Increasing incidence of steroid resistant rejection in kidney transplantation.
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Antilymphocyte Serum↗
Biomedical subjects
A Humar
Publications and source records attributed to A Humar.
Kidney transplant using pediatric donors--effect on long-term graft and patient survival.
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Adolescent↗
Living liver donor surgery: report of initial anesthesia experience.
The charts and anesthetic records of 12 patients who donated the left lateral segment of their liver to a related infant or child to treat liver failure were retrospectively reviewed. Blood loss, need for transfusion, fluids administered, surgical length, and perioperative complications were investigated. The records also were examined to determine the hemodynamic stability of patients undergoing donor hepatectomy to assess their need for invasive monitoring. There were no episodes of hypotension or hemodynamic instability. The average operating time was 9.6 +/- 1.1 hours. The blood loss was 562 +/- 244 mL (range 300 to 1100 mL). Four patients received their own cell saver blood (200 mL, 220 mL, 300 mL, 475 mL), and one patient received 1 U (350 mL) of predonated autologous blood. The average hemoglobin decreased significantly (p = 0.001) from a preoperative value of 14.1 +/- 1.2 to 12.3 +/- 1.8 g/dL in the recovery room. All patients were extubated in the operating room or recovery room. Patients were discharged home in 6.9 +/- 1.3 days (range 5 to 9 days). Living-related liver resection can be performed with noninvasive monitoring and without the need for heterologous blood products.
Adult↗
Living related liver transplantation in infants and children: report of anesthetic care and early postoperative morbidity and mortality.
STUDY OBJECTIVE: To determine those infants at high risk for perioperative complications and mortality following living, related liver transplantation. DESIGN: Retrospective chart review. SETTING: Large metropolitan teaching hospital. MEASUREMENTS AND MAIN RESULTS: The charts and anesthetic records of the 12 infants and children who received the left lateral hepatic segment from a living relative the past 2 years at our institution were reviewed. The records were examined to determine the causes of perioperative morbidity and to identify patients at high risk for serious complications and mortality. All infants and children (mean +/- SD age, 29+/-30 months; weight, 13.6 +/-6.8 kg) survived the operation (8.3+/-1.7 hours) without intraoperative complications. The average blood loss, including 500 mL of recipient blood used to flush the liver before reperfusion, was 1483 +/-873 mL (119+/-70 mL/kg). Three infants developed portal vein thrombosis, and one of these infants also had hepatic artery thrombosis. The risk of vessel thrombosis was significantly higher (3/3 vs. 0/9; p<0.0045) in infants less than 9 kg body weight, as was the risk of death (2/3 vs. 0/9; p<0.045). Both children who died had vascular thrombosis. Other serious complications were bleeding, 6; infection, 7; acute rejection, 3; and bile leak, 2. CONCLUSIONS: Infants and children can successfully undergo living, related liver transplantation. However, the risks of vascular complications and death are greater in infants less than 9 kg body weight.
Anesthesia↗
Steroid withdrawal in pancreas transplant recipients.
BACKGROUND: Numerous studies of steroid withdrawal have been carried out in kidney and liver transplant recipients, but only a few in pancreas transplant recipients. Yet, pancreas transplant recipients could have significant long-term benefits from steroid withdrawal. METHODS: We performed a retrospective analysis to determine the feasibility of steroid withdrawal in pancreas transplant recipients. RESULTS: Of 360 recipients who underwent a pancreas transplant between January 1, 1994 and June 30, 1998, 14 attempted steroid withdrawal (12 simultaneous pancreas-kidney [SPK]; 2 pancreas transplant alone [PTA]). Reasons for steroid withdrawal were bone fractures (n = 3), psychiatric disorders (n = 2), severe acne (n = 1), recurrent infections (n = 4), and problems with hypercholesterolemia or hypertension (n = 4). All 14 were maintained on tacrolimus and mycophenolate mofetil (MMF) immunosuppression, except for 1 who was on tacrolimus and azathioprine (AZA). Of the 14 recipients, 11 had no episodes of acute rejection before steroid withdrawal. The remaining 3 had one or more acute rejection episodes. Of the 14 recipients, 10 (72%) currently remain off steroids (mean follow-up 18 months, range 5-51 months). However, 4 recipients have resumed steroids: 2 after an acute rejection episode (at 2 and 21 months post-withdrawal) and 2 because of leukopenia (WBC < 3000) and an inability to tolerate full-dose MMF. Steroid withdrawal was unsuccessful in both PTA recipients and in 2 of the 12 SPK recipients. All 14 recipients currently have a functioning pancreas graft. However, 1 of the SPK recipients, in whom steroid withdrawal failed, has developed chronic kidney rejection and is now back on hemodialysis awaiting a retransplant. CONCLUSION: Steroid withdrawal is possible in up to 70% of pancreas transplant recipients. Further studies are necessary to define ideal candidates for steroid withdrawal. Based on the results of this analysis, we have launched a prospective, randomized trial of steroid withdrawal in pancreas transplant recipients.
Adult↗
Should I accept this kidney?
BACKGROUND: Transplant candidates frequently ask whether they should, based on information available at the time, accept a cadaver kidney or wait for a potentially better one. METHODS: We analyzed 937 first and second cadaver transplants done between January 1, 1984 and December 31, 1997 to determine if information available at the time an offer is made could be used to predict long-term graft survival. RESULTS: By Cox regression, risk factors for worse long-term graft survival were older donor age, cardiovascular or cerebrovascular cause of donor death, and delayed graft function (DGF). HLA-ABDR mismatch was marginally significant. Whether DGF will occur is not known at the time of an offer, but risk factors can be determined; we found these to be older donor age and > 10% panel-reactive antibodies (PRA) at transplantation (by Cox regression). Using these variables (PRA, ABDR mismatch, donor age, and donor cause of death) known at the time of an offer, we calculated the relative risk of worse long-term graft survival for each subgroup (Table 3 in manuscript). In general, older age and donor death from cardiovascular or cerebrovascular disease were associated with worse outcome. Kidneys from donors of < 50 yr had the best outcome, irrespective of match. CONCLUSION: The data provided can be used to help guide patients as to whether they are better off accepting an offered kidney or waiting for a potentially better one. If an offer is declined, the next kidney may have a potentially worse outcome.
Adolescent↗
Prolonged preservation increases surgical complications after pancreas transplants.
BACKGROUND: Prolonged preservation of the donor organ may result in delayed graft function or nonfunction after most organ transplants. We studied whether or not prolonged preservation increases surgical complications after pancreas transplants. METHODS: Between January 1, 1994, and September 30, 1998, a total of 294 recipients underwent cadaver pancreas transplants at our institution. Recipients were analyzed in 2 groups: those with pancreas preservation time < or = 20 hours (n = 211) versus > 20 hours (n = 83). RESULTS: Demographic data were similar between the 2 groups, except that mean donor age in the prolonged preservation group was significantly lower. Despite use of younger donors, prolonged preservation was associated with an increased incidence of surgical complications, most notably leaks, thrombosis, and wound infections. Grafts with prolonged preservation were more often noted by the transplant surgeon to be edematous after reperfusion, although the incidence of hyperamylasemia posttransplant did not differ between the 2 groups. Graft and patient survival rates also did not differ between the 2 groups. The incidence of early graft loss (< 3 months) was, however, higher in the prolonged preservation group (20.5% versus 9.0%, P = .04). CONCLUSIONS: Prolonged preservation of the donor organ increases the incidence of surgical complications after pancreas transplants. All attempts should be made to minimize preservation time, keeping it below 20 hours, if possible.
Adult↗
Surgical risks and outcome of pancreas retransplants.
BACKGROUND: The increased popularity of pancreas transplants has led to an increased number of potential candidates for retransplants after the initial graft has been lost to technical failure or rejection. We studied a group of recipients who underwent pancreas transplants at a single center to determine whether retransplant recipients were at higher risk of complications. METHODS: Between June 1, 1994, and Dec 31, 1997, a total of 213 pancreas transplants were performed at the University of Minnesota. Of these, 187 were primary transplants and 26 were retransplants. Demographically, the two groups were not significantly different. We analyzed and compared the two groups with respect to incidence of surgical complications, graft survival rates, and patient survival rates. RESULTS: Surgical complications such as bleeding and vascular thrombosis were slightly more common after retransplants, but this trend did not quite reach statistical significance. Infectious complications and leaks were equivalent between the two groups. The incidence of acute rejection was higher after retransplants (P =.02). At 3 years posttransplant, patient survival was no different between the two groups, but pancreas graft survival was lower after retransplants (P =.08). The incidence of early graft loss (by 6 months posttransplant) was significantly higher in retransplant recipients (27% vs 14%, P =.04). CONCLUSIONS: Pancreas retransplants can be performed with a minimal increase in surgical complications. However, graft survival after retransplants is slightly inferior to that after primary transplants, probably for both immunologic and nonimmunologic reasons. Retransplants can be offered to suitable candidates, but they may require more aggressive monitoring for rejection.
Adult↗
Decreased surgical risks of pancreas transplantation in the modern era.
OBJECTIVE: To document the decreased incidence of surgical complications after pancreas transplantation in recent times. SUMMARY BACKGROUND DATA: Compared with other abdominal transplants, pancreas transplants have historically had the highest incidence of surgical complications. However, over the past few years, the authors have noted a significant decrease in the incidence of surgical complications. METHODS: The authors studied the incidence of early (<3 months after transplant) surgical complications (e.g., relaparotomy, thrombosis, infections, leaks) after 580 pancreas transplants performed during a 12-year period. Patients were analyzed and compared in two time groups: era 1 (June 1, 1985, to April 30, 1994, n = 367) and era 2 (May 1, 1994, to June 30, 1997, n = 213). RESULTS: Overall, surgical complications were significantly reduced in era 2 compared with era 1. The relaparotomy rate decreased from 32.4% in era 1 to 18.8% in era 2. Significant risk factors for early relaparotomy were donor age older than 40 years and recipient obesity. Recipients with relaparotomy had significantly lower graft survival rates than those without relaparotomy, but patient survival rates were not significantly different. A major factor contributing to the lower relaparotomy rate in era 2 was a significant decrease in the incidence of graft thrombosis; the authors believe this lower incidence is due to the routine use of postoperative low-dose intravenous heparin and acetylsalicylic acid. The incidence of bleeding requiring relaparotomy did not differ between the two eras. Older donor age was the most significant risk factor for graft thrombosis. The incidence of intraabdominal infections significantly decreased between the two eras; this decrease may be due to improved prophylaxis regimens in the first postoperative week. CONCLUSIONS: Although a retrospective study has its limits, the results of this study, the largest single-center experience to date, show a significant decrease in the surgical risk associated with pancreas transplants. Reasons for this decrease are identification of donor and recipient risk factors, better prophylaxis regimens, refinements in surgical technique, and improved immunosuppressive regimens. These improved results suggest that more widespread application of pancreas transplantation is warranted.
Adult↗
5,000 kidney transplants--a single-center experience.
Between 6/1963 and 12/1998, 5,069 kidney transplants were done at the University of Minnesota. Of these, about half have been living donor, half cadaver. The majority (83%) have been primary transplants. Recipients were grouped in 6 eras based on changes in our immunosuppressive protocols--6/63-12/67 (n = 98); 1/68-7/79 (n = 1,188); 8/79-6/84 (n = 789); 7/84-9/90 (n = 1,006); 10/90-12/95 (n = 1,050; 1/96-12/98 (n = 718)--and their outcomes were compared. Recent eras contained a higher proportion of recipients aged > 50. Since the inception of the program, there has been a steady improvement in actuarial patient survival, graft survival, and death-censored graft survival. Short-term outcome for primary and retransplant recipients has been similar; however, long-term outcome seems worse for retransplant recipients. Importantly, acute rejection and infectious death have become rare causes of graft loss. Chronic rejection and death with function (most often due to a cardiovascular event) have become the predominant causes of graft loss. Recent changes in immunosuppressive protocols (Era VI) have included more aggressive attempts to maintain CsA levels > 150 ng/ml (by HPLC) in the first 3 months and the substitution of mycophenolate mofetil for azathioprine. As a result, the incidence of acute and chronic rejection has decreased and graft survival has improved.
Adolescent↗
The University of Toronto Liver Transplant Program: Toronto General Hospital, Hospital for Sick Children.
The University of Toronto Liver Transplant Program began in 1985 at a time when the procedure had already evolved from an experimental form of surgery to an accepted treatment for many forms of liver failure. The program was established not only to provide clinical care for patients but also to address academically the barriers that impeded success. The program brought together experts in medicine, surgery, pathology, and the basic sciences of immunology, virology and molecular biology. Significant advances over the past decade and a half in immunosuppressive drugs and monitoring, patient selection, and infectious management have contributed to markedly improved patient and graft survival rates. Nevertheless, we continue to face 2 major challenges: a growing scarcity of donor organs, a problem partially addressed through development of living-related liver donation, and recurrent viral hepatitis. We expect to remain on the forefront of ongoing research to provide solutions to these and other barriers to the full deployment of liver transplantation in the year 2000.
Adult↗
Immunologic factors: the major risk for decreased long-term renal allograft survival.
BACKGROUND: Both antigen-dependent (immunologic) and non-antigen-dependent (nonimmunologic) factors have been implicated in long-term renal allograft loss. Differentiating between these two factors is important because prevention strategies differ. METHODS: To isolate the importance of these 2 factors, we studied long-term actuarial graft survival in a cohort of adult kidney recipients who underwent transplants at a single institution between January 1, 1984 and October 31, 1998. Excluded were recipients with graft loss as a result of death with function, technical failure, primary nonfunction, and recurrent disease, leaving 1587 recipients (757 cadaver [CAD], 830 living donor [LD]) who would be at risk for graft loss secondary to both immunologic and nonimmunologic factors. These recipients were analyzed in the following 2 groups: those treated for a previous episode of acute rejection (AR) (Group1; n = 588; 328 CAD, 260 LD) and those with no AR (Group 2: n = 999; 429 CAD, 570 LD). Actuarial graft survival and causes of graft loss were determined for each group. Presumably, graft loss in Group 1 would be caused by immunologic and nonimmunologic factors; graft loss in Group 2 would be caused primarily by nonimmunologic factors. RESULTS: The 10-year graft survival rate (censored for death with function, technical failure, primary nonfunction, and recurrent disease) in Group 2 was 91%. In contrast, the 10-year graft survival rate in Group 1 was 45% (P<0.001 vs. Group 2). Causes of graft loss in Group 2 were chronic rejection in 1.8% (3.0% CAD, 0.9% LD), de novo disease, 0.4%; sepsis, 0.2%; discontinuation of immunosuppressive therapy, 0.3%; and unknown, 0.6%. In contrast, 23.8% (29.9% CAD, 16.2% LD) of recipients in Group 1 had graft loss caused by chronic rejection (P = 0.001 vs. Group 2). CONCLUSIONS: This very low incidence of chronic rejection in recipients without previous AR suggests that immunologic factors are the main determinants of long-term kidney transplant outcome; nonimmunologic factors in isolation may have only a minimal impact on long-term graft survival.
Adult↗
Association between cytomegalovirus disease and chronic rejection in kidney transplant recipients.
BACKGROUND: It has long been suggested that cytomegalovirus (CMV) disease plays a role in the pathogenesis of chronic rejection (CR). However, its role has been difficult to prove, given the strong association between acute rejection and CMV, and the even stronger association between acute rejection and CR. To try to isolate the relative contribution of CMV infection in the pathogenesis of CR, we used multivariate techniques to examine risk factors for CR, including CMV disease. METHODS: Our study population consisted of adult recipients of a first kidney graft who underwent transplantation at a single center between 1/1/85 and 6/30/97 (n = 1339). RESULTS: Multivariate analysis using time to CR as the dependent variable demonstrated acute rejection to be the strongest risk factor (relative risk [RR] = 17.8, P = 0.0001), followed by older donor age (RR = 1.46, P = 0.01). The presence of CMV disease showed a trend toward increased risk for CR (RR = 1.30, P = 0.10), although the association was not as strong as with the other two variables. Comparing only those recipients with acute rejection and CMV disease versus those with acute rejection but no CMV disease, the relative risk of developing CR was 1.37 times higher in the former group. Recipients with acute rejection and CMV developed CR sooner and with a higher incidence versus those with acute rejection but no CMV (P = 0.002). It is interesting, however, that CMV disease was only a risk factor for CR in the presence of acute rejection. Recipients with no acute rejection and CMV disease did not have a higher incidence of CR versus those with no acute rejection and no CMV (P = NS). CONCLUSION: CMV disease seems to play some role in the pathogenesis of CR but only in the presence of acute rejection. Reasons may include (i) the inability to adequately treat acute rejection due to the presence of CMV disease or (ii) the increased virulence of latent CMV virus in recipients being treated for acute rejection. Our data may suggest a role for more aggressive prophylaxis against CMV disease, especially at the time of treatment for acute rejection.
Acute Disease↗
Clinical utility of quantitative cytomegalovirus viral load determination for predicting cytomegalovirus disease in liver transplant recipients.
BACKGROUND: The early detection of cytomegalovirus (CMV) after liver transplantation may form the basis of a preemptive strategy for prevention of active CMV disease. METHODS: We prospectively analyzed the clinical use of weekly quantitative polymerase chain reaction-(PCR) based plasma viral load determinations and the antigenemia assay for predicting the development of active CMV disease in 97 consecutive liver transplant recipients. RESULTS: CMV disease occurred in 21/97 patients. Using a positive cut-off of >400 copies/ml plasma, PCR had a sensitivity of 100%, specificity 47.4%, positive predictive value 34.4% and negative predictive value 100% for prediction of CMV disease. Respective values for a positive antigenemia (>0 positive cells/slide) were 95.2, 55.3, 37.0, and 97.7%. Different cut-off points for a positive test were analyzed using receiver-operating characteristic (ROC) curves. The optimal cut-off for viral load was in the range of 2000-5000 copies/ml (sensitivity 85.7%, specificity 86.8%, PPV 64.3%, NPV 95.7% for >5000 copies/ml). The optimal cut-off for antigenemia was in the range of four to six positive cells/slide. Mean peak viral load in symptomatic patients was 73,715 copies per/ml versus 3615 copies/ml in patients with asymptomatic CMV reactivation (P<0.001). In a multivariate logistic regression analysis of risk factors for CMV disease (CMV serostatus, acute rejection, and induction immunosuppression), peak viral load and peak antigenemia emerged as the only significant independent predictors of CMV disease (for PCR, odds ratio=1.40/1000 copy/ml increase in viral load, P=0.0001; for antigenemia odds ratio=1.17/1 positive cell/slide). CONCLUSIONS: Plasma viral load by quantitative PCR is useful for predicting CMV disease and could be used in a preemptive strategy.
Adolescent↗
Features of acute rejection that increase risk for chronic rejection.
BACKGROUND: Acute rejection (AR) has been shown to be a significant risk factor for chronic rejection (CR) in kidney transplant recipients, yet many recipients with AR do not progress to CR. The purpose of this study was to determine if certain AR episodes are associated with a worse prognosis. METHODS: The study group consisted of 279 kidney transplant recipients, all treated for a single episode of biopsy-proven AR. All AR episodes were initially treated with steroids; steroid-resistant rejection was managed with an antibody preparation. RESULTS: First, by univariate techniques, we determined the clinical impact of severity of AR (as estimated by delta creatinine [dCr], defined as the change in baseline serum creatinine level 6 weeks after AR treatment) on two different endpoints--biopsy-proven CR and graft survival. Irrespective of 6-week dCr, all recipients with AR had a significantly increased risk of CR vs. those with no AR (P<0.01). Recipients with dCr between 0.5 and 1.0 mg/dl had a significantly higher incidence of CR vs. those with dCr <0.5 mg/dl (P<0.05), but a significantly lower incidence vs. those with dCr >1.0 mg/dl (P<0.05). We then performed multivariate analysis. We used severity of AR in addition to other variables (e.g., timing of AR, donor age) to determine which factors were most associated with risk for CR and graft loss. Risk for CR increased with AR episodes occurring >6 months after transplant (relative risk [RR] = 3.8, P = 0.005); with moderate or severe (vs. mild) AR episodes (RR = 2.7, P = 0.05); and with dCr >0.5 mg(dl (vs. <0.5 mg/dl) at 6 weeks after AR treatment (RR = 2.3, P = 0.1). Findings were similar when graft survival (death-censored) was the endpoint instead of CR. CONCLUSIONS: All AR episodes are associated with some increase in the risk for CR. But AR episodes occurring >6 months after transplant and those of increased severity (as assessed qualitatively by histologic grading and quantitatively by dCr) confer the greatest risk. Recipients with these risk factors could be targeted with measures to decrease their risk for CR, including trials of novel immunosuppressive regimens.
Acute Disease↗
Long-term follow-up of living kidney donors: quality of life after donation.
The University of Minnesota has been a strong advocate of living donor kidney transplants. The benefits for living donor recipients have been well documented. The relative low risk of physical complications during donation has also been well documented. Less well understood is the psychosocial risk to donors. Most published reports have indicated an improved sense of well-being and a boost in self-esteem for living kidney donors. However, there have been some reports of depression and disrupted family relationships after donation, even suicide after a recipient's death. To determine the quality of life of our donors, we sent a questionnaire to 979 who had donated a kidney between August 1, 1984, and December 31, 1996. Of the 60% who responded, the vast majority had an excellent quality of life. As a group, they scored higher than the national norm on the SF-36, a standardized quality of life health questionnaire. However, 4% were dissatisfied and regretted the decision to donate. Further, 4% found the experience extremely stressful and 8% very stressful. We used multivariate analysis to identify risk factors for this poor psychosocial outcome and found that relatives other than first degree (odds ratio=3.5, P=0.06) and donors whose recipient died within 1 year of transplant (odds ratio=3.3, P=0.014) were more likely to say they would not donate again if it were possible. Further, donors who had perioperative complications (odds ratio=3.5, P=0.007) and female donors (odds ratio=1.8, P=0.1) were more likely to find the overall experience more stressful. Overall, the results of this study are overwhelmingly positive and have encouraged us to continue living donor kidney transplants.
Adolescent↗
Cytomegalovirus disease recurrence after ganciclovir treatment in kidney and kidney-pancreas transplant recipients.
BACKGROUND: With the introduction of ganciclovir, the clinical pattern of cytomegalovirus (CMV) disease has changed; CMV disease recurrence after successful treatment of the initial episode has emerged as a more common problem. We studied CMV disease recurrence in kidney transplant (KTx) and simultaneous kidney-pancreas transplant (SPK) recipients, and identified risk factors for recurrence. METHODS: Between January 1987 and December 1995, of 1272 KTx and 287 SPK recipients, 332 developed CMV disease and were treated with a 14-day course of i.v. ganciclovir, followed by a 10-week course of oral acyclovir. Among these 332 recipients, 103 (31%) developed CMV disease recurrence more than 30 days after treatment for the initial episode; this group was compared with those recipients who did not develop recurrence (n=229). Risk factors examined were age, presence of diabetes, type of transplant (KTx vs. SPK), donor source (cadaver vs. living donor), treatment for acute rejection, pretransplant CMV serologic status, evidence of tissue-invasive CMV, and treatment of the initial episode with human immune globulin in addition to ganciclovir. RESULTS: Univariate analysis found that patients with recurrence were more likely to be diabetic (70.9% vs. 53.7%; P=0.04), to have undergone an SPK (39.8% vs. 20.5%; P=0.004), to have received a cadaver organ (78.6% vs. 61.6%; P=0.002), and to have received treatment for acute rejection (78.6% vs. 59.8%; P=0.001). Using multivariate analysis, two statistically significant risk factors were found: receiving a cadaver organ (relative risk [RR]=1.90; P=0.03) and treatment for acute rejection (RR=2.02; P=0.008). Diabetes (RR=1.44; P=0.18) and a cadaver SPK transplant (RR=1.55; P=0.12) tended toward increased risk for recurrence, but the difference did not reach statistical significance. The remaining variables were not significant. Interestingly, CMV recurrence did not significantly diminish 5-year graft survival (52.0% vs. 54.4%; P not significant) or patient survival (67.0% vs. 68.3%; P not significant) rates. CONCLUSIONS: CMV disease recurs in roughly one-third of KTx and SPK recipients after treatment of the initial episode with ganciclovir. A cadaver organ source and treatment for acute rejection were the most significant clinical risk factors for recurrence. Clinical predictors of recurrence such as these may help to identify those recipients who need more intensive therapeutic and prophylactic regimens.
Antiviral Agents↗
Disseminated Bartonella infection with granulomatous hepatitis in a liver transplant recipient.
Disseminated infection with Bartonella spp with granulomatous hepatitis was diagnosed in a liver transplant recipient presenting with fever of unknown origin. Pathological findings on liver biopsy were atypical, with scant granulomas seen only after a second biopsy. The patient responded promptly to antibiotic therapy. Infections caused by Bartonella spp should be considered in transplant recipients with fever of unknown origin.
Adult↗