High-dose intravenous rituximab for multifocal, monomorphic primary central nervous system posttransplant lymphoproliferative disorder.

Primary central nervous system (CNS) posttransplant lymphoproliferative disorder (PTLD) is a well-recognized but rare complication of solid organ transplantation. Most of these disorders are B-cell in origin and generally carry poor prognosis. Rituximab, an anti-CD20 monoclonal antibody, has been used effectively in patients with systemic PTLD. However, its role in primary CNS PTLD is doubtful because it does not cross blood-brain barrier efficiently (<5%). Also, mechanisms, by which rituximab operates are not optimally effective in CNS. Here, we describe a renal transplant patient with monomorphic, multifocal, CD20-positive, primary B-cell CNS PTLD, who was treated with high-dose intravenous rituximab given in dose-escalation protocol, which has been used effectively for the patients with chronic lymphocytic leukemia. At 1-year follow-up, magnetic resonance imaging (MRI) showed complete resolution. High-dose rituximab may have a role in highly selected patients with primary CNS PTLD.

Complications after a 5-year experience with laparoscopic donor nephrectomy: the Indiana University experience.

BACKGROUND: Laparoscopic donor nephrectomy (LDN) is becoming the standard of care for living donor nephrectomy. However, questions have been raised about the safety of LDN for the donor and about the potentially increased rates for ureteral complications experienced by the recipient. In this report, the authors review their 5-year experience with 253 living laparoscopic donor nephrectomies. METHODS: A retrospective chart review was performed for 253 laparoscopic live donors. Graft function and survival were compared using recipient postoperative creatinine values up to 12 months. RESULTS: The overall rate of complications in the investigated series was 10.3%. There were seven intraoperative complications (2.8%), three of which required open conversion. There were 19 postoperative complications (7.5%), three of which required reexploration for bleeding. The majority of complications were minor including 62% grade 1, 8% grade 2, 31% grade 3, and no grade 4 or 5 complications. There were no intraoperative complications in the right-sided donor group. There was a 5% complication rate for patients with a body mass index (BMI) exceeding 25. The findings showed that 11.2% of the recipients had slow graft function, and 4.4% had delayed graft function. Less than 1% of the recipients experienced ureteral stricture requiring permanent stent placement or reoperation. Overall, there was a 2% graft loss rate. CONCLUSIONS: The findings show a low rate of intraoperative and postoperative complications, most of which were minor complications. There was an increase in operative time and hospital stay in the right-sided group, but no increase in complication rate. There was no significant difference in outcome or complication rate for the overweight patients.

Pharmacokinetics of neoral in stable renal transplant recipients with long-term diabetes mellitus.

Therapeutic drug monitoring (TDM) of Neoral has been studied widely and C2 monitoring has been shown to be superior to C0 monitoring in predicting outcomes. However, data are scarce in diabetic renal transplant recipients who may have gastroparesis. We studied 0 to 8 hour pharmacokinetic profiles (AUC(0-8h)) of Neoral on 3 consecutive days in 18 diabetic adults who had stable renal function for at least 6 months after transplantation and no overt symptoms of diabetic gastroparesis. All patients had diabetes mellitus (DM) for at least 5 years. Intrapatient variability of C2 levels was 28% (range, 6%-68%); it was < or =20% in 9 patients (50%) and >60% in 2 patients. Correlation coefficients between AUC(0-8h) and AUC(0-4h), between C2 and AUC(0-8h), and between C0 and AUC(0-8h) were 0.95, 0.86, and 0.77, respectively. Exposure phase (85% of AUC(0-8h)) was longer than 4 hours in all completed (48/54; 89%) profiles; it was longer than 6 hours in 20 profiles. C4 levels had good correlation with AUC(0-8h) (0.86) and low intrapatient variability (16% +/- 11%; range, 2%-39%). Thirteen of 18 patients (72%) had intrapatient variability of C4 < or = 20%. We conclude that the exposure phase of Neoral is prolonged more than 4 hours in adult renal transplant recipients with long-term diabetes, even in the absence of symptoms of gastroparesis. Because of very high intrapatient variability in this group of patients, C2 levels may not be reliable for TDM of Neoral despite high correlation with AUC(0-8h). C4 level may be a valid alternative for these patients.

Transplantation of a cadaveric polycystic kidney in a patient with autosomal dominant polycystic kidney disease: long-term outcome.

INTRODUCTION: Kidneys from donors affected by autosomal dominant polycystic kidney disease (ADPKD) were considered unusable for transplantation. To the best of our knowledge, seven cases worldwide have now been described in the English literature since 1967 suggesting such donor organs may be acceptable under certain conditions. Most of these reports have only short-term follow-up. METHODS: We provide a review of these patients and share our experience with an ADPKD patient who had a cadaveric ADPKD transplant and has been closely followed for 10 years. RESULTS: During the 10-year period, the patient had three transplant biopsies without complication. This creatinine is currently 1.2 mg/dL. Serial computed tomography imaging indicated that the cystic disease slowly progressed during this time period. He eventually developed intractable pain in his native left kidney and underwent a laparoscopic nephrectomy. CONCLUSIONS: Normal functioning cadaveric kidneys that show early signs of polycystic kidney disease should be considered acceptable for renal donation. These organs provide the recipient a safe, reasonable period of graft survival and have not been shown to cause adverse effects.

Sirolimus and mycophenolate mofetil for calcineurin-free immunosuppression in renal transplant recipients.

Calcineurin inhibitors, such as cyclosporine and tacrolimus, have been available for almost 20 years. Although these drugs are highly effective and represent the mainstay of transplant immunosuppression, they are associated with acute and chronic nephrotoxicity. Acute nephrotoxicity, which occurs in the early period after transplantation, leads to a higher rate of dialysis, and chronic nephrotoxicity may eventually result in graft loss. Acute and chronic nephrotoxicity is becoming more common as the use of marginal kidneys for transplantation increases. Two recently available immunosuppressive agents, mycophenolate mofetil and sirolimus (rapamycin), have no nephrotoxicity. The use of these drugs in combination with other agents has led to the development of new paradigms of immunosuppressive therapy. This paper reviews the results of clinical trials that have investigated these new approaches to immunosuppression in renal transplant recipients.

Physiological flow variations in the periorbital arteries in Zambian Africans. A screening with bidirectional Doppler ultrasound.

Directional Doppler sonography with direct evaluation of the extracranial carotid artery system and scanning of the periorbital arteries has been performed in 49 black Zambian hypertensive patients and in 19 controls without cardiovascular risk factors. Direct evaluation of the extracranial carotid artery system did not show any abnormalities. In contrast to this periorbital Doppler examination revealed positive findings with retrograde flow direction in the supratrochlear artery in 19% and 21% of all examined carotids in the hypertension and control group, respectively. Compared to direct carotid angiography, 66% of the positive supratrochlear and 13% of the positive supraorbital findings in the hypertensive patient group could be shown to be false positive results. As a possible explanation of this high incidence of a retrograde flow direction in periorbital arteries a different flow physiology in the ophthalmic artery of black Zambians compared to Caucasians is discussed.