Chang-Kwon Oh

UNI- AND MULTI-VARIATE ANALYSIS OF RISK FACTORS FOR EARLY AND LATE HEPATIC ARTERY THROMBOSIS AFTER LIVER TRANSPLANTATION

Background. Hepatic artery thrombosis (HAT) is a significant cause of morbidity after liver transplantation. The aims of this study are to identify and compare risk factors that might contribute to HAT. Methods. A total of 424 liver transplants performed at the University of Virginia were reviewed. HAT was defined as complete disruption of arterial blood flow to the allograft and was identified in 29 cases (6.8%). HAT was classified as early (less than 1 month posttransplant, 9 cases: 2.1%) or late (more than 1 month posttransplant, 20 cases: 5.4%). Possible risk factors for HAT were analyzed using Pearson &khgr;2 test for univariate analysis and logistic regression for multivariate analysis. Results. Multiple transplants, recipient/donor weight ratio >1.25, biopsy-proven rejection within 1 week of transplant, recipient negative cytomegalovirus (CMV) status, arterial anastomosis to an old conduit (defined as a previously constructed aorto-hepatic artery remnant using donor iliac artery), and CMV negative patients receiving allograft from CMV positive donors were found to be significant risk factors for developing early HAT. After logistic regression, factors independently predicting early HAT included arterial anastomosis to an old conduit [odds ratio (OR)=7.33], recipient/donor weight ratio >1.25 (OR=5.65), biopsy-proven rejection within 1 week posttransplant (OR=2.81), and donor positive and recipient negative CMV status (OR=2.66). Female donor, the combination of female donor and male recipient, recipient hepatitis C-related liver disease, donor negative CMV status, and the combination of recipient CMV negative and donor CMV negative were found to be significant risk factors for late HAT. Factors independently predicting late HAT by logistic regression included negative recipient and donor CMV status (OR=2.26) and the combination of a female donor and male recipient (OR=1.97). Conclusion. Therefore, in nonemergency situations attention to these factors in donor allocation may minimize the possibility of HAT.

Implication of advanced donor age on the outcome of liver transplantation.

Historically, age has been considered to be a relative contraindication for organ donors. The use of elderly donors for liver transplantation remains controversial due to the fear of inferior outcome. According to United Network for Organ Sharing (UNOS) data, the proportion of older donors has been increasing annually. This study describes the short‐ and long‐term outcomes for transplantation of elderly donor livers. Three hundred and seventy‐four primary liver transplantations, which had been performed at the University of Virginia Health System from 7 February 1988 to 31 December 1998, were included. Graft survival, incidence of primary non‐function, and hepatic artery thrombosis (HAT) after transplantation according to the different age groups of liver donors were analyzed. Cases were analyzed by donor age (group I, n=106: aged <20 yr; group II, n=217: aged between 20 and 49 yr; group III, n=51: aged ≥50 yr), and by donor age in comparison with recipient age (group IV, n=65: recipients transplanted with organs from donors within 5 yr of their age; group V, n=266: recipients from donors> 5 yr younger than their age; group VI, n=43: recipients from donors> 5 yr older than their age). Group III or VI (group of advanced donor age) and group II or V (control group) were compared by age, gender, race, body weight, height, pre‐transplantation cytomegalovirus (CMV) status of the recipients donors, cause of brain death of donors, total or warm ischemic time, ABO matching, and degree of human leucocyte antigen (HLA) mismatching. No significant difference in 5 yr graft survival was found between the groups by donor age (p=0.604) and by donor age compared with recipient age (p=0.567). Moreover, no significant differences in the incidence of primary non‐function and HAT after transplantation were found between the groups by donor age and by donor age compared with recipient age. Older donors were more likely to be women and to have antibodies to CMV, as well as to have died by cerebrovascular causes. Race, body weight, height of both recipients and donors, total or warm ischemic time of grafts, ABO matching, and degree of HLA mismatching were not significantly different between the groups. We conclude from this study that advanced donor age is not a contraindication to liver transplantation if careful assessment of donors is made on a case‐by‐case basis. There is a need to maintain an open mind with regard to the use of livers from older donors due to the current situation of serious organ shortages.

Gene expression of perforin by peripheral blood lymphocytes as a marker of acute rejection.

Background: Previous findings have demonstrated that the expression of cytotoxic effector molecules is increased in acute rejection of renal allografts. In the present study, we serially examined the gene expression of perforin, granzyme B and Fas ligand (FasL) in peripheral blood lymphocytes (PBLs) of renal allograft recipients to assess the potential of their expression as a marker of acute rejection. Methods: PBLs were isolated from blood samples taken on days 2, 4, 6, 8, 10 and 12 after transplantation. Competitive PCR was performed to evaluate the abundance of mRNA of perforin, granzyme B and FasL. The mean value + 2 SD of each molecule in the control group was set as a discriminatory level for that particular molecule. Results: When all measured samples were compared, perforin expression was significantly higher in patients with acute rejection than in the control group (1.84 ± 3.01 vs. 0.71 ± 0.48, p = 0.01). The percentage of perforin expression exceeding the discriminatory level was also significantly higher in patients with acute rejection (p = 0.0003). Five patients in the rejection group (5/7, 71.4%) showed perforin expression exceeding the discriminatory level, while only 1 patient in the control group did so (1/8, 12.5%) (p = 0.02). Perforin expressions of days 0 and 1 of rejection crisis were the highest over the study period. No consistent pattern of granzyme B and FasL expression was identified in relation to rejection crisis. Conclusion: Gene expression of perforin by PBLs was upregulated in accordance with acute rejection, thus offering the possibility that it may be utilized as a marker of acute rejection.

Characteristics of infectious complications associated with mortality after solid organ transplantation

Infection remains a common source of morbidity and mortality after solid organ transplantation. The purpose of this study was to characterize the continuously changing patterns of post‐transplantation infections, analyze early post‐transplantation infections, and evaluate characteristics associated with mortality. A secondary analysis was performed on prospectively collected data for all episodes of infection occurring between 10 December 1996 and 28 October 1998 on the surgery services at a university medical center. Post‐transplantation infections were compared with those in non‐transplantation patients randomly matched by severity of illness. Further analysis was performed on post‐transplantation infections occurring during the admission of transplantation compared with those in subsequent admissions. To evaluate factors associated with mortality, episodes occurring in survivors and non‐survivors were compared. The results demonstrated that infections in transplantation recipients (n=303) were associated with a younger age and had significantly lower white blood cell counts (WBC) compared with non‐transplantation patients. There was no difference in mortality (15.5 vs. 16.5%, p=0.74). Post‐transplantation infectious complications during the initial hospitalization (n=105) occurred at 38±6 compared with 695±66 d (p<0.0001) after transplantation and were associated with a longer length of stay (LOS) and increased mortality (30.5 vs. 7.6%, p<0.0001) compared with those occurring in subsequent admissions (n=198). Although multiple characteristics of post‐transplantation infections were associated with mortality, only the Acute Physiology and Chronic Health Evaluation (APACHE) II score was an independent predictor of mortality. Post‐transplantation infections remain a significant source of morbidity and mortality. The leukocyte response to infection was suppressed in the transplantation population. Post‐transplantation infections which occur during the admission for transplantation have a markedly increased mortality.

Gender-related differences of renal mass supply and metabolic demand after living donor kidney transplantation

Abstract: Kidney donation from female donors to male recipients has been reported to be associated with decreased allograft survival. Whether there was a gender‐related inadequacy between donor nephron supply and recipient functional demand was investigated in this study. One hundred ninety‐five living donor kidney transplant recipients that had neither ischemic injury, episode of rejection, nor any complication were included. Weights and heights of both donors and recipients were recorded to calculate body surface area, lean body weight, and body mass index. The donated kidney was weighed just after cold flush, and the recipients serum creatinine (Scr) was measured on a daily basis post‐operatively. When the recipients Scr reached the baseline, a 24‐h urine was collected for the amount of proteinuria (Upr), creatinine excretion (Ucr) and creatinine clearance (Ccr) calculation. The effect of donor and recipient gender was analysed by independent sample t‐test. On average, male donors and recipients were heavier and taller than females. However, the mass of kidneys donated from men and women were not statistically different. The gender‐related differences in post‐transplant Scr and Ucr of recipients were associated with the differences in the parameters of metabolic demands of recipients rather than with the weight of implanted kidney (renal mass supply) or with pre‐operative renal functions of donors (functional supply). The early graft function is not determined by donor gender. The effect of recipient gender on the graft function depends on the metabolic demands, which are higher in male recipients.

Safety and efficacy of the early introduction of everolimus with reduced-exposure cyclosporine a in de novo kidney recipients.

Background Everolimus and cyclosporine A (CsA) exhibit synergistic immunosuppressive activity when used in combination. We examined the safety and efficacy of the use of everolimus with a cyclosporine-sparing strategy in de novo renal transplant recipients. Methods A comparative, parallel, randomized, open-label 1-year study has been performed in 148 patients from five transplant centers to compare the efficacy and tolerability of everolimus and reduced exposure CsA (the investigational group) or enteric-coated mycophenolate sodium and standard-exposure CsA (the control group) in combination with basiliximab and steroids. The eligible subjects were randomly assigned at 1 month after transplantation. Efficacy failure (biopsy-proven acute rejection, death, graft loss, or loss to follow-up), safety, and renal function were evaluated. Results One graft loss has been reported in the control group and no patient death were reported in either group. The incidence of biopsy-proven acute rejection until 12 months after transplantation of the investigational group was 7.5%, compared to 11.1% of the control group (P=0.565). The mean estimated glomerular filtration rates of the investigational group at 12 months after transplantation was significantly higher (68.1±16.8 ml/min/1.73 m2) than that of the control group (60.6±15.8 ml/min/1.73 m2; P=0.016). There was no significant difference (P>0.05) in the incidence of discontinuations and serious adverse events between the groups. Conclusion The results of this study provide the evidences that (1) the calcineurin inhibitor (CNI) minimization by the introduction of everolimus after 1-month posttransplantation keeps the incidences of acute rejection and addtional risks as low as the conventional immunosuppression; (2) it allows minimizing CNI exposure, consequently reducing CNI nephrotoxicity and preserving renal function.

Impact of the ratio of graft kidney volume to recipient body surface area on graft function after live donor kidney transplantation

Lee JH, Won JH, Oh C‐K. Impact of the ratio of graft kidney volume to recipient body surface area on graft function after live donor kidney transplantation. 
Clin Transplant 2011: 25: E647–E655.

Chronologically different impacts of immunologic and non-immunologic risk factors on renal allograft function

Abstract:  Introduction:  Upon analysis of the risk factors affecting renal graft survival and function, the time‐dependent effects of each risk factor should be differentiated from their net effects. To evaluate the chronologically different impacts of risk factors on graft renal function, we reviewed 390 recipients who received a kidney from 1‐haplotype‐matched living‐related donors.

Predicting the ideal serum creatinine of kidney transplant recipients by a simple formula based on the balance between metabolic demands of recipients and renal mass supply from donors.

Serum creatinine (Scr) is the most frequently used test to estimate graft function after kidney transplantation. Our previous study demonstrated that the independent predictors of recipient posttransplantation Scr included the ratio of graft weight to recipient body weight, the ratio of graft weight to recipient body surface area (BSA), and the ratio of graft weight to recipient body mass index (BMI). A prospective analysis about the impact of the balance between metabolic demands and renal supply on posttransplantation Scr of recipients was previously reported. We plotted the scatter graph using the X-axis as the independent predictors of Scr by linear regression and the Y-axis as the recipient Scr. To generate the predictive formula of Scr, we calculated a fit of the line of plotted cases using a linear regression method with 2 regression lines for prediction of the upper and lower 95% confidence intervals. Each line was converted into a predictive formula: Scr = -0.0033* (Graft weight(g)/Recipient BSA(m2))+1.75. Under 95% confidence, the Scr ranges from -0.0033* (Graft weight(g)/Recipient BSA(m2))+1.07 to -0.0033* (Graft weight(g)/Recipient BSA (m2))+2.44. Scr = -0.1049* (Graft weight(g)/Recipient body weight(kg))+1.72, which ranges from -0.1049* (Graft weight(g)/Recipient body weight(kg))+1.06 to -0.1049* (Graft weight(g)/Recipient body weight(kg))+2.37. Scr = -0.0158* (Graft weight(g)/Recipient BMI(kg/m2))+1.56, which ranges from -0.0158* (Graft weight(g)/Recipient BMI(kg/m2))+0.75 to -0.0158* (Graft weight(g)/Recipient BMI(kg/m2))+2.26. Prediction of posttransplantation Scr may be achieved by measuring graft weight as well as recipient weight and height. When recipient Scr is significantly higher than that predicted by the formula, a clinician should suspect an underlying graft injury.

Clinical significance of prophylactic antibiotics in renal transplantation.

INTRODUCTION The use of new selective immunosuppressants as well as the emergence of new antimicrobial resistances raise the use of prophylactic antibiotics as a matter of controversy. The purpose of this study was to retrospectively analyze the clinical significance of prophylactic antibiotics in kidney transplantation. METHODS This retrospective study included 174 renal allograft recipients who were divided into two groups: group A including patients who received perioperative prophylactic antibiotics and group B, who did not receive them. We analyzed who the incidence of infectious complications as well as the causative micro-organisms and their antimicrobial resistance within 1 month after kidney transplantation. RESULTS Overall bacterial infections were observed during the first postoperative month in 13 cases (7.4%): 6 (3.4%) surgical site 4 (2.3%) urinary tract, 2 (1.1%) bacteremic, and 1 (0.6%) central catheter infections. There was no respiratory infection. The incidence of bacterial infection was not significantly different between the two groups. The major micro-organisms isolated after kidney transplantation, were Staphylococcus aureus and Escherichia coli; both of which had already shown multidrug resistance at the initial time of infection. CONCLUSION Not only did use of prophylactic antibiotics have little impact to prevent bacterial infections after kidney transplantation, but also it may induce antimicrobial resistance against the antibiotics used for prophylaxis. Moreover, the increased antibiotic resistance prior to kidney transplantation hampers the effectiveness of prophylactic antimicrobial agents. Guidelines for perioperative antibiotic prophylaxis should be therefore revised.