A self-administered quality of life questionnaire for renal transplant recipients.
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Kidney Transplantation↗
Biomedical subjects
M D Pescovitz
Publications and source records attributed to M D Pescovitz.
Predictive value of enzyme-linked immunosorbent assay-detected IgG anti-HLA antibodies for pediatric renal allograft rejection.
BACKGROUND: Measurement of panel-reactive antibody (PRA) with an enzyme-linked immunosorbent assay using soluble HLA class I molecules (PRA-STAT) in adult renal transplant recipients predicted graft loss and rejection. We sought to confirm this finding in pediatric recipients, an immunologically distinct group. METHODS: The population consisted of 158 renal transplants in 146 patients (age range, 1-21 years). PRA was determined with PRA-STAT and microlymphocytotoxicity (CDC), using final cross-match sera. An elevated test was defined as > or =5% reactivity. Statistical analysis for rejection used the chi-square test and for graft survival used the log-rank test. RESULTS: Thirty-five patients (22%) had %PRA-STAT > or =5%, compared with 26 (16%) with %PRA-CDC > or =5%. The percentage with elevated %PRA-STAT was found to correlate with subsequent transplantations (first, 15%; second, 67%; third, 75%). Subsequent analyses utilized only the 136 primary recipients, of whom 20 (15%) had %PRA-STAT > or =5% and 16 (12%) had %PRA-CDC > or =5%. Elevated %PRA-STAT correlated with rejection at 3 months (65% vs. 36%), 12 months (84% vs. 50%), and 24 months (84% vs. 54%) (P<0.05). No association was found between elevated %PRA-CDC and rejection. Patients with %PRA-STAT > or =5% vs. %PRA-STAT <5% had graft survival at 1 year of 89% vs. 84%, at 2 years of 88% vs. 77%, and at 3 years of 61% vs. 72% (not significant). CONCLUSIONS: Use of %PRA-STAT > or =5% identifies pediatric recipients who are at increased risk for rejection and may benefit from more potent immunosuppression and/or closer monitoring of graft function.
Adolescent↗
Randomised trial of efficacy and safety of oral ganciclovir in the prevention of cytomegalovirus disease in liver-transplant recipients. The Oral Ganciclovir International Transplantation Study Group [corrected].
BACKGROUND: Cytomegalovirus (CMV) disease is a frequent cause of serious morbidity after solid-organ transplantation. The prophylactic regimens used to prevent CMV infection and disease have shown limited benefit in seronegative recipients. We studied the safety and efficacy of oral ganciclovir in the prevention of CMV disease following orthotopic liver transplantation. METHODS: Between December, 1993, and April, 1995, 304 liver-transplant recipients were randomised to receive oral ganciclovir 1000 mg or matching placebo three times a day. Seronegative recipients of seronegative livers were excluded. Study drug was administered as soon as the patient was able to take medication by mouth (no later than day 10) until the 98th day after transplantation. Patients were assessed at specified times throughout the first 6 months after surgery for evidence of CMV infection, CMV disease, rejection, opportunistic infections, and possible drug toxicity. FINDINGS: The Kaplan-Meier estimate of the 6-month incidence of CMV disease was 29 (18.9%) of 154 in the placebo group, compared with seven (4.8%) of 150 in the ganciclovir group (p < 0.001). In the high-risk group of seronegative recipients (R-) of seropositive livers (D+), incidence of CMV disease was 11 (44.0%) of 25 in the placebo group, three (14.8%) of 21 in the ganciclovir group (p = 0.02). Significant benefit was also observed in those receiving antibodies to lymphocytes, where the incidence of CMV disease was 12 (32.9%) of 37 in the placebo group and two (4.6%) of 44 in the ganciclovir group (p = 0.002). Oral ganciclovir reduced the incidence of CMV infection (placebo 79 [51.5%] of 154; ganciclovir 37 [24.5%] of 150; p < 0.001) and also reduced symptomatic herpes-simplex infections (Kaplan-Meier estimates: placebo 36 [23.5%] of 154; ganciclovir five [3.5%] of 150; p < 0.001). INTERPRETATION: Oral ganciclovir is a safe and effective method for the prevention of CMV disease after orthotopic liver transplantation.
Administration, Oral↗
Safety and tolerability of cyclosporine microemulsion versus cyclosporine: two-year data in primary renal allograft recipients: a report of the Neoral Study Group.
BACKGROUND: The new microemulsion formulation of cyclosporine (CsA-ME) is more bioavailable than cyclosporine (CsA) in de novo renal transplant patients. Therefore, it was of interest to compare the safety profile of each formulation in such patients. METHODS: In a multicenter, double-blind, parallel-group study, 101 renal transplant recipients were randomized after transplantation to receive either CsA (n=50) or CsA-ME (n=51) capsules twice daily for 2 years. Of these patients, 54 (CsA, n=26; CsA-ME, n=28) completed 1 year of the study and entered the second-year, double-blind extension. Initial dose at the time of transplantation was 5 mg/kg b.i.d.; doses were titrated to target trough levels. METHODS: The mean (+/- SD) doses at the end of 2 years were 4.6 +/- 1.8 and 3.8 +/- 1.1 mg/kg per day for CsA- and CsA-ME-treated patients, respectively. The mean (+/- SD) CsA trough levels at end point were 187 +/- 63 and 210 +/- 95 ng/ml for CsA- and CsA-ME-treated patients, respectively. At least one adverse event was reported by 25/26 (96%) of CsA- and 27/28 (96%) of CsA-ME-treated patients. No patient discontinued the study because of adverse events. No deaths occurred during the study. Renal function, as measured by serum creatinine levels, and blood pressure were comparable over time in both treatment groups. CONCLUSIONS: There was no significant difference in safety and tolerability between CsA- and CsA-ME-treated kidney recipients for 2 years after transplantation.
Adolescent↗
Intraoperative placement of a Wallstent for portal vein stenosis and thrombosis after liver transplantation.
We report a case of orthotopic liver transplantation, in which portal vein thrombosis developed in the immediate postoperative period. Surgical thrombectomy and intraoperative placement of a large caliber Wallstent resulted in long-term patency. The unique feature of this case is the intraoperative placement of the stent via the inferior mesenteric vein under fluoroscopic guidance. The use of a large caliber (16 mm) stent obviated the need for postoperative anticoagulation.
Adult↗
Histology of rat small bowel transplants: cyclosporine A ameliorates features of rejection including apoptosis and ganglion cell reduction.
The histology of rat small bowel transplants (SBT) was examined in orthotopic isografts and allografts with and without immunosuppression. Lewis to Lewis isografts were examined 7 days after transplant, and LBNF1 to Lewis allografts were examined 2, 4, 7, and 10 days after transplant; one group received cyclosporine A (CyA), and their allografts were examined 7 days after transplant. Compared with similar intestinal segments from unoperated animals, allografts at 4, 7, and 10 days after surgery showed progressive inflammation, cryptitis, villous atrophy, and transmural necrosis. In contrast, SBT in animals given CyA did not significantly differ from normal in any histological parameter. The number of apoptotic structures per 100 crypts in SBT at day 4 (58.25 +/- 32.98) and day 7 (31.86 +/- 27.63) after transplant were significantly increased compared with unoperated bowel (5.23 +/- 13.41) (P < .05); the number in CyA-treated allografts (11.57 +/- 29.56) did not differ significantly from normal. The number of intermyenteric ganglion cells was significantly reduced (P< .05) in allografts 7 and 10 days after transplant (mean and [range] = 31 [18 to 38] and 25 [23 to 27], respectively) but the number in allografts from CyA-treated animals (47 [24 to 72]) did not differ from unoperated bowels (52 [30 to 88]). We conclude that CyA treatment significantly reduces the histological abnormalities associated with transplant rejection including adverse effects on epithelial and ganglion cells; therefore, the absorptive capacity and motility characteristics of the CyA-treated SBT should be preserved compared with untreated allograft controls.
Animals↗
Equivalence of cyclosporine blood level assays in patients receiving cyclosporine microemulsion or cyclosporine. The Sandoz Neoral Study Group N103.
The more rapid absorption of the cyclosporin A (CyA) microemulsion formulation (Neoral, NEO) compared to Sandimmune (SIM) might bypass intestinal metabolism resulting in differing amounts of CyA metabolites in blood as compared to SIM. If true, then CyA levels obtained with a CyA monoclonal antibody assay (TDx) that has metabolite cross-reactivity might differ depending on the CyA formulation received by the patient, thereby affecting safety and efficacy. Fifty-one NEO vs. 50 SIM treated de novo renal transplant recipients from a multicenter double-blind randomized trial had morning, whole-blood, trough-samples obtained at the ends of weeks 1, 4, 8, and 12 post-transplant assayed for CyA by HPLC and TDx. The slopes (ratio of TDx value to HPLC value) for the regression lines between TDx and HPLC levels as a function of time post-transplant and CyA formulation were determined using a general linear model. For NEO, the slopes at each week (1.21-1.41 x HPLC) did not differ significantly (p = 0.82). For SIM, the week 1 slope (1.2) was significantly (p = 0.006) less than the other weeks (1.4-1.44). The slopes (NEO vs. SIM) were not different at either week 1 (1.21 vs. 1.22, p = 0.82) or at pooled weeks 4, 8, and 12 (1.33 vs. 1.4, p = 0.1). These results indicate that despite the improved absorption, TDx values obtained on NEO are qualitatively similar to those obtained on SIM.
Absorption↗
Oral ganciclovir in pediatric transplant recipients: a pharmacokinetic study.
An oral formulation of ganciclovir (GAN) has been shown to be effective as prophylaxis of cytomegalovirus (CMV) after liver transplantation in an adult population. There are no data on the use or dose of oral GAN in pediatric transplant recipients. We evaluated the pharmacokinetics of oral GAN in a group of such patients. Nine patients (4 kidney and 5 liver transplant recipients, age 0.9-13 yr) were treated with the commercial formulation of oral GAN after transplant. All patients were considered at risk for CMV disease based on the use of anti-lymphocyte antibody (n = 5), and/or the use of a CMV positive organ in a CMV negative recipient (n = 5) or based on being a recipient of a liver transplant (n = 4). They received oral GAN for 84 +/- 29 d. All recipients had normal renal function as estimated by the Schwartz formula. While on a stable dose of oral GAN for at least 4 d (mean +/- SD 8.4 +/- 7, range 4-27 d), 1-ml serum samples were obtained before and at various times after dosing for the measurement of GAN levels. GAN levels were determined at a central laboratory by high-performance liquid chromatography. In 7 of the patients, a sufficient number of levels were obtained post-dosing to calculate the area under the curve using the linear trapezoidal rule. Cmin, the morning trough concentration, and Cmax, the peak concentration, were determined by inspection. Doses of oral GAN were increased if Cmin levels were less than 0.5-1.0 microgram/ml. Adequate levels of GAN were achieved in these patients at doses of 21.8-38.5 mg/kg or 568-990 mg/m2 every 8 h. There was a better correlation between the maximum GAN blood concentration and body surface area (R2 = 0.52, p = 0.008) than with body weight (R2 = 0.36, p = 0.04). Oral GAN was well tolerated in the 7 patients without evidence of leukopenia, thrombocytopenia, or nephrotoxicity. No CMV disease occurred, although one patient had probable CMV syndrome with the development CMV IgM antibodies. These data suggest that oral GAN may be safely administered to pediatric transplant recipients. With normal renal function, the dosing should be in the range 20-40 mg/kg or 500-700 mg/m2 q 8 h. Further data in children with impaired renal function is required.
Administration, Oral↗
Persistence of cyclosporine after withdrawal of the drug in a patient with chronic liver transplant rejection. Role of the monoethylglycinexylidine test.
Patients with chronic rejection of liver allografts may show persistently high cyclosporine levels. This phenomenon may be due to a down-regulation of the P450 cytochrome system. The monoethylglycinexylidine test was useful in confirming this hypothesis.
Adult↗
The pharmacokinetics of a microemulsion formulation of cyclosporine in primary renal allograft recipients. The Neoral Study Group.
This study was a randomized, double-blind, 12-week comparison of the pharmacokinetics, safety, and tolerability of two cyclosporine (CsA) formulations, cyclosporine emulsion capsules and oral solution for microemulsion and cyclosporine, in the postoperative management of renal transplant patients. Of the 101 patients, aged 18 to 65, who entered the study, 89 were evaluable for pharmacokinetics. Initial dosage was 10 mg/kg per day, administered twice daily in two equal doses. Dosages were adjusted to achieve target CsA concentrations. The pharmacokinetic (PK) parameters (dose-normalized) of greatest interest were maximum blood concentration (C(max)/dose), time to reach maximum concentration (t(max), area under the blood concentration-vs.-time curve (AUC/dose), and trough blood concentrations (Co h/dose). The relative CsA bioavailabilty was found to be significantly enhanced with cyclosporine emulsion compared with cyclosporine with a 16% to 31% increase in AUC and a 32% to 42% increase in C(max). Intrapatient variability of PK parameters was significantly lower with cyclosporine emulsion than with cyclosporine for AUC, C(oh), t(max), and C(max) in many instances. This indicates a more consistent, rapid, and more complete total absorption of CsA. Despite higher CsA C(max) levels and AUCs with cyclosporine emulsion, safety and tolerability (detailed in a parallel report) were comparable to those of cyclosporine. The PK advantages of cyclosporine emulsion over cyclosporine are either independent of food conditions or possibly reflective of more consistent absorption of CsA with cyclosporine emulsion. The findings suggest that de novo use of cyclosporine emulsion may simplify and improve management of organ transplant recipients and that the PK advantages of cyclosporine emulsion may translate into clinical benefits.
Adolescent↗
The safety and tolerability of cyclosporine emulsion versus cyclosporine in a randomized, double-blind comparison in primary renal allograft recipients. The Neoral Study Group.
A 12-week, randomized, double-blind, multicenter pharmacokinetics study was conducted to compare the clinical safety and tolerability of cyclosporine capsules and oral solution for microemulsion and cyclosporine in 101 primary renal transplant recipients Cyclosporine emulsion has more complete absorption and improved bioavailability compared with cyclosporine, and dosing of both cyclosporine formulations was adjusted to achieve comparable whole-blood trough levels. Mean serum creatinine values were higher in the cyclosporine emulsion group at baseline, 8, and 12 weeks (P<0.05). The incidence of acute rejection was similar in both treatment groups although fewer patients required monoclonal antibody therapy in the cyclosporine group (31% vs. 82%, respectively). Despite the increased bioavailability of cyclosporine emulsion, no significant differences in the incidence of adverse events were observed; the safety, tolerability, and efficacy of cyclosporine emulsion and cyclosporine were comparable.
Administration, Oral↗
The natural history of chronic myelogenous leukemia in a renal transplant recipient.
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Humans↗
Improved absorption of cyclosporine for microemulsion in a pediatric liver transplant recipient with cystic fibrosis.
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Child↗
Alpha-1-proteinase inhibitor prolongs small intestinal graft preservation and survival.
Organ preservation solutions currently used for cold storage of human donor organs are less effective in preserving small intestinal grafts than other organ grafts. The maximal safe period of cold preservation for human small intestinal graft is only about 6 hours. The pathology of preserved and reperfused small intestinal grafts is characterized by mucosal autolysis and sloughing. The authors speculated that the preservation/reperfusion injury results from a proteinase/proteinase-inhibitor imbalance in the graft that favors tissue degradation. This study evaluates whether the addition of an alpha-1-proteinase inhibitor (alpha-1-PI) to the preservation solution can improve graft survival after small bowel transplantation. Forty small intestinal grafts (20 cm long) were harvested from Lewis rats. The grafts were divided randomly into three groups and were preserved in one of the following solutions: normal saline (NS) (n = 10), alpha-1-PI (25 mg/mL; n = 20), or proteinase-free bovine serum albumin (BSA) (25 mg/mL; n = 10). After 12-hour cold storage in the respective solutions, the grafts were transplanted orthotopically into syngeneic recipients. Full-thickness graft biopsies were performed before and 1 hour after revascularization. The effectiveness of preservation was judged by graft histopathology and recipient survival. Histological studies showed that there was less mucosal autolysis and sloughing of the grafts in the alpha-1-Pl group than in the other two groups. All recipients in the NS and BSA groups died of graft failure within 7 days (NS: median, 4 days; range, 2 to 5 days; BSA: median, 6 days; range, 4 to 7). However, 60% (12 of 20) of the recipients in the alpha-1-PI group survived more than 90 days (median, > 90 days; range, 4 to > 90 days; P < .005 v NS or BSA groups, log-rank method). These data suggest that the inclusion of alpha-1-PI in the preservation solution may enhance graft integrity and improve the surgical outcome after small bowel transplantation.
Animals↗
The Second International Swine CD Workshop.
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Animals↗
Proteinuria in recipients of liver transplants.
We investigated the incidence and significance of proteinuria in recipients of liver transplants. The overall incidence of proteinuria was 59.72%. The peak incidence of proteinuria was at 3 months and at the end of 1 yr posttransplant. Proteinuria was higher in those patients who developed posttransplant diabetes mellitus, and those who developed both posttransplant diabetes and posttransplant hyperlipidemia. Patients who received higher total dosage of steroids and CsA had significantly greater proteinuria. Patients who had a Cr Cl greater than 50 ml/min had greater proteinuria posttransplant for the first 6 months, but the trend was reversed later. We did not find any association of proteinuria with age, weight, rejection episodes, or with the etiology of liver failure. Hypertension was a common occurrence in our patients, and therefore its significance in the causation of proteinuria could not be defined.
Adolescent↗
Metabolic problems in recipients of liver transplants.
We analyzed the metabolic problems in recipients of liver transplants. Immunosuppression consisted of cyclosporine, steroids and azathioprine. With a mean follow up of 3.5 yr, 37% of 71 recipients were rendered permanently diabetic and hyperlipidemic. Recipients who developed posttransplant diabetes had higher cholesterol levels and proteinuria, but decreased creatinine clearance. Transplant recipients who developed posttransplant hyperlipidemia had greater proteinuria, but their sugars and creatinine clearance were comparable to those who did not have hyperlipidemia. The most significant factor responsible for these metabolic complications was the total dosage of prednisone and cyclosporine. There was no effect of risk antigens on the development of diabetes.
Adult↗
The arteriovenous fistula for hemodialysis access: gold standard or archaic relic?
A five year retrospective review was undertaken to evaluate the patency rates of arteriovenous fistulae (AVF) in patients with end stage renal disease. From July 1989 through June 1994, 150 fistulae were created in the wrists of 144 patients. Thirty-four percent of the patients had diabetes mellitus. Patient death or irreparable fistulae were considered end points in the study. Patency rates were calculated by the Kaplan-Meier Actuarial Analysis. An analysis to assess the impact of the demographic characteristics, underlying renal disease, and effect of revisions on patency rates was calculated. The results demonstrate a high initial failure rate (less than 1 month) of 13 per cent in the entire cohort undergoing fistulae replacement. The 1 and 5-year patency rates were 56 per cent and 30 per cent, respectively. Diabetics had a significantly lower patency rate at 1 and 5 years (42% and 18%) respectively. Others, who had poor patency rates, include patients 70 years old or greater (40% patency at one year). The results suggest that the AVF should not be the first choice of access in elderly diabetics and that these patients would be better served with other modes of access, such as synthetic conduits or permanent indwelling venous catheters.
Adult↗