bluuebunny/crossref_metadata_2025 huggingface dataset:
Risk factors for chronic rejection in heart and lungs – Why do hearts and lungs rot?
Authors: Wallwork John
Published: September 2024

The major cause of graft loss and patient death during the 1st yr after heart transplantation is progressive coronary occlusive disease. All survival curves show progressive and persistent graft loss over time. To improve the overall results of heart transplantation, attention must be directed to the etiology, prevention, and treatment of coronary occlusive disease. This condition affects both small and large vessels, and most probably results from a continuous immune insult that generates smooth muscle proliferation and subsequent development of atheromatous plaque. Multivariate analysis suggests that highly significant risk factors for the development of coronary occlusive disease include preoperative diagnosis of ischemic heart disease, age of recipient, and age of donor. Other risk factors, notably cytomegalovirus (CMV) infection, have not proved to be independent causes of coronary occlusive disease in our series. Diagnosis before the occlusive disease sets in, as well as the development of new therapeutic strategies, may prevent or delay the onset of coronary artery disease, thereby improving overall results of heart transplantation. Graft loss from lung transplantation after the 1st yr is associated with obliterative bronchiolitis. This final end‐stage progressive loss of small airways can be seen not only in transplanted lungs but in lungs with chronic infection. It appears to be a final common pathway for lung injury, but following transplantation it is most likely to be mediated by rejection. Risk factor analysis in our series indicates that severe or persistent rejection in the first few months is associated with the subsequent development of obliterative bronchiolitis. CMV does not appear to be an independent causal variable in obliterative bronchiolitis, although it may have a role through its association with the development of rejection. Another possible etiology is damage to the bronchopulmonary vasculature; this would be of particular importance in isolated lung transplantation without revascularization of the bronchial arteries, in which case the bronchial circulation is reliant on collaterals through the pulmonary circulation. It is yet to be seen whether this is a significant issue in the development of obliterative bronchiolitis.
Pneumocystis cariniipneumonia after liver transplantation in adults
Authors: Hayes M. J. , Torzillo P. J. , Sheil A. G. R. , McCaughan G. W.
Published: September 2024

ProvenPneumocystis cariniipneumonia (PCP) occurred in 8 (5.2%) of 154 adult liver transplant recipients between January 1986 and December 1992. The interval between transplantation and PCP ranged from 69 to 131 days with a mean of 95 days (SD 20 days). The PaO2 breathing room air at diagnosis ranged from 40 mmHg to 75 mmHg with a mean of 59.6 mmhg (SD 13 mmHg). Bronchial washings taken at bronchoscopy stained positively forPneumocystis cariniiand confirmed the diagnosis. Transbronchial biopsy was unnecessary for diagnosis. One patient died from PCP while the remainder recovered. Patients transplanted immediately before the index patients served as controls. Patients who developed PCP had more episodes of rejection (p<0.05), received more OKT3 (p<0.05), and were receiving more prednisone (p<0.05) than controls. They also had lower levels of albumin (p<0.01), and higher levels of alkaline phosphatase (p<0.05), alanine(p<0.01), and aspartate aminotransferase (p<0.001), and gamma‐glutamyltranspeptidase (p<0.02). This study raises the possibility of selecting patients at risk of PCP for chemoprophylaxis.
Complications of ureterovesical anastomosis in kidney transplant patients: The Minnesota experience
Authors: Hakim Nadey S. , Benedetti Enrico , Pirenne Jacques , Gillingham K. J. , Payne William D. , Dunn David L. , Sutherland David E. R. , Gruessner Rainer , Gores Paul F. , Matas Arthur J. , Najarian John S.
Published: September 2024

We reviewed urologic complications of 1183 consecutive primary or secondary renal transplants performed with bladder anastomoses at the University of Minnesota Hospital between 1985 and 1993. The Politano‐Leadbetter (PL) technique of ureteroneocystostomy was used in 410 patients; the multistitch (MS) extravesical technique modified from the methods of Witzel, Sampson, and Lich in 295; and the extravesical single‐stitch (SS) technique in 478. Urologic complications occurred in 81 patients (6.8%). Of these complications, 68 (5.7%) were early (<4 months) and 13 (1.1%) late; 32 (7.8%) were after PL. 17 (5.8%) after MS, and 32 (6.7%) after SS. A total of 13 patients had an anastomotic leak, 7 (1.7%) after PL, 4 (1.4%) after MS, and 2 (0.0004%) after SS; 49 patients had a ureterovesical obstruction, 16 (4.0%) after PL, 12 (4.0%) after MS, and 21 (4.2%) after SS; 5 patients had a ureteropelvic obstruction, 2 (0.5%) after PL, 2 (0.7%) after MS, and 1 (0.2%) after SS; and 14 patients had hematuria, 7 (1.7%) after PL, 1 (0.34%) after MS, and 6 (1.3%) after SS. Of the 81 patients with urologic complications, one (1%) resolved spontaneously; 30 (37%) were treated with temporary percutaneous nephrostomy, 17 (21%) with dilatation and stent; the 14 (17.3%) with hematuria were treated via cystoscopy; 19 (23%) required reoperation. Only 2 (2.5%) patients lost their graft. For both cadaver and living donor recipients, there was no difference between techniques for early and late complications of leakage, stricture, and hematuria. Each technique has certain advantages. and each should be in every surgeon's repertoire.
Recurrent focal segmental glomerulosclerosis in pediatric renal transplant recipients: successful treatment with oral cyclophosphamide
Authors: Kershaw David B. , Sedman Aileen B. , Kelsch Robert C. , Bunchman Timothy E.
Published: September 2024

Focal segmental glomerulosclerosis (FSGS) is the most common glomerulopathy leading to end‐stage renal disease in children and transplantation is complicated by recurrent disease in a significant percentage of children. Treatment of recurrent FSGS has included high‐dose steroids, high‐dose cyclosporine (CSA), plasmapheresis, and ACE inhibitors with mixed results. We have had a consistent approach using oral cyclophosphamide (CTX) to treat recurrent FSGS since 1982. Three patients with ESRD secondary to nephrotic syndrome had recurrent disease. Biopsies in all 3 were consistent with recurrent FSGS. Patients were begun on a 8‐12 week course of 1‐2 mg/kg/day of CTX and dosage was adjusted for WBC count. Azathioprine was with held during CTX. Patients' dosage at the end of 12 weeks ranged from 0.89‐1.75 mg/kg/day. All patients. tolerated CTX well. After 8‐12 weeks of treatment, 2 patients with nephrotic syndrome normalized their serum albumin and had negative to trace protein on urinary dipstick. One patient with proteinuria decreased his protein excretion from 770 to 340 mg/m2/day. At follow‐up at 8, 38, and 125 months post‐transplant, these 3 patients have stable graft function and negative to trace protein on urinalysis. The patient followed for 125 months has had 2 additional relapses at 51 and 82 months post‐transplant that were treated successfully with pulse intravenous steroids. Three pediatric patients with recurrent focal segmental glomerulosclerosis postrenal transplant were treated with oral CTX and had significant improvement in proteinuria and preservation of graft function. This suggests that oral CTX is a potentially effective and well‐tolerated treatment for recurrent FSGS in children.
Sclerosing peritonitis
Authors: Bowers Victor , Ackermann John R. , Richardson William R. , Carey Larry
Published: September 2024

Sclerosing peritonitis (SP) is an uncommon and devastating problem which involves the visceral and parietal peritoneal surfaces of the abdominal cavity. SP has been reported in association with peritoneal dialysis, with medications, and following peritonitis. No clear etiology or preventative treatment exists for this unusual problem. Herein, we report 3 cases with the unusual aspect of apparent progression of this fibrotic and sclerosing process after the termination of the peritoneal dialysis and successful renal transplantation. Each of these cases resulted in a mechanical small bowel obstruction secondary to a densely fibrosing and encasing peel of reactive connective tissue visibly different from the usual postoperative adhesions. Sclerosing peritonitis should be included in the differential diagnosis of a current peritoneal dialysis patient who exhibits signs of partial small bowel obstruction with a continual decrease in peritoneal clearance and/or successfully transplanted patients who had utilized peritoneal dialysis therapy in the past and now exhibit signs and symptoms of a mechanical small bowel obstruction.
De novo cancer in cyclosporine‐treated and non‐cyclosporine‐treated adult primary renal allograft recipients
Authors: Gruber Scott A. , Gillingham Kristin , Sothern Robert B. , Stephanian Edic , Matas Arthur J. , Dunn David L.
Published: September 2024

We compared the incidence of de novo tumors developing in 1165 primary adult renal allograft recipients treated with azathioprine (AZA)‐ prednisone (Pred)‐antilymphocyte globulin (ALG) (CONV group) with that in 722 patients receiving cyclosporine (CSA) as part of double (CSA‐ Pred), triple (CSA‐Pred‐AZA), or quadruple‐therapy (CSA‐Pred‐AZA‐ ALG) protocols. Mean±SD follow‐up was 9.5±6.4 years for the CONV group and 6.2±2.7 years for the CSA group. Overall, 124 patients (10.6%) in the CONV group and 34 patients (4.7%) in the CSA group developed malignancies, with nonmelanoma skin cancers and lymphomas comprising 55% and 13% of cancers in the CONV group and 65% and 3% of cancers in the CSA group, respectively. There were no significant differences in overall cancer (p=0.41) or skin cancer (p=0.97) incidence between non‐CSA‐ treated and CSA‐treated patients by Kaplan‐Meier life‐table analysis; however, CONV‐treated patients demonstrated a higher incidence of lymphoma (p=0.05). The mean (SD) time to overall and skin cancer occurrence was significantly shorter in the CSA group: 37 +22 versus 90+ 52 months (p<0.001) and 40±24 versus 92 +52 months, respectively. When the Cox Proportional Hazard Model was utilized to assess the relative importance of age, diabetic status, donor source, sex, and immunosuppressive regimen in determining cancer development, age ≥50 years and nondiabetic status were significant independent prognostic indicators, while immunosuppressive regimen was not. Graft and patient survival were significantly greater in CONV‐treated patients developing cancer than in those who did not. In contrast, there were no significant differences in either patient or graft survival between the small group of CSA‐treated patients who developed de novo neoplasms and the much larger group who did not. In conclusion, we find no significant differences in overall or skin cancer incidence but a decrease in lymphoma incidence in primary adult renal allograft recipients following the introduction of CSA at our institution. Longer follow‐up of renal allograft recipients on CSA therapy may reveal changes in the pattern of cancer development.
Risk of steroid withdrawal in pediatric renal allograft recipients (a 5‐year follow‐up)
Authors: Roberti Isabel , Reisman Lewis , Lieberman Kenneth V. , Burrows Lewis
Published: September 2024

Withdrawal of steroid therapy in renal allograft recipients remains controversial despite the many side effects of this treatment. We have previously presented data on 16 pediatric renal transplant recipients in whom prednisone was withdrawn 6 months or later post‐transplantation. To assess the impact of steroid withdrawal, we retrospectively compared this group of patients (Group 1) with a group of 12 patients (Group 2) with renal transplants who continued on prednisone. The groups were compared as to age, sex, ethnicity, source of graft, number of HLA‐DR mismatches and incidence of ATN in the immediate postoperative period. The only significant difference was that Group 2 was older. Group I had significantly fewer episodes of early acute rejection in the first 6 months post‐transplantation than the control group (3/16 vs 8/12, p=0.009) but nevertheless, without prednisone, had significantly more late acute rejections (11/16 vs 3/12, p=0.03). Acute rejections occurred as late as 4 years after withdrawal of steroids. Only 5 of the 16. patients in Group I have maintained stable graft function without steroids. All of these patients are now alive more than 5 years after steroid withdrawal. In comparing these patients to the other 11, who failed a trial of steroid withdrawal, we found that a serum creatinine of less than 1.7 mg/dl at the time of withdrawal of steroids was predictive of a successful outcome (p=0.03). In conclusion, withdrawing steroids in pediatric renal allograft recipients has a high risk of late acute rejection and subsequent graft loss, especially for those who have higher baseline creatinine levels.
Pharmacokinetics of methylprednisolone during acute renal allograft rejection
Authors: Tornatore Kathleen M. , Walshe J. Joseph , Reed Kristine , Venuto Rocco C.
Published: September 2024

High dose methylprednisolone is administered empirically by fixed daily boluses to renal transplant recipients who are experiencing acute rejection episodes. Little information is available characterizing the pharmacokinetics of high‐dose methylprednisolone in these individuals, who are often acutely ill. Therefore, 5 renal transplant recipients (2 men; 3 women) were studied during an acute rejection episode (mean serum creatinine 2.6±0.7 mg/dl) which occurred within the first 8 months posttransplantation. The rejection episode was characterized clinically by at least two of the following: fever, leukocytosis, graft tenderness and an increase in serum creatinine. All patients received bolus doses of methylprednisolone for 3 consecutive days during the rejection episode. All patients were studied on the 3rd day of bolus dosing and received 250 mg methylprednisolone by an i.v. infusion. In phase II, 4 patients were studied during a period of stable renal function when the methylprednisolone was given at lower chronic immunosuppressive doses. Serum samples were taken prior to infusion and serially over the following 24 hours. The serum samples were analyzed for methylprednisolone with high‐performance liquid chromatography (HPLC) and pharmacokinetic parametes were generated. During rejection episodes, the methylprednisolone clearance values were 523±154 ml/h/kg with a corresponding mean volume of distribution of 1.89±0.72 1/kg. The mean methylprednisolone half‐life was 2.61±0.62 h. During Phase II, the methylprednisolone clearance was 358 95 ml/h/kg with a half‐life of 3.05 h. This observation indicates that methylprednisolone metabolism is increased during acute rejection compared to that seen during chronic immunosuppressive dosing with this agent.
Anomalous ureteral insertion in VATER syndrome complicating renal transplantation
Authors: Shenoy Surendra , Hovsepian David , Brennan Daniel C. , Hudson M'Liss A. , Howard Todd K. , Flye M. Wayne
Published: September 2024

We report a renal transplantation with uretero‐ureterostomy to a normal ureter in a patient with VATER syndrome who had agenesis of the ipsilateral kidney. Anomalous insertion of the native ureter into the cjeculatory duct was subsequently identified when his post‐operative course was complicated by an ureteric leak and hydronephrosis. To our knowledge, this anomaly has not been previously reported. Transplant function is now excellent following temporary percutaneous nephrostomy. Contrast delineation of genito‐urinary anatomy is recommended, before utilizing existing anatomical structures in the urinary tract, in patients. with VATER syndrome.
Toxicity versus rejection ‐ Or why conversions between cyclosporine A and FK506 were performed after liver transplantation
Authors: Platz Klaus‐Peter , Mueller Andrea R. , Jonas Sven , Blumhardt Gerhardt , Bechstein Wolf‐Otto , Lobeck Hartmut , Neuhaus Peter
Published: September 2024

The introduction of cyclosporine A (CSA) and FK506 significantly improved the outcome of liver transplantation. However, the postoperative course and outcome of liver transplant recipients is still compromized by rejection, over‐immunosuppression‐induced infection and immunosuppression‐associated toxicity. In the present study, we evaluated the reason for conversion between immunosuppressive regimens in 121 patients, 61 treated with FK506 and 60 patients treated with CSA‐based immunosuppression, Five patients treated primarily with CSA (8.3%) were converted to FK506 therapy because of refractory acute or chronic rejection within 12 months following liver transplantation (LTX). In 2 patients, conversion was performed after Re‐LTX. In 4 of these 5 patients, rejection was successfully treated according to histological and laboratory investigations, while in the remaining patient, graft function improved with persisting histological evidence of chronic rejection. Moderate and severe neurologic symptoms during the carly postoperative period, i.e. organic brain syndromes (OBS), seizures, hemiparesis, dysphasia, dysathria and cerebellar symptoms were observed in 21.3% of patients treated with FK506 and in 11.7% of patients treated with CsA (p=n.s.). Five patients treated primarily with FK506 were converted to CSA due to severe neurotoxicity. Early postoperative renal insufficiency was observed to a similar extent with 42.6% of FK506‐ and 36.7% of CsA‐treated patients. 8.3% of FK506‐treated patients and 11.7% of CSA‐treated patients required hemodialysis (p=n.s.) There patients were converted from FK506 to CSA due to persisting renal insufficiency. Moderate and severe neurologic symptoms were observed more frequently under treatment with FK506 than CSA, and all conversions from FK506 to CsA (13.3%) were performed because of neuroor nephrotoxicity. However, immunosuppressive potency of FK506 was superior to CSA, as all 5 (8.3%) conversions from CSA to FK506 therapy were performed due to refractory acute or chronic rejection. The superior potency of FK506 is supported by a significantly lower incidence of refractory acute and chronic rejection in the FK506 group.
Rejection with duodenal rupture after solitary pancreas transplantation: An unusual cause of severe hematuria
Authors: Esterl Robert M. , Stratta Robert J. , Taylor Rodney J. , Radio Stanley J.
Published: September 2024

A common urologic complication after pancreas transplantation with bladder drainage is hematuria. However, hematuria is usually mild and self‐limiting and raraly requires open surgical intervention. We report an unusual case of refractory hematuria that began 17 days after solitary pancreas transplantation due to severe rejection. The patient developed severe duodenal segment swelling with mucosal rupture that eventually required operative therapy. This case is illustrative of the diagnosis and management of gross hematuria after pancreas transplantation and demonstrates the limitations of cystoscopic techniques. This unusual complication must be considered in the differential diagnosis of refractory hematuria with pancreas allograft dysfunction and may represent a problem unique to solitary pancreas transplantation until better immunosuppressive strategies are available.
Hypomagnesemia in renal transplant patients: Improvement over time and association with hypertension and cyclosporine levels
Authors: Ramos E. L. , Barri Y. M. , Kubilis P. , Peterson J. C. , Pfaff W. W. , Howard R. J. , Parris C. J. , Patton P. R. , Karlix J. L
Published: September 2024

Hypomagenesemia is frequently encountered early after kidney transplantation, especially in patients receiving cyclosporine (CSA). However, there have been no studies addressing the natural history of this disorder in adult transplant recipients. We conducted this investigation to study the change in the prevalence of hypomagnesemia over time in renal transplant patients as well as to determine the factors associated with this change. Three patient groups were studied: 24 CSA‐treated patients followed longitudinally at 1, 3 and 6 months post‐transplant (Group la, lb, lc); 33 CsA‐treated patients at least 2 years post‐transplant (Group 2; mean follow‐up 55±25 months); and 31 non‐CsA‐treated patients at least 2 years post‐transplant (Group 3; mean follow‐up 132±57 months). The following parameters were monitored: serum and urine magnesium levels; serum potassium; creatinine clearance; fractional excretion of magnesium; and trough CsA levels. In group 1 patients, longitudinal follow‐up showed a significant linear trend for improvement in the serum magnesium over time (1.6±0.3, 1.7±0.2, 1.8±0.2 mg/dl; p=0.0015) as well as a decline in the whole blood CsA level (316±103, 251±82, 194±67 ng/ ml; p=0.0015) at 1, 3 and 6 months, respectively. The serum magnesium was significantly higher in group 2 (1.8±0.2 mg/dl) compared with group la (1.6±0.2 mg/dl; p=0.0024), but did not achieve the level observed in the non‐CsA‐treated group‐3 patients (2.0±0.2 mg/dl; p<0.00004, group 2 vs 3). While the fractional excretion of magnesium showed a decreasing trend over time in CSA‐treated patients, this was not statistically significant. However, the fractional excretion of magnesium was significantly lower in group 3 (6.4±2.4%) compared with groups la (8.7±3.9; p= 0.009) and lb (8.7±3.9; p=0.01). Hypomagnesemia was noted in 11% and 49% (p=0.001) of patients who were normotensive and hypertensive, respectively. Furthermore, of patients requiring 0, 1 or ≥2 antihypertensive medications, 12, 45 and 58% (p=0.001) respectively, were noted to have hypomagnesemia. In our study, hypomagnesemia improves with time in CSA‐treated patients, but not to the level of non‐CsA treated patients. The improvement in the serum magnesium levels in CSA‐treated patients appears to be related to declining CSA levels. The hypomagnesemia is the result of urinary magnesium loss. Finally, hypertension and the severity of hypertension are associated with low serum magnesium levels.
Recurrence of hepatitis B virus cirrhosis and hepatocellular carcinoma: An indication for retransplantation?
Authors: Ringe Burckhardt , Böker Klaus , Schlitt Hans Jürgen , Sproviero Jorge , Hundrieser Joachim , Tillmann Hans Ludger , Chavan Ajay , Flemming Peer , Galanski Michael , Pichlmayr Rudolf , Manns Michael P.
Published: September 2024

Hepatitis B virus reinfection as well as recurrence of hepatocellular carcinoma are frequent complications in liver allograft recipients. This is the report of a patient who had two liver transplantations with a 6‐year interval, both for the same indication ‐ postnecrotic cirrhosis and liver cancer. Following first and second transplantation, hepatitis B reinfection occurred at 12 and 6 months, and allograft cirrhosis developed after 20 and 10 months, respectively. Intrahepatic recurrence of hepatocellular carcinoma was found after 69 months. Two years following retransplantation, the patient is tumor‐free, and has normal graft function. In selected patients with hepatitis B‐related liver disease, and hepatocellular carcinoma liver replacement is indicated when combined with effective immunoprophylaxis, and other adjuvant therapy. Late recurrence of both diseases is unusual, and retransplantation may come into question.
Clinical features of nosocomial rotavirus infection in pediatric liver transplant recipients
Authors: Fitts Steven W. , Green Michael , Reyes Jorge , Nour Bakr , Tzakis Andreas G. , Kocoshis Samuel A.
Published: September 2024

A retrospective survey of nosocomial rotavirus infection in pediatric liver transplant recipients was performed. Immunocompetent children with nosocomial infections served as controls. Co‐pathogens were not identified. A total of 12 transplant cases and 12 controls could be evaluated. New onset vomiting occurred in 7/8 cases and 6/11 controls lasting an average of 2.8 days per case and 0.8 days per control (p<.05). New onset fever (>38°C) was noted in 8/12 cases and 9/12 controls. New onset occult blood was noted in 7/11 cases and 1/12 controls (p<.01). A concomitant rise and fall in transaminases was noted in 5/12 transplant recipients. Eleven of the 12 were maintained on constant or increased immunosuppression doses without the development of fulminant disease. The presence of increased days of vomiting and occult blood in stools suggests that rotavirus causes a more invasive process in the intestinal mucosa of transplant recipients compared to immunocompetent children. However, the process remains self‐limited despite the use of potent immunosuppressives.
Normocalcemic hyperparathyroidism associated with relatively low 1:25 vitamin D levels post‐renal transplant can be successfully treated with oral calcitriol
Authors: Lobo Peter I. , Cortez Maria S. , Stevenson William , Pruett Timothy L.
Published: September 2024

Since endogenous 1:25 vitamin D (1:25VD) is principally involved with involution of secondary hyperparathyroidism post‐renal transplant we correlated 1:25VD levels with intact PTH in 82 random patients with a serum creatinine of <2 mg/dl and with normal hepatic function. All patients studied were normocalcemic with normal phosphorus and received azathioprine, cyclosporin A and prednisone. Of considerable interest, of the 42 patients studied after 2 years post‐transplant, there were 8 (19%) patients with intact PTH of more than twice the upper limit of normal (normal 10‐65 pg/ml) and other 15 (36%) with PTH levels above normal. Secondly, in no patient did we see 1:25VD above normal (normal 15‐60 pg/ml) despite levels of PTH of >200 pg/ml. Of concern, 20% of 73 patients had 1:25VD deficiency (<15 pg/ml). This may not have been previously appreciated because of the number of patients studied. Like previous investigators, we failed to understand why 1:25VD levels were relatively low. There was no correlation between 1:25VD and serum creatinine. Of 25 patients with a serum creatinine of 1.4 or less, there were 10 patients (40%) with 1:25VD of less than 20 pg/ml. Since persistently high PTH can contribute to bone demineralization, which is not uncommon post‐transplant, we treated 8 patients with small doses of oral 1:25VD (rocaltrol). In less than 6 months PTH levels returned to normal in 7 of the 8 patients. The current studies clearly indicate that asymptomatic hyperparathyroidism is common even after 2 years post‐renal transplant. Monitoring for PTH and 1:25VD will help prevent bone disease posttransplant now that rocaltrol is available.
An analysis of predictors of long‐term cadaveric renal allograft survival
Authors: Cole Edward , Naimark David , Aprile Marie , Wade Judith , Cattran Daniel , Pel York , Fenton Stanley , Robinette Michael , Zaltsman Jeffrey , Bear Robert , Cardella Carl
Published: September 2024

To determine factors predictive of long‐term graft function in patients treated prophylactically with an antilymphocyte antibody, 670 first cadaveric adult renal transplant procedures performed between 1985 and 1991 were reviewed. The actuarial 1‐ and 5‐year patient survival in this group was 95% and 87% respectively, and graft survival was 84% and 70% respectively. The final analysis was based on a study group of 635 patients which excluded 28 patients who lost grafts to early technical failures and 8 patients who were not induced with an antilymphocyte preparation. Multivariate analysis showed that 5‐year graft survival was lower in patients with delayed graft function (p=0.0001), in those who had an acute rejection episode in the first 6 months post‐transplant (p=0.0001), in rccipients greater than 55 years of age at the time of transplant (p=0.0001), in patients who were highly sensitized at the time of transplant (p=0.0331) and, finally, in those who received a graft from an older donor (p=0.044). The 209 patients with delayed graft function had a 16% lower long‐term graft survival than 425 patients with early graft function (62% vs. 78% respectively at 5 years). One or more rejection episodes in the first 6 months post‐transplant (329 patients) reduced long‐term graft survival by 13% compared to those who did not have a rejection episode (67% vs. 80% respectively at 5 years). 219 patients who were free of early rejection episodes and had early graft function had a 5‐year graft survival of 85% compared to 60% in the 122 patients who had early rejection and delayed graft function (p<0.0005). Recipient age of over 55 years reduced graft survival at 5 years because of death with a functioning graft. The other two independent variables, degree of sensitization and donor age, had a weaker effect on graft survival by increasing the risk ratio to 1.013 for sensitization and to 1.104 for donor age. There was only a minor interaction between time to graft function and rejection activity. 52% of the 219 patients were free of rejection episodes whereas only 42% of the 209 patients with delayed function had no rejection (p<0.05). HLA matching did not have an independent effect on long‐term graft outcome, but did interact with rejection in that of 57% of patients with 2 or fewer BDR mismatches were free of rejection as compared to 44% of patients who had more than 2 mismatches free of rejection (p<0.0001). Serum creatinine at 6 months was a dependent variable that influenced longterm survival. Patients with a serum creatinine at 6 months of ≤200 μmol/ 1 (2.27 mg%) had a 27% increase in long‐term survival compared to those with more impaired function (86% vs. 59% actuarial survival at 5 years. post‐transplant) (p<0.0005).
Hemoconcentration prior to serology testing in hemodiluted cadaver bone and tissue donors
Authors: LeFor William M. , Shires Dana L. , McGonigle Arlene F. , Shires Dana L.
Published: September 2024

Concern about false negative serology tests for infectious diseases in hemodiluted cadaver donors resulted in issuance of new regulations and guidelines from the FDA and CDC. Bone or tissue from donors receiving 24 units of blood, blood products, colloids or crystalloids within 48 h of sampling must be quarantined unless: (a) a pretransfusion serum is available; or (b) an adequate algorithm is employed to ensure hemodilution is insufficient to alter test results, i.e. cause false negatives. Left undefined in these regulations is, what is an adequate algorithm and what amount of hemodilution would cause false negatives. A pretransfusion sample was not available for about 20% of our donors and many had incomplete infusion histories. We used the unambiguous quantitation of serum albumin and total protein to define hemodilution and, if present, hemoconcentration of sera by ultrafiltration to normal protein levels prior to serology testing. Control experiments showed excellent correlation between serum dilution and protein concentration (r>0.99) and a quantitative recovery of 96.9±1.4% upon hemoconcentration. Known positive sera (CMV‐Ab; HTLV‐1Ab; HIV‐1,2Ab; HBsAb; HCV‐Ab; HBsAg) were spiked into normal sera and diluted up to 1:2000, well beyond detectable levels. A qualitative recovery of 100% and a quantitative recovery of 97.6±7.5% of antibody or antigen reactivity was achieved upon hemoconcentration and retesting. In two studies, 14% (30/210) and 43% (23/54) of cadaver donors had serum proteins below normal limits and their sera was hemoconcentrated. All 53 tested negative in our standard battery of 8 scrologies with both the preand post‐hemoconcentration samples, suggesting the assays have sufficient analytic sensitivity even with hemodiluted donors. Nevertheless, we advocate hemoconcentration, when necessary, prior to serology testing to further increase the safety of bone and tissue transplantation.
Proximal renal tubular acidosis secondary to FK506 in pediatric liver transplant patients
Authors: O'Gorman Molly A. , Fivush Barbara , Wise Barbara , Colombani Paul , Burdick James , Schwarz Kathleen B.
Published: September 2024

We hereby report our experience with an index case of a pediatric liver transplant patient in whom FK506 administration was associated with the development of proximal renal tubular acidosis (RTA), as well the prevalence of acidosis and renal dysfunction in all pediatric liver transplant patients in our institution followed long term during a 6‐year period. Data were grouped according to immunosuppressant regime: cyclosporine (CSA) only, FK506 only, or CSA with conversion to FK506. A 23‐month‐old female treated with FK506 after orthotopic liver transplantation (OLT) performed 15 months earlier presented with a 1‐wk history of fever, watery diarrhea and metabolic acidosis. Although the acidosis did not improve following correction of her hydration status, administration of oral bicarbonate was effective. Discontinuation of this therapy resulted in acidosis. Since other indirect measurements of renal tubular function were normal, the patient was judged to have an isolated proximal RTA. In our group of pediatric liver transplant patients converted from CsA to FK506, FK506 administration was associated with a decline in serum bicarbonate (19±1 vs. 16±1 mEq/l, p<0.02); neither blood urea nitrogen nor serum creatinine differed between the two groups. The number of rejection episodes/patient/month was comparable, allowing clinically relevant comparison of relative drug nephrotoxicities. We conclude that proximal RTA may be a relatively common treatable complication of FK506 administration in children.
Alternate‐day prednisone in the maintenance immunosuppressive therapy after orthotopic liver transplantation
Authors: Pedrosa M. C. , Rohrer R. M. , Kaplan M. M.
Published: September 2024

Glucocorticoids have been an important part of maintenance immunosuppressive therapy following orthotopic liver transplantation (OLT). However, long‐term daily glucocorticoid use is associated with a high incidence of unpleasant side effects. In an effort to minimize side effects while maintaining adequate immunosuppresson, we have treated 48 adult patients with low dose alternate‐day prednisone, 15 mg q.o.d. Pre‐ OLT diagnoses included primary biliary cirrhosis (16 patients), alcoholic liver disease (8 patients), sclerosing cholangitis (8 patients), cryptogenic cirrhosis and/or non‐A, non‐B hepatitis (11 patients), acute hepatic failure (3 patients), and hepatocellular carcinoma and bile duct carcinoma (1 patient each). Conversion to alternate‐day prednisone was attempted when patients were clinically stable and the daily prednisone dose was 15 mg. The average interval between OLT and beginning of the conversion to alternate‐day prednisone was 38 weeks. The mean time for conversion to alternate‐day prednisone was 35 weeks, but decreased as more experience was gained. The mean follow‐up was 106 weeks. Cushingoid side effects diminished in all. In 47 of the 48 patients, there were no clinical laboratory or histologic changes suggestive of rejection after the initiation of alternate‐day prednisone. A single episode of rejection occurred during the taper. This episode responded promptly to increased glucocorticoid therapy, and the patient was casily converted to alternate‐day prednisone at a later date. There was no increase in concurrent immunosuppressives dosage after the conversion. Alternate‐day prednisone is effective and safe for chronic immunosuppression after OLT in patients receiving cyclosporine and azathioprine.
Evaluation of an organ‐donor‐card campaign in Sweden
Authors: Sanner1 Margareta A. , Hedman Håkan , Tufveson Gunnar
Published: September 2024

One of the aims of this study was to evaluate an information campaign carried out in three geographical areas of Sweden in the winter of 1992‐93. The campaign was intended to increase public awareness of organ donation and to increase the signing of donor cards. Another objective was to test the effects of different kinds of information. These were: A) an extensive “package” of information including training of key groups, lecturing at meetings and exhibitions, and advertisements of donor cards: B) a brochure to households including two donor cards; and C) a combination of A and B. Yet another aim was to reassess public opinion on transplantation issues, which had been surveyed before in 1987, 1988, and 1990. Random samples of the population in three campaign areas and a control sample were surveyed before and after the campaign, altogether 5600 persons. The average response rate was 69% (1992) and 68% (1993). In the two areas where the brochure had been distributed to the households, the rate of donor card holders had more than doubled (from 3% and 5% to 13% and 12%). In the two areas where the brochure had not been distributed, the rate was unchanged (5%). In the “brochure areas” also a somewhat larger number of people had informed their relatives about their decisions, compared with people in the other areas. In all campaign areas considerably more people were aware of the cards than in the control area. No attitude changes could be shown in any area. Thus, the mailed brochure was the most effective in increasing people's signing of the donor cards and informing their families. The more elaborate campaign could possibly have long‐term effects, but this remains to be studied. The attitudes toward organ donation have been rather constant in Sweden from 1987 to 1993, with only slight variations.

A “frankness gradient” was confirmed in this study as well as in an earlier study, where those who were negative toward donation of their own organs had discussed this issue least with their families, followed by those who were undecided, whereas those who were positive (and above all those positive who were card‐holders) had discussed this the most with their relatives.
Re‐evaluation of skin‐explant model in graft‐versus‐host disease prediction
Authors: Şahin(özgün) Ş. , Akoğrlu T. F. , Gürbüz O. , Ergun T. , Küllü S. , Sav A. , Ahıskalı R. , Tüzüner N. , Doğrusoy G.
Published: September 2024

An in vitro skin explant model has been proposed for prediction of graft versus host disease and reported to be highly sensitive and specific for this purpose. In this study we have re‐evaluated this model in both HLA full‐matched BMT recipient‐donor sibling pairs and also in HLA one haplotype‐matched parent‐children pairs. All assessments were made blindly by 3 independent observers. The predictive value of the test for the occurrence of clinical GvHD in 14 BMT patients was found to be less sensitive than reported previously (correlation coefficients were +0.019, +0.067 and ‐0.061 between clinical GvHD and in vitro primed allogeneic, primed mixed and unprimed allogeneic settings, indicating “poor” correlation). False positive and false negative results were high and there were also significant discrepancies between three blind observations in the grading of skin changes. Weighted kappa analysis revealed that there were “fair” correlations between the 3 observers (K=0.25). These results indicated that the skin explant model is an unpredictable test system and there are great problems in standardization of the method.
Pancreatic allograft thrombosis: Diagnostic and therapeutic importance of splenic venous flow velocity
Authors: Nghiem D. D.
Published: September 2024

Thrombosis of pancreatic transplant is usually diagnosed so late that graft pancreatectomy is the only possible operative recourse. We report 3 patients with portal vein thrombosis which was diagnosed by the triad decreased splenic vein velocity, decreased urinary amylase and slowly rising glycemia. Thrombosis was confirmed at the time of surgery. Thrombectomy was performed in 2 patients. One patient achieved longterm insulin independence while the other graft was lost to recurrent thrombosis and failure of thrombectomies. The third graft was removed primarily. This experience led us to assess the role of Duplex Color Doppler in five normal volunteers and 11 insulin‐independent pancreatic transplant recipients.
Correlation between venous and capillary blood samples for cyclosporine monitoring in pediatric liver transplant patients
Authors: Profumo Robert J. , Foy Thomas M. , Kane Robert E.
Published: September 2024

Venipuncture has traditionally been required to monitor serum cyclosporine levels. This is a difficult if not impossible task in pediatric patients. Capillary blood sampling has eliminated the need for venous access in the majority pediatric laboratory investigations. Although the practice of capillary sampling for cyclosporine monitoring is discouraged, there has never been any investigation into the reliability of this method. Thus, we compared 18 capillary cyclosporine levels from 4 pediatric liver transplant patients to simultaneous venipuncture serum levels. The correlation coefficient of the paired samples (range 32‐1005 ng/ml) was 0.914. This excellent correlation between the two sampling methods suggests that capillary cyclosporine levels may be adequate to monitor the immunosuppression of pediatric liver transplant patients.
Monitoring of allograft recipients for the development of HLA‐specific antibodies: Elimination of OKT3 as a complicating factor
Authors: Mulligan David , Gentry Laura , Dombrausky Lori , Klintmalm Goran , Nikaein Afzal
Published: September 2024

In this report we demonstrate that the use of immunoabsorbent beads to remove the OKT3 monoclonal antibody (MoAb) from the sera of transplant recipients is necessary in order to avoid the false positive reactivity in panel reactive antibody (PRA) assay. We have shown that the presence of OKT3 MoAb in patient's sera can give a positive reactivity in PRA, which may be interpreted as antibody development. Rabbit antimouse immunoglobulin covalently linked to sepharose can effectively remove the OKT3 MoAb from patients sera, but has no effect on anti‐HLA antibodies. The absorbance of OKT3 MoAb, therefore, is necessary to obtain accurate results in respect to humoral rejection, which may lead to mismanagement of patients.
The utility of retroperitoneal kidney placement in simultaneous kidney pancreas transplantation
Authors: Kuo Paul C. , Krieger Nancy R. , Alfrey Edward J. , Scandling John , Dafoe Donald C.
Published: September 2024

Simultaneous kidney‐pancreas (SPK) transplantation has become an accepted therapeutic modality for patients with Type I diabetes mellitus‐mediated end‐stage renal disease (ESRD). However, the intraperitonel placement of the renal allograft may pose technical problems when attempting percutaneous biopsy or Doppler ultrasound examination. Recently, the Stanford University Transplant Center adopted the technique of retroperitoneal placement of the renal allograft with intraperitonel placement of the pancreas allograft (RETRO). From August 1993 to August 1994, a total of 12 patients underwent SPK with this new technique. Twelve patients who had received SPK with the standard technique served as historical controls (INTRA). Demographic data, followup, operative time, creatinine and amylase on discharge, length of stay, intraoperative fluid requirements, rejection episodes, thrombotic complications, infections, and number of open and closed renal biopsies were compared between the two groups. Average length of follow‐up was greater in the INTRA group (29.3±1.7 vs. 15.9±1.1 months). In addition, the RETRO group had significantly fewer open renal biopsies (1/15) in comparison to the INTRA group (7/12) (p<0.001). The two groups otherwise did not dilfer in any of the parameters studied. We conclude that retroperitoneal kidney and intraperitoneal pancreas allograft placement is associated with a significantly decreased requirement for open renal biopsy with its associated operating room and anesthetic costs. In addition, the option of transcystoscopic or percutaneous needle biopsy of the pancreas allograft is preserved. This technique should be considered as an alternative to intraperitoneal placement of both the pancreas and renal allografts.
Cardiovascular complications following liver transplantation
Authors: Dec G. William , Kondo Nicholas , Farrell Mary Lin , Dienstag Jules , Cosimi A. Benedict , Semigran Marc J.
Published: September 2024

Background ‐ As the indications for liver transplantation broaden to include older and more critically ill patients, the likelihood of encountering unsuspected cardiovascular disease increases. Purpose ‐ This study examined the frequency, type, and subsequent outcome of intraand postoperative cardiovascular complications that occurred during the first 6 months following liver transplantation. Methods ‐ The records of 146 consecutive patients who underwent primary liver transplantation were reviewed retrospectively to determine the occurrence of major (myocardial infarction or reversible ischemia, pulmonary edema, cardiogenic shock, symptomatic rhythm disturbances, or pulmonary embolism) and minor (transient hypertension, hypotension, atrial or ventricular premature beats) cardiac events. The relation between such events and actuarial patient survival was evaluated. Stepwise logistic regression analysis was also employed to identify those pre‐operative variables that predicted an increased risk of postoperative events or mortality. Results ‐ Cardiac events directly caused or contributed to 4 deaths (2.7%). Ventricular tachycardia/fibrillation was the most frequent intra‐operative cardiac complication (3.4%); transient hypotension (post‐reperfusion syndrome) was the most common minor event (20%). Thirty‐four recipients (23%) developed a major postoperative cardiac complication including pulmonary edema (9%), myocardial ischemia or infarction (5.4%), new dilated cardiomyopathy (3.4%), and ventricular tachycardia (2.7%). Pre‐existing cardiac disease and older age (mean age 49±8 years) at transplantation were the only independent predictors of a major complication. Major cardiac events did not affect 6 month survival but were associated with a lower 5‐year survival rate (event: 32% vs event‐free: 52%; p=0.04). The frequency of major intraoperative (21% vs 2%; p=0.0005) and postoperative (57% vs 17%; p=0.0001) cardiac complications was significantly higher for recipients with known heart disease (Group A) compared with those without pre‐existing heart disease (Group B). Five‐year survival in Group A patients was 36% versus 50% for Group B patients; p=0.45. Conclusion ‐ One or more cardiovascular complications occurred in over 70% of liver transplant recipients. Major events were associated with a lower likelihood of long‐term survival. Older patients, particularly those with pre‐existing but compensated heart disease, are at greatest risk for a major cardiac event and may require more extensive preoperative risk assessment.