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PubMed1999

Evolution in pancreas transplantation techniques: simultaneous kidney-pancreas transplantation using portal-enteric drainage without antilymphocyte induction.

OBJECTIVE: To report initial experience with the combination of a novel technique of portal-enteric pancreas transplantation with newer immunosuppressive strategies that eliminate antilymphocyte induction therapy. BACKGROUND: A new surgical technique of pancreas transplantation has been developed with portal venous delivery of insulin and enteric drainage of the exocrine secretions (portal-enteric). The introduction of potent immunosuppressive agents may allow simultaneous kidney and pancreas transplants (SKPT) to be performed without antilymphocyte induction. METHODS: From September 1996 to November 1998, the authors performed 28 primary SKPTs with portal-enteric drainage and no antilymphocyte induction. All patients received triple immunosuppression with tacrolimus, mycophenolate mofetil, and steroids. The study group had a mean age of 38 years and a mean preoperative duration of diabetes of 25 years. Four patients (14%) had prior kidney transplants. RESULTS: All patients had immediate renal allograft function. Actual patient, kidney, and pancreas graft survival rates were 86%, 82%, and 82%, respectively, after a mean follow-up of 12 months. Four patients died, three as a result of cardiac events unrelated to SKPT. Five kidney and five pancreas grafts were lost, including five deaths with function and three cases of chronic rejection. The mean length of stay and total charges for the initial hospital stay were 12.5 days and $99,517. The mean number of readmissions was 2.9, and 10 patients (36%) had no readmissions. Six patients (21 %) developed acute rejection, with five (18%) receiving antilymphocyte therapy. Seven patients (25%) underwent relaparotomy, including two (7%) for intraabdominal infection. Nine patients (32%) had major infections, including three (11%) with cytomegaloviral infection. Of the 24 surviving patients, 22 (92%) are both dialysis- and insulin-free. CONCLUSION: These preliminary results suggest that SKPT with portal-enteric drainage without antilymphocyte induction can be performed with excellent outcomes.

Adult↗

PubMed2000

Immunosuppressive therapies after heart transplantation: best, better, and beyond.

Despite the significant advances in transplantation immunology and immunosuppressive therapies over the past 30 years, current immunosuppressive regimens are still inadequate in the majority of cardiac transplant recipients. Although short- and long-term survival rates have improved significantly, only 50% will survive 10 years and very few will survive 20 years. Complications of overimmunosuppression and underimmunosuppression account for the majority of these deaths. Only true "immunologic" tolerance can provide the outcome we pursue, namely, prolonged allograft function and otherwise normal immune function without chronic immunosuppressive therapy and its risks. Until a successful tolerance-inducing protocol is developed, we must use the current and upcoming immunosuppressive agents and techniques.

Cell Division↗

PubMed2000

Massive bone allograft reconstruction in high-grade osteosarcoma.

From 1986 to 1994, 112 bone allograft reconstructions were performed in patients with high-grade osteosarcoma in whom neoadjuvant chemotherapy was administered. The allograft reconstruction was used in arthrodesis in 44 cases (41 knees, three ankles), as an intercalary graft in 39 (28 femurs, 11 tibias), as an osteoarticular graft in 22 (three proximal and/or distal humeri, six distal femurs, 13 proximal tibias), and as an allograft and prosthesis composite in seven (two proximal humeri, one proximal femurs, four proximal tibias). In 20 patients an autologous vascularized fibula was used to augment the allograft. Functional results were excellent or good in 74% of the patients after the primary surgery, and in 83% of the patients after secondary surgery. Complications include delayed union (49%) and fracture (27%), although there were no cases of deep infection. The incidence of delayed union, but not infection or fracture, was increased by the use of chemotherapy.

Adolescent↗

PubMed1987

Development of metabolic alkalosis after massive transfusion during orthotopic liver transplantation.

Five patients undergoing orthotopic liver transplantation were investigated for changes in acid-base homeostasis secondary to large volume transfusions. All patients developed a transient acidemia during the operative period, followed by alkalemia which persisted into the early postoperative period. The patients received an estimated mean of 750 mEq of citrate, which appeared to cause metabolic alkalosis. The biochemical basis underlying the regulation of citrate metabolism that may have led to the timing, extent, and duration of the subsequent metabolic alkalosis is presented. Finally, the time course for the development of metabolic alkalosis may be a potentially sensitive indicator of early allograft function.

Acid-Base Imbalance↗

PubMed1997

Idiopathic thrombocytopenic purpura in a liver transplant recipient with previous primary biliary cirrhosis.

The loss of immunotolerance has been implicated in the pathogenesis of both primary biliary cirrhosis (PBC) and idiopathic, immune-mediated thrombocytopenic purpura (ITP). An association between these two autoimmune diseases has been well described. We describe a 41-year-old woman in whom ITP developed 457 days after liver transplantation for PBC while receiving immunosuppressive medications sufficient to maintain allograft function. Our case report, the first to describe post-transplant ITP in association with PBC, demonstrates the persistence of the underlying immune dysregulation of PBC after transplantation. The practice of decreasing the dosage of immunosuppressive medication to maintenance levels after transplantation may unmask the effects of this defect in immunotolerance.

Adult↗

PubMed1995

Urological evaluation of adult renal transplant recipients.

We retrospectively reviewed the charts of 150 consecutive patients who underwent renal transplantation at our institution in 1990 to determine the effectiveness of our pre-transplantation urological evaluation. Of 100 patients who met the inclusion criteria 74 were evaluated solely with a history and physical examination, urinalysis and a urine culture, while the other 26 underwent additional tests because of either a history of urological problems or abnormalities at the initial evaluation. Urological complications occurred in 18 patients. In 10 patients the complications were related to the operation and included postoperative hematuria from bleeding at the site of the ureteral reimplantation, symptomatic lymphocele formation and urinary fistula resulting from necrosis of the distal ureter. These complications could not have been anticipated by the pre-transplant evaluation. Urological complications in the other 8 patients were a febrile urinary tract infection (4), temporary urinary retention (2), hematuria and back pain requiring bilateral native nephrectomy (1), and lower tract obstructive symptoms (1 who eventually required transurethral resection of the prostate 15 months after transplantation). Only 1 of these complications might have been averted with more extensive preoperative testing and in none of these patients did the urological complication compromise allograft function. We conclude that most patients with end stage renal disease require only minimal evaluation before renal transplantation. More extensive evaluation is necessary only in patients with a strong history of urological disease or with abnormalities found during the basic examination.

Adolescent↗

PubMed1989

Primary acute renal failure ("acute tubular necrosis") in the transplanted kidney: morphology and pathogenesis.

"Acute tubular necrosis" (ATN) in the transplanted kidney, when properly differentiated from other causes of acute renal failure, appears to be a relatively benign condition. It has been widely assumed to be pathologically identical to ATN in the native kidney, but its histopathologic features have not been studied in detail. Because immunosuppressive therapy with cyclosporine adds an additional layer of complexity to the morphologic changes observed, in the present study we have confined our observations to patients immunosuppressed with steroids and azathioprine. Thirteen renal allograft biopsies from patients with ATN and 5 biopsies from patients with normal allograft function were compared with the previously obtained series of 57 native kidney ATN biopsies and 20 control biopsies. Both qualitative and quantitative differences between transplant and native kidney ATN were found. Compared with native kidney ATN, transplant ATN showed significantly less thinning and absence of proximal tubular brush border and less variation in size and shape of cells in individual tubular cross-sections. There were also significantly fewer casts and less dilatation of Bowman's space and a significantly greater number of polarizable crystals presumed to be oxalate in transplant ATN. In native kidney ATN the tubular injury sites were mostly characterized by desquamation of individual epithelial cells leaving areas of bare basement membrane (the "non-replacement" phenomenon). In transplant ATN, sites of tubular injury, although rare and affecting only short tubular segments, were characterized by the actual presence of identifiable necrotic tubular cells, a finding seldom seen in native kidney ATN. There also was a greater interstitial infiltrate of mononuclear inflammatory cells in transplant ATN compared to native kidney ATN. Electron microscopic studies of 9 transplant ATN biopsies showed a mild reduction in proximal tubular brush border compared with controls but this alteration was significantly less than that observed in native kidney ATN. There was no significant alteration in proximal or distal basolateral infoldings and this contrasted sharply with the marked reduction in basolateral infoldings of the plasma membrane observed in native kidney ATN. Disintegrated necrotic cells were found by electron microscopy in transplant ATN whereas these were not observed in native kidney ATN. There were significantly more cells with apoptosis (shrinkage necrosis) in transplant ATN than in native kidney ATN. There were significantly more cells with apoptosis (shrinkage necrosis) in transplant ATN than in native kidney ATN. On the other hand, there were significantly greater numbers of "non-replacement" sites in the distal tubules in native kidney ATN compared to transplant ATN.(ABSTRACT TRUNCATED AT 400 WORDS)

Actins↗

PubMed1982

Long-term results of renal transplantation in recipients with a functioning graft for 2 years.

The late results of renal transplantation are reviewed in 214 recipients with a functioning allograft for 2 years. Graft survival was better (P less than 0.001) in living related recipients (t 1/2 = 17 years) compared with cadaver graft recipients (t 1/2 = 7.7 years). Graft survival was also significantly different (P less than 0.001) in patients with a 2-year serum creatinine level of less than or equal to 2.0 (t 1/2 = 16.4 years), 2.1 to 3.0 (t 1/2 = 6.5 years), or greater than 3.0 mg/dl (t 1/2 = 2.9 years). A greater proportion of patients with a 2-year serum creatinine level of greater than 3 mg/dl had experienced greater than two rejection episodes (P less than 0.0001). Among recipients with a 2-year serum creatinine level of less than or equal to 2.0 mg/dl, living related grafts achieved better graft survival than cadaver grafts (P less than 0.05). Major complications of transplantation were more common in patients with a cadaver graft, 2-year serum creatinine level of greater than 3 mg/dl, or age greater than 45 years. One hundred and forty-two patients are currently alive, 93% of whom have achieved complete rehabilitation.

Adolescent↗

PubMed1982

Percutaneous transluminal angioplasty treatment of renal transplant artery stenosis.

Since June 1979, percutaneous transluminal angioplasty (PTA) has been the procedure of choice for renal transplant artery stenosis (RTAS) at the Hospital of the University of Pennsylvania. Of 241 renal allograft recipients, 17 (7%) when studied by arteriogram because of suspected RTAS proved to have significant stenosis (the mean reduction in luminal width for the group being 68%) and underwent PTA. RTAS was equally prevalent in cadaver and related kidney allografts and was no less common in HLA-identical related donor grafts, arguing against the importance of immune factors in etiology. RTAS was equally prevalent whether the anastomotic technique was end to end or end to side. However, when RTAS occurred after end to side anastomoses, it was usually postanastomotic. Fifteen of 17 of the attempts at dilation by PTA were successful by angiographic analysis. Thirteen of the 15 successfully dilated patients had long-term allograft survival and in all of these instances blood pressure (BP) was decreased after PTA. After a mean of 67 weeks, BP decreased from a systolic of 184 +/- 24 mm Hg pre-PTA to 135 +/- 15 mm Hg (P less than 0.001) and from a diastolic of 115 +/- 10 mm Hg pre-PTA to 87 +/- 11 mm Hg (P less than 0.001). The majority of patients continue to require antihypertensive drugs but in a less vigorous regimen than pre-PTA. Serum creatinine level fell following PTA from 1.9 +/- 0.6 to 1.7 +/- 0.5 mg/100 ml (P less than 0.01). Repeat angiographic study was done in nine patients, an average of 61 weeks after PTA, and no recurrent RTAS was identified. Three minor complications of PTA occurred but none led to long-term sequelae. Thus, we believe PTA of RTAS is relatively safe, carrying less mortality and morbidity than operative treatment, and is capable of improving BP control and renal allograft function.

Adult↗

PubMed1984

Effect of renal transplantation on zinc metabolism and taste acuity in uremia. A prospective study.

The effect of successful renal transplantation on zinc metabolism and taste acuity was determined prospectively in 15 adult uremic patients. Before transplantation all patients had subnormal concentrations of zinc in plasma and hair, as well as abnormal taste detection and recognition thresholds for sodium (salty), sucrose (sweet), hydrochloric acid (sour), and urea (bitter). Following renal transplantation, abnormalities of taste acuity and zinc metabolism persisted and were accompanied by increased urinary zinc excretion in all patients. Normalization of zinc concentration in plasma and hair as well as taste acuity did not occur until one year after transplantation and was associated with a concomitant decrease in urinary zinc excretion. The plasma zinc levels and daily urinary zinc excretion were inversely related (r = 0.62, P less than .001) in all patients with normal allograft function. None of the zinc parameters was significantly related to azathioprine or corticosteroid dosage. The results of this study suggest that zinc deficiency and taste abnormalities of uremia persist up to one year posttransplant and may be related to increased urinary zinc losses. The mechanisms underlying post-transplant hyperzincuria as well as clinical significance of zinc deficiency following transplantation remain to be determined.

Adult↗

PubMed1985

Total parathyroidectomy for posttransplantation hyperparathyroidism.

The acute and short-term clinical course of 19 subjects who underwent total parathyroidectomy and forearm implantation for persistent hyperparathyroidism following successful kidney transplantation (mean [+/- SD] time after transplant 43.7 +/- 29.5 months) is described. Their mean preoperative serum calcium level of 10.8 +/- 0.5 mg% decreased to a nadir of 7.9 +/- 0.9 mg%, 62.5 +/- 27.7 hr after the operation. The lowest serum ionized calcium (1.80 +/- 0.2 mEq/L) was recorded 57 +/- 49 hr postoperatively. After an average of five hospital days, the patients were discharged with a mean serum total calcium concentration of 8.3 +/- 1.0 mg%. Three months following the operation, the mean serum total calcium concentration was 9.5 +/- 0.6 mg%. With an average follow-up of 19 months (range 3-36 months) serum total calcium was 9.6 +/- 0.6 mg%, with only one subject requiring calcium supplementation. Total parathyroidectomy with forearm implantation was associated with normalization of serum-immunoreactive parathyroid hormone concentrations and maintenance of stable allograft function. Our experience suggest that this procedure is an effective modality with a predictable postoperative recovery of parathyroid function when used to treat persistent hyperparathyroidism in the long-term survivor of renal transplantation.

Adolescent↗

PubMed1987

The relevance of pressure changes in transplanted hearts and kidneys in immunosuppressed rats.

The pressure within rat cardiac and renal allografts has been observed to rise during rejection. We wished to see if this pressure rise could be prevented or reversed with immunosuppression. Transplants were performed from Lewis or DA donors to Lewis recipients. The rats received either a heterotopic cardiac transplant or an orthotopic renal transplant and were then treated with different immunosuppressive protocols. Intramyocardial pressure was recorded using a fine-gauge needle connected to an air pressure manometer. In the case of the renal transplants, a pressure transducer was used as well and the two methods compared. Intramyocardial and intrarenal pressures rose dramatically in unimmunosuppressed recipients of DA allografts. No such rise was seen in isografted organs, although the pressures recorded remained significantly higher than those found in untransplanted hearts and kidneys. Cyclosporine 20 mg/kg/day was effective in suppressing rejection in both models, and inhibited any rise in intraorgan pressure. Cyclosporine 10 mg/kg/day was less effective, and with 2 mg/kg/day allograft function was considerably impaired, one-third of the cardiac grafts being rejected by 16 days. In both models intraorgan pressures became raised. The addition of methylprednisolone 16 mg/kg i.p. on days 7 and 8 to this low dose regimen of cyclosporine 2 mg/kg/day rapidly reversed the rise in pressure and restored graft function to normal. Intraorgan pressure levels therefore accurately reflected the state of function of transplanted hearts and kidneys. When a manometer and a transducer were compared as a means of measuring the pressure in the renal transplants, the manometer method was found to be superior.

Animals↗

PubMed1988

Urinary calculi in renal transplant recipients.

UNLABELLED: Urinary calculi are an uncommon complication in renal transplant recipients. During a 15-year period, in 544 cases of kidney transplantation with a functioning allograft for more than 3 months, and a long-term follow-up, we have observed 9 cases (1.7%) of urinary calculi. Calculi occurred in 6 male and 3 female patients, 6 patients were recipients of living related and 3 of cadaveric kidneys. Calculi were diagnosed as early as 3 months and as late as 3.5 years after transplantation, but most were detected within the first year. The location of the calculi was the bladder in 4 cases, the transplant in 3, and indeterminant in 2. Crystallographic analysis of retrieved stones revealed calcium oxalate and/or phosphate in 4 cases, triple phosphate in 2, and uric acid in 1. All patients had one or more stone-predisposing factors, such as obstructive uropathy and recurrent urinary tract infection (4 cases), hyperoxaluria (3), or hypercalciuria (2). During long-term follow-up (mean 60 months), only one patient lost the renal graft, 14.5 years after transplantation, primarily from causes unrelated to urinary calculi. One instance of stone recurrence was noted. IN CONCLUSION: (1) urinary calculi after renal transplantation are relatively uncommon; (2) predisposing factors and crystallographic composition of the calculi are identical in type, but not frequency, to those of nontransplant patients; and (3) with proper medical and surgical management, post-transplant urolithiasis does not appear to affect graft prognosis.

Adult↗

PubMed1989

Serum F protein estimation in liver allograft recipients with graft dysfunction.

Serum levels of F protein, a 44 kD cytoplasmic protein mainly found in hepatocytes, became elevated during episodes of graft dysfunction following orthotopic liver transplantation. In a study of 27 liver transplant recipients, the rise in F protein did not precede rises in the other conventional biochemical indices of hepatic dysfunction. Serum F protein concentration significantly correlated with serum levels of aspartate aminotransferase, gamma-glutamyltransferase, alkaline phosphatase, and bilirubin (all P less than 0.001) and also with the prothrombin time (P = 0.048). Despite its high concentration in liver cells, this marker does not provide any additional benefit in the diagnosis of graft dysfunction or in monitoring liver allograft function following transplantation.

Adolescent↗

PubMed1990

Lovastatin treatment of hypercholesterolemia in renal transplant recipients.

The treatment of hypercholesterolemia in renal transplant recipients has been problematic. In the present double-blind study, 11 patients were treated with diet for at least 4 weeks. They were then randomized to placebo or the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, lovastatin (20 mg/day) for 6 weeks, followed by crossover to an additional 6 weeks of lovastatin or placebo. All patients had stable allograft function 8.4 +/- 1.2 years (mean +/- SEM) after transplantation, and received low-dose prednisone and azathioprine immunosuppression. Compared with diet alone, lovastatin caused a 21% reduction in total cholesterol from 307 +/- 14 mg/dL to 244 +/- 13 mg/dL (P less than 0.05). Lovastatin reduced LDL cholesterol 28% from 214 +/- 12 mg/dL to 155 +/- 11 mg/dL (P less than 0.05). Trends toward favorable changes in HDL cholesterol, serum triglycerides, and apolipoproteins were not statistically significant. Liver enzymes, creatine phosphokinase, and renal function remained stable. With lovastatin there was a 27% increase in the WBC (from 6220 +/- 530 cells/mm3 to 7780 +/- 510 cells/mm3, P less than 0.05) that was attributable to a 45% increase in neutrophils (P less than 0.05). This effect of lovastatin, possibly the result of reduced azathioprine bone marrow suppression, could have important implications for immunosuppressive therapy in this patient population. Altogether, these results suggest that lovastatin may be a safe and effective treatment for hypercholesterolemia in renal transplant recipients receiving conventional immunosuppression.

Adolescent↗

PubMed1990

The role of cold ischemia in a provincial organ-sharing program in the cyclosporine era.

Prolonged cold ischemia has been associated with impaired early cadaver renal allograft function. The role of CsA in potentiating these effects is not well understood, but CsA has been implicated in promoting delayed graft function and potentiating renal ischemic injury. In order to establish whether CsA is safely tolerated by kidneys subjected to protracted cold ischemia, we examined patient and graft outcome in a series of 1081 patients receiving cadaver-kidney transplants over an 8-year period (1981-1988). All patients received a standard immunosuppressive regimen that included CsA. Overall actuarial 1-year patient and graft survival rates were 96% and 80%, respectively. Renal preservation was achieved either by pulsatile perfusion (n = 261, 24%) or simple cold storage (n = 820, 76%). Results were analyzed according to total cold ischemic time as follows: 0-23 hr (n = 512; range, 0-23.9 hr); 24-35 hr (n = 380; range, 24.0-35.9 hr); 36-47 hr (n = 161; range, 36.0-47.7 hr); greater than or equal to 48 hr (n = 28; range, 48.0-70.6 hr). These groups did not differ significantly in recipient age, sex, incidence of diabetes, number of pretransplant blood transfusions, level of presensitization, or HLA match. There were no differences in overall actuarial 1-year patient or graft survival rates, incidence of rejection, or renal function at 1 year. There was a higher incidence of impaired early graft function for kidneys preserved greater than or equal to 48 hr, but eventual graft outcome, including serum creatinine at 1 year, was unchanged. Delayed introduction of CsA resulted in improved 1-year graft survival (84.4% vs. 74.7%, P less than 0.05) compared to CsA treatment begun at the time of transplantation ("initial CsA"). This improvement was present regardless of total cold ischemia time. The incidence of permanent graft nonfunction, which has been previously reported to increase with CsA therapy, was influenced by the timing of CsA therapy (initial: 12%; delayed: 3%, P less than 0.05) but was not affected by duration of cold ischemia. Thus, safe preservation of cadaver kidneys for up to 70 h can be achieved by standard techniques even when CsA is incorporated into the immunosuppressive regimen. The most important determinants of graft survival in these patients are the timing of CsA therapy and the presence of early graft function, not the duration of renal preservation.

Blood Group Incompatibility↗

PubMed1990

The impact of extended preservation on clinical liver transplantation.

The introduction of UW solution into clinical transplantation has permitted extended cold storage preservation of the liver. Over a 46-month period, we have performed 308 orthotopic liver transplants (266 primary, 42 retransplants) in 266 recipients. Our experience is divided into cold-storage preservation in Eurocollins (163 transplants in 140 recipients) and UW (145 transplants in 131 recipients) solutions. Donor and recipient factors were comparable between the two groups. The use of UW solution has permitted an increase in the mean preservation time from 5.2 +/- 1.0 [EC] to 12.8 +/- 4.3 [UW] hr (P less than 0.001). The mean total operating time was reduced but intraoperative blood loss was unchanged with UW preservation. The number of transplants performed during the daytime hours has increased dramatically (21.5% [EC] vs. 71% [UW], P less than 0.001). The incidence of primary nonfunction, hepatic artery thrombosis, 1-month graft survival, and early retransplantation were similar in the 2 groups. Initial allograft function as determined by bile production, histology, and clinical assessment were likewise similar. Mean serum bilirubin, transaminase, and prothrombin levels were virtually identical by 5 days posttransplant. The enhanced margin of safety afforded by extended preservation has increased the capability for distant organ procurement and sharing, minimized organ wastage, and improved the efficiency of organ retrieval. With the relaxation of logistical constraints, our rate of liver import has nearly doubled (20.9% [EC] vs. 39.3% [UW], P less than 0.001). Extended preservation has permitted the development of reduced-size liver grafting (n = 12), resulting in a significant reduction in the number of deaths occurring while awaiting transplantation. Therefore, we advocate the use of UW solution with selective extension of preservation based not only on donor and recipient factors but also on manpower, resource, and logistical considerations.

Adenosine↗

PubMed1991

Prevention of graft-versus-host disease following small bowel transplantation with polyclonal and monoclonal antilymphocyte serum. The effect of timing and route of administration.

Graft-versus-host disease is a potential problem following small bowel transplantation. We have previously shown that a two-day intraperitoneal course of polyclonal antilymphocyte serum completely prevents GVHD without impairing allograft function in a unidirectional rat small bowel transplant model. In the present study we sought to determine the optimum route and timing of ALS administration and whether donor pretreatment with the anti-T cell receptor monoclonal antibody R73 would be similarly effective in preventing GVHD. Both intravenous and intraperitoneal injection of ALS effectively prevent GVHD in this model. ALS must be given to donors at least 48 hr prior to graft procurement for maximum effectiveness. Prevention of GVHD correlates with lymphocyte depletion in mesenteric lymph nodes, as opposed to peripheral blood or small bowel lamina propria. Donor pretreatment with the monoclonal antibody R73 significantly delays the onset of GVHD in this small bowel transplant model but appears less effective than polyclonal ALS.

Animals↗