yr.

Conclusion

Patients with IgAN have higher kidney allograft survival rates than patients with CGN, PN, PKD. Immunologic dysfunction in IgAN patients is probably responsible for higher kidney allograft survival in those patients, and may provide clues as to how similar results can be achieved for other patients.
Role of lipid disturbances in the atherosclerosis of renal transplant patients
Authors: Abdulmassih Zlad , Chevalier Alain , Bader Cyrille , Drüeke Tilman B. , Kreis Henri , Lacour Bernard
Published: September 2024

Atherosclerosis is a major long‐term complication of renal transplantation. In the present retrospective study, we examined the possible role of lipid disturbances as a pathogenetic risk factor. We used deep‐frozen sera from 54 kidney graft recipients with a follow‐up of 11.8 ± 4.2 yr (mean ± SD) after transplantation: 25 patients with one or more ischemic event(s) and 29 with none. The two groups were matched for age, sex, body weight and height, duration of chronic renal failure before and time after transplantation. The serum samples had been drawn 1‐6 months prior to the first vascular event in patients with cardiovascular accident and the length of serum storage time was comparable in patients without cardiovascular accident. The major finding was that patients with cardiovascular accident had significantly higher serum total cholesterol (p < 0.02), triglycerides (p < 0.001), apolipoprotein (apo) B (p < 0.003), apo CII (p < 0.02), apo CIII (p < 0.006), and apo E levels (p < 0.006) than patients without cadiovascular accident. By discriminant factor analysis, 70% of patients were correctly allocated to the respective group on the basis of combined triglycerides, apo B and apo E levels. In addition to serum lipids, three other risk factors were identified, namely cigarette smoking, antihypertensive drug therapy, and atherosclerotic lesions of the iliac artery at time of transplantation. In conclusion, disturbances of lipoprotein metabolism probably favor the occurrence of ischemic vascular disease in kidney graft recipients.
Pancreatic complications following orthotopic liver transplantation
Authors: Yanaga Katsuhiko , Shimada Mitsuo , Gordon Robert D. , Tzakis Andreas G. , Makowka Leonard , Marsh J. Wallis , Stieber Andrei C. , Todo Satoru , Iwatsuki Shunzaburo , Starzl Thomas E.
Published: September 2024

During fiscal year 1986, 40 out of 196 patients (21%) developed hyperamylasemia following orthotopic liver transplantation. The placement of a retropancreatic aortohepatic arterial interposition graft was associated with hyperamylasemia (p < 0.025). Eight patients (20%) developed clinically significant acute pancreatitis and its sequelae; abscesses and pseudocysts each in 2. Pancreatitis was attributable to the retropancreatic arterial graft in 4, viral infection in 2 and obstruction of the pancreatic duct in 1 patient. All 4 patients with arterial graft‐related pancreatitis exhibited poor graft function immediately postoperatively, of whom 2 required retransplantation ‐ both of which failed to function. Five patients died (63%); 2 from primary graft non‐function, 2 due to sepsis and 1 from systemic cytomegalovirus infection. We conclude that acute pancreatitis after liver transplantation is a life‐threatening complication which is often associated with graft non‐function.
Peritonitis due to Mycoplasma hominis in a hepatic transplant recipient
Authors: Dugernler T. H. , Laterre P. F. , Noriega L. M. , Reynaert M. S.
Published: September 2024

A case of life‐threatening intra‐abdominal infection with Mycoplasma hominis is described in a hepatic transplant recipient. Predisposing conditions included profound immunosuppression and perihepatic hemorrhage. Mycoplasma hominis was isolated from samples of perihepatic hematoma and intra‐abdominal fluid obtained during surgery. Susceptibility to erythromycin was demonstrated by in vitro testing. Surgical drainage and antimicrobial therapy resulted in correction of the septic syndrome and achieved the cure of the patient. A greater awareness of the role of this potential pathogen in susceptible patients is mandatory.
Influence of concomitant medication on cyclosporine dosage and blood concentrations in renal allograft recipients1
Authors: Sridhar N. , Schroeder Timothy J. , Hariharan Sundaram , Pesce Amadeo J. , First M. Roy
Published: September 2024

The pharmacokinetics of cyclosporine (CyA) may be altered by concomitantly administered drugs in allograft recipients. This requires changes in dosage to optimize blood levels and to minimize CyA toxicity. The interactions of CyA with oral verapamil, nifedipine, diltiazem, ketoconazole and metoclopramide, and intravenous methylprednisolone were studied. No multiple combination interactions were considered in this study; patients were on maintenance CyA doses when these drugs were introduced. Two groups of patients, who were not receiving any medication that could influence CyA pharmacokinetics, were selected as controls. The alteration in CyA dosage was expressed as a % change from precombination values. The greatest decrease in CyA dose was in the ketoconazole‐treated patients (82%) followed by the diltiazem (31%), metoclopramide (20%), verapamil (13%), and nifedipine (8%). No decreases in CyA dose were required in patients receiving methylprednisolone. Despite dose reductions, HPLC trough blood concentrations were unchanged in the treatment and the control groups. In conclusion, significant dosage reductions are needed in patients receiving ketoconazole, diltiazem, verapamil, nifedipine and metoclopramide. Such changes are not required in patients receiving methylprednisolone.
Treatment of a B‐cell lymphoproliferative disorder in a liver transplant patient with interferon alfa and gamma globulin: A case report
Authors: Kane R. E. , Bunchman T. E. , Vogler G. , Brems J. J.
Published: September 2024

Epstein‐Barr virus (EBV) infection in immunosuppressed organ transplant recipients has been associated with the development of lymphoproliferative disorders (LPD), including malignant lymphoma of the gastrointestinal tract. A 4‐year‐old boy who received a liver transplant for acute fulminant hepatitis C developed steroid‐resistant rejection 3 weeks after transplant which was successfully treated with the monoclonal antibody, OKT3. Three months post‐transplant he developed fevers, severe watery diarrhea and a protein‐losing enteropathy. Endoseopy revealed EBV‐positive LPD of the jejunum so he was started on acyclovir and his immunosuppression decreased. Ten days later he was explored surgically because of a perforation of a lymphomatous tumor mass in the ileum. Two areas of lymphomatous tumor were resected in the mid‐jejunum and ileum. Cytomorphology and immunoperoxidase stains of the small bowel tumors and mesenteric nodes were consistent with a EBV‐driven, polyclonal, polymorphous B‐cell LPD. He was treated with interferon alpha 3 times/wk and gamma globulin infusions weekly for 4 months. There was no evidence of recurrence of the LPD despite conventional immunosuppression with cyclosporine and prednisone. In this patient, surgical resection of small bowel tumors, followed by reduced immunosuppression and treatment with interferon alpha, gamma globulin and acyclovir were successful in treating a EBV‐driven LPD without compromise of the liver allograft.
Flow cytometry PRA, a new test that is highly correlated with graft survival
Authors: Cicciarelli J. , Helstab K. , Mendez R.
Published: September 2024

IgM antibodies present in the recipient sera are not necessarily harmful to the outcome of the graft. However, one primarily measures IgM with panel‐reactive antibody (PRA) determined by microcytotoxicity. In order to develop a potentially more correlative PRA measurement, we have utilized the flow cytometer to measure IgG antibody to a panel of lymphocytes representing HLA antigens. This was accomplished by measuring the median channel shift associated with the patient's serum antibody binding to pooled target cells. The correlation between flow PRA and graft outcome was analyzed in 59 regraft recipients using current serum prior to transplantation. The PRA was determined by both cytotoxicity and flow cytometry. One‐year follow up was available on all transplant recipients with 62% 1‐yr actuarial graft survival. Cytotoxic PRAs were divided into greater than 10% and less than or equal to 10%, with a 72% vs 70% graft survival at 6 months and 62% vs 62% 1 yr graft survival, respectively. Flow cytometry PRA was divided into greater than 10 and less than or equal to 10 channel shift with 63% vs 86% graft survival at 6 months, and 53 vs 79% 1 yr graft survival respectively (p < 0.05 for both time intervals). Serum creatinine levels were concomitantly lower at 1 and 3 months in the flow PRA‐negative recipients. Flow PRA was a simple, rapid test which eliminates “false” positives due to IgM and detects non‐complement fixing IgG, which occurred in 25% of the samples. Flow PRAs were significantly correlated with graft survival and represented a new test which can be utilized as an in vitro correlate for immune response in the transplant candidate.
Risk factors associated with the development of squamous cell carcinomas in immunosuppressed renal transplant recipients
Authors: Roeger L. S. , Shell A. G. R. , Disney A. P. S. , Mathew T. H. , Amiss N.
Published: September 2024

The risk factors associated with the development of squamous cell carcinomas (SCC) in immunosuppressed renal transplant recipients were assessed. Data concerning 2573 patients aged 18 years or older at the time of renal transplantation between January 1, 1981 and October 31, 1989 were extracted from the Australia and New Zealand Combined Dialysis and Transplant Registry (ANZDATA). Certain groups of patients, including those with a diminished (non‐caucasians [p < 0.01]) or increased (those with SCC prior to or within 90 days of transplantation [p < 0.01]) risk of developing SCC were excluded. A final sample of 2115 patients was derived, 122 or whom developed a SCC. Statistical analyses of a number of potential risk factors were made. Increased age at the time of transplantation was shown to be a significant risk factor (p < 0.01). Patients who received their grafts in transplant units with increased sun exposure (lower latitude) were at significantly greater risk (p < 0.01). Females tended to be at less risk (p < 0.10) than males. The type of donor (living or cadaver) and whether or not the patient received immunosuppression for greater than 3 months pre‐dialysis were not significant factors. There were no significant differences in risk of SCC development amongst patients with different primary renal diseases (although patients with diabetes tended (p < 0.10) to be at less risk than patients diagnosed with glomerulonephritis), those analyzed according to tissue matching results, or those with cytotoxic antibodies in their sera at the time of transplantation. Higher levels of the maximum serum cytotoxic antibody reactivity were found to be associated with decreased risk (p < 0.05). There was no significant difference in the risk of groups of patients treated with a variety of different immunosuppressive regimes. Patients treated with cyclosporine, alone or in combinatinn with other agents, were at similar risk to those receiving azathioprine and prednisolone. It appears that the increased risk of SCC development in renal transplant recipients immunosuppressed with azathioprine will persist in the cyclosporine era.
Malignant lymphomas in children with primary immunodeficiency diseases
Authors: Purtilo David T.
Published: September 2024

X‐linked lymphoproliferative disease (XLP) is characterized by exquisite vulnerability to Epstein‐Barr virus (EBV). It serves as a model for studying EBV‐induced non‐Hodgkin's lymphoma in immunodeficient patients. EBV was etiologically linked with African Burkitt lymphoma (BL), nasopharyngeal carcinoma (NPC), and infectious mononucleosis (IM) prior to the discovery of XLP in 1975. Studies of males affected with XLP have shown that EBV is responsible for diverse diseases well beyond the three diseases discovered during the initial decade (1964‐1974) following isolation of the virus. The study of patients with XLP has provided a vista for viewing a broad spectrum of diseases that occur in many other individuals who clearly do not have XLP. Many patients with primary immune deficiency diseases suffer from defects which render them unable to sustain low numbers of EBV‐infected B cells or, alternatively, immune regulatory disturbances are triggered by EBV infection. Immunoprophylaxis with immunoglobulin‐containing neutralizing antibodies and the use of a vaccine when it becomes available will probably benefit the patients who are EBV‐seronegative. Also, bone marrow transplantation can restore immunity and prevent EBV‐induced non‐Hodgkin's lymphoma (NHL). Cotton‐top tamarins and mice with severe combined immune deficiency are excellent models for studying EBV‐induced NHL in immunodeficient patients.
Post‐transplant lymphoproliferative disease in cardiac transplant patients receiving OKT3 therapy
Authors: Ratkovec Ranae M. , O'Connell John B. , Bristow Michael R. , Jones Kent W. , Gay William A. , Rasmussen Linda G. , Renlund Dale G. , Program The UTAH Cardiac Transplant
Published: September 2024

An increased incidence of malignancy has been observed in recipients of organ transplantation, with a large proportion of the tumors comprised of lymphoproliferative disorders. A recent report implicating OKT3 in the development of a marked increase in the frequency of lymphoma has stimulated controversy regarding the safety of OKT3 in organ transplantation. To determine the incidence of post‐transplant lymphoproliferative disorder (PTLD) in a large cohort of patients receiving OKT3, and to determine if a correlation exists between the dose of OKT3 and the development of PTLD, we reviewed the clinical course of 305 cardiac transplant recipients given OKT3. The indication for OKT3 therapy was rejection prophylaxis in 246 (80.7%), treatment of acute rejection in 11 (3.6%), or for both indications in 48 (15.7%). The mean follow‐up period was 27.7 ± 18 months. A diagnosis of post‐transplant lymphoproliferative disorder was made at 16.3 ± 14 months post‐transplantation in 4 (1.3%) of the 305 patients. In patients with PTLD, the total OKT3 dose was similar to those without PTLD (m ± sem, 78.8 mg ± 14.2 vs. 74.7 mg ± 1.4; p = NS). Furthermore, the incidence of PTLD in the 69 patients who received more than 75 mg of OKT3 was not significantly different when compared with the 236 patients who received ≤ 75 mg of OKT3 (2.85% vs. 0.8%; p = NS). Of the 4 patients who developed a PTLD, 3 had an abdominal immunoblastic (large cell) lymphoma and died within 6 months of diagnosis. The patient with a polymorphic lymphoid proliferation in the lung was in clinical remission; however, he died from sepsis 10 months after the diagnosis of PTLD. At autopsy, he was found to have immunoblastic lymphoma. We conclude that, in a large population of cardiac transplant patients receiving OKT3, the incidence of post‐transplant lymphoproliferative disorders is low (1.3%) and that OKT3 therapy alone does not account for an increase in the prevalence of PTLD, as previously reported.
Induction of interleukin‐6 and interleukin‐10 by the OKT3 monoclonal antibody: Possible relevance to posttransplant lymphoproliferative disorders
Authors: Goldman Michel , Gérard Catherine , Abramowicz Daniel , Schandené Liliane , Durez Patrick , De Pauw Luc , Kinnaert Paul , Vereerstraeten Pierre , Velu Thierry
Published: September 2024

Before exerting its potent immunosuppressive properties, the OKT3 monoclonal antibody induces the activation of T cells and monocytic cells. In this paper, we present evidence that this activation step results in the release of interleukin‐6 (IL‐6) and interleukin‐10 (IL‐10). Since IL‐6 favors the outgrowth of Epstein‐Barr virus (EBV)‐infected cells and IL‐10 impairs the T‐cell defences against EBV, we suggest that these cytokines could be involved in the pathogenesis of EBV‐associated lymphoproliferative disorders developing in transplant patients receiving multiple courses of OKT3.
Donor criteria for liver transplantation: A comparative study of the effects of donor liver selection
Authors: Pruim Jan , TenVergert Elisabeth M. , van Andringa de Kempenaer Martinus G. , Bonsel Gouke J. , Slooff Maarten J. H.
Published: September 2024

In a case‐control study, the relevance of donor parameters used for donor selection on final transplant outcome was studied. Two matched groups of 17 donors were created: one group of ‘ideal’ donors and a control group not meeting the criteria for ‘ideal’ donors. Recipients of livers from both groups were matched for liver disease, Karnovskyscore, Child‐Pugh sumscore, and preservation solution used (EuroCollins or UW‐solution). The effect of the donor liver selection criteria on transplant outcome was measured by comparing the following parameters in both groups: intra‐operative blood loss, the ALT in the first 3 days after grafting, occurrence of major postoperative complications, ICU‐stay and graft and patient survival. Although, in the control group, bacterial infections and abdominal hemorrhages occurred more frequently, while leakage from the bile duct anastomosis was more prevalent in the ‘ideal’ group, the results for the other parameters studied indicated no statistical differences between the two groups. It was concluded that adherence to strict selection criteria for liver donors did not improve final transplant outcome. However, use of less strict criteria possibly may cause a more complicated course directly after transplantation.
Tranexamic acid reduces blood loss during orthotopic liver transplantation
Authors: Yassen Khaled , Bellamy Mark C. , Sadek Sami A. , Webster Nigel R.
Published: September 2024

We have studied bleeding and fibrinolysis in 20 patients undergoing orthotopic liver transplantation. Ten were randomized to receive tranexamic acid during the anhepatic (stage II) and reperfusion (stage III) phases as prophylaxis against fibrinolysis. The other 10 patients acted as controls. Overall blood loss was less (p<0.05) and abnormal clot lysis (defined as a dilute whole blood clot lysis time of less than 2 hours) was seen less frequently (p=0.0015) in the treatment group as compared with the control group. Clot formation rate as assessed by thrombclastography (TEG) was also significantly belter in the treatment group (p < 0.05). Blood product requirements were reduced in the treatment group as compared with the controls but this difference failed to reach significance in this study. Tranexamic acid has an important role to play in the prophylaxis of major hemorrhage in patients undergoing liver transplantation.
HLA B and DR mismatching, a risk factor for cytomegalovirus infection after renal transplantation
Authors: Pouteil‐Noble Claire , Ecochard René , Betuel Hervé , Dubernard Jean‐Michel , Aymard Michèle , Touralne Jean‐Louis
Published: September 2024

The aim of the study was to analyze the influence of HLA A, B, DR matching on the incidence and on the severity of cytomegalovirus (CMV) infection in renal transplantation. 191 consecutive cadaveric‐renal‐transplant patients were checked for CMV infection once a week for the 1st month and then on day 90, 180, and then every 6 months. CMV infection was defined virologically by a positive virus isolation in blood or in urine or a fourfold increase in specific anti‐CM V IgG or the detection of specific anti‐CMV IgM. The incidence of CMV infection was 60.7%. A poor HLA B + DR matching, i.e. HLA B + DR≤2 matching, significantly influenced the incidence of CMV infection since, among the 153 patients with a HLA B+DR≤2 matching, 65% were infected as compared to 44% of the 32 patients with a HLA B + DR>2 matching (p< 0.037). In a multivariate analysis, this association remained significant even after taking into account risk factors likely to be linked with CMV infection and its severity, such as the age of the recipient and of the donor, the donor and the recipient CMV pretransplant serologies, the degree of anti‐HLA immunization, the number of transplantations – first or iterative – the type of immunosuppressive therapy and the occurrence of rejection episodes before CMV infection. No influence of HLA B + DR matching was observed on the occurrence of rejection before CMV infection. The seropositivity of the recipient was also associated with an increased incidence of CMV infection (p< 0.005) and a model with two variables (HLA B + DR matching and recipient serology) could be proposed to predict the occurrence of CMV infection. The risk of CMV infection was 4.02 times as high in seropositive recipients with a HLA B + DR ≤2 matching than in seronegative patients with a HLA B + DR>2 matching, whatever the donor serology was. A good HLA B + DR > 2 matching could be proposed as an efficient means first to prevent CMV infection and therefore to decrease subsequent acute rejection episodes and chronic rejection.
Chronic vascular rejection and hyperlipoproteinemia in renal transplant patients
Authors: Dimény Emöke , Fellström Bengt , Larsson Erik , Tufveson Gunnar , Lithell Hans
Published: September 2024

The lipoprotein pattern was investigated in 46 renal transplant recipients with histologically confirmed chronic vascular rejection (CVR) as an approach to studying its role for development and progression of CVR or transplant atherosclerosis. Renal transplant patients without evidence of chronic rejection and other renal patients with varying degrees of renal function impairment and/or proteinuria served as controls. Patients with CVR had more advanced lipoprotein disturbances as compared to patients with stable graft function. CVR patients had higher VLDL, LDL and total cholesterol and triglyceride levels, a more triglyceride‐rich VLDL and LDL fraction and a more atherogenic distribution of the lipoproteins as compared to control renal transplant patients. Impaired renal function and proteinuria, which are common in CVR, explain these lipid abnormalities only in part, since patients with CVR constitute a different cluster in this respect when compared with other patients with renal dysfunction. It is concluded that lipoprotein abnormalities and oxidative modification may play a crucial role for a growth factor‐driven progression of CVR.
Early vascular complications of renal transplantation
Authors: van Roys Stefaan F. S. , van der Vliet J. Adam , Hoitsma Andrles J. , Reinaerts Harry H. M. , Buskens Frans G. M.
Published: September 2024

Early vascular complications were studied in 1300 consecutive renal transplantations performed in 1065 patients in a single institution. Vascular complications requiring surgical reintervention in the first 10 postoperative days occurred in 68 patients (5.2%). There were 33 instances of graft vessel thrombosis, 6 anastomotic and 30 extra‐anastomotic hemorrhages. The overall mortality as a result of these complications was 0.08%. Transplant nephrectomies were performed in 45/68 cases (66%), accounting for 3.5% graft loss of the complete series. Multiple renal arteries and veins, their reconstruction and multiple arterial or venous anastomoses were not associated with an increased chance of graft loss. The absence of an aortic patch, renal artery and vein lesions and extravascular graft anomalies did not exert a negative influence on the graft outcome. Intraoperative events leading to complete or partial revision of the venous anastomosis or repair of a troublesome venous hemorrhage proved to be associated with the occurrence of vascular complications requiring surgical reintervention. Vascular complications ensued most frequently when size discrepancy of graft and recipient was present.
Lymphocyte‐endothelial interactions and tolerance induction
Authors: Orosz Charles G.
Published: September 2024

It is now apparent that mAb to a growing number of intracellular adhesion molecules can not only promote allograft survival but also stimulate allogeneic tolerance in rodent transplant models. Intercellular adhesion molecules are responsible for a variety of immune functions, including proper lymphocyte migration and productive lymphocyte activation. Vascular endothelial cells have carefully regulated expression of adhesion molecules, which they use to control the homeostatic and inflammatory patterns of lymphocyte trafficking. This leads to the hypothesis that an impairment of lymphocyte trafficking by anti‐adhesion molecule mAb results in prolonged allograft survival and/or allogeneic tolerance. In the broader view, endothelial cells belong to a small group of cell types that can serve as APC to T cells, and this APC function is strongly influenced by adhesion molecules. This leads to the hypothesis that an impairment of APC function by anti‐adhesion molecule mAb results in allograft survival and allogeneic tolerance. The two hypotheses are not mutually exclusive, and both need to be tested. In general, however, it appears that intracellular adhesion molecules are intimately involved not only in the mechanisms of graft‐induced alloactivation and but also in the mechanisms of allogeneic tolerance induction by virtue of their essential role in lymphocyte‐endothelial and/or lymphocyte‐APC interactions.
Steroid withdrawal after renal transplantation
Authors: Schulak James A. , Hricik Donald E.
Published: September 2024

Corticosteroid therapy following renal transplantation has been a mainstay in immunosuppression for three decades despite the numeroud side effects associated with its use. Because of these, steroid‐free immunosuppression has been a persisting goal in clinical transplantation. We have demonstrated that early (within the 1st week of transplantation) steroid withdrawal in renal transplantation, although safe as measured by ultimate graft survival, is associated with an increased rate of severe rejection episodes. Late steroid withdrawal (6 months or later). however, could be successfully achieved in the majority of patients when maintenance therapy consisted of azathioprine and cyclosporine. Immunologic and hematologic consequences included rejection episodes (25%). decreased cyclosporine requirement (higher levels with lower doses), and leukopenia that required azathioprine dosage reduction. More importantly, metabolic consequences included reduced incidence of hypertension, improved glycemic control, and reduced total levels of serum lipids. In regard to the latter, however, nondiabetic patients experienced a rise in their total/HDL cholesterol ratios because of a selective decrease in HDL cholesterol while diabetic patients experienced significant lowering of all lipid levels. All patients looked and felt better after elimination of chronic steroid therapy. The long‐term consequences of steroid‐free cyclosporine‐based immunosuppression on graft survival in renal transplantation are not yet clear.
Role of changes in the vascular endothelium in chronic inflammation
Authors: Jutila Mark A.
Published: September 2024

The recruitment and activation of lymphoid effector cells into grafted tissue is central to the chronic rejection process. The endothelial cells lining inflamed vessels appear to be important in initiating and perpetuating these events through their expression of adhesion proteins for circulating leukocytes, as well as through their production of cytokines and chemokines to attract leukocytes into the inflamed tissues and to activate effector functions. Described here is our current understanding of the role of the vascular endothelium in leukocyte recruitment into inflamed tissues. A model of leukocyte‐endothelial cell interactions is outlined.
Functional and histologic characteristics of chronic renal allograft rejection
Authors: Paul Leendert C.
Published: September 2024

Chronic allograft rejection very probably results from the inter‐actions between allogeneic immune injury, tissue reactions in response to injury, and local intragraft hemodynamic adaptations to the progressive loss of functioning organ mass. We examined each of these components in a rat model of chronic renal allograft rejection. Although immunofluorescence studies of renal allografts with chronic rejection usually reveal nondiagnostic patterns of immunoglobulin deposits, we found, using Western blot analysis, donor‐directed antibodies against novel glomerular basement membrane antigens in the sera of animals with chronic rejection‐associated transplant glomerulopathy. Stop‐flow micropuncture studies have shown that the glomerular capillary pressure in transplanted kidneys resembles that of the donor strain kidney in response to renal ablation. Northern blots for growth factor transcripts showed induced expression of mRNA levels for various growth factors in long‐surviving renal transplants. Reduction in intraglomerular pressure was associated with increased recipient survival, preservation of renal function, decreased amounts of proteinuria, and less severe structural lesions in the glomeruli. We conclude that the glomerular lesions of chronic rejection may arise from a combination of antiglomerular (allo) antibodies in conjunction with increased intraglomerular pressures and local production of growth factors. The vascular lesions and interstitial scarring of chronic rejection. may arise from previous episodes of graft vasculitis and interstitial inflammation, respectively.
Chronic rejection in renal transplant recipients – Risk factors and correlates
Authors: Matas Arthur
Published: September 2024

To effectively study risk factors, a uniform definition of chronic rejection must be agreed upon. The definition must describe a typical clinical course ‐ e.g., gradual deterioration in graft function starting at least 3 months post‐transplant and lasting at least 6 months in combination with a characteristic biopsy. Numerous kidney transplant studies indicate that an acute rejection episode is an important predictor of 1‐year graft survival and half‐life (the time it takes for half the grafts that survive the 1st year to subsequently fail). However, in each of these studies there are multiple potential causes of graft loss ‐ acute rejection, chronic rejection, patient death, and recurrent disease. We have tried to eliminate this problem by studying patients with biopsyor nephrectomy‐proven chronic rejection. In a univariate analysis we found that an acute rejection episode significantly increased the risk of developing biopsy‐proven chronic rejection (p<0.001). Risk was higher in patients with more than one acute rejection episode and in patients whose rejection episode occurred more than 60 days after transplant. In a separate multivariate analysis, we studied the impact of the following variables on the incidence of biopsy‐proven chronic rejection: transplant number (first or retransplant), age at transplant (over 18, 18 to 50 years old, under 50), gender, HLA‐ABDR match, peak and transplant panel reactive antibody, number of acute rejection episodes, infection, donor age, and cyclosporine (CSA) dose at 1 year (less than 5 mg/kg versus more than 5 mg/kg). Individual analyses were carried out for recipients of cadaver grafts and living‐related donor grafts. For both groups, the most important variable was acute rejection; other significant variables were infection and CSA dose at 1 year. Other factors may be important in the development or prevention of chronic rejection. Noncompliance, for one, appears to be associated with an increased incidence of chronic rejection. Second, some patients develop anti‐HLA antibodies following transplant; reports indicate that these patients experience increased late graft loss. Third, some patients with acute rejection subsequently develop donor antigen specific hyporesponsiveness; these patients have a low incidence of chronic rejection.
Rapid detection of cytomegalovirus antigen on alveolar cells in bronchoalveolar fluid from transplant patients with cytomegalovirus pneumonia
Authors: Heurlin Nadja , Markling Lola , Barkholt Lisbeth , Lönnqvist Berit , Andersson Jan , Ringdén Olle
Published: September 2024

Cytomegalovirus‐specific mouse monoclonal antibodies and immunomagnetic beads conjugated with sheep anti‐mouse immunglobulin G were used to screen for cytomegalovirus (CMV) antigen expressed on the surface of alveolar cells in bronchoalveolar lavage (BAL) fluid from 23 transplant recipients with interstitial pneumonia. The beads formed rosettes around the cells when CMV antigen was present on the cell surface. Results could be evaluated by light microscopy within 2 hours of receiving the specimen. Cells in BAL fluid obtained from 15 immunocompetent individuals served as controls. Cytomegalovirus antigen was expressed on the surface of the alveolar cells from 12 transplant recipients and detected by this method as rosette formation on 1‐8% of the cells. CMV was isolated from culture of cells in BAL fluid and blood from all these patients except 1, while intracellular CMV antigen was detected by monoclonal antibodies and immunofluorescence in 3 only. Serological changes, indicating an active CMV infection, were present in 11/12 patients. One patient with a CMV pneumonia, later confirmed by autopsy, failed to respond with any antibody titer. No rosette formation occurred on alveolar cells from any of the 15 immunocompetent controls. Thus, the method studied appears to be a valuable complement to other diagnostic methods for CMV pneumonia in transplant recipients. When correlated with the isolation of CMV from culture, the sensitivity was 100% and specificity 92%.
Pre‐emptive renal transplantation in children: Report of the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS)
Authors: Fine Richard N. , Tejani Amir , Sullivan E. Kenneth
Published: September 2024

Of 2213 primary transplants reported to NAPRTCS between 1/1/87 and 10/31/92, 581 (26.3%) were performed without prior dialysis. The rate of pre‐emptive transplantation (PET) differed by donor source, 35.7% LD and 16.1% CD (p<0.001); gender, 29.6% male and 21.1% female (p<0.001); race, 30.1% white, 16.1% black, 19.5% hispanic, and 20.2% other (p<0.001); recipient age, 0‐1 yr 18.7%, 2‐5 yr 27.9%, 6‐12 yr 30.5%, and 13‐17 yr 22.8% (p<0.001). The graft survival rate was significantly better for both the LD (p<0.01) and CD (p=0.01) grafts in the pre‐emptive group; however, the differences were not significant after adjustment for other variables. The major reasons for pre‐emptive transplantation were the parents' desire to avoid dialysis and the recommendation of the nephrologist/surgeon. The data indicate that preemptive transplantation does not adversely impact on transplant outcome and that the desire to avoid dialysis is the primary motivating factor.
Soluble interleukin‐2 receptor monitoring during bacterial and viral infections in liver transplant recipients: A comparative evaluation1
Authors: Rossi Stephen J. , Schroeder Timothy J. , Muth Karen L. , Hanto Douglas W. , Balistreri William F. , Ryckman Frederick C.
Published: September 2024

We evaluated the significance of serial sIL‐2R serum levels as a differential marker of immune activation during bacterial versus viral infections in liver transplant recipients. A comparative evaluation of sIL‐ 2R levels was performed in 76 liver transplant recipients (51 pediatric and 27 adult) during bacterial versus viral infections at 7 days prior to infection diagnosis (DAY‐7), the day of diagnosis (DAY 0), peak sIL‐2R level and at the end of therapy (END). There were no significant elevations at any time point during bacterial infections in either adult or pediatric transplant recipients. However, adult recipients demonstrated significant elevations during viral infections when comparing DAY‐7 to PEAK (3840±830 vs 7225±2814 p=0.03), with PEAK levels significantly higher during viral versus bacterial infections in this population (7225±2814 vs 4195±1819). Pediatric recipients demonstrated similar increases in SIL‐2R serum levels during viral infections from DAY‐7 to PEAK (4932±887 vs 11323±2794 p=0.0012). Significant decreases from PEAK to END were noted during viral infections in both adult and pediatric recipients (72252814 vs 29111376 p=0.01 and 11323±2794 vs 5214±2403 p= 0.006). Pediatric recipients had higher mean sIL‐2R levels than adult recipients at all time points during viral infections. In conclusion, significant elevations in mean sIL‐2R serum levels were observed during viral but not bacterial infections in pediatric and adult liver transplant recipients. This suggests that serial sIL‐2R monitoring is a valuable immunologic marker of viral pathogenesis and may be useful in monitoring the progression of viral infections as well as response to antiviral therapy.
Incidence of vascular complications in kidney transplantation: Is there any interference with the nature of the perfusion solution?
Authors: Benoit G. , Jaber N. , Moukarzel M. , Douguet D. , Bensadoun H. , Blanchet P. , Jardin A. , Charpentier B.
Published: September 2024

Two non‐randomized groups of 100 kidney transplants each were compared in relation to the flush‐out solution used. The two groups were similar with the exceptions of the number of multiple artery kidneys and the proportion of kidneys procured in our center. The rate of vascular complications such as arterial venous thrombosis and renal artery stenosis. was higher in the Eurocollins (19) group than in the UW group (4) p<0.01, even if the multiple artery kidneys are excluded. These results need to be confirmed by a randomized study but it is clear that the use of the UW solution leads to a better arterial flow with fewer vascular complications.
Mouse antibody‐coated lymphocytes during OKT3 therapy in liver transplantation
Authors: Broughan Thomas A. , Valenzuela Rafael , Escorcia Eduardo , Secic Michelle , Vogt David P.
Published: September 2024

Flow cytometry has been a technique in search of a use in transplantation. With each new monoclonal antibody, it has been hoped that the secrets of rejection would be unlocked. The usefulness of CD3+ T‐ lymphocyte counts to predict successful treatment of organ transplant rejection has been called into question. CD2+, CD3+, and mouse antibody‐coated CD3 lymphocytes were followed by flow cytometry in 44 liver transplant patients during OKT3 therapy for induction or rejection. CD3+ lymphocyte counts did not predict successful management of rejection by OKT3. When expressed as percentages of the total lymphocyte count, an increasing trend in CD2+ and mouse antibody‐coated CD3+ lymphocytes after day 7 of OKT3 therapy portended persistent or recurrent rejection within 2 months of treatment. It is uncertain if the increasing population of mouse antibody‐coated CD3 cells is due to an immune phenomen or decreased clearance by an ailing liver. Care should be taken when using CD3 lymphocyte counts as indicators of adequate OKT3 therapy in liver transplantation.
Preservation injury in clinical liver transplantation: Incidence and effect on rejection and survival
Authors: Katz Eliezer , Mor Eytan , Schwartz Myron E. , Theise Neil , Patel Truptil , Miller Charles M.
Published: September 2024

The distribution of the severity of preservation injury (PI), its association with acute early rejection, and its effect on graft and patient survival were examined in 151 patients transplanted between 9/88 and 12/91. PI was graded into mild, moderate and severe using prothrombin time (PT) on the 2nd POD and peak AST and ALT levels of the first 3 days after transplant. Of the 151 patients, 104 (68.8%) had minimal, 24 (15.9%) had moderate, and 23 (15.3%) had severe PI. The rate of early rejection, within 21 days after transplant, (54.8% vs 54.2% vs 52.2%) and its timing (10.0±0.5 vs 8.8±0.8 vs 8.9±1.4 days) as well as the incidence of steroid‐resistant rejection (21.4% vs 33% vs 30%) did not differ significantly among groups. Graft survival was significantly lower in the severe PI group than among patients with minimal PI at 3 months and 24 months (65.2% vs 86.2%; p<0.05 and 58.3% vs 82.7%; p<0.05, respectively). Patient survival at 3 and 24 months was similar among the groups (91.1% vs. 95.8% vs 86.9% and 81.9% vs 91.1% vs. 74.3%). We conclude that the cellular damage associated with preservation injury does not predispose to development of acute rejection.
The effect of rabbit antithymocyte serum (RATS) and OKT3 on peripheral blood mononuclear cell subsets following renal transplantation
Authors: Zaltzman Jeffrey S. , Cole Edward H. , Freedman John
Published: September 2024

Fifty‐five renal transplant recipients were studied prospectively for changes in monoclonal antibody‐defined mononuclear cell subsets (MCS) over the first 45 days posttransplant. Patients received induction. immunotherapy with either monoclonal OKT2(n=29) or polyclonal RATS (n=26) preparation. Sequential examinations showed characteristic patterns of MCS depletion, which differed according to the type of therapy received and which subset was examined. In general, induction therapy with RATS resulted in greater and more sustained reduction of most MCS than was seen with OKT3 therapy. In recipients who received OKT3 induction there was a correlation between allograft rejection and an increase in lymphocytes expressing pan‐T cell markers and in naturalkiller cells. In contrast, rejection episodes in patients receiving RATS were associated with increases in subpopulations of T cells including helper, inducer and suppressor/cytotoxic T‐cell subsets. There was no correlation of rejection with B cells or T‐cell activation markers. The different patterns of MCS depletion with different antilymphocyte preparations and the association between changes in different MCS and rejection warrant further investigation.
Should elderly donors be accepted in a live related renal transplant program?
Authors: Kumar Anant , Kumar R. Vijay , Srinadh Eddy S. , Bhandari Mahendra , Sharma Raj Kumar , Gupta Amit , Kher Vijay
Published: September 2024

It is a matter of concern that the elderly donor may have increased risks in the peri‐operative period due to age‐related changes in various organs. Nephrosclerosis, atherosclerosis and low GFR of an elderly kidney may portend a poor graft outcome. A retrospective analysis of our live related renal transplant program (from June 1989 to December 1993) revealed that 27 of the donors were above 60 years of age. 21 of the recipients have been followed up for more than 1 year. These patients. were compared with a cohort of 25 patients (donor age <45 years) with similar HLA match, immunosuppressive protocol, and follow‐up period more than 1 year. Graft survival at 1 year was 86% and 88% in the recipients from elderly and younger donors respectively; 1 patient in the control group died of fulminant sepsis. Mean follow‐up was 21.6 months in the study group and 22.8 months in the control group. Allograft function was evaluated by serum creatinine and differential GFR by Te DTPA scan. Serum creatinine (mg %) was 1.3±0.2 and 1.4±0.2 in the study group and 1.3±0.3, 1.2±0.3 in the control group at 3 and 12 months respectively. Glomerular filtration rate (ml/min) was 36.5±11.6 and 43.7±12.4 in the recipients from elderly donors whereas those from the younger donors had GFR (ml/min) of 40.6±9.6 and 49.6±14.2 at 3 and 12 months respectively. GFR continued to improve in both groups with follow‐up. There was no difference in incidence or severity of ATN in the two groups. Acute rejection (17:12) and infectious episodes (18:22) were comparable. The number of antihypertensive drugs requirement per patient was 2.27:1:7 in the two groups. There was no added morbidity in elderly donors in comparison to younger donors. In view of acute donor shortage it can be concluded that, if elderly donors are properly screened, they can be accepted for donation without increasing the risk to donor or graft outcome.
Increased incidence of rejection in patients with delayed graft function
Authors: Howard Richard J. , Pfaff William W. , Brunson Mathew E. , Scornik Juan C , Ramos Eleanor L. , Peterson John C. , Fennell Robert S. , Croker Byron P.
Published: September 2024

Because of the difficulties in diagnosing rejection in patients with delayed graft function, such patients were routinely biopsied 7‐10 days after kidney transplantation. We found histologic evidence of rejection in 48% of the cases during the 1st month posttransplant, a proportion that was significantly higher than in patients with immediate graft function. Furthermore, the 2‐year graft survival in patients with delayed graft function and rejection, but not in those without rejection, was significantly lower than in patients with immediate function. The results suggest that there is an association between delayed graft function and rejection and that rejection is the component responsible for the decreased graft survival previously reported for patients with delayed graft function.
Correlates of noncompliance among renal transplant recipients
Authors: Frazier Patricia A. , Davis‐Ali Susan H. , Dahl Karin E.
Published: September 2024

The purpose of this study was to identify variables that are associated with noncompliance among adult renal transplant recipients, including demographic characteristics, transplant‐related variables, and psychosocial factors. The measurement of noncompliance was improved by assessing noncompliant behaviors (i.e., noncompliance with medications and the follow‐up regimen) prior to the onset of complications and/or graft loss and by measuring compliance as a continuous rather than dichotomous variable. Two‐hundred‐and‐forty‐one renal transplant recipients completed the Beck Depression Inventory, the anxiety and hostility subscales of the Brief Symptom Inventory, the Multidimensional Health Locus of Control Scale, the Inventory of Socially Supportive Behaviors, the Coping Strategies Inventory, a measure of transplant‐related stressors, and self‐report measures of compliance with medications and the follow‐up regimen. Approximately half of our sample reported at least some degree of noncompliance. Recipients who were younger, female, unmarried, retransplanted, and with lower incomes tended to be noncompliant with medications (all p's<0.05). Recipients who were unmarried, low income, not insulin‐dependent, and with a longer time since transplant tended to be noncompliant with the follow‐up regimen. In addition, recipients who reported higher stress and more depression, who coped with stress by using avoidant coping strategies, and who believed that health outcomes are beyond their control were less compliant with both medications and follow‐up (all p's<0.05). Regression analyses revealed that stress was the strongest predictor of both medication and follow‐up compliance.