bluuebunny/crossref_metadata_2025 huggingface dataset:
Unrelated living donor kidney transplantation: A comparison with well‐matched cadaver grafts
Authors: Reding R. , Squifflet J. P. , Pirson Y. , Jamart J. , Alexandre G. P. J.
Published: September 2024

Since 1966 we have performed 16 renal transplants from unrelated living donors (ULD) (14 were “emotionally related”). The recipients were non‐diabetic, ABO‐compatible (mean age 39.3 yr) and had a negative T‐cell crossmatch with their donor. We compared their results with those of 16 recipients of cadaver donor kidneys, matched for age, sex, immunosuppressive regimen and year of transplant. In addition to the standard immunosuppressive regimen, 15 ULD recipients were given a 3‐d pre‐transplant course of ALG. All recipients were given pretransplant blood transfusions, 10 underwent thoracic duct drainage, 11 were splenectomized, and 4 received donor‐specific transfusions. The results of transplantation from poorly‐matched ULD were as good as those obtained with well‐matched cadaveric grafts, perhaps because of the better preparation of the ULD recipients.
OKT‐3 monoclonal antibody for severe acute renal allograft rejection
Authors: Roberts R. , Belitsky P. , Cohen A. , MacDonald A. S. , Gupta R.
Published: September 2024

We treated 12 renal transplant recipients (9 cadaveric and 3 1‐haploidentical) demonstrating severe rejection with OKT‐3 monoclonal antibody. Rejection was confirmed by fine needle aspirate (FNA) or needle biopsy, or both. All had initial immunosuppression induction with low dose oral cyclosporine (CyA) (10 mg/kg/d) and alternate‐day reducing dose prednisone. Of the 12 patients, 10 received OKT‐3 for steroid resistant rejection (SRR), and 2 as primary treatment for accelerated acute rejection (ARR). Eight of 10 SRR and 1 of 2 ARR responded initially. Four of 8 SRR responders had recurrent rejections within 5 d of discontinuing their OKT‐3: 2 responded to traditional high‐dose steroids, 2 required nephrectomy. Seven of 12 transplants (58%) still function after 5 to 10 months – 6 with SRR, 1 with ARR. In 3 of 4 SRR and 1 ARR who did not experience a recurrent rejection, azathioprine (AZA) had been added electively to CyA immediately on discontinuing the OKT‐3. Patients who did not respond to OKT‐3, or re‐rejected on discontinuing the OKT‐3, had histological evidence or interstitial hemorrhage and endothelial intimal reaction. A blastogenic reaction on FNA on completion of OKT‐3 favored recurrent rejection. Three of the first 4 patients had fulminant herpetic and fungal infections. Subsequent patients were treated prophylactically with oral acyclovir and mycostatin and had no further infection. We suggest that (1) OKT‐3 with antimicrobial prophylaxis is safe and effective for SRR, (2) needle biopsy and serial FNA may be predictive of response of recurrent rejections, (3) the addition of AZA to CyA on completion of OKT‐3 may prevent recurrent rejection.
The relevance of transplant aspiration cytology (TAC) for the clinical management of renal allograft recipients
Authors: Surachno S. , van Oers M. H. J. , Kox C. , Wilmink J. M.
Published: September 2024

To assess the relevance of transplant aspiration cytology (TAC) for the clinical management of renal allograft recipients we analyzed 250 TAC which were performed in 65 unselected renal allograft recipients in the first 2 to 3 wk after grafting. All patients were initially treated with cyclosporin A (4 mg/kg i.v. followed by 10–12 mg/kg orally) with or without low‐dose prednisolone (10 mg daily). From the 250 TAC performed, 196 samples were suitable for analysis. We compared the initial clinical diagnosis (ID) with the aspirate diagnosis (AD) and final clinical diagnosis (FD) which was established retrospectively on the basis of clinical signs and symptoms, laboratory investigations, radiological and other imaging techniques, response to therapeutic measures and in some cases histological picture. The AD was not considered at all in making the ID and FD. FD could be established with certainty in 167/196 cases. In 113/167, ID and AD were in accordance with FD; in 40/167 ID was incorrect while AD was in accordance with FD; in 7/167 ID was correct while AD was incorrect and, in 7/167, both ID and AD were incorrect. So, if AD was regarded as decisive in cases of discrepancy between ID and AD then in 40/54 cases a correct diagnosis and subsequent treatment could be given. In 14 cases AD was incorrect, further analysis shows that this could lead to unnecessary antirejection treatment in 7 cases only.
High‐density lipoprotein‐associated amyloid A protein after liver transplantation: Raised levels in serum and enhanced expression in hepatocytes during rejection
Authors: Maury C. P. J. , Höckerstedt K. , Lautenschlager I. , Scheinin T. M.
Published: September 2024

Serial measurements of high‐density lipoprotein‐associated serum amyloid A protein (SAA) concentrations were carried out in 9 consecutive patients following liver transplantation. On the basis of clinical findings and repeated fine‐needle aspiration biopsies of the transplants, 11 rejection episodes were diagnosed in these patients. SAA increased significantly during all 11 rejections: peak SAA values ranged from 55 to 265 mg/1 (median 165 mg/l; SAA in healthy control subjects < 5 mg/l, range < 5 to 15 mg/l). A weak positive correlation (rs = 0.58) was found between peak cytology scores and peak SAA levels during rejections. Ten out of the 11 rejections were associated with a concentration of SAA > 80 mg/l. With this cut‐off level, and excluding the surgery‐induced SAA peak occurring on post‐transplant day 2 or 3, there were 2 false positive SAA readings with respect to rejection; 1 of these was associated with a severe septic complication. Immunoperoxidase staining for SAA of the transplant aspiration biopsies showed increased intensity in the hepatocytes during rejection episodes, suggesting that the rejection‐associated increase in SAA production occurs in the graft. The results suggest that serial measurements of SAA may be a useful, noninvasive aid in the detection of acute graft rejection episodes after liver transplantation.
Successful sequential liver‐kidney transplantation in patients with preformed lymphocytotoxic antibodies
Authors: Fung John J. , Makowka Leonard , Griffin Marian , Duquesnoy Reno J. , Tsakis Andreas , Sfarzl Thomas E.
Published: September 2024

Two patients with preformed lymphocytotoxic antibodies and strongly positive pretransplant crossmatches were transplanted with sequential liver and renal allografts from single donors. Following revascularization of the liver, demonstrable falls in the preformed lymphocytotoxic antibody levels were noted and subsequent crossmatches against the donor were negative. The renal allografts from the respective donors were transplanted without difficulty and in 2 instances both organs functioned well immediately. In instances when allograft rejection occurred in the post‐transplant period, successful reversal was accomplished by immunotherapy with OKT3 monoclonal anti‐human T cell antibody. The artifact caused by the use of OKT3 in crossmatches was also investigated. A sustained negative donor‐specific crossmatch was noted during the posttransplant period as well as a persistent decline in the percent reactive antibody levels.
Comparison of cyclosporine levels in samples obtained from central venous catheter with samples from peripheral sites in allogeneic bone marrow transplantation: Implications in therapeutic monitoring of cyclosporine
Authors: Soto J. , Alsar M. J. , Avendaño C. , Sacristan J. A. , Zubizarreta A.
Published: September 2024

Routine use of a central venous catheter (CVC) is frequent in patients receiving an allogeneic bone marrow transplantation; cyclosporine (CyA) is used in the prevention of graft‐versus‐host disease in these patients. In this study we have compared the concentrations of CyA assayed from samples obtained simultaneously from CVC and from peripheral veins. This study conducted in 11 bone marrow‐transplanted patients using a CVC made of silicone in 4 of them and CVCs made of polyurcthane in the rest. The determination of CyA parent was performed by radioimmunoassay and that of CyA parent plus metabolites by fluorescence polarization immunoassay. CyA parent concentrations were significatively higher in samples from CVC than in samples from peripheral veins (470 and 184 ng/ml respectively). Similar findings were obtained when CyA parent plus metabolites were measured (829 and 506 ng/ml respectively). The correlation between all the samples from CVC and those from peripheral vein was r = 0.19 for CyA parent, and r = 0.30 for CyA parent plus metabolites, without significance (NS). Due to the great difference found between CyA concentrations in samples from CVC and peripheral veins, and to their poor correlation, it is not possible to apply a “conversion factor” to determine concentrations of peripheral veins through CVC concentrations. Routine monitoring of whole blood levels of samples obtained from peripheral vein is recommended to prevent to occurrence of immunosuppressive inefficacy.
Cytomegalovirus appendicitis in a liver transplant recipient
Authors: Perkal Melissa F. , Haber Marian M. , Nelson Kelly , Marks William H. , Reuben Adrian , West A. Brian , Lorber Marc I.
Published: September 2024

Cytomegalovirus has been documented as one of the most significant causes of morbidity and mortality following organ transplantation, and colonic involvement has become an increasingly well recognized problem. Appendicitis, however, has been uncommonly reported among these patients. A 37–year‐old male developed fever with associated right‐sided rebound abdominal tenderness approximately 2 months following orthotopic liver transplantation. He underwent operation where an inflamed appendix was identified. The histologic examination of the removed specimen revealed perivascular foci of inflammation, largely lymphocytic, in association with cells containing pathognomonic nuclear and cytoplasmic CMV inclusions. This patient suffering CMV appendicitis represents the first documented incident among solid organ transplant recipients, and 1 of only 6 patients identified in the literature. Although an uncommon disease entity, CMV appendicitis should be considered a component of the differential diagnosis among organ transplant recipients with abdominal complaints.
Severe gingival overgrowth associated with cyclosporine and verapamil therapy
Authors: Perkal Melissa F. , Gulino Dante , Delfini Ronald H. , Siegel Norman J. , Gaudio Karen , Marks William H. , Lorber Marc I.
Published: September 2024

Gingival overgrowth has ranged in frequency between 3–30% among the neuroectodermal side‐effects of cyclosporine (CsA) administration to organ transplant recipients. This problem has usually been controlled successfully with CsA dose reduction, but operative gingivectomy has occasionally been required. We report the association of CsA gingival hyperplasia exacerbated by concomitant verapamil antihypertensive therapy in a cadaveric renal transplant recipient. The patient underwent renal transplantation at age 18: mild gingival hyperplasia was noted 6 months later that became severe approximately 1 year posttransplant. The advanced gingival disease required periodontal operative intervention including 4 quadrant gingivectomy with gingivoplasty, debridement and root planing. Despite an excellent early result, gingival regrowth was severe within 2.5 months following the initial operative procedure. Reoperation became necessary when the lesion progressed to a level nearly identical to that observed preoperatively. Verapamil was discontinued with a change to atenolol‐based antihypertensive therapy prior to the 2nd operative intervention, and the patient has remained stable without significant gingival regrowth for greater than 1 yr. Possible underlying mechanisms of CsA‐associated gingival hyperplasia and a recommended therapeutic strategy for these patients are discussed.
Monitoring renal allograft rejection with duplex sonography
Authors: London Nicholas J. , Aldoori Munther I. , Bates Jane A. , Lodge Virginia G. , Irving Henry C. , Giles Geoffrey R.
Published: September 2024

Thirty‐six renal allograft recipients were monitored by serial duplex Doppler ultrasound studies post‐transplant and during early rejection. A separate reproducibility study demonstrated no significant interor intra‐operator variability in measurements of resistive index of an interlobar artery (RI) (2.1% [1.5%] and 3.2% [2.3%] respectively, mean [standard error] of coefficients of variance). Twenty‐one patients had rejection within 3 weeks of transplantation. These grafts showed greater overall rises in the RI, from day 2 to day 5 post‐transplant, than the grafts which had no rejection. Eleven of the 21 patients required more than one course of methyl‐prednisolone for persistent or recurring rejection. These grafts had higher RI on the day rejection was diagnosed (81 [7.3], median [interquartile range]) compared with the remaining 10 patients (68.6 [8.7]). The 11 grafts with persistent rejection had higher RI (p< 0.005, Mann‐Whitney U‐test) on day 2 post‐transplant (76 [3.9]) compared with the 10 grafts successfully treated with a single course of methyl‐prednisolone (63.2 [10.9]). This study demonstrates that grafts with an RI of greater than 70 on day 2 post‐transplant are likely to have rejection requiring additional treatment (sensitivity —100%, specificity –80%). These patients may be candidates for earlier or alternative antirejection therapy.
Long‐term graft survival and renal function in cyclosporin‐treated renal allograft recipients: lack of evidence of nephrotoxicity
Authors: Snider J. , Francis D. M. A. , Kincaid‐Smith P. , Walker R. G.
Published: September 2024

Three‐hundred‐and‐thirty‐nine consecutive primary cadaveric renal allografts were studied retrospectively for evidence of long‐term nephrotoxicity of cyclosporin (CyA). A “triple” therapy regimen including CyA was compared to a historical “conventional” therapy group who received prednisolone and azathioprine only. Patients on “triple” therapy had a superior graft survival at 1 year (31% difference) which was still evident at 6 years (33% difference). Analysis of serial serum creatinine values revealed that renal function of surviving grafts remained stable over time and did not significantly differ between the “conventional” and “triple” therapy groups. Our results confirm and extend the findings reported in the literature that CyA retains its beneficial effects on graft survival in the long term and there is little evidence, based on sequential measures of renal function (serum creatinine), of progressive nephrotoxicity.
Successful paratopic pancreas transplantation: A report of three cases with venous portal drainage and enteric exocrine drainage
Authors: Ishitani Michael B. , Rosenlof Lynn K. , Hanks John B. , Pruett Timothy L.
Published: September 2024

Pancreatic transplantation is able to produce euglycemia in patients with Type I diabetes mellitus. Current surgical techniques utilize revascularization of the graft through the recipient iliac vessels and drainage of the exocrine pancreatic secretions through a duodenal conduit into the bladder. We describe a technique utilized in 3 patients whereby venous pancreatic drainage is into the portal venous circulation via the proximal splenic vein. The exocrine pancreatic secretions are drained into the proximal jejunum via a side‐to‐side donor duodenum to proximal small bowel anastomosis. Results and complications of this technique are presented. Potential short‐term and long‐term advantages and disadvantages of this technique are discussed. Our early experience suggests that paratopic pancreatic transplantation with venous drainage into the portal vein and exocrine drainage into the proximal jejunum is both feasible and desirable.
Functional studies on the human transplanted small intestine
Authors: Knutson L , Meurling S. , Wahlberg J. , Ewald O. , Hällgren R. , Tufveson G.
Published: September 2024

Intestinal transplantation is currently under development for treatment of short bowel syndrome. It was our purpose to examine the release of inflammatory mediators in a 1‐year‐old child with congenital aganglionosis following small intestinal transplantation (ligament of Treitz to colon; ileostomy). After obtaining institutional and parental consent, studies were performed at the 6th, 7th and 8th week after surgery and while the patient was receiving enteral nutrition (human breast milk). Prior to each investigation the ileal mucosa was examined endoscopically and biopsies were obtained. A 3‐cm segment of ileum was isolated between balloons and perfused with an isoosmolar solution at 2 ml/min at 37°C. Effluents were analyzed for: albumin, histamine, hyaluronan (hyaluronic acid), eosinophilic cationic protein (ECP) and PGE2. Although control values were unavailable in infants, data obtained from the adult jejunum served as control. Endoscopically the mucosa revealed loss of valvulae conniventes and progressive aphthous to deep mucosal ulcerations. Histologically this was detected as increased number of mononuclear cells, edema and fibrosis. After transplantation the appearance rate of histamine and ECP were low, but increased progressively. PGE2 was markedly increased at the start of the studies (5566 pg/cm/h compared to 11.7 ±3.0 in controls, mean ± SEM; n = 35), but did not profoundly increase further. Albumin and particularly hyaluronan, however, increased more than 30‐fold versus controls (21 420 pg/cm/h vs controls 669±46, n = 66 and 20 558 ng/cm/h vs controls 660±44, n = 66, respectively) in line with clinical deterioration. We conclude: 1) The technique for segmental intestinal perfusion can be used to monitor inflammatory mediators and mucosal leakage in a small bowel allograft. 2) The transplanted small intestine undergoes progressive ulceration associated with histological fibrosis; and, 3) The excessive accumulation of interstitial hyaluronan can influence water transport and thereby also intestinal circulation.
Acute polyradiculoneuritis associated with cytomegalovirus infection in renal transplantation
Authors: Pouteil‐Noble C. , Vial C. , Moreau T. , Aymard M. , Touraine J. L.
Published: September 2024

We report 3 cases of acute polyradiculoneuritis associated with an active cytomegalovirus (CMV) infection that occurred in 1 patient with a renal transplant and in 2 patients with simultaneous renal and pancreatic transplants. The time association with CMV infection was shown by the detection of positive viremia and viruria and by the presence of specific anti‐CMV IgM at the onset of the neurological signs. It was a recurrent infection in the 3 patients. One patient developed a recurrent polyradiculoneuritis which was associated with a relapse of the CMV infection. In all the patients, immune complexes were present together with a decrease in serum complement. All 3 patients underwent an immunosuppressive therapy, which consisted in a quadruple therapy: steroids, azathioprine, cyclosporine A, and a second treatment against a steroid‐resistant rejection, by either a monoclonal antibody (OK.T3) or rabbit antithymocyte globulin at the time of the polyneuritis. The electrophysiological analysis showed findings characteristic of a CMV polyneuropathy with mixed axonal and demyelinating lesions. Several factors might have triggered the neuropathogenicity of the CMV: the presence of specific anti‐CMV IgM involved in the formation of the immune complexes, the second course of globulin therapy, and the existence of a previous diabetic and uremic neuropathy. The clinical course was positive for the 3 patients undergoing ganciclovir therapy and without plasmapheresis, including the 2 patients who required assisted ventilation because of a respiratory failure and CMV pneumonitis.
Two masqueraders of transplant renal artery Stenosis (TRAS)
Authors: Alfrey E. J. , Smythe R. , Friedman A. , Meranze S. , Grossman R. A. , Perloff L J. , Naji A. , Barker C. F. , Dafoe D. C.
Published: September 2024

Seven patients presented after kidney transplantation with hypertension and creatinine elevation. Only 4 of 7 (57%) had a discernible bruit. Four had iliac stenosis proximal to the transplant renal artery and 3 had biopsy‐induced parechymal AV fistulae. All stenoses were successfully balloon‐dilated. Two of the A‐V fistulae were corrected with coil embolization. In general, treatment for both of these conditions stabilized the blood pressure, although most patients remained on some antihypertensive medication. The creatinine also stabilized after treatment. We believe patients with proximal iliac artery stenosis should be treated with balloon angioplasty and parenchymal A‐V fistula with coil embolization to allow stabilization of blood pressure and prevent further deterioration in renal function.
OKT3 reversal of biopsy‐proven allograft rejection occurring during Minnesota antilymphoblast globulin induction in the pediatric renal recipient
Authors: Bunchman Timothy E. , Kershaw David B. , Merion Robert M. , Ham John M. , Sedman Aileen B. , Kelsch Robert C. , Walter Mala B. , So Samuel K. S.
Published: September 2024

Allograft rejection occurring during induction with antilymphocyte agents is a rare event usually associated with a high risk of allograft loss. In two separate pediatric renal transplant programs. 6 children out of a total of 43 (14%) had biopsy‐proven rejection at 8 ±0.7 days of Minnesota antilymphoblast globulin (MALG) therapy. Conversion to OKT3 resulted in allograft survival in all 6. Of the 6 patients, none had complications of viral illness; yet 2 required a second course of OKT3 and subsequently did develop lymphoproliferative disease (LPD). The LPD in both patients subsided after a decrease in immunosuppression and intravenous acyclovir. Our data support the observation that allograft rejection during MALG induction is common. Rapid identification of rejection by use of an allograft biopsy permits salvage of the allograft with OKT3 therapy. Observation for potential complications of LPD is mandatory because the increase in immunosuppression places the patient at increased risk for viral or LPD complications.
Cyclosporine A and ursodeoxycholic acid interaction
Authors: Sharobeem Reda , Bacq Yannick , Furet Yves , Grezard Olivier , Nivet Hubert , Breteau Michel , Bagros Philippe , Lebranchu Yvon
Published: September 2024

Drug interactions with cyclosporine A(CsA) have frequently been reported. We used ursodeoxycholic acid (UDCA) as a symptomatic treatment for chronic active hepatitis C in a kidney transplanted patient with CsA monotherapy and we found such an interaction. After treatment with UDCA. gamma glutamyl transpeptidase (GGT), alkaline phosphatase (A. Ph) and alanine aminotransferase (ALAT) normalized and the patient felt well. Nevertheless, the CsA whole blood trough level increased from 150 ng/ml to 500 ng/ml. The daily dose was gradually decreased from 3.3 mg/kg to 1.76 mg/kg to obtain normal cyclosporinemia of about 150 ng/ml. This increase was mainly due to increased CsA absorption by improvement in cholestasis and by the direct effect of bile and bile salts on absorption of lipids and lipid soluble drugs.
Pancreas graft thrombosis: Prompt diagnosis and immediate thrombectomy or retransplantation
Authors: Fernandez‐Cruz Laureano , Gilabert Rosa , Sabater Luis , Saenz Alejandro , Astudillo Emillano
Published: September 2024

The cause of venous thrombosis in pancreas transplantation is generally not known and usually requires urgent pancreatectomy. In this report we describe 2 patients with pancreas graft thrombosis that occurred 2 and 6 days posttransplant in which surgical treatment was successful with immediate retransplantation in 1 case and portal venous thrombectomy in the other. When venous thrombosis is suspected, duplex‐Doppler ultrasonography should be performed and, with findings of well‐localized thrombi with absent venous flow in the presence of well‐preserved arterial supply, a thrombectomy should be attempted as the first choice; this operation should be performed in the presence of a suitable donor to offer retransplantation. Complication in the patient with pancreas retransplantation was one episode of kidney rejection; a urinary fistula arose in the patient in whom venous thrombectomy was performed. Both patients have kidney and pancreas grafts functioning after more than 1 and 2 years.
Effect of race on renal transplant outcome1
Authors: Hariharan Sundaram , Schroeder Timothy J. , First M. Roy
Published: September 2024

Renal transplant outcome was compared in whiles and blacks at a single center. All recipients transplanted between 1984 to 1991 were included in this study. White and black recipients were followed for a mean period of 37.6 (1–96) months. The age, sex, follow‐up period, immunosuppressive protocol, number of retransplants, HLA mismatches and etiology of renal disease were comparable in the two races. Overall graft survival was lower in black recipients (p = 0.0300). Graft survival in all cadaver (p = 0.0520) and primary cadaver (p = 0.1430) transplants was lower in blacks, though this was not statistically significant. Percentage of graft losses during the follow‐up was higher in black 53/108 (49%), than white recipients 82/257 (32%) (p = 0.002), as were cadaver graft losses due to rejection, 39/92 (42%) in blacks, 54/190 (28%) in whites (p = 0.02). There was no significant difference in graft losses due to rejection between races in the 1 yr post transplant, but there were significantly more graft losses after 1 yr in blacks 16/83 (19%) compared to whites (16/156 (10%) (p = 0.05). In cadaver grafts functioning for 6 months, subsequent survival was lower in black recipients (p = 0.0418). There was lower patient survival in blacks during the mean follow‐up period of 37.6 months (1–96). In conclusion, lower graft survival in blacks can be partially explained by fewer LRD transplants in black recipients. Persistent lower graft survival in all black recipients and significantly more losses due to rejection beyond 1 yr may be related to immunological differences, poor compliance, or a combination of both.
Erythromycin‐induced hearing loss in immunosuppressed transplant patients
Authors: Sternberg Richard I. , Baughman Robert P. , First M. Roy
Published: September 2024

The ototoxic effects of erythromycin are rare and appear to be associated with high dosage and altered renal function. Erythromycin, along with cyclosporine and azathioprine, immunosuppressive agents used in the transplant population, are extensively metabolized in the liver. We have retrospectively identified and describe 3 transplant recipients on immunosuppressive drugs ‐ furosemide and erythromycin ‐ who developed altered hepatic function and ototoxicity that was reversible with withdrawal of erythromycin.
Successful transplantation of an HPA‐la‐positive kidney in a recipient with anti‐HPA‐la antibodies
Authors: Surachno Janto , Berge Ineke ten , de Waal Leo , Goldschmeding Roel , Kr von dem Borne Albert
Published: September 2024

We report a successful transplantation of a kidney from a donor who was positive for the platelet bloodgroup HPA‐la into a HPA‐la‐negative recipient with preexisting anti‐HPA‐la antibodies. There occurred no thrombocytopenia nor purpura or other adverse effects. This observation suggests that an incompatibility for the HPA‐1 a alloantigen of platelets and endothelium need not be taken into account for matching of renal allografts.
Intensity of cytomegalovirus infection and frequency of acute heart allograft rejection in different categories of recipient/donor seropositivity
Authors: Koskinen Petri , Lemström Karl , Lautenschlager Irmeli , Krogerus Leena , Nieminen Markku S. , Häyry Pekka , Mattila Severi
Published: September 2024

A scoring table to quantify the intensity (average clinical score) of CMV infection in 54 heart allograft recipients was created. Scores were assigned on the basis of presence and severity of each particular clinical CMV‐related symptom or sign. In total, 35 CMV infections occurred in 54 patients (65%). Symptomatic CMV infection developed in 19 patients (35%) of which 7 were primary infections and 11 reactivations/reinfections. It was noticed that the seropositive donor had a significant influence on the outcome of the seronegative recipient: all 7 symptomatic primary infections occurred in recipients with seropositive allografts (p<0.05). The severity of infection in preoperalively seropositive recipients was significantly milder than that in seronegalivce recipients with seropositive donors (clinical score 2.25 vs. 5.43, respectively; p<0.05). In our study no correlation between CMV infection and acute biopsy proven rejection could be found.
Development of an index to predict posttransplant diabetes mellitus
Authors: Hathaway Donna K. , Tolley Elizabeth A. , Blakely Martin L. , Winsett Rebecca P. , Gaber A. Osama
Published: September 2024

The objectives of this study were to (1) identify risk factors and develop a prediction index for posttransplant diabetes mellitus (PTDM), (2) validate the risk factors and assess the index's predictive ability, and (3) modify the index to enhance its predictive accuracy. Preoperative variables included gender, race, age at transplantation, donor source, number of previous transplants, percentage of ideal body weight, family history of diabetes, and HLA type. Postoperative variables were glucose intolerance on postoperative days 0‐3 and 4‐7. Age, family history, glucose intolerance during postoperative d 4‐7, and specific HLA types were significant independent risk factors for PTDM. No independent effects of race, gender, or donor source were detected. The four independent risk factors produced an equation that accurately predicted PTDM in 77% of the patients. Specificity and negative predictive values reached 75% and 97%, respectively, for the population of men.
Immunologic monitoring during OKT3 therapy
Authors: Chatenoud Lucienne
Published: September 2024

The monoclonal antibody OKT3 is a potent immunosuppressant inducing both T‐cell depletion and antigenic modulation of the CD3/T‐cell receptor complex. CD3+ lymphocytes are cleared from the circulation within I hour of intravenous administration of OKT3. Periodic monitoring of remaining or reappearing CD3+ lymphocytes gauges the adequacy of OKT3 dosing and OKT3 consumption by anti‐OKT3 antibodies. The maximum acceptable concentration of CD3+ lymphocytes for maintaining the effectiveness of OKT3 therapy remains controversial due to variable sensitivity of the methods used. Intravenously administered OKT3 has a half‐life of approximately 18 hours and results in trough serum levels ranging from 500 to 1000 ng/ml in 3 to 4 days. The antibody response to OKT3 is oligoclonal, and both IgM and IgG antibodies to OKT3 may develop, showing restricted specificity; anti‐isotypic and/or anti‐idiotypic antibodies can be detected. The IgG anti‐idiotypic antibodies are the ones that neutralize the therapeutic activity of OKT3, and their specific detection involves the use of an immunofluorescence method that tests their ability to block the binding of OKT3 to normal T cells. The production of OKT3 antibodies has been shown to be affected by concomitantly administered immunosuppressive agents. Studies have demonstrated that OKT3 can be successfully reused in allograft recipients who do not present anti‐idiotypic blocking antibodies. The acute clinical syndrome regularly observed upon the first OKT3 injection is related to massive, although transient, release of several cytokines, which may be easily monitored with currently available radioimmunologic or immunoenzymatic tests.
Corticosteroid inhibition of the OKT3‐induced febrile and nephrotoxic responses during treatment of renal allograft rejection
Authors: Pescovitz Mark D. , Milgrom Martin L. , Leapman Stephen B. , Filo Ronald S.
Published: September 2024

The anti‐CD3 monoclonal antibody OKT3, highly effective at treating renal allograft rejection, is associated with a severe first‐dose reaction (FDR), two components of which are high fever and nephrotoxicity. This FDR is thought to be caused by lymphokines (LK) released following administration of OKT3. High‐dose corticosteroids (HDS) block LK release when used as part of a renal transplant OKT3 induction protocol. The effect of HDS on the febrile response and renal function of established transplants has not been well studied. We sought to lest the hypothesis that HDS would also block the FDR when OKT3 was used for the treatment of biopsy proven, acute cellular, renal allograft rejection. Forty‐two renal transplant recipients were retrospectively analyzed. Background immunosuppression consisted of prednisone, azathioprine (AZA), and cyclosporine (CyA). At the time of rejection, the oral prednisone dose was increased to 1–2 mg/kg/d. and both CyA and AZA doses were maintained at pre‐rcjection levels. HDS (>5 mg/kg. mean 24.9±6. n = 29) and low‐dose (LDS) (<5 mg/kg. mean 0.8±0.4, n = 13) groups were defined by the dose of intravenous steroids given at the time of OKT3 treatment. Premedication also included diphenhydramine and acetaminophen. Maximum temperature (Tmax) on days 1 and 2 after OKT3, total days febrile, the serum Creatinine (Cr) on days 0, 1.2, 3, 7, 14, and 28, and the frequency of anli‐OKT3 antibody formation and infections were compared using ANOVA or Chi Square. HDS decreased Tmax on day 1 (37.5 C vs. 38.3°C. p = 0.03) but not on day 2 (38.2 ± 1 vs. 38.6 ±0.7. p = 0.18). There was no effect on the number of days febrile (2.7 vs. 2.8. p = 0.8). The optimal steroid dose for complete suppression was about 25 mg/kg. The degree of suppression decreased with time over the interval of 0.5 to 5.75 hours indicating an optimal time of 1 hour or less. The protective effect of HDS on renal function was seen as a significantly reduced increase in Cr on day 2 after OKT3 (0.2±0.4 mg/dl vs. 0.8±0.9. p = 0.008) in the HDS group. The nephrotoxicity was not completely inhibited even at the highest doses of steroids. The rate of OKT3Ab formation was substantially less in the HDS group (10% vs. 38%, p=0.03). The incidence of infections requiring hospitalization was similar (38% vs. 46%, p = 0.62). No post‐OKT3 lymphomas occurred to date in this cohort. In conclusion. HDS at the time of OKT3 dulled the initial febrile response, decreased the nephrotoxicity, and protected against OKT3Ab formation. These advantages of HDS were achieved without a short term increase in the rate of infections or the appearance of lymphomas. The lack of complete suppression of the nephrotoxicity, even at dose of steroids that completely suppressed the febrile response, suggests that its mechanism might be different from that of the febrile response.
Primary failure of OKT3 antibody for rejection prophylaxis in orthotopic heart transplantation
Authors: Vigneswaran Wlckii T. , Rodeheffer Richard J. , Katzmann Jerry A. , Tazelaar Henry D. , McGregor Christopher G. A.
Published: September 2024

Cytolytic immunosuppression with OKT3 antibody has been shown to be highly effective in reducing the frequency of early allograft rejection in cardiac transplantation. Failure of OKT3 immunosuppression in the absence of anti‐OKT3 antibodies is a rare event, having been reported in only 3 patients who manifested predominantly vascular (humoral) rejection during OKT3 therapy. We report the first case of hemodynamically serious cellular rejection, without a demonstrable vascular rejection component, in a cardiac allograft recipient during OKT3 treatment. This case underscores the need to remain vigilant for signs of rejection in cardiac recipients during OKT3 immunosuppression.
Proliferation and activation of endomyocardium‐infiltrating lymphocytes derived from allografted human hearts require IL‐4
Authors: Marubayashi Mirian , Fernández‐Arcás Nieves , García‐Cózar Francisco J. , Montero Anastasio , Arizon Jose M. , Concha Manuel , Peña José , Santamaría Manuel
Published: September 2024

The regulatory mechanisms implicated in the development of human allograft rejection are still poorly understood and further studies are required for a better understanding of rejection events. We have studied the capacity of endomyocardium‐infiltrating lymphocytes (EIL) to produce IL‐4 and its relation with rejection episodes. We have found that the IL‐4 production levels are closely related with histological rejection. Interestingly IL‐4 does not synergize with IL‐2 effects in the proliferative response in vitro. Indeed, addition of anli‐IL‐4‐nculralizing mAb to the cultures strongly inhibits T‐lymphocyte proliferation, even in the presence of rIL‐2. These findings clearly support an important contribution of IL‐4 to the regulation of allogeneic immune response leading to transplanted human heart rejection.
Risks of acquired renal cystic disease in long‐term renal transplant recipients: Report of one case and general review
Authors: Oliveras A. , Puig J. M. , Lloveras J. , Mir M. , Muriné A. , Aubia J. , Masramón J.
Published: September 2024

Acquired renal cystic disease (ARCD) is a pathological condition occurring in patients undergoing hemodialysis. While often asymptomatic, these patients may present serious complications such as pain, hematuria, renal enlargement, massive hemorrhage and development of renal cell carcinoma. It is known that renal transplantation (RT) may delay the progression of the acquired cysts or even make them regress. However, although rare, severe complications may occur, as is reported in this case of acute severe bleeding 5 years after RT.
Incidence of posttransplant lymphoproliferative disease in OKT3‐treated renal transplant recipients1
Authors: Anderson Patricia , Schroeder Timothy J. , Hariharan Sundaram , First M. Roy
Published: September 2024

Posttransplant lymphoproliferative disease (PTLPD) has been reported in solid organ transplant recipients since 1968. The development of this disorder has been related to the use of potent immunosuppressive therapy and infection with the Epstein‐Barr virus (EBV). In certain series, a high incidence of PTLPD has been reported following the use of the monoclonal antibody, OKT3, especially when used in high doses and/or repeated courses. A retrospective analysis was made of 189 kidney and kidney/pancreas transplant recipients treated with OKT3. Twenty‐six of these patients received more than one course of OKT3. Two cases of PTLPD occurred in these 189 patients. However, neither of these patients was in the retreatment or high‐dose OKT3 group. Consideration should be given to the use of prophylactic antiviral therapy in patients receiving potent immunosuppressive therapy, including OKT3, for induction or rejection.
Use of immune globulin to prevent symptomatic cytomegalovirus disease in transplant recipients ‐ A meta‐analysis
Authors: Glowacki L Shannon , Smaill Fiona M.
Published: September 2024

The objective of this meta‐analysis was to review the evidence for the use of immune globulin in the prevention of symptomatic cytomegalovirus (CMV) disease in transplant recipients. A computerized search of Medline from 1980 to October 1991 was conducted using the textword “cytomegalo:” and the subheading “prevention and control” for studies in all languages. Reference lists, a manual search of relevant literature and communication with internationally recognized experts were used to locate additional studies. Of the studies identified, 18 met the inclusion criteria (population: transplant recipients; intervention: immune globulin; outcome: symptomatic cytomegalovirus disease; study design: randomized controlled trial). The meta‐analysis of the 18 studies showed a reduction in the incidence of symptomatic CMV disease in the group receiving immune globulin as compared to the untreated group. The common odds ratio was 0.58 (95% C.I. 0.42 to 0.77). Analyses of combining trials by subgroups of polyvalent immune globulin, hyperimmune globulin, bone marrow recipients and solid organ recipients resulted in common odds ratios comparable to the overall common odds ratio. Common odds ratios for the trials reporting cytomegalovirus interstitial pneumonia, cytomegalovirus death, overall death and graft loss ranged from 0.47 to 0.69. Common odds ratios for the effect of immune globulin prophylaxis analyzed by pre‐transplant patient/donor cytomegalovirus antibody status ranged from 0.32 to 0.50. In conclusion, the use of immune globulin as passive immunization for the prevention of symptomatic cytomegalovirus disease in the transplant population is supported by this meta‐analysis. The response is similar in both bone marrow and solid organ transplant recipients. There appears to be no significant clinical advantage in the use of hyperimmune globulin over polyvalent immune globulin.
Orthotopic cardiac transplantation for dilated cardiomyopathy after allogeneic bone marrow transplantation
Authors: Ramrakha Punit S. , Marks David I. , O'Brien Stephen G. , Yacoub Magdi , Schofield John B. , Goldman John M.
Published: September 2024

We report the case of a 26‐year‐old man with acute myeloid leukemia (AML) who underwent bone marrow transplantation (BMT) from an HLA‐identical sibling‐donor when in first complete remission. He developed a dilated cardiomyopathy 9 months post‐BMT and subsequently underwent orthotopic heart transplantation. He remains in complete hematological remission more than 12 months after surgery with normal cardiac function and an excellent performance status. Although cardiac transplantation has been carried out for chemotherapy‐induced cardiomyopathy in cancer patients, to our knowledge cardiac transplantation following BMT has not been reported previously.
Quality of life after successful pancreas‐kidney transplantation
Authors: Esmatjes E. , Ricart M. J. , Fernández‐Cruz L. , Gonzalez‐Clemente J. M. , Sáenz A. , Astudillo E.
Published: September 2024

Quality of life assessment has emerged as an important approach to evaluate the effect of pancreas transplantation in diabetic patients with end‐stage renal failure (ESRD). The aim of this stuty was to evaluate the impact of the ESRD treatment modality on the quality of life in patients with Type I (insulin–dependent) diabetes mellitus. Thirty‐two patients of similar age, sex and diabetes duration, treated for more than 1 year with simultaneous kidney and pancreas transplantation (Group 1, n= 12), or kidney transplantation (Group 2, n= 10), or hemodialysis (Group 3, n= 10) were studied. Quality of life was assessed using a questionnaire (34 questions with 103 possible answers) including social (sickness pension, working capacity) and subjective (general health perception), index of Spizer and index of reintegration to normal life of Wood Dauphine) quality of life indicators, working capacity, as well as physical ability (Karnofsky index), sports training and sexual activity. Patients in Group 1 showed highest scores on general health perception (p=0.012), Karnofsky index (p = 0.076) and sexual activity (p = 0.026). There were no significant differences between groups on social index, as well as index of Spizer, index of reintegration to normal life and sport activity. Patients on hemodialysis treatment presented the lowest scores in all the items evaluated. In conclusion, in our experience simultaneous pancreas and kidney transplantation is the treatment modality that offers better quality of life to diabetic patients with ESRD; however, this does not translate into a higher socio‐labor yield.
Glomerular endothelial cell detachment in paired cadaver kidney transplants: Evidence that some cadaver donors have pre‐existing endothelial injury
Authors: Parmar Malvinder S. , Kjellstrand Carl M. , Solez Kim , Halloran Philip F.
Published: September 2024

Poor initial function is common in cadaveric renal transplantation, and is usually attributed to acute tubular necrosis (ATN) brought about by ischemia during harvesting/implantation. However, this is often an assumption rather than a specific diagnosis. Recently, in 4 kidneys from 2 cadaver donors, we found evidence of severe endothelial injury, prior to exposure to cyclosporine or other known endothelial toxins. The biopsies at the time of completion of the transplant revealed apparent loss of glomerular endothelial cells on light microscopy, corresponding on electron microscopy to shrinkage of the endothelial cells away from the basement membranes of the capillary loops. Extensive microvascular thrombi were present. All 4 grafts displayed impaired initial function, which partially recovered with time. The finding of these unusual lesions in both kidneys from each of 2 donors suggested donor factors, although the only factor common to both donors was massive brain disruption. Thus, in the differential diagnosis of poor initial function in kidneys transplanted from cadaver donors, one should consider renal endothelial injury, which could lead to microthrombus formation, abnormal vasomotion, and functional impairment in the transplant.
Pulsatile kidney perfusion for evaluation of high‐risk kidney donors safely expands the donor pool
Authors: Tesi Raymond J. , Elkhammas Elmahdl A. , Davies Elizabeth A. , Henry Mitchell L. , Ferguson Ronald M.
Published: September 2024

Pulsatile preservation of cadaveric kidney allografts allows effective organ preservation and the opportunity to obtain information about the quality of the organ during storage. The use of information obtained by measuring FLOW (ml/min) and renal resistance (mean perfusion pressure/FLOW(ml/min)) while kidneys are undergoing pulsatile perfusion offers quantitative data to determine suitability of an organ for transplant. This may be more accurate than the combination of demographic variables with past and current medical information that has been traditionally used to evaluate donor suitability. Wc have evaluated 82 kidneys that received a period of pulsatile preservation at our institution. Kidneys were from consecutive donors age ≥42 years and were stratified into three high risk groups: donor age ≥60 (48%), the presence of hypertension (52%), and IMPORT kidney (48%). All IMPORT kidneys were obtained through UNOS after the local center considered them unacceptable for transplant and none were 6‐antigen match organs. Kidneys were discarded if they failed to have a FLOW≥70 ml/min or RR≤0.4. Twelve kidneys (15%) failed to meet these criteria and were discarded. All 12 kidneys were from donors age ≥60 (p = 0.002). The average FLOW and RR of transplanted kidneys svas 103 ml/min and 0.3283 respectively. Six of 69 (8.6%) transplanted organs required dialysis (ATN). No pump parameters predicted the development of ATN although 5 of 6 kidneys were IMPORTs. Recipient outcome data, including 72‐hour urine output and day 10 serum Cr, were affected by organ risk group, but these did not impact on patient care. Overall 2‐year graft survival was 82%. Two year graft survival was 25% worse in IMPORT compared to LOCAL kidneys (p = 0.0105). Multivariate analysis to determine the risk of dialysis and the risk for graft loss identified IMPORT kidney as the single independent variable. Wc conclude that the use of pulsatile perfusion parameters allows safe selection of kidneys from high‐risk CAD donors with a ATN rate substantially below the national average without compromising patient outcome. Wc believe that these data demonstrate that the use of pump perfusion parameters to select organs for transplantation will allow safe utilization of the marginal CAD donor, especially as programs develop “non‐heart beating donor” protocols.
Can a diagnosis of renal allograft rejection be based on histology alone?
Authors: Midtvedt K. , Hartmanna A. , Sund S.
Published: September 2024

Acute renal allograft rejection is suspected by the clinician when the serum creatinine value increases in a patient for no other particular cause. A renal allograft biopsy may confirm the diagnosis. This report describes 2 patients with stable serum creatinine; however, protocol biopsy showed acute rejection changes according to the Banff criteria. No anti‐rejection treatment was started and their graft function remained stable for 6 months. These two cases focus on the fact that renal allograft rejection should first of all be regarded as a clinical diagnosis which could be substantiated by histological findings.