bluuebunny/crossref_metadata_2025 huggingface dataset:
Immunogenetic factors that may contribute to ethnic differences in renal allograft survival
Authors: Ward Frances E. , MacQueen J. Marilyn
Published: September 2024

In the United States, allocation of cadaveric kidneys is federally regulated and based on the concept of equal access to all patients, regardless of race, sex, age, or socioeconomic status. Nevertheless, it has been widely reported that African American patients with renal disease wait longer for kidney transplantation and, once transplanted, have poorer graft survival. We have assessed immunogenetic factors that may contribute to ethnic differences in allograft survival by examining the distributions of ABO blood groups, HLA antigens and haplotypes, percent reactive antibody (PRA), age, and gender in our local patient population. Approximately 62% of patients at our transplant center waiting for renal transplantation are African American; 39% are female. Age distribution is comparable to that reported nationally. ABO blood groups of patients on the waiting list are distributed similarly to those reported nationally for other renal patients. Sensitization to HLA antigens, through either blood transfusion, prior transplant, or pregnancy, has been strongly associated with poorer graft survival. Although, as expected, distribution of PRA was significantly different for males versus females at one time point, it did not differ between ethnic groups in our patient population. HLA polymorphism was assessed by comparisons of HLA allele and haplotype frequencies determined by analyses of African American and Caucasian families typed in our program since 1991. Haplotypes observed in each ethnic population were subjected to a variety of statistical analyses. Coefficient of contingency and Cramer's V statistic (measures of degree of association) were consistently higher for Caucasian haplotypes than for those of African Americans. Significantly more unique HLA haplotypes were observed among African American families than among Caucasian families. Thus, our data provide evidence for greater HLA linkage disequilibrium in Caucasians than in African Americans. HLA antigen and haplotype polymorphisms are likely, therefore, to be major immunogenetic factors contributing to ethnic differences in renal allograft survival.
Disproportionate HLA matching may contribute to racial disparity in patient survival following cardiac transplantation
Authors: Park M. H. , Tolman D. E. , Kimball P. M.
Published: September 2024

The purpose of this study is to investigate the impact of recipient race as well as HLA matching upon long‐term survival following heart transplantation (HTx). The study also determines whether the degree of HLA matching between Caucasians and African Americans differs. This study was a retrospective analysis of 336 males (77% Caucasians and 23% African Americans) transplanted between 1983 and 1994, all having received cyclosporine‐based immunosuppression. The results showed African Americans were transplanted at a significantly younger age than Caucasians (39.1±11.2 vs. 48.2±10 yr). The composition of end stage cardiac disease was startlingly different. Caucasians demonstrated 62% CAD, 31% IDCM and 7% other, whereas African Americans exhibited 24% CAD, 69% IDCM and 7% other. The ten‐year survival rate for African American male recipients was inferior to Caucasian males. Survival at 1, 3, 5, 7 and 9 yr was 83%, 73%, 63%, 51%, 46% for Caucasians and 70%, 58%, 51%, 38% and 32% for African Americans. Furthermore, African Americans received more poorly matched organs compared to Caucasians. Among Caucasians for Class I, 46%, 53% and 1% received poor, moderate and well matched hearts, respectively. In contrast, African Americans were allocated 65%, 33% and 0% of poor, moderate, or well matched hearts. An analysis of Class II data revealed the same pattern (63%, 35%, 2% of Caucasians and 78%, 18%, and 4% of African‐ Americans received poor, moderate or well matched hearts). Survival for Caucasians improved when moderately versus poorly matched for Class I. Class II matching did not have an effect. African Americans showed a similar trend, although statistical significance was not reached. When comparing equivalent degrees of matching, African Americans had inferior survival rate when poorly matched for Class I relative to Caucasians. No statistical difference was observed for moderate matched Class I or for Class II analysis.
Routine early biopsy of allografts with delayed function: correlation of histopathology and transplant outcome
Authors: Gaber Lillian W. , Gaber A. Osama , Hathaway Donna K. , Vera Santiago R. , Shokouh‐Amiri M. H.
Published: September 2024

Approximately 25–30% of our cadaveric renal transplant recipients have required post‐transplant dialysis. In an attempt to discern the etiology, routine biopsies were performed 7‐10 d post‐transplant and repeated weekly. All patients received a triple‐therapy cyclosporine‐based regimen with (N=61) or without (N=10) antilymphocyte induction. Rejection was classified as ‘early’ when it appeared on the first biopsy (8.9±0.3 d), ‘delayed’ when it appeared only on the second biopsy (17.9±1.0 d) and persistent when present on both biopsies. Adequate biopsy material was obtained from 71 patients who provided a total of 117 biopsies. Acute tubular necrosis was the most common finding (50%) in the first biopsy, while rejection occured in 30% of biopsies. Rejection on the first biopsy was strongly associated with primary nonfunction (PNF) (8 of 21 vs. 1 of 40, p≤0.0001). In contrast, eight patients without rejection on Biopsy I developed delayed rejection on Biopsy 2; only one was associated with PNF DGF persisted beyond the second week in 38 patients; 17 (38%) of which had rejection. Nine patients had persistent rejection 55% of whom experienced PNF compared to 6% without persistent rejection (p≤0.001). The occurrence of early rejection was associated with pretransplant peak PRA levels >50% (p=0.01). Graft survival for all patients was 79% and 65% at 1 and 2 yr. Rejection influenced 1‐yr graft survival for patients with persistent rejection who had 55% incidence of primary nonfunction and 1‐ and 2‐ yr graft survival rates of 42% and 37%. These data indicate that early biopsies are useful in unmasking rejection during DGF and at predicting primary nonfunction. Based on these data we recommend the routine utilization of biopsies for all patients with DGF.
Renal allograft rupture: a clinical review
Authors: Azar G. J. , Zarifian A. A. , Frentz G. D. , Tesi R. J. , Etheredge E. E.
Published: September 2024

Rupture of a renal allograft (RAR) is an uncommon but serious complication of renal transplantation. A recent RAR prompted a review of our experience, with the purpose of (1) identifying conditions that may predispose this complication and (2) defining strategies for prevention. A 5‐yr, consecutive living‐related (LRD) and cadaver donor (CD) cohort of 331 patients was studied retrospectively. Twelve patients (3.6%) had RAR. Donor characteristics, procurement and preservation conditions, and recipient characteristics were major study categories. Data analysis was computer‐based and included multivariate analysis. The nine White and two Black cadaver donors were “ideal”, mean age 29 yr, with mean high creatinine (CR) of 1.3 and terminal CR of 1.1 mg/dl, and mean terminal urine output of 423 ml/min. Nine of 11 CD had low‐dose dopamine use (terminal, mean 8, range 5‐13 μg/kg/min). Eleven of 11 donors had procurement en‐bloc, 9 of which were multiple organ procurement. All had 4+/4+ flush and cold storage with UW solution. Mean cold ischemia time (CIT) was 22 h, 28 min (range 15 h, 16 min to 40 h). For patients with RAR mean age was 39 yr; there were 12 Black patients and 7 males, 5 females. HLA match was 1 antigen (AG) for 3, 2 AG for 8, and 4 AG for 1 (mean 1.9). Nine patients had delayed or declining renal function requiring dialysis. The panel reactive antibody was at peak, mean 47% (range 0–100%) and current, mean 18% (range 0–84%). Six of 12 had OKT3 therapy at time of RAR and six had biopsies. Day of RAR was mean 10, median 9 (range 4–21). Pain and drop in hematocrit were observed in most. There was one fatality (8%), and all kidneys were removed. All kidneys showed at least minimal rejection but six had severe acute tubular necrosis (ATN) with edema and minimal rejection. Statistically significant associations with RAR were older recipient age (p= 0.04), donor‐recipient race mismatch (White donor to Black recipient) (p= 0.007), and dialysis requirement (p<0.0001). Other variables were not statistically correlated: gender, race, CIT, transplant number, LRD vs. CD, peak or current PRA, and total HLA and BDR mismatch. The data suggest that ATN and rejection act synergistically to cause RAR and that early delayed function requires intensive and perhaps novel immunosuppression, especially in Black recipients.
Immunohistochemical manifestations of unilateral kidney ischemia
Authors: Ibrahim Sherif , Jacobs Frank , Zukin Yakov , Enriquez Debi , Holt David , Baldwin William , Sanfilippo Fred , Ratner Lloyd E.
Published: September 2024

Events in the early post‐transplant period have been correlated with increased renal allograft loss. Immunologic reactions and ischemic injury have been implicated in this process. While the immunologic aspects of allograft injury have been studied extensively, ischemic effects remain less well understood. To study the effects of ischemia in rats with different genetic backgrounds without the introduction of an alloimmune response, a clamp was placed on the vascular pedicle of the left kidney for 60 min. The short‐term effects (1 wk) of ischemia were studied in groups of PVG (RT1c), LEW (RT11), DA (RT1a) and WF (RT1u) rats. Immunoperoxidase staining demonstrated limited infiltration of monocytes, macrophages, and T‐cells accompanied by upregulation of low levels of MHC class II antigens on tubular epithelial cells, peritubular capillaries, and interstitial cells in kidneys of PVG and WF rats. Kidneys of LEW and DA rats had greater influxes of monocytes, macrophages, and T cells in addition to higher amounts of MHC class II antigen upregulation on tubular epithelium and interstitial cells. The long‐term effects of ischemia were studied in kidneys of WF rats. These kidneys had a progressive increase in infiltrating T cells, monocytes, macrophages and MHC class II expression on the tubular epithelium and the interstitial cells at 14, 30, and 90 d after the ischemic insult. The differences in MHC class II expression between ischemic kidneys of PVG and LEW rats were not associated with differences in production of mRNA for IL‐2, IFN‐γ, and TNF‐α. In summary, transient renal ischemia in the absence of an allogeneic immune response triggers a progression of inflammatory responses, including leukocyte infiltration, cytokine production and MHC class II antigen upregulation which appears to be strain‐dependent.
Renal function in cardiac transplant recipients: retrospective analysis of 133 consecutive patients in a single center
Authors: Tinawi Mohammad , Miller Leslie , Bastani Bahar
Published: September 2024

We retrospectively studied 133 consecutive cardiac transplant patients who had lived more than 5 months post‐transplantation. All patients had received a cyclosporine (CyA) based triple immunosuppressive protocol. Mean (± SE) duration of follow‐up was 32±1.8 months (range 5‐60 months). Serial mean serum creatinines significantly increased from 1.26±0.025 mg/dl at 1‐2 months post‐transplant to 1.4±0.05 at 3 months, 1.48±0.03 at 6 months, and 1.55±0.04 at 9 months with a subsequent plateau in serum creatinine levels up to 60 months of follow‐up, at which point it had reached 1.66±0.1 mg/dl. The reciprocal creatinine (1/Cr) curve also showed a biphasic decline in renal function, with a rapid decline in the first 6 months followed by no further decline up to 60 months of follow‐up. Approximately 4% of the patients at 1‐2 months, 8% at 3 months, and 12‐ 17% at 6‐60 months had serum creatinine ≥ 2.0 mg/dl. None of the patients developed end‐stage renal disease requiring dialysis. At all time points, patients with serum creatinines ≥2.0 mg/dl received a lower CyA dose than those with serum creatinines <2.0 mg/dl (3.1±0.1 vs. 4.0±0.1 mg/kg/d, respectively, p<0.0001), suggesting that the CyA dose had been appropriately reduced in response to a rise in serum creatinine. There was no significant rise in serum potassium (4.4±0.04 vs. 4.5±0.1 meq/1, 1‐2 vs. 60 months, respectively, p=NS) or serum cholesterol (205.5±4.1 vs. 211±6.5 mg/dl, 1‐2 vs. 60 months, respectively, p=NS). However, there was a significant rise in systolic (134±1.5 vs. 140.5±2.7 mmHg, p<0.05), diastolic (84±1.0 vs. 90±2.1 mmHg, p<0.05), and mean arterial (101±1.0 vs. 107 2.1 mmHg, p<0.05) pressures at 1‐2 vs. 60 months. Serum trough CyA levels and CyA doses were significantly reduced over the follow‐up period (1746.7 vs. 110.5 12.5 ng/ml, and 4.4±0.1 vs. 2.5±0.2 mg/kg/d, at 1‐ 2 vs. 60 months, respectively, p<0.05). At 1 yr, 56% of the patients were treated with antihypertensive medications (predominately calcium channel blockers) and 14% received lipid lowering medications (predominately an HMG‐CoA reductase). We conclude, after an initial rise in serum creatinine and decline in 1/Cr curve, during the first 6‐9 months post‐cardiac transplant, renal function remains stable up to 5 yr of follow‐up, if serum CyA levels and CyA doses are monitored and adjusted closely. However, we cannot rule out the possibility of subclinical progressive histopathologic changes, due to chronic CyA nephrotoxicity, which could become clinically apparent after a longer duration of follow‐up.
Recurrent type I membranoproliferative glomerulonephritis after renal transplantation and protective role of cyclosporine in acute crescentic transformation
Authors: Ahsan Nasimul , Manning Eric C. , Dabbs David J. , Gifford Robert R. M. , Yang Harold C.
Published: September 2024

Almost all diseases affecting the native kidney may recur in the transplanted kidney, with one of the most frequent being recurrent glomerulonephritis. Among the glomerulonephritides, membranoproliferative glomerulonephritis (MPGN), immunoglobulin A nephropathy (IgA), and focal‐segmental glomerulosclerosis (FSGS) have the highest rates of recurrence. Here we report a patient who, after living‐related kidney transplantation, suffered allograft loss shortly after surgery due to recurrence of glomerulonephritis. Two weeks prior to transplant nephrectomy light microscopic examination of the allograft biopsy failed to show glomerulonephritis. Subsequent histopathology of the transplant nephrectomy specimen demonstrated a crescentic form of type I MPGN following withdrawal of cyclosporin A (CSA) and intense course of oral steroid therapy. The entity of recurrent type I MPGN in kidney transplantation is reviewed, and a possible protective role of CSA against rapidly progressive crescentic type I MPGN is explored.
Rescuing Prometheus: a policy proposal to alleviate excess demand for liver transplantation
Authors: Ferguson Melissa E. , Ferguson Ronald M.
Published: September 2024

A growing demand for liver transplantation coupled with a static supply of organs results in an excess demand crisis. Excess demand for liver transplantation equals the number of patients left on the UNOS waiting list at the end of the year who have not expired, undergone transplant, or been withdrawn. Only in the arena of transplantation doses the United States medical community confront a true rationing dilemma stemming from a scarcity of livers available for transplantation. An excess demand crisis intensifies debate in policy areas such as allocation and patient listing criteria. A cohesive rationing policy should manage both the demand for transplantation and the supply of transplantable organs. Demand‐side management as applied to liver transplantation could decrease the incidence of critically ill patients waiting for transplants, the number of retransplants performed and the total cost of transplantation to the health care system.
Application of a tissue expander for stabilizing graft position in living‐related liver transplantation
Authors: Inomata Yukihiro , Tanaka Koichi , Egawa Hiroto , Uemoto Shinji , Kiuchi Tetsuya , Satomura Kazunari , Uyama Shiro , Okajima Hideaki
Published: September 2024

In living‐related liver transplantation, a portion of the whole liver, usually the left lateral segment or the left lobe, is harvested for use as the graft liver. A relatively small graft may twist around the hepatic venous anastomosis, causing outflow blockage. After an initial experience of such a complication in the early post‐transplantation period in one case, we began to apply a tissue expander to obliterate the dead space left after emplacement of a relatively small graft. Commercially available tissue expanders, ordinary employed in plastic surgery, were used for five pediatric recipients (6–14 yr old) whose ratio of graft weight to recipient body weight ranged from 0.74 to 1.72. The expander, filled with 240‐350 ml saline, was put into the space to the right of the graft. Aspiration of the expander content was started after the 5th‐7th postoperative day (POD), at a rate of 50 ml of fluid a day. The expanders were taken out on the 11th‐14th POD after complete removal of the content. Complications observed in the five cases were right shoulder pain (5/5), fluid collection after removal of the expander (2/5), chylous ascites (1/5), and one instance of bile leakage. All the complications were successfully managed and controlled conservatively. There was no outflow obstruction detected by Doppler ultrasonography before or after removal of the expander. This is a simple and safe method for preventing the early onset of outflow block after partial liver transplantation.
A liver transplantation technique in a patient with a thrombosed portal vein and a functioning renal‐lieno shunt
Authors: Sheil A.G. Ross , Stephen Michael S. , Chui Albert K.K. , Ling Juanita , Bookallil Michael J.
Published: September 2024

A liver transplant technique is described in a patient with a thrombosed portal vein and a functioning surgically created renal‐lieno shunt. Permanent portal inflow to the graft was provided by division of the left renal vein (LRV) at its junction with the inferior vena cava and anastomosis of the LRV end‐to‐end with the donor portal vein. Although this results in splanchnic blood traversing a 360° roundabout from the superior mesenteric vein via the splenic and disconnected left renal veins to the donor portal vein, the anastomosis lay well and the procedure was successful.
Successful reversal of acute vascular rejection in a renal allograft with combined mycophenolate mofetil and tacrolimus as primary immunotherapy
Authors: Ahsan Nasimul , Holman Michael J. , Katz Douglas A. , Abendroth Catherine S. , Yang Harold C.
Published: September 2024

Despite the use of newer immunosuppressive drugs, early allograft rejection is still a major cause of graft loss and diminished graft survival. The pathological picture of acute interstitial rejection usually responds to high dose steroids, whereas the treatment of acute vascular (AVR) rejection characterized by an intense vasculitis and/or endotheliolitis is more formidable. The use of newer monoclonal antibodies specific for T lymphocytes and their subsets has only been occasionally successful in reversing AVR. Here we report a case of successful reversal of acute vascular renal allograft rejection with mycophenolate mofetil (MMF) and tacrolimus as primary therapy.
Bench reconstruction of pancreas for transplantation: experience with 192 cases
Authors: Gill Inderbir S. , Sindhi Rakesh , Jerius John T. , Sudan Debra , Stratta Robert J.
Published: September 2024

Whole organ pancreaticoduodenal transplantation with bladder drainage by the duodenal segment technique is currently the preferred method of vascularized pancreas transplantation but is associated with a finite risk of surgical complications. Meticulous bench reconstruction of the pancreaticoduodenal allograft may minimize complications following transplantation. Over a 6.5‐yr period, 192 pancreas transplants were performed in 181 diabetic patients by the same transplant team. A retrospective review was performed in order to describe a stepwise approach to bench preparation of the pancreaticoduodenal allograft that has developed from this experience. In this series of 192 consecutive pancreaticoduodenal reconstructions, no procured pancreas was deemed non‐usable solely from an anatomic standpoint. The mean backtable pancreas preparation time was 2 h. The operative complication rate was 19%, the incidence of technical graft loss was 6.8%, and there was no mortality related to technical problems. Conclusions: Using a standardized approach, meticulous bench reconstruction of the pancreaticoduodenal allograft: 1) can be performed in virtually any anatomic setting; 2) decreases complications following transplantation; 3) improves initial allograft function; and 4) minimizes organ wastage.
Magnetic resonance venography in potential pediatric liver transplant recipients
Authors: Cheng Yu Fan , Huang Tung Liang , Lui Chun Chung , Lee Tze Yu , Chen Chao Long
Published: September 2024

Vascular anomalies may be hazardous to liver transplantation, and pre‐operative vascular evaluation is important for a safe and successful operation. The purpose of this study was to assess the utility and accuracy of time‐of‐flight (TOF) magnetic resonance venography (MRV) with threedimensional (3D) reconstruction as an alternative for conventional catheter angiography in evaluating the portal venous system and inferior vena cava (IVC) in potential pediatric liver transplant recipients. Twenty consecutive cases of small children with biliary atresia were evaluated with TOF MRV with 3D reconstruction by Advantage Window workstation. All 20 cases underwent conventional angiography; two cases received transhepatic portography and three cases received splenoportographic study. The whole MRV examination and filming required less than 30 min. Findings of portal vein and IVC completely agreed with or were superior to the successful catheter angiographic images. The portal vein was occluded in five cases. and patent in fifteen cases which included: twelve hepatopetal flow, two hepatofugal flow and one small caliber portal vein. Varices were found in 18 cases. In the case of the IVC, 18 of them were normal and 2 had congenital abnormalities which included paired vena cava and hypoplasia vena cava with compensatory enlargement of the azygos and hemiazygos systems. Eight of the cases received liver transplantation, and the MRV findings totally correlated with the final anatomy as found intraoperatively. MRV is accurate for evaluating the condition of the portal venous system and IVC, detection, and determining the distribution and extents of the varices. It is a reliable, noninvasive and rapid technique which can be considered as an alternative workup for the invasive angiography and or portography in small children for pre‐transplantation evaluation.
Interaction between panel reactive antibodies, auto‐ and cold reactive antibodies, and a positive B cell cross‐match in renal and cardiac allograft survival
Authors: Creemers Pauline , Brink Johan , Kahn Delawir
Published: September 2024

We analyzed the influence on allograft survival of pretransplant panel reactive antibodies (PRA) <10%, PRA>10%, autoantibodies, cold antibodies and a positive B cell crossmatch in 807 renal and 237 cardiac transplant recipients. Donors and recipients were predominantly of mixed ancestry (Khoi, San, Xhosa and Caucasoid). Log rank analysis showed that PRA<10%, cold antibodies, and a positive B cell cross‐match did not influence allograft survival. Autoantibodies were present only in renal recipients; they appeared to have a beneficial effect on allograft survival (P=0.06). PRA>10% appeared to have a detrimental effect on allograft survival in both renal (P=0.07) and cardiac (P=0.06) recipients. Since autoantibodies and PRA>10% had opposing effects, the results of renal recipients were reanalyzed after omission of the recipients with autoantibodies and coexisting and ghoul PRA>10%. This resulted in augmentation of the protective effect for autoantibodies (P=0.027) and of the detrimental effect for PRA>10% (P=0.020), Two‐year survival curves showed that when autoantibodies coexisted with PRA>10%, the long term, but not the short‐term, detrimental effect of PRA>10% was attenuated. Patients with a positive B cell cross‐match clustered in the PRA>10% group in both renal (PRA negative vs. PRA<10%: P=0.0251; PRA<10% vs. PRA>10%: P=0.0011) and cardiac (PRA negative vs. PRA>10%: P=0.0085) recipients. We conclude that PRA>10% is the best indicator to identify recipients at high risk for rejection, and that the influence of antibodies on graft survival can not reliably be established without taking coexisting antibodies into account.
A randomized controlled trial of pentoxifylline for the prevention of delayed graft function in cadaveric kidney graft
Authors: Noël Christian , Hazzan Marc , Coppin Marie‐Christine , Codaccioni Marie‐Xavière , Pruvot François‐René , Labalette Myriam , Lelièvre Gaston
Published: September 2024

Ischemia/reperfusion has been implicated in the mechanism of delayed graft function (DGF). Pentoxifylline (PTX) has been shown to suppress TNFa (released by activated macrophages, inhibiting subsequent superoxide anion release from neutrophil activation. In addition, PTX decreases cyclosporine (CSA) induced renal endothelial release and vasoconstriction. Thus, administration of PTX to renal transplant patients could be an excellent approach to prevent DGF and vascular toxicity of CsA in the early graft period. One hundred‐and‐forty consecutive patients receiving cadaveric kidney transplantation were registered in a randomized doubleblind study comparing PTX vs. a placebo. PTX had no demonstrable effect on the incidence of DGF, on the rapidity of the renal function recovery, and on the ability to use higher doses of CsA in the first month post‐graft.
Allograft infiltrating cytotoxic T lymphocytes recognize kidney‐specific human minor histocompatibility antigens
Authors: Poindexter Nancy , Shenoy Surendra , Howard Todd , Flye M. Wayne , Mohanakumar T.
Published: September 2024

The role of minor histocompatibility antigens (mH) in allograft immunity has been proposed, but the nature of these antigens and their immunogenicity are not well understood. We have shown that tissue‐specific cytolytic T lymphocytes (CTL) can be isolated form graft infiltrating lymphocyte (GIL) populations from renal transplant recipients undergoing acute cellular rejection. In most cases these CTL were allorestricted recognizing donor mismatched kidney MHC class I antigens. In contrast, one patient's GIL T cells demonstrated specific lytic activity against HLA‐B35 expressed on primary kidney epithelial cell lines (KCL) but not on B‐lymphoblastoid cell lines (LCL). Since HLA‐B35 was a shared antigen between donor and recipient, these results suggest that CTL within the GIL population are recognizing a tissue‐specific minor histocompatibility antigen presented in the context of self‐HLA‐B35.
Highly successful long‐term outcome of kidney transplantation in Chinese recipients: an enhancing race effect?
Authors: Hawkins Brian R. , Chan Peter , Chan Y. T. , Cheng Ignatius K. P. , Cheung K. O. , Fenn John , Ho K. K. , Lai K. N. , Li C. S. , Lui S. F. , Opelz Gerhard , Tong Matthew K. L.
Published: September 2024

We report on 352 cadaveric kidney transplants and 294 living related transplants performed over a 25‐yr period among the Chinese population of Hong Kong. There is a marked preference for transplanting male patients, especially from living donors, and we argue that this represents a cultural phenomenon within the Chinese population. The 10‐yr graft survivals for related and cadaveric transplants are 86.2% and 67.4%, respectively. These figures are appreciably higher than corresponding figures in Caucasian populations. We show beneficial effects of using cyclosporin A, minimizing the cold ischemia time and avoiding very young and very old donors. There is a clear benefit of transplanting kidneys with zero or one mismatched HLA antigen against the recipient but no stepwise decrease in outcome as the number of mismatched antigens increases. There is close concordance between the outcome of living related grafts with zero, one, and two mismatched haplotypes against the recipient and no observable benefit of haplotype matching. We show that Chinese renal transplant recipients in other centers also have better long‐term graft outcome than Caucasians, both for cadaveric and living related transplants. We draw attention to the existence of a detrimental “race effect” in other studies when Black recipients are compared with Caucasians and consider whether an enhancing. race effect exists for Chinese or whether the better outcome reflects different underlying diseases in Chinese.
Development of microchimerism in pediatric patients after living‐related liver transplantation
Authors: Ueda Mikiko , Hundrieser Joachim , Hisanaga Michiyoshi , Tanaka Koichi , Wonigeit Kurt , Pichlmayr Rudolf , Schlitt Hans J , Yamaoka Yoshio
Published: September 2024

Microchimerism has been suggested to play an important role in the long‐term acceptance of allogeneic organ grafts by transplant patients and for the maintenance of a state of donor‐specific low responsiveness. In order to elucidate the kinetics of the development of chimerism we have performed a follow‐up analysis in 10 pediatric patients with living‐related liver transplantation (LRLTX). Blood samples obtained during the first 6 months and at 18 months post‐transplant and skin biopsies taken at one month were analysed for the presence of donor cells by PCR using donorspecific HLA‐DRB1 primer pairs or primers for a Y chromosome‐specific sequence. Furthermore 13 long‐term patients more than 2 yr after LRLTX were studied at two different time points. In the follow‐up studies donor cells could be demonstrated in the blood of all patients immediately after transplantation. After a gradual decline all patients became chimerism‐negative for several weeks or months. At 6 months, however, in five of eight patients tested and at 18 months in six of nine patients donor cells had reappeared. This biphasic pattern in the development of chimerism is proposed to reflect the occurrence of different donor‐derived cell populations in the recipient. The population giving rise to the first wave of chimerism probably represents matured cells with a limited lifespan which are released from the graft into the circulation of the recipient during the first weeks after transplantation. The population of cells occurring with the second wave of chimerism is likely to have been generated by donor‐derived cells with stem cell potential located either in the graft or in the hematopoetic organs of the recipient after emigration from the graft. This model may be able to explain fluctuations in the incidence and degree of microchimerism described in other patient populations during the first year post‐transplant. Of the 13 long‐term patients, chimerism could be demonstrated in 11. In seven patients it was detected in both blood and skin, in three patients the results obtained for blood and skin were discordant. In one patient only blood was analysed. It is not clear whether the negative results really reflected the absence of chimerism or whether the number of donor cells was below the level of detectability.
Liver transplantation: treatment of choice for hepatic and neurological manifestation of Wilson's disease
Authors: Schumacher Guido , Platz Klaus P. , Mueller Andrea R. , Neuhaus Ruth , Steinmüller Thomas , Bechstein Wolf O. , Becker Michael , Luck Werner , Schuelke Markus , Neuhaus Peter
Published: September 2024

Liver transplantation (LTX) is an approved method to treat patients with end‐stage liver cirrhosis and acute liver failure due to Wilson's disease. Initially, there was some consideration about the indication for LTX in the case of Wilson's disease with severe neurological impairment but normal liver function. From 1988 until 1995, 13 out of 700 LTX (1.9%) were performed for Wilson's disease. Indications for LTX were (I) intractable neurological impairment with normal liver function (n=4; including one patient with Child A cirrhosis), (II) fulminant hepatic failure (n=3), and (III) end‐stage liver cirrhosis (n=6) (Child B, n=1; Child C, n=5). There were 8 females and 5 males with a mean age of 27 yr (range 15‐34 yr). All patients of group I required continuous nursing care before LTX, in spite of pretreatment with d‐penicillamine and zinc. The most frequent symptoms in these patients were dysphagia (n=4), dysarthria (n=4), tremor (n=4), sialorrhea (n=3), ataxia (n=3), dystonia (n=3) and handwriting difficulties (n=3). All patients of group II presented with hemolytic anemia. The survivalrate was 100%, and all patients were doing well after a mean follow‐up period of 32.8 months (range 8‐68 months). The postoperative course was without severe infectious and other complications. All patients of group I revealed the first signs of improvement for all types of neurological symptoms 4‐6 wk after LTX. One patient has been without any symptoms from 18 months until 5.5 yr after LTX. Two patients with short‐term follow‐up also had noticable improvement of neurological impairment, but residual symptoms are still present. One patient showed only slight improvement. We conclude that Wilson's disease may be a good indication for LTX for both neurological manifestation with stable liver function and hepatic manifestation with cirrhosis or acute liver failure.
Effects of cyclosporin A and FK 506 on lipid metabolism and fibrinogen in kidney transplant recipients
Authors: Hohage H. , Arlt M. , Brückner D. , Dietl K. H. , Zidek W. , Spieker C.
Published: September 2024

After allogenic transplantations a dramatic increase in the development of arteriosclerotic plaques can be observed, which might be due to metabolic alterations, influenced by changes of the transplant organ or immunosuppression. In this study the effects of FK 506 in kidney transplant patients on cardiovascular risk factors were compared to cyclosporin A (CSA) immunosuppression. Both groups showed no statistical differences in number, kidney function, age, body weight, sex distribution, steroid dosage and follow‐up time after transplantation. Total cholesterol was similar in FK 506‐treated patients (231±22 vs. 278±52 mg/dl) as compared with patients with CsA immunosuppression. Furthermore, there were no differences in triglycerides (220±72 vs. 210±67 mg/dl), HDL‐cholesterol (67±14 vs. 52±18 mg/dl) and fasting glucose (112+36 vs. 116±17 mg/dl). However, the concentration of LDL‐cholesterol (114±21 vs. 167±37 mg/dl), the independent risk factor Lp(a) (11±9 vs. 27±8 mg/dl) and fibrinogen (216±71 vs. 297+47) was lower in FK 506‐treated patients. Our results indicate that FK 506 immunosuppression offers some advantages in cardiovascular risk factors.
Clinical features of acute reversible tacrolimus (FK 506) nephrotoxicity in kidney transplant recipients
Authors: Katari S. R. , Magnone M. , Shapiro R. , Jordan M. , Scantlebury V. , Vivas C. , Gritsch A. , McCauley J. , Starzl T. , Demetris A. J. , Randhawa P. S.
Published: September 2024

This study was designed to (a) estimate the contribution of tacrolimus nephrotoxicity to episodes of renal allograft dysfunction investigated by needle biopsy, (b) describe the temporal evolution of nephrotoxicity and its response to therapy, and (c) ascertain how often renal dysfunction is associated with concurrent extra‐renal toxicity.

Patients were selected based on a rising serum creatinine, normal ultrasound, and biopsy findings leading to a reduction in the dose of tacrolimus and a fall in serum creatinine. Twenty two (17%) cases of nephrotoxicity were identified amongst 128 consecutive kidney transplant biopsies with sufficient clinical data for analysis.

There were 13 males and 9 females, 17‐75 yr in age. Tacrolimus was administered initially as a 0.075‐0.1 mg/kg/d IV continuous infusion followed by an oral dose of 0.15 mg/kg twice daily. The onset of nephrotoxicity in this study occurred 1‐156 wk post‐operatively. The mean baseline creatinine was 212.2±168.0 μmol/l (range 88.4‐875.2) and rose 40.6%±14.2% (range 11–66) during episodes of nephrotoxicity (p<0.001). The highest recorded plasma and whole‐blood tacrolimus levels during the toxic episodes were respectively 2.7±0.8 ng/ml (range 1.1‐3.5) and 31.6±10.6 ng/ml (range 14.5‐50.5). The drug levels were considered to be beyond the therapeutic range in 18/22 (82%) patients. The highest tacrolimus level preceeded the rise in serum creatinine in 20 cases by an interval of 1.6±1.8 d. A mean reduction in tacrolimus dosage of 41%±21% (range 11–89) led to a 86% ± 18% (range 45–100) fall in the serum creatinine within 1‐14 d (p<0.001). Interactions between tacrolimus and clarithromycin, diltiazem, or itraconazole modified the pharmakokinetic parameters in three cases. Serum potassium >5.0 mequiv./1 was recorded in 9/22 (41%) cases. Three or more elevations in blood glucose >7.7 mmol/l (140 mg/dl) were recorded in 4/11 (36%) non‐diabetic patients. Hand tremors were seen in two (9%) cases and elevated diastolic blood pressure > 90 mmHg in seven (32%) patients.

In conclusion, tacrolimus nephrotoxicity accounted for 17% of graft dysfunction episodes investigated by biopsy. Concurrent hyperglycemia, hyperkalemia, or tremors were noted in several patients. Nephrotoxicity responded well to reduction in the drug dosage.
Risk factors for prolonged hospitalization after kidney transplants
Authors: Matas Arthur J. , Gillingham Kristen J. , Elick Barbara A. , Dunn David L. , Gruessner Rainer W. G. , Payne William D. , Sutherland David E. R. , Najarian John S.
Published: September 2024

A major variable in the cost of kidney transplants is the length of initial hospitalization. Using multivariate analysis, we studied risk factors for hospital stay > 10 d post‐transplant. Between 1 January 1985 and 31 August 1995 a total of 1588 patients underwent first or second kidney transplants at the University of Minnesota. Antibody was used for 1 wk in cadaver donor recipients and for 2 wk in pediatric recipients (resulting in a long stay for all pediatric recipients). Adult living related donor recipients were immunosuppressed with triple therapy.

Donor risk factors studied were age (<15, 15‐50, > 50 yr) and, for cadaver recipients, preservation time (< 12, 12‐18, 18‐24, 24‐30, >30 h) and cause of death (trauma, cerebrovascular accident, or cardiac). Recipient risk factors studied were age (< 18, 18‐55, > 55 yr); sex; transplant number; antigen mismatch; peak PRA; PRA at transplant (< 11, 11‐50, >50); diabetic status; pretransplant dialysis (vs. pre‐emptive transplant); pretransplant cardiac, peripheral vascular, or respiratory disease; and delayed graft function (DGF) (dialysis in the first week vs. no dialysis). Risk factors were analyzed separately for living donor and cadaver donor recipients. For cadaver donor recipients, DGF was the major risk factor (p < 0.0001); others were age 55 yr (p=0.03) and diabetes (p=0.02). For living donor recipients, DGF was also a risk factor (p=0.003); others were diabetes (p=0.01), retransplant (p=0.006), PRA at transplant > 50 (p < 0.0001), age > 55 yr (p=0.02), pretransplant respiratory disease (p=0.005), and pretransplant dialysis (p=0.005).

Because DGF was the major risk factor for a prolonged stay, we then studied risk factors for DGF using multivariate analysis. For cadaver donor recipients, risk factors were recipient weight > 90 kg (p=0.004), preservation time 24 h (p=0.03), PRA at transplant > 50 (p=0.03), and donor age < 15 or > 50 yr (p=0.002). For living donor recipients, risk factors were recipient age 18 yr (p=0.01), donor age > 50 yr (p=0.03), female sex (p=0.05), pretransplant respiratory disease (p=0.1), pretransplant peripheral vascular disease (p=0.05), and recipient weight > 90 kg (p=0.1).

From our data, a profile emerged of recipients likely to have a longer hospital stay. Important variables, either simultaneous with or related to DGF, include donor and recipient age, diabetes, pretransplant recipient weight, PRA at transplant, preservation time, and pretransplant respiratory or peripheral vascular disease.
Diagnosing cytomegalovirus disease in CMV seropositive renal allograft recipients: a comparison between the detection of CMV DNAemia by polymerase chain reaction and antigenemia by CMV pp65 assay
Authors: Lo C. Y. , Ho K. N. , Yuen K. Y. , Lui S. L. , Li F. K. , Chan T. M. , Lo W. K. , Cheng I. K. P.
Published: September 2024

The optimal diagnostic test for CMV disease in renal allograft recipients in a locality with a high CMV seropositive rate has not been fully determined. We compared the usefulness of the CMV pp65 antigenemia (CMVAg) assay with the detection of DNAemia by a nested polymerase chain reaction (PCR) method in diagnosing CMV disease in 56 renal allograft recipients, of whom 50 (89.2%) were CMV seropositive prior to transplant (tx). Positive CMV‐Ag assays were found in 126/281 samples (44.8%) of 27 patients (48.2%) of whom five had seven episodes of CMV disease. The remaining 22 patients were asymptomatic. The symptomatic patients had significantly higher median peak CMV‐Ag levels than the asymptomatic patients [800 (160–1380) vs. 5 (1–604) per 2 × 105 peripheral blood leukocyte (PBL), p<0.0001]. One hundred and eight samples were tested by both CMV‐Ag and PCR methods. Out of the 108 samples, 89 showed concordant results (37 positive and 52 negative for both tests). Seventeen samples of 11 patients were CMV‐Ag negative / PCR positive. Out of these 11 patients, two had CMV disease and the discrepancy in the results was due to blood samples taken after the start of ganciclovir therapy. Falsely negative PCR tests were found in two samples of two patients with positive CMV‐Ag assays. With a cutoff antigenemia level of 100 per 2 × 105 PBL, the sensitivity, specificity, positive and negative predictive values for diagnosing CMV disease were 100, 96, 71.4 and 100%, respectively. On the other hand, CMV DNAemia was detected in many asymptomatic patients, and the PCR test results correlated poorly with the clinical manifestations of the disease. In symptomatic patients undergoing ganciclovir therapy, the quantification of antigenemia level allowed the assessment of treatment efficacy. In addition, positive CMV‐Ag assays at the end of therapy were associated with the subsequent relapse of CMV disease in two patients. The high specificity, together with the short processing time of 4 h, make the CMV‐Ag assay the test‐of‐choice for diagnosing CMV disease in a renal transplant population with a predominance of CMV seropositive patients.
Treatment of steroid‐resistant and recurrent acute cardiac transplant rejection with a short course of antibody therapy*
Authors: Cantarovich Marcelo , Latter David A. , Loertscher Rolf
Published: September 2024

The purpose of this study was to assess the efficacy of short courses of OKT3 and ATG, respectively, for steroid resistant or recurrent acute allograft cardiac rejection (AR). Between June 1988 and March 1994, 101 heart transplant patients were treated with a quadruple sequential immunosuppression protocol (ATG, azathioprine, CSA, and prednisone). AR was diagnosed by endomyocardial biopsy (EMB), and patients with scores. >2 (ISHLT) received pulse methylprednisolone, 500 mg i.v. on 3 consecutive days. In cases of steroid‐resistant or recurrent AR, OKT3 (5 mg/d) or ATG (1.5‐2.5 mg/kg/d), was administered for 5‐7 d instead of the usual 10‐14 d course. OKT3 (17 courses; 10 steroid resistant, 7 recurrent AR; 5.3±0.7 doses) was given to 16 patients (4F/12M, 45±11 yr), 29‐269 d after transplantation. ATG (8 courses; 5 steroid resistant, 3 recurrent AR; 4.9±0.6 doses) was given to 8 patients (1F/7M, 53±7 yr), 23‐503 d after transplantation. Successful treatment of AR with a score <2 at the first and second EMB after treatment was 88% and 88% with OKT3, and 87.5% and 100% with ATG, respectively. Throughout follow‐up (50+22 months after OKT3; 49+28 months after ATG), there was a trend towards lower incidence of subsequent AR after ATG (25% vs. 69%, P=0.09), and similar incidence of infections, graft atherosclerosis and mortality. No cases of lymphoproliferative disorder were observed. We conclude that short courses of OKT3 or ATG are safe and effective for the treatment of steroid resistant or recurrent AR, with a similar incidence of complications. These results may have cost‐effectiveness implications and need to be confirmed in a randomized study.
Leuconostoc bacteremia after liver transplantation: another cause of vancomycin resistant gram‐positive infection
Authors: Espinoza Ricardo , Kusne Shimon , Pasculle A. William , Wada Suzanne , Fung John , Rakela Jorge
Published: September 2024

Leuconostoc sp. are gram‐positive bacteria intrinsically resistant to vancomycin, which can be confused with streptococci based on routine microbiological characteristics. Infections secondary to Leuconostoc are uncommon, and usually affect patients with underlying diseases, prior use of vancomycin and those with central lines. The most common clinical presentation is fever secondary to a central line infection. We report the first case of Leuconostoc infection in a solid organ transplant recipient. The patient developed Leuconostoc bacteremia secondary to peritonitis, 60 d after undergoing liver transplantation. He was treated with clindamycin, gentamicin and underwent surgical debridement, but succumbed to other complications.
Induction immunosuppressive therapy is associated with a low rejection rate after liver transplantation
Authors: McVicar John P. , Kowdley Kris , Emond Mary J. , Barr Darlene , Marsh Christopher L. , Carithers Robert L. , Perkins James D.
Published: September 2024

Despite advances in immunosuppression, allograft rejection occurs frequently after liver transplantation. The use of induction therapy with cytolytic antibodies may decrease the frequency of rejection in liver transplant recipients, but may also increase the rate of cytomegalovirus (CMV) infection. It has been our center's strategy to use induction therapy in our liver transplant recipients. To determine the outcome of our strategy, we retrospectively reviewed all liver transplants performed in the first 5 yr of our liver transplant program. The frequency of acute rejection in the first year after liver transplantation was only 34% in patients who received induction therapy. The type of induction therapy antibody did not affect the rejection rate. Clinically significant CMV infection (requiring treatment) occurred in 22% of patients. These results suggest that use of induction therapy with. cytolytic antibodies does not lead to a high incidence of CMV infection and decreases the incidence of rejection after liver transplantation.
Combined kidney‐pancreas and parathyroid transplantation: a case report
Authors: Rahusen Frans , Munda Rino , Hariharan Sundaram , First M. Roy , Demmy Ann
Published: September 2024

We report the first successful multiorgan kidney‐pancreas and parathyroid tissue transplant in a patient with autoimmune polyglandular syndrome and medullary cystic disease. Successful transplantation included. quadruple drug induction therapy consisting of antithymocyte globulin, azathioprine, cyclosporine and prednisone. All three grafts are functioning 2 yr after transplantation.