Assessing cardiovascular risk in the prerenal transplant population: Comparison of myocardial perfusion imaging and coronary angiography with risk factor stratification.

INTRODUCTION: Patients with end-stage renal disease (ESRD) have a higher incidence of coronary artery disease (CAD). Hence, it is crucial to evaluate CAD before renal transplantation. This study compares the utility of pharmacologic single-photon emission computed-tomography (SPECT) imaging directly to coronary angiography for diagnosis of CAD with correlation to cardiovascular risk factors. METHOD: Retrospective review of asymptomatic renal failure patients who underwent both SPECT and coronary angiography to identify obstructive CAD between the years 2008-2016. Ninety-four ESRD subjects were evaluated. RESULTS: Myocardial perfusion SPECT study found, when compared to coronary angiography demonstrated for CAD, the sensitivity of 93.3% with a specificity of 73.4%. Importantly, the negative predictive value for coronary artery disease was 96%. With seven or more cardiac risk factors, 66.7% of patients had obstructive coronary artery disease. Among all the risk factors examined, patients with a previous history of coronary artery disease had a 68% risk of obstructive coronary artery disease. CONCLUSION: Comparing myocardial perfusion imaging SPECT findings with coronary angiography in patients with ESRD, a sensitivity of 93.3% and a specificity of 73% were observed. Of all the risk factors examined, patient with the previous history of CAD was the single most significant risk factor for CAD in 68% of cases.

Aggressive use of ribavirin and prolonged course of peginterferon to improve the rate of viral response in liver transplant patients with recurrent hepatitis C viral infection.

OBJECTIVES: There are different approaches for treating recurrent hepatitis C viral infection after a liver transplant. However, sustained virologic response is achieved in < 40% of infected allografts. We examined sustained virologic response improvement using a prolonged course of peginterferon and aggressive use of ribavirin. PATIENTS AND METHODS: From October 1998 to May 2008, 24 patients (13 male, 11 female; mean age at transplant, 49.4 +/- 7.7 years) received a prolonged course of peginterferon and ribavirin (range, 48-180 weeks). The mean interval from liver transplant to hepatitis C antiviral therapy was 26.6 +/- 27.8 months. Patients began weight-based standard dosages of peginterferon and ribavirin. In case of hemolysis, patients were treated with Epogen, with and without blood transfusions. RESULTS: Fourteen patients (58.3%) had an end of treatment response, and 8 patients (33.3%) maintained sustained virologic response after the first course of therapy. Of 10 patients who did not respond to the first course, 6 received an extended course of antiviral therapy after a mean of 15 +/- 4.6 weeks from completion of first course. Five of these 6 patients achieved end of treatment response and maintained a sustained virologic response, resulting in an overall end of treatment response in 17 patients and a sustained virologic response in 13 patients. Twenty-two patients experienced hemolysis and were treated with Epogen. Fifteen patients received blood transfusions. Ribavirin dosage was reduced in 12 patients, and peginterferon dosage was reduced in 2 patients. CONCLUSIONS: Aggressive use of ribavirin and prolonged course of peginterferon provided sustained virologic response in 54.1% of liver transplant recipients with recurrent hepatitis C virus-infection. More prospective studies are warranted to evaluate the benefit of this approach fully.

Effect of liver transplant on pulmonary functions in adult patients with alpha 1 antitrypsin deficiency: 7 cases.

OBJECTIVES: Alpha 1 antitrypsin (A1A) is a 52 kD glycoprotein that is mainly synthesized in the liver. As a major protease inhibitor, it binds to and neutralizes neutrophil elastase, thereby limiting the damage to the normal tissues after an inflammatory response. A deficiency in A1A leads to end-stage liver disease, both in children and in adults. In addition, the deficiency also has a detrimental effect in the lungs of the adult population. Alpha 1 antitrypsin deficiency is corrected with hepatic replacement; however, the changes in pulmonary functions have not been studied before and after liver transplant. The purpose of this study was to observe the changes in the pulmonary functions of patients who underwent liver transplant for the treatment of A1A deficiency. MATERIALS AND METHODS: Nine patients underwent liver transplant for A1A deficiency. Seven patients (5 men, 2 women; mean age, 49.95 -/+ 7.09 years) had their pulmonary function tests available before the liver transplant (mean, 5.6 -/+ 3.4; range, 0.9-10.1 months) and after the liver transplant (mean, 30.3 -/+ 18.4, range 7.8-48.1 months) for analysis. RESULTS: The mean, preliver, transplant, FEV1 was 2.69 -/+ 0.9 L, which was nearly unchanged after the liver transplant to a mean of 2.7 -/+ 1.2 L. During the mean total interval of nearly 3 years, an estimated decline of 250 mL in FEV1 was expected. CONCLUSIONS: It appears from the results of our study that liver transplant probably prevented the progression of pulmonary disease in A1A-deficient patients. Further study and close, postliver, transplant follow-up is warranted to support our initial findings.

Utility of transjugular intrahepatic portosystemic shunts in liver-transplant recipients.

BACKGROUND: Transjugular intrahepatic portosystemic shunts (TIPS) have been used to control symptomatic portal hypertension in patients awaiting liver transplant. Although their role in pretransplantation patients is well established, their role in posttransplantation patients is unclear. STUDY DESIGN: Retrospective analyses were performed for 18 liver-transplant recipients who underwent TIPS for recurrent end-stage liver disease. Patients were evaluated in regard to gender, age, diagnoses, allograft type, indication for TIPS, portal pressures, laboratory results, Model for End-Stage Liver Disease (MELD) score, and outcomes. RESULTS: Median days from transplant to TIPS was 939 days (range, 122 to 3,415 days). Indications included variceal bleeding (n=2) and ascites (n=16). Ten patients (56%) responded to TIPS; TIPS prevented bleeding in both patients with varices, and it achieved symptomatic benefit in half of all patients with ascites. TIPS reduced median portal pressures from 22 mmHg (range, 17 to 50 mmHg) to 16 mmHg (range, 11 to 22 mmHg) and median portosystemic pressure gradients from 18 mmHg (range, 8 to 30 mmHg) to 8 mmHg (range, 2 to 12 mmHg). It increased median Model for End-Stage Liver Disease scores from 16 (range, 12 to 29) to 17 (range, 10 to 34) immediately and to 22 (range, 10 to 35) at 1 month. Six patients (33%) underwent retransplantation at a median of 58 days (range, 21 to 71 days) post-TIPS. Of the remaining 12 patients, 3 (25%) were alive and well at a median of 90 days (range, 78 to 1,169 days) post-TIPS; 9 (75%) died at a median of 99 days (range, 13 to 1,400 days) post-TIPS. Subgroup analysis failed to demonstrate significant differences between patients whose ascites responded to TIPS (n=8) and patients whose ascites did not (n=8). Responders were younger, had higher baseline portal pressures, greater reductions in portal-systemic pressure gradients, and better hepatic function. CONCLUSIONS: Though small, this was the largest series to date of TIPS in liver-transplant recipients. Overall, 56% of patients responded to TIPS. No single factor predicted response or nonresponse of ascites to TIPS. Without retransplantation, 75% of patients died. Careful selection is necessary when considering TIPS for patients with ascites.

Rituximab (chimeric anti-CD20 antibody) for posttransplant lymphoproliferative disorder after solid organ transplantation in adults: long-term experience from a single center.

BACKGROUND: Occurrence of posttransplant lymphoproliferative disorder (PTLD) after transplantation is known. Drastic reduction or withdrawal of immunosuppression with anti-viral therapy for Ebstein-Barr virus (EBV) is the primary treatment for all PTLD. Many PTLD are B cell in origin have CD20 antigen on the cell surface. Rituximab is a chimeric anti CD20 antibody, which has been used to treat PTLD with variable success. This study aims to report long-term experience with rituximab for PTLD from a single center. METHODS: Seventeen patients (13 male, 4 female, mean age 51.2 years) received rituximab to treat PTLD. Five patients received rituximab with drastic reduction in immunosuppression (primary). Nine patients received rituximab after failure of primary therapy (rescue) and three patients received it after resolution of PTLD (prophylactic). Mean follow-up period was 60 months. RESULTS: Overall 1-, 3-, and 5-year patient survivals were 64.7%, 47.1% and 35.3%, respectively. In the primary group, three patients had complete and one had partial response; however, only two (40%) patients are currently alive. In the rescue group, none of the patients had a complete response, four patients had partial response, and only two (22%) patients are currently alive. In the prophylactic group, two patients died at 28 and 41 months due to recurrence and graft failure, respectively. CONCLUSION: Sixty percent (3 of 5) of patients who received rituximab as primary therapy had complete resolution, and 44% (4 of 9) of patients who received it as rescue therapy had partial response. Overall 5-year patient survival was a disappointing 35%.

Pregnancy after kidney and kidney-pancreas transplantation under tacrolimus: a single center's experience.

BACKGROUND: Chronic renal failure leads to amenorrhea, and successful pregnancy is rare. The aim of the present report is to examine the outcome of pregnancies under tacrolimus after kidney transplantation (KTx) and simultaneous kidney-pancreas transplantation (SPKTx). METHOD: All pregnancies under tacrolimus after KTx or SPKTx from 1993 to April 2002 were retrospectively examined. Renal function and the mother's survival were followed until December 2002. RESULTS: Thirteen mothers after KTx delivered 19 babies, and 2 mothers after SPKTx delivered 3 babies. All mothers survived the pregnancy and retained allograft function. One mother had a stillborn baby from an unrecognized amniotic fluid leak and a small ischemic placenta. The mean gestational period was 34.4 +/- 5.1 weeks. Mean birth weight was 2373 +/- 1001 g. Birth-weight percentile to gestational period was 40 +/- 28. None of the mothers experienced rejection during the pregnancy. Three pregnancies in mothers with KTx experienced toxemia of pregnancy, and one mother with SPKTx developed pre-eclampsia during both pregnancies. Five mothers (6 deliveries, 27.3%) required caesarian section. During the follow-up period, one mother died from a cerebrovascular accident. Another five mothers returned to dialysis 55.6 +/- 32.4 months after the last delivery and 99.4+28.5 months after the last KTx. Both SPKTx mothers have maintained normal renal and pancreatic allograft function 42 and 62 months postdelivery. CONCLUSION: All mothers survived the pregnancy. One baby was stillborn. Forty-one percent of babies were either preterm or premature, and 27% of babies were delivered by caesarean section. Toxemia of pregnancy or pre-eclampsia was observed in 23% of pregnancies postKTx and SPKTx. None of the mothers experienced rejection during their pregnancy.

Pregnancy after liver transplantation with tacrolimus immunosuppression: a single center's experience update at 13 years.

BACKGROUND: Chronic liver disease often leads to amenorrhea in women of childbearing age. There are several reports of successful pregnancy after liver transplantation (LTx) with cyclosporine A immunosuppression. Tacrolimus has been increasingly used in solid-organ transplantation, and the effect of the drug on pregnancy is still of interest to clinicians. This study updates our single-center experience. METHODS: All pregnancies after LTx with tacrolimus immunosuppression were followed prospectively. Patients' clinical courses during pregnancy and labor along with gestational period and birth weight were catalogued. Changes in liver function, renal function, and immunosuppression also were recorded. The birth weight percentile was calculated on the basis of the gestational period using a standard chart. RESULTS: Thirty-seven mothers delivered 49 babies. Three mothers delivered three times, and six mothers delivered two times. Thirty-six mothers (97%) survived the pregnancy, and 36 allografts (97%) survived. The one death and graft loss was in a patient who demonstrated infra-aortic arterial graft, which clotted by the gravid uterus during labor. The patient developed a gangrenous liver and died before she could undergo retransplantation. The mean gestational period was 36.4+/-3.2 weeks, excluding two premature deliveries at 23 and 24 weeks gestation. Twenty-two babies (46.9%) were delivered by cesarean section, and the other babies were delivered vaginally. In addition to the two premature babies, one baby, who was born to a mother with Alagille syndrome, died from congenital birth defects. The rest of the newborns survived. The mean birth weight was 2,797+/-775 g, with 38 babies (78%) weighing more than 2,000 g. The mean birth weight percentile to gestational period was 54+/-23. Four babies (8.5%) had a birth weight percentile of less than 25, and 28 babies (59.6%) had a birth weight percentile greater than 50. Twelve patients demonstrated an increase in hepatic enzymes without jaundice during the pregnancy. All of them responded to augmentation of immunosuppression. CONCLUSION: The present report reconfirms the safety of tacrolimus during pregnancy after LTx. Preterm delivery and low birth weight seem to be a persistent problem in all solid-organ transplantation under any form of immunosuppression. However, toxemia of pregnancy and new onset of hypertension seem to be have a low occurrence with the use of tacrolimus.

Effect of coadministered lopinavir and ritonavir (Kaletra) on tacrolimus blood concentration in liver transplantation patients.

With the advent of highly active antiretroviral therapy (HAART), HIV positivity is no longer a contraindication for liver transplantation. Some of the antiretroviral agents, particularly protease inhibitors (e.g., ritonavir, indinavir, and nelfinavir) have been described as potent inhibitors of the metabolism of certain immunosuppressive drugs. In this article we describe a profound interaction between tacrolimus and Kaletra (Abbott Laboratories, Chicago, IL) (a combination of lopinavir and ritonavir) in 3 liver transplantation patients. Patient 1, who was maintained on a 5 mg twice daily dose of tacrolimus with a trough blood concentration around 10.6 ng/mL, required only 0.5 mg of tacrolimus per week after addition of Kaletra to achieve similar tacrolimus blood concentrations, with a half-life of 10.6 days. In patient 2, the area under the blood concentration versus time curve for tacrolimus increased from 31 ng/mL/h to 301 ng/mL/h after addition of Kaletra, with a corresponding half-life of 20 days. When the patient was subsequently switched to nelfinavir, the half-life decreased to 10.3 days. Patient 3, who was maintained with 4 to 8 mg/d of tacrolimus and a corresponding blood concentration of 10 ng/mL before Kaletra, required a tacrolimus dose of 1 mg/wk and tacrolimus concentrations of 5 ng/mL with Kaletra. In conclusion, a combination of lopinavir and ritonavir led to a much more profound increase in tacrolimus blood concentrations than use of single protease inhibitor, nelfinavir. A tacrolimus dose of less than 1 mg/wk may be sufficient to maintain adequate blood tacrolimus concentrations in patients on Kaletra. Patients may not need a further dose of tacrolimus for 3 to 5 weeks depending on liver function when therapy with Kaletra is initiated. Great caution is required in the management of tacrolimus dosage when Kaletra is introduced or withdrawn in HIV-positive patients after liver transplantation, particularly in the presence of hepatic dysfunction.