Radi Zaki

Operative Start Times and Complications After Liver Transplantation

The recent national focus on patient safety has led to a re‐examination of the risks and benefits of nighttime surgery. In liver transplantation, the hypothetical risks of nighttime operation must be weighed against either the well‐established risks of prolonging cold ischemia or the potential risks of strategies to manipulate operative start times. A retrospective review was conducted of 578 liver transplants performed at a single institution between 1995 and 2008 to determine whether the incidence of postoperative complications correlated with operative start times. We hypothesized that no correlation would be observed between complication rates and operative start times. No consistent trends in relative risk of postoperative wound, vascular, biliary, or other complications were observed when eight 3‐h time strata were compared. When two 12‐h time strata (night, 3 p.m.–3 a.m., and day, 3 a.m.–3 p.m.) were compared, complications were not significantly different, but nighttime operations were longer in duration, and were associated a twofold greater risk of early death compared to daytime operations (adjusted OR 2.9, 95% CI 1.16–7.00, p = 0.023), though long‐term survival did not differ significantly between the subgroups. This observation warrants further evaluation and underscores the need to explore and identify institution‐specific practices that ensure safe operations regardless of time of day.

Concomitant proton pump inhibitors with mycophenolate mofetil and the risk of rejection in kidney transplant recipients.

Background Recent pharmacokinetic studies have demonstrated that proton pump inhibitors (PPI) reduce exposure of mycophenolic acid. However, the clinical significance of this drug–drug interaction on transplantation outcomes has not been determined. Methods This was a retrospective cohort study in kidney transplant recipients who were prescribed rabbit antithymocyte globulin, calcineurin inhibitor, mycophenolate mofetil, and steroids. We evaluated the impact of PPI use on the 1-year rates of biopsy-proven acute rejection (BPAR). Results Two hundred thirteen patients who were prescribed PPI were compared with 384 patients who were on standard acid-suppressive therapy with ranitidine. BPAR occurred in similar rates in both groups (15% vs. 12%; P=0.31). In a multivariable analysis, black race was associated with a higher risk of rejection (risk ratio [RR], 2.38; 95% confidence interval [CI], 1.41–4.03). While controlling for rejection risk factors, PPI exposure was associated with an increased risk of rejection in black patients (RR, 1.93; 95% CI, 1.18–3.16) but not in non-black patients (RR, 0.54; 95% CI, 0.19–1.49). At 1 year, BPAR type, BPAR grade, patient and graft survival, graft function, and time to BPAR were not associated with PPI exposure. Conclusion In this retrospective study, PPI use in the first transplant year was associated with an increased risk for BPAR in black patients but not in non-black patients. It is possible that a reduction in mycophenolic acid exposure contributed to the increased risk.

Immediate postoperative sonography of renal transplants: vascular findings and outcomes.

OBJECTIVE The purpose of this study was to determine the frequency and types of significant vascular findings on bedside sonography immediately after renal transplantation and which abnormalities would suggest a benefit from early surgical revision. MATERIALS AND METHODS Five hundred seventy-five renal transplant sonograms obtained within 4 hours of surgery were retrospectively reviewed for major vascular abnormalities: lack of renal artery (RA) or renal vein (RV) flow, elevated peak systolic velocity (PSV)>300 cm/s, parvus tardus waveforms, and markedly decreased or no color parenchymal flow. Clinical outcomes of abnormal cases were reviewed, including reoperations and percutaneous interventions. RESULTS Thirty-two (5.6%) patients underwent repeat surgery within the first week, 16 for nonvascular causes. Forty-seven (8.2%) patients had positive sonography findings. In 16 patients, sonography impacted the decision for reoperation, with 14 confirmed vascular diagnoses: compartment syndrome (n=7), RV thrombosis (n=3), RA thrombosis (n=1), RA and RV thromboses (n=2), and vascular steal (n=1). All were salvaged except the three RV thromboses. Two patients had no vascular abnormality at surgery. All 16 had markedly decreased color flow and varying abnormalities of PSV and waveforms. Outcomes of the remaining 31 cases were infarct (n=1), renal or iliac artery stenoses eventually requiring stents (n=4), and normalized (n=26). These 26 had elevated PSV with normal or near-normal color flow. Unpaired Student t tests showed no significant difference in PSV between patients requiring surgery or stents and those who normalized (p=0.34). CONCLUSION Immediate postoperative sonography has a spectrum of vascular findings, of which markedly decreased color flow is most likely to benefit from immediate reoperation.

Perioperative management of spontaneous splenorenal shunts in orthotopic liver transplant patients.

OBJECTIVES Spontaneous splenorenal shunts cause significant vascular steal from the liver. There is no accepted algorithm for treating spontaneous splenorenal shunts before, during, or after liver transplant, and evidence for efficacy of treatments remains limited. MATERIALS AND METHODS We reviewed the literature, and our institutions experience regarding spontaneous splenorenal shunts, including a case series of 6 patients with spontaneous splenorenal shunts undergoing transjugular intrahepatic porto-systemic shunts, a case of intraoperative ligation of a large spontaneous splenorenal shunts during transplant, and 1 patient requiring multiple endovascular interventions to embolize recurrent spontaneous splenorenal shunts after orthotopic liver transplant. RESULTS Small spontaneous splenorenal shunts may not need intervention, as involution after liver transplant is well known. Transjugular intrahepatic porto-systemic shunts may decrease the porto-systemic gradient in patients with large spontaneous splenorenal shunts, as shown in our review of 6 patients with large spontaneous splenorenal shunts undergoing transjugular intrahepatic porto-systemic shunts. We have demonstrated re-establishment of physiologic flow after ligation of a large spontaneous splenorenal shunt at the time of transplant, supporting operative ligation may be justified if intraoperative compression of the spontaneous splenorenal shunts demonstrates significant improvement of allograft portal venous flow. Ligation of the left renal vein for large spontaneous splenorenal shunts is a safe and effective method of preventing portal venous steal. For concomitant spontaneous splenorenal shunts and portal vein thrombosis, renoportal anastomosis can be performed. We report transient success with endovascular embolization of large spontaneous splenorenal shunts in a patient posttransplant who required multiple interventions. CONCLUSIONS Experience in the approach to and treatment of spontaneous splenorenal shunts in liver transplant recipients is limited. Further investigation into the best approach to treat spontaneous splenorenal shunts is warranted as the presence and persistence of spontaneous splenorenal shunts can lead to allograft dysfunction and possible allograft loss.

Evaluating safety and efficacy of rabbit antithymocyte globulin induction in elderly kidney transplant recipients.

OBJECTIVES The optimal immunosuppression regimen for elderly kidney transplant recipients is poorly defined. We sought to evaluate the short-term efficacy and safety of thymoglobulin in geriatric recipients of deceased-donor kidneys. MATERIALS AND METHODS A single-center, retrospective analysis was undertaken between elderly (≥ 65 years) (n=137) and nonelderly (n=276) kidney transplant recipients who received rabbit antithymocyte globulin induction and calcineurin inhibitor, mycophenolic acid, and prednisone maintenance. RESULTS The mean age was 70 versus 52 years. Fewer elderly patients had an earlier transplant or panel reactive antibodies > 20%, but had more machine perfused, older, and extended criteria donor kidneys. Elderly patients received lower rabbit antithymocyte globulin (5.4 vs 5.6 mg/kg; P = .04) and initial mycophenolic acid doses (1620 vs 1774 mg; P = .002), and experienced less delayed graft function (31.1% vs 50.0%; P < .001). Death-censored graft survival and graft function at 3 years and biopsy-proven acute rejection at 1 year were comparable; however, there was lower 3-year patient survival in elderly patients. Donor age was the only factor associated with reduced patient survival. Rates of malignancy, infection, or thrombocytopenia were similar; however, leukopenia occurred less frequently in elderly patients (11.7% vs 19.9%; P = .038). CONCLUSIONS Elderly kidney transplant recipients receiving rabbit antithymocyte globulin did not experience different short-term graft survival, graft function or rates of infection, malignancy or hematologic adverse reactions than did nonelderly patients; they experienced fewer episodes of delayed graft function, but had lower 3-year patient survival.

Operative start times and complications after kidney transplantation.

The worldwide focus on work hour regulations and patient safety has led to the re‐examination of the merits of night‐time surgery, including kidney transplantation. The risks of operating during nontraditional work hours with potentially fatigued surgeons and staff must be weighed against the negative effects of prolonged cold ischemic time with resultant graft compromise. The aim of this study was to evaluate the impact of performing renal transplantation procedures during evening versus day time hours. The main outcome measures assessed between the day and night cohorts included comparisons of the postoperative complication rates and survival outcomes for both the renal allograft and the patient. A retrospective review of 633 deceased donor renal transplants performed at a single institution was analyzed. Three statistically significant results were noted, namely, a decrease in vascular complications in the nighttime cohort, an increase in urologic complications on subgroup analysis in the 3 AM to 6 AM cohort, and the 12 AM to 3 AM subgroup had the greatest odds of any complication. There was no statistical difference in either patient or graft survival over a twelve month period following transplantation. We conclude that although the complication rate varied among cohorts this was clinically insignificant and there was no overall clinically relevant impact on patient or graft survival.

Vascular Steal of the Portal Vein After Orthotopic Liver Transplant Intraoperative Sonographic Diagnosis

Spontaneous splenorenal shunts (SSRSs) are portosystemic connections between the splenic vein and the left renal vein (LRV) that develop commonly in patients with portal hypertension. 1 They reportedly occur in 18% to 19% of patients evaluated for a liver transplant. 2, 3 As the liver become more cirrhotic, a major steal phenomenon may occur, whereby blood is shunted from the high‐resistance venous bed of the liver to the lower systemic pressure of the LRV. 4 Not infrequently, an SSRS will go undetected during orthotopic liver transplantation because dissection is limited to the right upper quadrant.

Extraction time of kidneys during organ procurement impacts function

Osband AJ, Zaki RF. Extraction time of kidneys during organ procurement impacts function. 
Clin Transplant 2011: 25: 235–238.

Falsely Elevated Tacrolimus Levels Caused by Immunoassay Interference Secondary to β-Galactosidase Antibodies in an Infected Liver Transplant Recipient

Careful interpretation of tacrolimus levels is essential to ensure optimal immunosuppressive therapy while avoiding toxicity. Interference with tacrolimus assays may be an underreported event that has the potential to result in negative patient outcomes through unnecessary modifications of therapy. We describe a 55–year‐old liver transplant recipient who had falsely elevated tacrolimus levels that led to the eventual disruption of his immunosuppressive therapy and subsequent rejection of his allograft. Although his increased tacrolimus levels did not correlate with clinical signs and symptoms of tacrolimus toxicity, interruption of therapy in this patient was supported by an acute infection and a slight elevation in serum creatinine concentration. Tacrolimus levels were analyzed by using an antibody conjugated magnetic immunoassay method, and levels as high as 79.7 ng/ml were observed, despite discontinuation of tacrolimus. We conducted an evaluation for assay interference by using an alternative assay method (microparticle enzyme immunoassay), by testing plasma samples that were not hemolyzed, and by analyzing levels of an unrelated drug that uses the same technology as the initial tacrolimus assay. β‐Galactosidase antibodies were ultimately confirmed as the cause of the immunoassay interference. In patients receiving tacrolimus, spuriously high tacrolimus levels should be carefully evaluated, and drastic adjustments to therapy should be made only within the context of clinical toxicity.

Satisfactory outcomes with usage of extended criteria donor (ECD) kidneys in re-transplant recipients.

BACKGROUND The use of extended criteria donor (ECD) kidneys have increased substantially and the benefit recognized in certain populations. Our institution has maintained a policy of aggressively utilizing ECD kidneys, even among those who have failed a previous transplant. Previous reports on the benefit of ECD in re-transplants have shown equivocal outcomes. We sought to determine if our experience would support or refute this finding. MATERIAL AND METHODS This is a retrospective study of 19 ECD re-transplants between 2002 and 2010. We compared 1 and 3 year outcomes with 95 patients with standard criteria donor (SCD) re-transplant and 169 patients with first time transplant using ECD kidneys. Outcomes and demographics were evaluated including delayed graft function (DGF), HTN, DM, cold ischemia time (CIT), BMI, donor age and prior allograft nephrectomies using a Cox Proportional Hazard model. We compared patient and graft survival using the log rank test. RESULTS Patient survival were similar among the first time ECD and ECD re-transplant groups at 1 year (p=0.9547) and at 3 years (p=0.8287). Graft survival was also similar between first time ECD and ECD re-transplant groups at 1 year (p=0.4781) and at 3 years (p=0.8519). As expected, SCD re-transplant had better outcomes than the other groups. CONCLUSIONS 1 and 3 years graft and patient survival among first time ECD transplants and ECD re-transplants are similar. As the list of patients on dialysis is ever growing, it may be prudent to aggressively explore the utility of using ECD kidneys in re-transplant patients.