Showing papers in "Clinical Transplantation in 1998"

Risk factors for acute renal failure requiring dialysis after liver transplantation.

Abstract: Acute renal failure (ARF) is a common and severe complication after liver transplantation (LT). The aim of this study was to ascertain the impact of ARF requiring dialysis in the outcome of LT and to analyze the risk factors leading to this event in the early post-operative period. From October 1988 to December 1994, 172 LT were performed in 158 patients. Postoperative ARF occurred in 88 transplants (51.1%) during the early postoperative period: mild ARF was found in 46 (serum creatinine 1.5-3 mg/dl), moderate ARF in 12 (serum creatinine > 3 mg/dl) and severe ARF in 30 (serum creatinine > 3 mg/dl with dialysis requirement). Preoperative, intraoperative, and postoperative variables were studied, comparing patients presenting severe ARF with the remaining patients. Postoperative mortality in the dialysed group was much higher than in the non-dialysis group (50% vs. 13.4%)(p 1.5 mg/dl (OR = 4.4, p = 0.006) and graft dysfunction grades III-IV (OR = 8.9, p = 0.001). In conclusion, ARF is a severe complication post-LT; its appearance could be predicted in patients with pre-transplant renal dysfunction, severe graft dysfunction, or both. However, in many cases renal function may revert to normal if treated aggressively with early dialysis support.

Two-hour cyclosporine level determination is the appropriate tool to monitor Neoral therapy.

Abstract: To assess the safety profile of Neoral dose adjustment using cyclosporine (CsA) trough levels (C0) compared with levels obtained 2 h after the morning dose (C2), 30 stable adult heart transplant patients 1 yr or more after surgery were converted from Sandimmune to Neoral. After a baseline visit (before conversion), initial follow-up included two visits (2 and 4-6 wk after conversion). After the first visit, patients were randomized to Group I (C0: 100-200 ng/ml) or Group II (C2: 200-400 ng/ml). Abbreviated pharmacokinetics were obtained for the estimation of the AUC0-4 h. Renal function was assessed by serum creatinine and the cimetidine-modified creatinine clearance. C2 correlated better than C0 with the AUC0-4 h (r = 0.91 vs. 0.63). Initial Neoral dose (mg/kg/d) was similar in both groups (2.8 +/- 0.5 and 2.8 +/- 0.8), and was lower in Group II at the second visit (2.0 +/- 0.7 vs. 3.0 +/- 0.6, p = 0.0001). C2 levels decreased in Group II from 912 +/- 438 to 555 +/- 271 ng/ml (p = 0.01), without evidence of acute rejection on endomyocardial biopsies. After the second visit,-both groups were monitored with C2, and the range was increased to 300-600 ng/ml. At the last visit (additional follow-up of 5 +/- 1 months), Neoral dose (mg/kg/d) was reduced to 2.0 +/- 0.3 in Group I (p < 0.001) and 1.8 +/- 0.4 in Group II. Serum creatinine was lower in Group II at the second visit (138 +/- 59 vs. 168 +/- 37 mumol/L, p = 0.01) and was similar in both groups at the last visit. Neoral dose reduction based on C2 levels was not associated with acute rejection. The better correlation with the AUC0-4 h suggests that C2 may be more reliable than C0 for Neoral dose adjustment.

Liver transplantation in the United States from 1987-1998: updated results from the Pitt-UNOS Liver Transplant Registry.

Abstract: CENTERS Between 1988-1997, the total number of liver transplantations performed in the US more than doubled from 1,713-4,158, and the number of centers performing liver transplantations increased from 59-107. In recent years, the yearly net gain in the number of operating centers has slowed, and the differences in LT volume across centers has remained stable. OUTCOMES During the first year following transplantation, patient survival was approximately the same for adults and children, while retransplantation-free survival was poorest among children. Thereafter, survival declined more rapidly among adults than among children. SURVIVAL AMONG PEDIATRIC RECIPIENTS The estimated cumulative probability of a pediatric recipient surviving for 10 years following transplantation was .80, and surviving for 10 years without retransplantation was .59. In general, few deaths or retransplantations were observed more than 4 years after the initial transplantation. Factors independently associated with patient and retransplantation-free survival among children were year of transplantation, recipient age, being on life support while awaiting transplantation, primary liver disease, serum creatinine, total bilirubin, donor age, donor race, and warm ischemic time. Recipient race, a multi-organ transplant procedure, and serum albumin level were significantly associated with patient survival only. The use of a reduced-size or split liver for transplantation in children was independently associated with retransplantation-free survival, but not with patient survival. SURVIVAL AMONG ADULT RECIPIENTS The estimated cumulative probability of an adult recipient surviving for 10 years following transplantation was .61, and surviving for 10 years without retransplantation was .46 with the median retransplantation-free survival time estimated at 9.2 years. Factors independently associated with patient and retransplantation-free survival among adults were year of transplantation, recipient age, recipient race, recipient location awaiting transplantation, primary liver disease, serum creatinine and albumin levels, hepatitis B surface antigen status, donor age, donor anti-CMV status, warm ischemic time, sex match, pretransplant ventilator or inotrope use, and recipient anti-HCV status. Pre-transplant bilirubin level, a multi-organ transplant procedure, and the finding of an incidental tumor were significantly associated with patient survival; and donor race, ABO match, and uncontrolled variceal bleeding were associated with retransplantation-free survival.

Urinary tract infections following renal transplantation.

Abstract: The incidence of urinary tract infections (UTIs) in 363 adult renal transplant recipients transplanted during the period 1990-96 has been analysed. UTI occurred in 96 patients (26%), most frequently during the first year after transplantation. Female recipients had significantly more UTI than male recipients (49% vs. 14%, p < 0.0001). There was no difference in the incidence of UTI between recipients receiving pig-tail catheters as ureteral stents or not, the figures being 21% vs. 28%, respectively. Age had no influence on the incidence of UTI. In 341 patients treated with cyclosporine the incidence of UTI was 28%, while in 15 patients treated with FK-506 only 1 patient (7%) had a UTI (ns). The majority of organisms cultured were gram-negative (76%), with approximately 1/3 being Escherichia coli and 1/5 being Enterococcus and Klebsiella/Enterobacter. The bacterial spectrum was not influenced by the recipient's age. UTI had no effect on the number of rejections, or on graft and patient survival in living donor transplant recipients. No significant difference was found in graft and patient survival rates at 3 yr between patients who had UTI or no UTI.

Quality of life after pancreas transplantation: a review.

Abstract: For persons with diabetes and end stage renal disease, successful combined or sequential pancreas/kidney transplant is an attractive therapeutic alternative to insulin and dialysis. There is considerable controversy regarding pancreas transplantation (p Tx), however, as some recent reviews have concluded, p Tx results in at most only modest reductions in secondary complications and has increased morbidity and costs compared with kidney transplant alone. While the impact on patients' quality of life (QOL) is a major consideration for p Tx, the literature on this topic has not been carefully considered. The purpose of this review is to evaluate studies of QOL after p Tx and identify well-validated findings. Comparative cross-sectional and longitudinal studies have shown that the QOL outcomes of p Tx recipients who achieve insulin-independence are better than those of candidates or of recipients with pancreas graft loss. More positive health perceptions, improved social interaction and increased vitality/energy are significantly associated with successful p Tx. Researchers have found few areas where the QOL benefits of p Tx significantly exceed or differ from those that occur with kidney transplant alone. A consistent finding across studies is that p Tx improves patient perceptions about diabetes-specific issues such as satisfaction with diet flexibility and health management, while kidney transplant does not. Future studies should attempt to accrue sufficient sample sizes to permit statistical adjustment for selection biases; follow patients for several years to permit differences in rates of progression of secondary complications to impact QOL; and use current graft loss and morbidity statistics to estimate any added risks of p Tx over kidney-only transplant. It is still an open question as to whether or not there are sufficient QOL benefits from p Tx long-term to out-weigh added risks, and this needs to remain an active area of investigation.

Procalcitonin in the early phase after renal transplantation--will it add to diagnostic accuracy?

Abstract: The determination of serum procalcitonin (PCT) was tested for its utility in detecting invasive bacterial infection and acute rejection during the first 6 wk after kidney transplantation. Fifty-seven kidney graft recipients were prospectively included in the study. In 13/57 patients, 16 episodes of acute biopsy-proven rejection occurred and were treated with high-dose steroids (n = 14) or with OKT3 (n = 2). Seventeen out of 57 patients experienced 19 invasive bacterial infections; 2/57 had partial graft necrosis due to malperfusion. Twenty-five out of 57 graft recipients experienced an uncomplicated postoperative course. A total of 116 samples were analyzed and the following data obtained: PCT, C-reactive protein (CRP), white blood cell (WBC) count, corresponding body temperature and serum creatinine. Procalcitonin values for patients with rejection did not differ significantly from those of the healthy transplant recipients (p = 0.47). In contrast, PCT was clearly elevated with invasive bacterial infection or partial graft necrosis (p < 0.01). OKT3 treatment of rejection led to a more than 10-fold increase in PCT. C-reactive protein, unlike PCT, was elevated to a variable extent in patients with graft rejection, though CRP values were significantly more elevated in patients with infection than in those with rejection (p < 0.01). The specifity for detection of invasive bacterial infection was 0.7 for PCT and 0.43 for CRP, whereas sensitivity was 0.87 for PCT and 1.0 for CRP. There was no correlation between PCT and serum creatinine (r = 0.06). Haemodialysis did not lower PCT serum concentrations. Procalcitonin values rose postoperatively to peak levels on the first and second days and mostly declined to normals within 1 wk. In conclusion PCT, not being influenced by acute kidney graft rejection but serving as a specific indicator of systemic bacterial infection, could help to discriminate between both types of inflammation.

Liver transplantation in hyponatremic patients with emphasis on central pontine myelinolysis.

Abstract: Patients awaiting liver transplantation may suffer from severe hyponatremia. It has been suggested that hyponatremia or its treatment might be associated with central pontine myelinolysis (CPM), a serious complication that can be seen after orthotopic liver transplantation (OLT). We undertook this study to assess the outcome of hyponatremic patients after OLT and to evaluate the risk factors in the development of CPM. A total of 379 adult OLT performed in 347 patients between March 1993 and December 1995 was studied using a prospectively-collected data base and retrospective chart review. The following risk factors for the development of CPM were analyzed: primary liver disease, nutritional status, alcoholism, diuretic use, hepatic encephalopathy, United Network for Organ Sharing (UNOS) status, preoperative serum sodium, magnesium and cholesterol levels, increase in serum sodium concentration during surgery, and immunosuppressive treatment. Overall 12 patients (3.5%) underwent OLT in a hyponatremic state (serum sodium < or = 127 meq/L). At a median follow-up of 14 months, 8 patients were alive without any neurological sequel. Six of the 12 patients developed neurological complications in the early post-operative period including CPM in 3, confusion in 2, and seizure in 1. The 3 patients who developed CPM expired within 3 months of OLT. The changes in serum sodium concentration during OLT in patients with and without CPM were 20.7 +/- 8.1 and 7.0 +/- 5.1 meq/L, respectively (p = 0.005). No other risk factor could be identified in the development of CPM. It is concluded that prognosis of hyponatremic patients after OLT is poor if they develop CPM. Slow correction of hyponatremia perioperatively may be critical in preventing this devastating complication.

Post kidney transplant quality of life prediction models

Abstract: UNLABELLED Quality of life (QoL) is generally found to improve for renal transplant recipients, although some patients continue to experience health-related problems. It was within this context that we undertook our investigation which focused on identifying the factors predictive of QoL following kidney transplantation. METHODS The sample included 91 non-diabetic patients of which 69 provided 6-month data and 68 provided 12-month data. Three QoL questionnaires were administered to capture as many QoL dimensions as possible. Repeated measure analyses of variance with multiple post hoc comparisons of LS means was conducted to determine how QoL outcomes differed over time. Correlational analyses were performed on the 12-month dataset to determine which variables to include in the modeling process. Multiple stepwise regression with forward and backward entry were used in the prediction modeling. RESULTS Essentially all patients experienced a significant improvement in QoL and the improvement occurred early and appeared to be sustained. Five separate prediction models were constructed, each including number of hospital days in first 6 months, employment, and social support. CONCLUSIONS The similarity of the five models is of note. It is not necessarily these specific variables per se that predict QoL outcomes, but rather what they conceptually represent. These findings provide direction for interventions designed to enhance post-transplant QoL.

Giving and taking - to whom and from whom? : People's attitudes toward transplantation of organs and tissue from different sources

Abstract: The aims of the study were: 1) to describe the willingness of the public to receive material of different origins in one's own body; 2) to compare the willingness to donate and receive body material; 3) to compare the willingness to donate while alive and after death; 4) to compare the willingness to donate to a next-of-kin and unknown recipients. A random sample of 1500 inhabitants, 18 to 70 yr old, in the county of Uppsala, Sweden, were sent a questionnaire asking about their opinion on transplantation and transfusion issues. The response rate was 71%. Ninety-five percent accepted to receive blood transfusion, 89% bone-marrow transplantation, and 85% transplantation of a solid organ. Organs from living donors were preferred (77%), then organs from decreased donors (69%), then artificial organs (63%), and last animal organs (40%). More than half of those accepting transplants made exceptions for some types of organs. The youngest and those with higher education were more positive toward receiving all types of organs than the older ones and those with lower education. Women were less prepared than men to accept animal organs. Those who accepted organs from animals usually also accepted all other types of organs, and were willing to donate organs and tissue more often than those who did not accept to receive animal organs. The readiness to support a sick family member by giving bone-marrow and even a kidney was considerable, 89 and 81%, respectively. The attitudes were less positive with regard to giving blood and bone-marrow to unknown recipients, 54 and 41%, respectively. Sixty-one percent of the respondents were positive toward donating their own organs after death. Of those who were positive, 10% made exceptions for special organs that they did not want to donate, mostly heart, eyes, and brain. Individuals with higher education and young people were more often positive than those with lower education and old people regarding donation of blood and organs, and bone-marrow donation to a relative. Women were somewhat more accepting to donate while alive than males. Thirty-one percent, more often women than men, had signed a donor card and/or registered with the Swedish Organ Donation Registry. The results with regard to receiving organs and tissue are discussed in terms of two different sets of explanations, which can be seen as different sides of the same coin, and mutually strengthening the reactions. The great readiness to donate to a family member as well as the discrepancy between giving in life and after death is commented upon.

Health-related quality of life and symptom frequency before and after lung transplantation.

Abstract: Health-related quality of life (HRQOL) and symptom frequency and severity were assessed in 17 lung transplant recipients both prior to and following the procedure. Using standardized assessment techniques we found that the following components of QOL significantly improved post-transplantation: physical functioning, general health, vitality and social functioning. Both prior to and following transplantation, lung transplant recipients had significantly lower scores on all health-related quality of life indices when compared with a normative sample. Perhaps as a consequence of immunosuppression medication, recipients reported increased frequency of symptomatology following the procedure; however, considered together the symptoms were not reported as significantly more problematic following transplantation. These findings document improved HRQOL for lung transplant recipients and provide useful information for patients considering this potentially life-saving treatment option.

Long-Term Quality of Life after Kidney and Simultaneous Pancreas-Kidney Transplantation

Abstract: We are using a validated questionnaire (SF-36) to annually assess health-related quality of life (QOL) in kidney and pancreas-kidney transplant recipients. The SF-36 consists of eight scales to assess physical functioning, general health, and mental functioning. Norms and 95% confidence intervals (C.I.) have been developed for the US population. At present, 1138 recipients with functioning grafts (520 Type I diabetic; 618 nondiabetic) 1-10 yr post-transplant have completed the questionnaire. Of the recipients, 446 completed the questionnaire once; 632 twice; and 53 three times (305 after 1 yr; 266 after 2 yr; 256 after 3 yr; 206 after 4 yr; 192 after 5 yr; 150 after 6 yr; 130 after 7 yr; 138 after 8 yr; 125 after 9 yr; 92 after 10 yr). For both diabetic and nondiabetic recipients, there was little change in average scores for each scale between years (p = NS). In relation to the US population, average scores for nondiabetics were below the 50th percentile on all 8 scales; for diabetics < 25th percentile on the physical functioning and vitality scales, < 50th percentile on all others. For both diabetic and nondiabetic recipients, average scores were higher than reported norms for patients with CHF, COPD, or depression but were similar to those with Htn or recent MI. Individual scores were then compared with age-matched means (+/- 2 SEMs) (95% C.I.) for the US population. At each year post-transplant, up to 40% of nondiabetic and up to 65% of diabetic recipients had scores below the 95% C.I. on individual scales (particularly the physical functioning and general health scales)--e.g. over 30% nondiabetic and up to 60% diabetic recipients had scores on the physical functioning scales below the 95% C.I. More diabetic recipients (vs. nondiabetics) reported poor QOL on the physical functioning, general health and social functioning scales. There was little difference in the mental health scales. For those with Type I diabetes, a similar percentage of kidney and K/P recipients reported QOL below the 95% C.I. for the age-matched population, except on the GH scale (better QOL for K/P recipients). We conclude that successful transplant recipients report health-related QOL below that of the age-matched general population but similar to those with other chronic diseases. Diabetic and nondiabetic recipients have similar scores on the mental health scales; nondiabetic recipients score better on the general health and physical functioning scales.

The UNOS OPTN waiting list and donor registry.

Abstract: 1. On October 31, 1998, there were 62,994 registrants on the combined UNOS waiting list. Of these, 66% were awaiting kidney transplantation, and 18% were awaiting liver transplantation. 2. The majority of patients on the UNOS waiting list on October 31, 1998 were blood type O (52%), White (60%) and male (58%). 3. Median waiting times (MWTs) have increased steadily for nearly every organ since 1988, especially for liver, kidney, and lung registrants. 4. For patients added to the waiting list in 1996. MWTs to transplant were longest for heart-lung registrants (742 days). The shortest waiting times for this cohort were among heart registrants (223 days). No median could be calculated for kidney registrants added in 1996. 5. Death rates per patients waiting at risk declined during 1988-1997. Death rates were higher for patients awaiting life-saving organs (liver, heart, lung, heart-lung) than for non-lifesaving organs (kidney, pancreas, kidney-pancreas). 6. There were 5,478 cadaveric and 3,820 living donors recovered in 1997, a 34% and 109% increase over those recovered in 1988. 7. Large increases were seen in the number of liver (45-84%), pancreas (14-24%), and lung (3-15%) donors between 1988-1997. 8. The number of cadaveric donors aged 50 or older has increased from 12% of all donors in 1988 to 28% of all donors in 1997. 9. The typical cadaveric donor in 1997 was a white male with ABO blood type O, between the ages of 18-34. In 1997, a typical living donor was a white female with ABO blood type O between the ages of 35-49. 10. Between 1988-1997, the percentage of minority donation increased for cadaveric donors (17-24%), and for living donors (23-27%). 11. The number of living donors who were either spouses or unrelated to the recipient increased from 4% in 1988 to 15% in 1997.

Distal tubular acidosis induced by FK506.

Abstract: This study was designed to investigate the effect of tacrolimus (FK506) and of cyclosporine (CsA) on tubular function in renal graft recipients. Patients were randomised after renal transplantation to immunosuppressive treatment with FK506 (n = 8) or CsA (n = 8). Patients had a mean age of 45.7 +/- 3.4 yr; there was no difference in age, sex, HLA status or CMV mismatches. Neither was there any difference in the frequency of episodes of acute kidney failure between the groups, nor was there a significant difference in the frequency of episodes of kidney rejection within the first year. The mean FK506 level at the time lay at 14.7 +/- 14.4 ng/mL whole blood, and the mean CsA level at the time of study was 162 +/- 25 ng/mL whole blood. We performed renal function studies 6 months after transplantation: CIn, CPAH, NaHCO3 loading, and Na2SO4 loading. There was no significant impairment of GFR in patients treated with FK506 with 53.6 +/- 2.5 mL/min as compared to 58 +/- 6 mL in group 2. Plasma renin activity (0.6 +/- 0.4 ng/mL vs 2.3 +/- 3; p < 0.01) and aldosterone (69 +/- 17 vs 157 +/- 28.2 pg/mL; p < 0.05) were significantly decreased during treatment with FK506. Fractional HCO3 excretion was low in both groups, indicating that bicarbonate reabsorption in the proximal nephron was unimpaired. Distal renal tubular acidosis was demonstrated in 4 patients of group 1 but in only 1 of group 2. Potassium levels were slightly increased in patients treated with FK506 (5.4 +/- 0.2 mmoL/L) as compared to cyclosporine (4.9 +/- 0.3 mmoL/L; p < 0.05). Distal hydrogen ion secretion, evaluated by the ability to increase urinary pCO2 in a highly alkaline urine, was impaired in patients treated with FK506 (U-B pCO2: 16.1 +/- 4 vs 36 +/- 5.8; p < 0.05) as compared to patients treated with CsA. The maximum acidification capability (NAE) was slightly lowered during therapy with FK506 (67.5 +/- 11.8 versus 86.6 +/- 16.5 mumoL/min, ns). We conclude that FK506 administration results in a decrease in the rate of hydrogen ion secretion by the collecting tubules. This defect was disclosed by the finding of a subnormal pCO2 in a highly alkaline urine. These results show that FK506 is able to induce distal tubular acidosis. Distal tubular acidosis is part of FK506 induced nephrotoxicity, the pathogenesis of this type of hyperkalemic metabolic acidosis found in patients treated with FK506 after renal transplantation has to be further elucidated.

Incidence of leukopenia and cytomegalovirus disease in kidney transplants treated with mycophenolate mofetil combined with low cyclosporine and steroid doses.

Abstract: Mycophenolate mofetil (MMF) combined with conventional cyclosporine and steroids doses efficiently prevents acute rejection in kidney transplants. However, this regimen has been associated with an increased incidence of cytomegalovirus (CMV) disease and leukopenia, specially in patients receiving MMF at 3 g/d, suggesting that the combination of two powerful immunosuppressants carries the risk of overimmunosuppression. For this reason, we treated a group of patients with MMF 3 g/d combined with low cyclosporine and steroids doses. Eighty-two kidney transplants performed at two centers and enrolled in the European Mycophenolate Mofetil Cooperative Study were randomized to receive: A) placebo (n = 27); B) MMF 2 g/d (n = 27); and C) MMF 3 g/d (n = 28). In this double blind study all patients received cyclosporine and steroids at conventional doses. Fifteen kidney transplants enrolled in an MMF open pharmacokinetic study were treated with MMF 3 g/day combined with low cyclosporine and steroid doses (group D). Efficacy was evaluated as the incidence of biopsy proven acute rejection, and safety focused on CMV disease and leukopenia. Patients receiving MMF showed a low incidence of biopsy proven rejection (B) 18.5%; C) 10.7%; and D) 13.3%). Patients of group C had a high incidence of CMV disease (35.7%) when compared with the other groups (lower than 8%). Incidence of leukopenia was higher in patients treated with MMF (B) 25.9%; C) 39.3%; and D) 40%) than in placebo treated patients (7.4%). Patients in group (C) displayed leukopenia mainly in the context of CMV disease, while patients of group (D) had leukopenia not related to CMV infection. All patients of group (D) who presented leukopenia recovered after MMF reduction dose, while in group (C) there were 5 out of 28 patients who required MMF withdrawal. We propose that a reasonable approach to take advantage of a powerful non-nephrotoxic immunosuppressant such as MMF, could be the administration of this drug at 3 g/d from the time of transplantation combined with low CsA and steroid doses.

Outcome of 22 successful pregnancies after liver transplantation

Abstract: To evaluate course and outcome of pregnancies in liver transplanted patients and to provide a brief summary on the development of these children, 22 pregnancies and 23 children (1 month-99 months old) of 16 patients who had been liver transplanted at our institution (mean interval from transplantation to pregnancy 43.1 months) were reviewed. Standard immunosuppressive regimen during pregnancy consisted of cyclosporine A (CyA), tacrolimus (FK), azathioprine (Aza) and/or a low-dose steroid therapy. CyA and FK whole blood trough levels were monitored on a routinely basis to keep therapeutic range (CyA 80-150 ng/mL; FK 4-8 ng/mL). No patient had a graft loss and there were no lethal complications. Beside de novo hypertension (n = 3) and preeclampsia (n = 3) problems during pregnancy included one steroid-sensitive rejection at 36 wk gestation, one case of tacrolimus toxicity at 24 wk with complete reconstitution, and one case of de novo choledocholithiasis with recurrent cholangitis. Three cases of infections occurred. In total, 23 children, including one set of twins, were born. Terms of gestation (mean = 38.1 wk, +/- 2.2 SD), deliveries (spontaneous n = 13, cesarean section n = 7, forceps n = 1, vacuum extraction (VE) n = 1) and birth weights (2876 g, +/- 589.3 SD) were typical. Three pregnancies were preterm, one being a twin pregnancy. Neither congenital malformations nor unusual infections were seen in the children. Postnatal follow-up revealed appropriate physical growth to date. Psychological development seems to be adequate. Our data indicate that successful pregnancies after liver transplantation (LTX) under careful management by transplant specialists, obstetricians and perinatalogists have a good outcome. So far, neither pre- nor postnatal child development appear to be influenced by maternal immunosuppressive therapy during pregnancy.

The role of tacrolimus in adult kidney transplantation: a review.

Abstract: The use of tacrolimus (FK506) in adult kidney-transplant recipients has been the subject of a number of single- and multi-center studies. This review article focuses on those studies in which tacrolimus was used either as rescue therapy in patients who developed refractory rejection on cyclosporine (CyA)-based regimens or as primary immunosuppression in adult renal-allograft recipients. Twenty-five prospective and retrospective studies conducted in the US, Japan and Europe, including single- and multi-center experiences, were identified in the medical literature. Of these studies, most show a 74-98% initial success rate for tacrolimus rescue therapy. Comparative studies reviewed herein demonstrate comparable patient- and graft-survival rates between tacrolimus- and CyA-treated patients. Many studies have shown that rejection episodes occur with similar or lower frequency among patients treated with tacrolimus than among those given CyA as primary immunosuppression. The major toxicities associated with tacrolimus are nephrotoxicity, neurotoxicity and diabetogenicity. Results from several studies have also demonstrated an association between these tacrolimus side effects and high whole-blood trough levels of tacrolimus. In many cases, a reduction in dosage can reverse these adverse effects. In summary, based on both single- and multi-center data, tacrolimus has been demonstrated to be efficacious when used for either primary immunosuppression or as rescue therapy for refractory acute rejection in adult renal-allograft recipients.

Analysis of United States (US) and non-US pancreas transplants as reported to the International Pancreas Transplant Registry (IPTR) and to the United Network for Organ Sharing (UNOS).

Abstract: As of November 1998, more than 11,000 pancreas transplants had been reported to the IPTR, including more than 8,800 US and more than 2,600 non-US cases. The 1994-98 cases (> 4,500) were analyzed, including more than 4,000 US and more than 500 non-US transplants. For all US 1994-98 SPK transplants (n = 3,409), one-year patient, pancreas and kidney graft survival rates were 94%, 90% and 83%, respectively; for all PAK cases (n = 375), one-year patient and graft survival rates were 95% and 71%; and for all PTA cases (n = 181), one-year patient and graft survival rates were 95% and 64%, respectively. Recipient age had only a small impact on outcome, with one-year patient survival rates for all recipients or = 45 years old (n = 758) (p = 0.005). Pancreas graft survival rates at one year for those or = 45 years old were 84% versus 78% in the SPK (p < 0.02), 70% versus 78% in the PAK (p = 0.13), and 62% versus 79% in the PTA (p = 0.23) categories, respectively). Nearly one-third of US pancreas transplants for 1994-98 were done by the ED drainage technique. For SPK transplants, the one-year pancreas graft survival rate was 83% for BD (n = 2,369) and 82% for ED (n = 912) (p < or = 0.09). For PAK and PTA transplants, pancreas graft survival rates were significantly higher with BD, 74% (n = 261) and 68% (n = 115), respectively, at one year. The drawback for BD was the need for conversion to ED in 7% of the cases at one year and 11% at 2 years. For TS transplants, the pancreas graft loss due to rejection was very low for SPK transplants, 2% at one year versus 9% for PAK and 15% for PTA cases. The various initial maintenance immunosuppressive regimens (Tac + MMF, Tac + Aza, CsA + MMF, CsA + Aza) resulted in only minor differences in pancreas graft survival rates in the SPK cases (80-86% at 1 year), but in PAK and PTA cases the Tac + MMF combination was associated with significantly higher pancreas graft survival rates. For BD PAK transplant recipients given Tac + MMF, the one-year pancreas graft survival rate was 83% (n = 100). For the corresponding BD PTA group it was 75% (n = 44). For non-US cases the outcomes were similar. For non-US SPK transplants (n = 586), one-year patient, kidney and pancreas graft survival rates were 93%, 85% and 81%, respectively. Cox multivariate analyses and logistical regression were done in each recipient category to assess the factors that influence pancreas graft loss. BD was associated with a significantly lower risk than ED in all categories. Increasing donor age was a risk factor in most categories. MMF was associated with a decreased risk for graft loss in the SPK category, and Tac in the PAK and PTA categories.

Patterns of acute rejection in portal-enteric versus systemic-bladder pancreas-kidney transplantation

Abstract: Portal-enteric (PE) transplantation of the pancreas allograft provides maintained physiologic drainage, and theoretically the portal delivery of transplantation antigens may have beneficial effects on the graft acceptance leading to improved graft survival. To determine whether the technique of pancreas placement affects the incidence of acute rejection we reviewed our experience in technically successful PE and systemic-bladder (SB) drained simultaneous pancreas and kidney (SPK) transplants performed between 1989 and 1994. Forty-seven recipients were included (SB = 30, PE = 17). All patients received cyclosporine based quadruple immunosuppression and survived at least 1 month. The two groups were comparable in HLA mismatches, cold ischemia time and level of immunosuppression at time of rejection. In the SB group the incidence of rejection was 1.04 kidney rejection/patient and 0.90 pancreas rejection/patient whereas the PE group experienced 0.53 kidney rejection/patient and 0.47 pancreas rejection/patient. The two groups were compared using incidence density statistics due to great variation in follow-up time. The SB group had a significant higher density of both kidney and pancreas rejections (p < or = 0.037 for kidney rejection and 0.058 for pancreas rejection). In addition, while 6 of 30 (20%) pancreas grafts and 4 of 30 (13%) kidney grafts were lost to irreversible rejection in the SB group, only 1 of 17 (6%) pancreas graft and 1 of 17 (6%) kidney graft were lost in the PE group. These data demonstrate, that the PE placement of pancreas allograft affects the rates of acute rejection and graft loss, and imply that there exist some important immunological advantages when the pancreas graft is drained into the portal circulation.

Intraoperative Doppler ultrasound in liver transplantation

Abstract: The purpose of this study was to determine the utility of intraoperative Doppler ultrasound for the diagnosis and reduction of the vascular complications in liver transplantation. This study included 19 pediatric and 5 adult patients. In the pediatric group, 12 patients received living related liver transplantation (LRLT), two splitting liver transplantation (SLT), three reduced-size liver transplantation (RLT) and two full-size pediatric liver transplants (FPLT). The hemodynamics and waveform of the hepatic vein, portal vein and hepatic artery were evaluated by intraoperative Doppler ultrasound (US) after reperfusion of the graft. Unsatisfactory hemodynamics was identified in nine cases, including decrease hepatic venous flow (6-9 cm/s) with non-pulsative flat waveform (adults, n = 2 and LRLT, n = 2); portal vein thrombosis (LRLT, n = 1); decrease portal flow (8 mL/min/kg) (LRLT, n = 1); occlusion of the portal vein (SLT, n = 1); poor arterial flow with dampened artery waveform (FPLT, n = 2). These abnormalities were all successfully re-reconstructed by surgical procedures and achieved a graft survival rate of 100%. Two late vascular complications including hepatic venous thrombosis and recurrent portal vein stenosis with splenorenal shunt were discovered 1 month later. They were treated effectively by surgical thrombolectomy and percutaneous balloon dilatation and metallic coils embolization respectively. Three patients died of non-vascular complications and all patients who underwent LRLT survived with a resultant 87.5% overall survival rate. In conclusion, intraoperative Doppler US is efficient in detecting abnormal hepatic hemodynamics, which permits early intervention and hence a better prognosis for the patients. Re-reconstructive procedures were monitored closely under Doppler US guidance until proper flow and wave-form were established. This reduces post-transplant vascular complications and thereby eliminates the likelihood of a lethal complication that might call for re-transplantation.

Relative risk of post-transplant renal thrombosis in patients with antiphospholipid antibodies.

Abstract: INTRODUCTION Antiphospholipid antibody syndrome (APAS) is a condition associated with recurrent arterial and venous thrombosis, recurrent abortions, and thrombocytopenia either with or without lupus. In this study we have evaluated the impact of APAS on the renal transplant outcome of 174 patients. METHOD Patients' APAS status was determined by the presence of anticardiolipin antibodies (ACA) and a history of clotting disorders. Serum samples from each patient were tested for the presence of ACA by the ELISA method. Transplant outcomes were monitored for > or = 1 yr. RESULTS Of 174 patients, 78 received renal transplants. Six of these 78 patients had APAS as evidenced by either recurrent microrenal angiopathy (2 patients), thrombocytopenia (1 patient) or frequent A-V shunt thrombosis (3 patients) along with high titers of ACA of IgM, IgG, or both subtypes at the time of their transplants. Each of these 6 patients thrombosed their renal allografts within a week of their transplants. The other 72 transplanted patients with no APAS were all doing well 1 yr post-transplant. The association between APAS and post-transplant renal thrombosis among these patients is highly significant (p < 0.0001). In contrast, no association was discerned between post-transplant thrombosis and prior sensitization to HLA CONCLUSION: Our data demonstrates that patients with APAS are at high risk for development of post-transplant renal thrombosis.

Infection and associated risk factors in the immediate postoperative period of pediatric liver transplantation: a study of 176 transplants.

Abstract: OBJECTIVE To describe the characteristics of infections occurring in the immediate postoperative period of orthotopic liver transplantation (OLT) in children in a pediatric intensive care unit (PICU) and the associated risk factors. DESIGN Retrospective cohort study. SETTING Multidisciplinary 16-bed pediatric intensive care unit in a tertiary university hospital. PATIENTS One hundred and thirty-three pediatric patients (range 6M to 22 yr) who underwent 176 liver transplantations and were admitted to the pediatric intensive care unit for at least 48 h. RESULTS A total of 180 infectious episodes (IE) occurred in 78 (59%) patients who underwent 96 (54.5%) liver transplantations (1.35 IE/patient; 1.02 IE/transplantation). The mean stay was 15.4 +/- 1.1 d (mean +/- SD) and 22 patients died in the pediatric intensive care unit. One hundred and thirty-one IE (72.8%) were bacterial, 31 (17.2%) fungal, and 14 (7.8%) mixed bacterial and fungal. 39% of the IE appeared in the first postoperative week and 27% in the second postoperative week. The most common sites of infection were abdomen (48.3%) and blood stream (26.1%). Bacteria, alone or with fungi, were present in 145 IE (1.1 IE/patient). Gram-positive aerobic bacteria (63%) predominated over gram-negative bacteria (54%) and fungi. Fungi were present in 45 IE; 53.4% of the infections occurred in lung (73% yeasts). The risk factors for infection that were identified were related with younger age, lower body weight, longer cold ischemia time, partial graft, and the volume of packed red blood cell transfusions. Infected patients had more postoperative complications and longer stay in the PICU (21 +/- 16 vs. 8 +/- 6 d), but no increase in mortality. The risk of infection increased 2.38 times with partial grafts and 1.1 times with each intraoperative transfusion of 20 ml/kg of packed red blood cells (RBC). CONCLUSIONS Infection in the immediate postoperative period of pediatric OLT was related with a high morbidity but was not related significantly with increased mortality. The main risk factors for infection in the postoperative period of OLT were related essentially with small recipient size and the inherent complexity of the operation. Routine oropharyngeal decontamination is recommended, as well as early administration of oral nystatin in preoperative intestinal decontamination. The risk of infection increased 2.38 times with partial grafts and 1.1 times with the transfusion of every 20 ml of packed RBC.

Carcinoma of the bladder in renal transplant patients. A case report and collective review of cases

Abstract: Bladder malignancy in the renal transplant recipient is an infrequent occurrence. The 11 previously reported cases reflect an aggressive tumor growth with invasion, requiring partial or complete cystectomy with or without conduit diversion. We report an additional case in a 40-yr-old woman with a living related renal transplant, who experienced rapid progression of her tumor over 3 wk from initial hematuria to a pelvic mass involving the anterior bladder. Her allograft ureter and native ureters, as well as her left iliac vein, became obstructed with tumor in another 2 wk. Biopsy showed poorly differentiated, invasive transitional carcinoma. Attempted resection was abandoned because of finding tumor involvement in most of the pelvis. Chemotherapy was not attempted. She died 2 wk after her attempted resection from tumor burden. Our report presents a collective review of these previously reported 11 cases plus our case. These bladder tumors demonstrate a rapid progression of invasive disease and respond poorly to chemotherapy. There is a possible association of bladder tumors with cyclophosphamide immunosuppression. An aggressive surgical approach should be followed, especially since these tumors present in a younger age group.

Endothelium-dependent vasodilation of the skin microcirculation in heart transplant recipients.

Abstract: Patients with heart failure demonstrate attenuated endothelium-dependent vasodilation of the peripheral circulation, while this is suggested to be reversed after heart transplantation. However, data from human subjects are limited and conflict with studies on the peripheral vasomotor tone in cyclosporine-treated animals, suggesting endothelial dysfunction. We recorded forearm skin perfusion responses following graded iontophoresis of 1% acetylcholine (endothelium-dependent) and 1% sodium nitroprusside (endothelium-independent) by laser Doppler perfusion measurements in 32 heart transplant recipients and 15 age-matched controls. In addition, the hyperemic response to 3 min of blood flow occlusion to the forearm was measured on the third finger pulp. With comparable baseline values, the increases in perfusion to the 4 applications of acetylcholine were significantly attenuated in heart transplant recipients compared with controls: 59 +/- 9 vs. 146 +/- 32, 242 +/- 39 vs. 492 +/- 77, 480 +/- 66 vs. 845 +/- 120 and 699 +/- 77 vs. 993 +/- 139% (mean +/- SEM; all p < 0.01). Peak hyperemia (134 +/- 4 vs. 153 +/- 12 arbitrary units (AU); p < 0.05)), time for the hyperemic perfusion to return to preocclusive baseline (52.4 vs. 102.9 s; p < 0.01) and hence the area under the perfusion curve (1469 +/- 244 vs. 4581 +/- 921 AU s; p < 0.01) were reduced among heart transplant recipients. The area under the perfusion curve correlated significantly with mean arterial blood pressure (r = -0.60; p < 0.01) and with the responses to iontophoresis of acetylcholine (r = 0.41; p < 0.01). Two non-invasive tests of vascular function demonstrate attenuated endothelial-dependent microvascular responses in heart transplant recipients. The relative impact of prior congestive heart failure and postoperative factors, such as treatment with cyclosporine, remains to be determined.

Multimodal treatment for hepatocellular carcinoma on cirrhosis: the role of chemoembolization and alcoholization before liver transplantation.

Abstract: The results of combined trans-arterial chemoembolization (TAE) and percutaneous ethanol injection (PEI) followed by liver transplantation for hepatocellular carcinoma (HCC) are described. Fourteen patients (G2) with tumour stages I-III received a mean of 2 times TAE and 4 times PEI prior to transplantation. Six patients (G1) received no pre-transplant therapy. Tumor size reduced from 37 +/- 16 to 28 +/- 16 mm and alpha-FP from 339 +/- 1057 to 224 +/- 711 ng/mL (p = n.s.). On histopathologic examination (G2 vs. G1) a 100% necrosis of the tumour nodules was seen in 80 vs. 0% (p = 0.001); 60-90% in 3 vs. 1 and 10-50% in 3 vs. 2. Eighty six percent of nodules in G2 and 36% in G1 had a tumour capsule (p = 0.02). After a median follow-up of 26 months (3-60), 2 patients in G1 developed a recurrence of HCC as compared to 0 in G2 (p = 0.0005). The actuarial patient disease-free survival after 48 months was 82% in G2 and 65% in G1. It is concluded that combined treatment with TAE and PEI is inducing necrosis in HCC associated with improved patient disease-free survival following liver transplantation.

Peritoneal metastasis of intracranial glioblastoma via a ventriculoperitoneal shunt preventing organ retrieval: case report and review of the literature.

Abstract: The case of patient with glioblastoma metastatic to the peritoneal cavity 9 months after ventriculoperitoneal shunt surgery precluding cadaver organ procurement is presented. Even though central nervous tumors rarely metastasize spontaneously, the literature indicates that systemic metastases are related to previous surgical procedures and especially shunt surgery. Central nervous tumors have been known to metastasize to lungs, liver, and kidneys and could be transmitted through transplanted organs as shown in the Cincinnati tumor registry. The transplant surgeon should be alerted to this possibility and thorough search for metastases should be undertaken before considering primary brain tumor patients as donors.

Antiproteinuric efficacy of fosinopril after renal transplantation is determined by the extent of vascular and tubulointerstitial damage

Abstract: BACKGROUND Angiotensin converting enzyme (ACE) inhibitors have been successfully used for treatment of proteinuria after renal transplantation (RTx). Factors possibly responsible for the great inter-patient variance of the antiproteinuric effect (APE) have not yet been investigated in renal-transplanted patients. METHODS 28 patients after RTx with a persistent proteinuria of more than 1.25 g/d were treated prospectively with does of fosinopril (10-15 mg/d) which were not effective on systemic arterial blood pressure. Prior to initiation of fosinopril, renal graft biopsy was performed in all patients and renal graft artery stenosis was excluded by duplex ultrasound. Serum creatinine and proteinuria were measured prior to, as well as 3 and 8 months after initiation of ACE inhibition, mean arterial pressure was controlled via 24-h measurement and repeated spot measurements. Reduction of proteinuria was correlated with renal histology, serum creatinine, creatinine clearance, mean arterial blood pressure, sodium excretion before therapy and the relative changes of these parameters during therapy respectively. RESULTS Therapy had to be stopped in 8/28 patients due to side effects including rise of serum creatinine (n = 4). Three patients were excluded due to non-compliance. In the remaining patients (n = 17) proteinuria was reduced from 2.94 +/- 1.66 to 1.82 +/- 1.39 and 2.48 +/- 3.05 g/d after 3 and 8 months respectively, in the mean +/- SD. There was a significant inverse correlation between the APE and the extent of benign nephrosclerosis, interstitial fibrosis and tubular atrophy. No correlation of the APE to any of the other parameters could be demonstrated. CONCLUSIONS Fosinopril can be administered effectively in a subgroup of proteinuric renal transplant recipients. However, because of a high proportion of patients developing side effects, careful monitoring is obligatory. Our results show that the lesser the degree of chronic morphological injury, the greater is the antiproteinuric effect. Thus, the degree of pre-existing histologically proven damage of the graft may serve as an indicator for the antiproteinuric efficacy of ACE inhibitor therapy after RTx.

Is cytomegalovirus infection related to mycophenolate mofetil after kidney transplantation? A case-control study

Abstract: Three multicenter studies have shown that the addition of mycophenolate mofetil (MMF) to an immunosuppressive regime consisting of cyclosporin A (CSA) and prednisone (PRED) decreases the incidence of acute rejection episodes when compared with azathioprine (AZA) or placebo (1-3). In those patients receiving 3 g/d of MMF, the highest dose used in the studies, there was a trend towards an increased incidence of cytomegaloviral sepsis (CMV). We postulated therefore that MMF may represent an independent risk factor for the development of CMV infection in patients receiving renal allografts and MMF at our institution. Having altered the triple drug regime from CSA, AZA (2-2.5 mg/kg/d) and PRED to CSA, MMF (2 g/d) and PRED in July 1995, we elected to study all patients undergoing kidney transplantation for the 33-month period January 1994-September 1996, by undertaking a case control analysis to determine independent risk factors for the development of CMV infection, as defined by CMV viremia or tissue-invasive CMV. Three CMV disease-free control patients were matched to each case, these patients having been randomly selected from the entire pool of patients in the observation period. There were 31 CMV case patients and 102 control patients. Univariate analysis indicated that gender, a concomitant pancreas transplant, acute rejection and CMV seropositivity in the donor were risk factors. However, multivariate analysis indicated that only acute rejection and donor CMV seropositivity were independently linked (p < 0.05) to CMV disease in this sample. Specifically, the odds ratio (OR) for CMV disease between MMF and AZA was 1.0 (95% confidence interval (CI): 0.46-2.18). Therefore, in this case control study we find no evidence that MMF at a dose of 2 g/d is an independent risk factor for primary CMV viremia or tissue invasion in renal allograft recipients.

Necrosis of the femoral head after kidney transplantation.

Abstract: We reviewed the medical records of 750 patients (445 men, 305 women), who had received a kidney transplant during the period 1968 1995, for any sign of necrosis of the femoral head. For post-operative immunosuppression. 374 patients had received high-dose corticosteroids (average 12.5 g during the first year post-operatively), while 376 patients had received low-dose corticosteroids (average 6.5 g during the first year post-operatively) and cyclosporin A. Survival curves according to Kaplan and Meier (J Am Stat Ass 1958 : 53: 457-481) were constructed. In the high-dose steroid group, 42/374 patients (11.2%) developed femoral head necrosis, at an average of 26.2 months post-transplantation. In the low-dose steroid group only 19/376 (5.1%) patients developed this complication, at an average of 20.5 months post-transplantation. This difference in numbers of femoral head necroses was highly significant (p < 0.005). We conclude that steroid doses should be minimized whenever feasible in post-transplant immunosuppression therapy.

Pregnancies following liver transplantation--how safe are they? A report of 19 cases under cyclosporine A and tacrolimus.

Abstract: The number of pregnancies following liver transplantation is increasing due to better patient and graft survival and quality of life. Out of 156 women of a reproductive age, there were 19 pregnancies in 16 women, 12 on CsA and seven on tacrolimus, which occurred between 7/92 and 1/97. The median age of the women was 27.9 yr, median time after transplantation 33 months. There were four spontaneous and two induced abortions in the first trimenon. Ten women delivered ten healthy babies; three newborns had problems (alcoholic embryopathy due to recurrent alcohol abuse of his mother, pneumonia, weight < 2000 g). In eight women mostly mild complications were observed, such as hypertension (n = 5), nonspecific elevation of liver enzymes (n = 2), infection (n = 3) and premature labor (n = 1). Mean gestational age was 39 wk and mean birth weight 2900 g. One case of prematurity and three cases of growth retardation occurred. Cesarean sections were performed in 7 patients (54%) for maternal hypertension (n = 2), presumed fetal hypoxia (n = 4) and breech position (n = 1). All children are normally developed, the oldest being 5 yr old. Although experience with tacrolimus is limited, pregnancies following liver transplantation carry an acceptable risk if carefully monitored by an experienced team of transplant surgeons and obstetricians.

Apoptosis and hepatic allograft reperfusion injury.

Abstract: Necrosis and apoptosis are distinct, but nonexclusive mechanisms of cell death. Until recently, investigators have focused upon necrosis as the sine qua non of lethal cell injury. Specifically, within the realm of liver transplantation, preservation strategies dealing with ischemia,reperfusion injury have concentrated upon minimizing the biochemical and histologic correlates associated with necrosis. Little is known of the role of apoptosis in reperfusion injury in human liver transplantation. Post-reperfusion liver biopsies from 35 patients were retrospectively analyzed for histologic evidence of necrosis. Apoptosis was identified histologically and using a chromogenic technique of in situ labeling of fragmented DNA. The number of apoptotic cells increased in parallel with the necrosis reperfusion score in a significant fashion (p = 0.003 by ANOVA). There was not a Zone 1, 2 or 3 predominance to the histologic distribution of apoptotic cells. The recipient peak serum transaminase values were also noted to increase with the reperfusion score (p = 0.001 by ANOVA). These results suggest that: I) apoptosis occurs in the setting of reperfusion injury during human orthotopic liver transplantation (OLT); and 2) the extent of apoptosis increases in parallel with pathologic and biochemical parameters of reperfusion injury. Given the distinct nature of apoptosis and the highly regulated and conserved pathway for its initiation, inhibition of apoptosis with specific molecular targets, may serve to decrease allograft reperfusion injury.