J. Donaldson

An Analysis of Early Renal Transplant Protocol Biopsies - the High Incidence of Subclinical Tubulitis

To investigate the possibility that we have been underestimating the true incidence of acute rejection, we began to perform protocol biopsies after kidney transplantation. This analysis looks at the one‐week biopsies. Between March 1 and October 1, 1999, 100 adult patients undergoing cadaveric kidney or kidney/pancreas transplantation, or living donor kidney transplantation, underwent 277 biopsies. We focused on the subset of biopsies in patients without delayed graft function (DGF) and with stable or improving renal function, who underwent a biopsy 8.2 ± 2.6 d (range 3–18 d) after transplantation (n = 28). Six (21%) patients with no DGF and with stable or improving renal function had borderline histopathology, and 7 (25%) had acute tubulitis on the one‐week biopsy. Of the 277 kidney biopsies, there was one (0.4%) serious hemorrhagic complication, in a patient receiving low molecular weight heparin; she ultimately recovered and has normal renal function. Her biopsy showed Banff 1B tubulitis. In patients with stable or improving renal allograft function early after transplantation, subclinical tubulitis may be present in a substantial number of patients. This suggests that the true incidence of rejection may be higher than is clinically appreciated.

Living Donor Renal Transplantation Using Alemtuzumab Induction and Tacrolimus Monotherapy

Alemtuzumab was used as an induction agent in 205 renal transplant recipients undergoing 207 living donor renal transplants. All donor kidneys were recovered laparoscopically. Postoperatively, patients were treated with tacrolimus monotherapy, and immunosuppression was weaned when possible. Forty‐seven recipients of living donor renal transplants prior to the induction era who received conventional triple drug immunosuppression without antibody induction served as historic controls. The mean follow‐up was 493 days in the alemtuzumab group and 2101 days in the historic control group. Actuarial 1‐year patient and graft survival were 98.6% and 98.1% in the alemtuzumab group, compared to 93.6% and 91.5% in the control group, respectively. The incidence of acute cellular rejection (ACR) at 1 year was 6.8% in the alemtuzumab group and 17.0% (p < 0.05) in the historic control group. Most (81.3%) episodes of ACR in the alemtuzumab group were Banff 1 (a or b) and were sensitive to steroid pulses for the treatment of rejection. There was no cytomegalovirus disease or infection. The incidence of delayed graft function was 0%, and the incidence of posttransplant insulin‐dependent diabetes mellitus was 0.5%. This study represents the largest series to date of live donor renal transplant recipients undergoing alemtuzumab induction, and confirms the short‐term safety and efficacy of this approach.

Pulmonary thromboembolism during adult liver transplantation: incidence, clinical presentation, outcome, risk factors, and diagnostic predictors

BACKGROUND Intraoperative pulmonary thromboembolism (PTE) is an often overlooked cause of mortality during adult liver transplantation (LT) with diagnostic challenge. The goals of this study were to investigate the incidence, clinical presentation, and outcome of PTE and to identify risk factors or diagnostic predictors for PTE. METHODS Four hundred and ninety-five consecutive, isolated, deceased donor LTs performed in an institution for a 3 yr period (2004-6) were analysed. The standard technique was a piggyback method with veno-venous bypass without prophylactic anti-fibrinolytics. The clinical diagnosis of PTE was made with (i) acute cor pulmonale, and (ii) identification of blood clots in the pulmonary artery or observation of acute right heart pressure overload with or without intracardiac clots with transoesophageal echocardiography. RESULTS The incidence of PTE was 4.0% (20 cases); cardiac arrest preceded the diagnosis of PTE [75% (15)] and PTE occurred during the neo-hepatic phase [85% (17)], especially within 30 min after graft reperfusion [70% (14)]. Operative and 60 day mortalities of patients with PTE were higher (P<0.001) than those without PTE (30% vs 0.8% and 45% vs 6.5%). Comparison of perioperative data between the PTE group (n=20) and the non-PTE group (n=475) revealed cardiac arrest and flat-line thromboelastography in three channels (natural, amicar, and protamine) at 5 min after graft reperfusion as the most significant risk factors or diagnostic predictors for PTE with an odds ratio of 154.32 [95% confidence interval (CI): 44.82-531.4] and 49.44 (CI: 15.6-156.57), respectively. CONCLUSIONS These findings confirmed clinical significance of PTE during adult LT and suggested the possibility of predicting this devastating complication.

Two Hundred Living Donor Kidney Transplantations Under Alemtuzumab Induction and Tacrolimus Monotherapy: 3-Year Follow-Up

Alemtuzumab has been used in off‐label studies of solid organ transplantation. We extend our report of the first 200 consecutive living donor solitary kidney transplantations under alemtuzumab pretreatment with tacrolimus monotherapy and subsequent spaced weaning to 3 years of follow‐up. We focused especially on the causes of recipient death and graft loss, and the characteristics of rejection. The actuarial 1‐, 2‐ and 3‐year patient and graft survivals were 99.0% and 98.0%, 96.4% and 90.8% and 93.3% and 86.3%, respectively. The cumulative incidence of acute cellular rejection (ACR) at the following months was 2%≤6, 9.0%≤12, 16.5%≤18, 19.5%≤24, 23.5%≤30, 24.0%≤36 and 25%≤42. The mean serum creatinine (mg/dL) and glomerular filtration rate (mL/min/1.73 m2) at 1 and 3 years were 1.4 ± 0.6 and 58.7 ± 21.6 and 1.5 ± 0.7 and 54.9 ± 20.9, respectively. Fifty (25%) recipients had a total of 89 episodes of ACR. About 88.7% of ACR episodes were Banff 1, and of those, 82% were steroid‐sensitive. Nine (4.5%) recipients had antibody‐mediated rejection (AMR). About 76.5% were weaned but only 46% are currently on spaced dose (qod or less) tacrolimus monotherapy, and 94.4% remained steroid‐free from the time of transplantation. Infectious complications were uncommon. This experience suggests the 3‐year efficacy of this approach.

Pediatric living donor kidney transplantation under alemtuzumab pretreatment and tacrolimus monotherapy: 4-year experience.

Background. Alemtuzumab has been used in off-label studies of solid organ transplantation. Methods. We analyzed the first 42 pediatric consecutive living donor kidney transplantations under alemtuzumab pretreatment with tacrolimus monotherapy and subsequent spaced weaning. We focused especially on the causes of recipient death and graft loss and the characteristics of rejection. Results. Laparoscopic live-donor nephrectomy was associated with no mortality and no delayed graft function. The actuarial 1, 2, 3, and 4 years patient and graft survivals were 97.6% and 97.6%, 93.5% and 85.4%, 93.5% and 85.4%, and 93.5% and 85.4%, respectively. The incidence of cumulative acute cellular rejection (ACR) at 1, 2, 3, and 4 years was 0%, 2.4%, 4.8%, and 4.8%, respectively. The mean serum creatinine (mg/dL) and glomerular filtration rate (mL/min/1.73 m2) at 1, 2, and 3 years were 0.8±0.4 and 94.0±36.8, 0.9±0.4 and 79.6±31.9, and 0.9±0.4 and 95.0±21.7, respectively. Two (4.7%) recipients had ACR, and both Banff 1a ACRs were steroid sensitive. No patients had antibody-mediated rejection. Weaning to spaced dose (qod or less) tacrolimus monotherapy was attempted in 16 (38%) and was successful in 12 (26%) patients. All patients are currently steroid free. There was no tissue invasive cytomegalovirus disease or infection, no BK/polyoma viral nephropathy, and no posttransplant proliferative disease. Conclusion. This experience confirms the 4-year safety and efficacy of this approach in pediatric recipients.

Role of liver transplantation for hepatobiliary malignant disorders

The role of liver transplantation for hepatobiliary malignant disorders remains controversial and will remain so until several crucial issues are resolved, the main difficulty being the shortage of organ donors. Furthermore, a consensus needs to be reached within the transplantation community on the tumour stage at which each disorder is too advanced to be salvaged by liver transplantation. Despite these limitations, there are generally accepted criteria that define when transplantation can, and should, be offered for hepatobiliary malignant disorders.

Posterior Reversible Encephalopathy Syndrome in Liver Transplant Patients: Clinical Presentation, Risk Factors and Initial Management

Posterior reversible encephalopathy syndrome (PRES) is an uncommon but well‐known complication after transplantation diagnosed by characteristic radiological features. As limited data on this complex syndrome exist we sought to better define the incidence, clinical presentation and risk factors for PRES in liver transplant (LTx) patients. We conducted a retrospective analysis of 1923 adult LTx recipients transplanted between 2000 and 2010. PRES was diagnosed radiologically in 19 patients (1%), with 84% of cases occurring within 3 months post‐LTX. We compared this cohort of PRES patients to 316 other LTx recipients also requiring radiographic imaging within 3 months after LTx for neurological symptoms. Seizure was the most common clinical manifestation in the PRES group (88% vs. 16%, p< 0.001) and 31% had an intracranial hemorrhage. Those with hemorrhage on imaging were more likely to be coagulopathic. PRES patients were significantly more likely to have had alcoholic liver disease and infection/sepsis. These factors may be related to a common pathway of vascular dysregulation/damage that appears to characterize this complex syndrome. Intracranial bleeding and seizures may be the end result of these phenomena. The relationship of these associated factors to the hypothesized pathophysiology of PRES is discussed.

A pilot trial of tacrolimus, sirolimus, and steroids in renal transplant recipients

In Renal transplant recipients, sirolimus has been studied extensively in combination with cyclosporine,1 but relatively few published studies have looked at the combination of sirolimus and tacrolimus.2-5 We performed a pilot trial of tacrolimus, sirolimus, and steroids, without antibody induction and with protocol biopsies, to look at the safety and efficacy of this combination. This report describes the early outcomes in the first 30 patients entered into the trial.

Cold heparinized lactated Ringers with procaine (HeLP) preservation fluid in 266 living donor kidney transplantations.

Since the 1960s simple inexpensive cold lactated Ringers with additives has been used for short-term cold preservation of kidneys from living donors. We performed 266 living donor kidney transplantations from January 22, 2003 to October 30, 2006. Donor allografts were recovered laparoscopically and flushed with cold heparin, lactated Ringers and procaine (HeLP) solution. Warm and cold ischemic times were typically <45 min and <90 min, respectively. The mean follow up was 21.6±12.2 months. There was no delayed graft function. Actuarial 1-year patient and graft survival were 98.6% and 98.1%, respectively. The creatinine at 1 year was 1.46±0.51 mg/dL. The cumulative incidences of acute cellular rejection at 6, 12, 18, and 24 months were 3.0%, 7.1%, 10.2%, and 11.7%. There were no identifiable side effects attributed to the HeLP solution. This study documents the effectiveness of cold HeLP as a flushing and short-term preservation fluid for living donor kidney transplantation with excellent results and significant cost benefit because of its low cost.

TO WEAN OR NOT TO WEAN TACROLIMUS MONOTHERAPY AFTER ALEMTUZUMAB PRETREATMENT IN LIVING DONOR KIDNEY TRANSPLANT RECIPIENTS: A COMPARATIVE STUDY.: 2039

H.P. Tan1, A. CHAUDHARY2, A. Humar1, J. DONALDSON1, A. Basu1, C. Morgan1, M. UNRUH3, J. McCauley3, C. Wu3, N. Shah4, P. Randhawa1, R. Shapiro1 1Surgery / Transplant, Thomas E. Starzl Transplantation Institute, Pittsburgh/PA/UNITED STATES OF AMERICA, 2Transplant Surgery, Thomas E. Starzl Transplantation Institute, Pittsburgh/PA/UNITED STATES OF AMERICA, 3Nephrology, UPMC, Pittsburgh/PA/UNITED STATES OF AMERICA, 4Internal Medicine/nephrology, UPMC, Pittsburgh/PA/UNITED STATES OF AMERICA