Marina Loucaidou

ABO incompatible living renal transplantation with a steroid sparing protocol.

Background. ABO incompatible (ABOi) live-donor renal transplantation is a successful and accepted form of treatment for patients with renal failure. Although there is significant controversy as to how antiblood group antibodies should be removed and their resynthesis prevented, subsequent immunosuppressive regimes have all involved steroids. We and other groups have successfully used steroid sparing regimes for conventional ABO compatible transplantation and this study describes the use of our steroid sparing protocol in ABOi transplantation. Methods. We have transplanted 10 ABOi patients using 1 week of steroids (prednisolone 1 mg/kg for 4 days, 0.5 mg/kg for 3 days and then stopped), tacrolimus and mycophenolate mofetil. Steroids were reintroduced in the event of rejection. Results. Patient- and allograft-survival 1 year posttransplantation is 100%. Three patients experienced antibody-mediated rejection within 2 weeks of transplantation, which was successfully reversed. There has been no late rejection. Allograft function was similar to our live-donor ABO compatible transplant patients receiving a similar steroid sparing regime (12-month mean creatinine 131±15 &mgr;mol/L vs. 138±48 &mgr;mol/L; mean CrCl 63.2±22 mL/min vs. 56.7±20 mL/min). Conclusions. This study shows that ABOi live-donor transplantation can be successfully accomplished using a steroid-sparing protocol.

The magnitude and time course of changes in mycophenolic acid 12-hour predose levels during antibiotic therapy in mycophenolate mofetil-based renal transplantation.

There is increasing evidence that monitoring predose plasma levels of mycophenolic acid (MPA) is of benefit in renal transplant recipients treated with mycophenolate mofetil (MMF). Concomitant treatment with oral antibiotics leads to a 10% to 30% reduction in MPA area under the curve (AUC)0-12, probably by reducing enterohepatic recirculation (EHR). Because of the timing of EHR (6 to 12 hours postdose), the magnitude of predose MPA level reduction may be disproportionately larger than that of AUC0-12. However, changes in predose MPA levels and the time course over which these changes occur and resolve during antibiotic treatment have not been studied. The purpose of this study was to define the extent and time course of MPA predose level reduction during antibiotic therapy. A total of 64 MMF-treated renal transplant recipients (with tacrolimus cotherapy) were prospectively studied. Clinically indicated cotherapy with either oral ciprofloxacin or amoxicillin with clavulanic acid resulted in a reduction in 12 hour predose MPA level to 46% of baseline within 3 days of antibiotic commencement. No demographic or biochemical variables were associated with the magnitude of MPA level reduction. No further fall in MPA level was seen by day 7, but MPA levels recovered spontaneously to 79% of baseline after 14 days of antibiotics. Levels normalized within 3 days of antibiotic cessation. No changes in daily MMF dose (normalized for body weight) were made during antibiotic treatment. This data should help the clinician to recognize the extent of MPA predose level reduction during antibiotic therapy, and to avoid inappropriate MMF dose escalation and potential risk of toxicity.

Analysis of Factors Influencing Tacrolimus Levels and Immunoassay Bias in Renal Transplantation

T is a potent immunosuppressant, and studies in renal transplantation suggest that trough levels of 10 to 15 ng/mL may optimize efficacy while minimizing adverse events. Most of these studies were conducted using immunoassay methodology; however, the antibody used in the immunoassay technique also cross-reacts with a variety of tacrolimus metabolites, some biologically active and some not. This results in higher tacrolimus levels observed with immunoassay monitoring compared with specific assay techniques based on highperformance liquid chromatography (HPLC), which measure only the parent tacrolimus molecule. This positive bias may also reflect patients’ hematocrit and serum albumin levels and the choice of anticoagulant in assay calibrators. Although tacrolimus monitoring with specific assays such as HPLC is recommended, the therapeutic range using these techniques has not yet been established. Our group has previously reported clinical outcomes comparing microparticle enzyme immunoassay (MEIA) and HPLC with mass spectroscopic detection (HPLC-MS) monitoring. Tacrolimus levels were targeted to a higher range in the MEIAmonitored patients in view of the 10% to 25% positive bias associated with immunoassay techniques. Although no difference in short-term clinical outcomes was seen in this small study, it remains possible that significant variation in immunoassay bias may occur when clinical circumstances vary, and therefore a knowledge of the factors affecting this bias may help the clinician to appropriately adjust tacrolimus levels to account for this. In contrast to numerous studies addressing the determinants of tacrolimus levels, few data are available to explain factors influencing immunoassay bias. The purpose of this study was to describe the associations between immunoassay bias and a variety of clinical and biochemical variables in renal transplant recipients treated with tacrolimus.

Paraprotein |[lsquo]|zippers|[rsquo]|

Vasiliki Bravou, Adam G. McLean, Marina Loucaidou, Tom D. Cairns, Herbert T. Cook and Candice A. Roufosse Department of Pathology, Agios Andreas Hospital of Patras, Patras, Greece; Department of Anatomy, School of Medicine, University of Patras, Patras, Greece; Imperial College Renal and Transplant Centre, Hammersmith Hospital, London, UK and Department of Histopathology, Hammersmith Hospital, Imperial College Healthcare NHS Trust, London, UK

Five-year results of kidney transplantation under tacrolimus-based regimes: the persisting significance of vascular rejection.

Background. Acute rejection has been the major risk factor for medium-term kidney graft loss because of chronic allograft nephropathy. We investigated whether the use of improved immunosuppression has altered the relationship between acute and chronic rejection by analyzing data from 245 renal transplant patients receiving Tacrolimus-based immunosuppression. Results. Five-year graft survival (censored for death with functioning graft) was 88.8% with no significant difference between living and cadaveric kidney transplants. The only significant predictor of medium-term graft loss was acute vascular rejection. Conclusion. Under Tacrolimus-based immunosuppression, the occurrence of acute interstitial rejection, even when occurring late, repeatedly, or with failure of graft function to return to baseline, was not associated with chronic allograft nephropathy or medium-term graft loss. Vascular rejection remains the major immunological obstacle to long-term transplant success. Five-year overall survival rates with a functioning graft of 80% with 90% graft survival censored for death with function seem to be realistic and achievable goals.

Invited Manuscript Poster on Renal-Related Education American Society of Nephrology, Nov. 16–21, 2010 Improving Access to Kidney Transplant Information has Increased Preemptive Living Kidney Donation

Abstract Transplantation provides the best outcomes and quality of life for people with end-stage renal disease and therefore offers the optimum treatment of choice. Preemptive living donor (LD) transplantation is an increasingly preferable alternative to dialysis as transplantation outcomes indicate lower morbidity and mortality rates and greater graft and patient survival rates compared to those who are transplanted after dialysis has commenced. Despite nursing and medical teams giving information to patients regarding transplantation and living donation, the number of people coming forward for preemptive transplant work-up remained limited. Changing the format, environment, and quality of information given to patients and families seemed necessary in order to increase the number of preemptive transplants. Our data show that we have improved the access to the information seminars with attendance rising from 5 to 15 attendees per seminar (3 per year) in 2005 to average 65 attendees per seminar (6 per year) in 2010. By expanding the access to information for patients, their families and friends, living donation has increased with a growth in the proportion of preemptive LD transplants from 28% (23/81) in 2006 to 44% in 2010 (29/66; p = 0.05). We can conclude that expanding the pool accessing information has increased the number of preemptive (LD) transplants in our center.