Milagros Samaniego

Plasmapheresis, CMV hyperimmune globulin, and anti-CD20 allow ABO-incompatible renal transplantation without splenectomy

The majority of preconditioning protocols developed to allow ABO‐incompatible (ABOi) renal transplantation include concurrent splenectomy as a prerequisite to successful engraftment. Our center has developed a preconditioning protocol that includes plasmapheresis (PP), low‐dose CMV hyperimmune globulin (CMVIg), and anti‐CD20 monoclonal antibody (rituximab) to allow ABOi renal transplantation without splenectomy. Our initial experience has included treatment of six recipients and successful transplantation from blood group A1, A2, and group B living donors. Mean (± SD) serum creatinine was 1.3 ± 0.1 mg/dL among the six recipients and no episodes of antibody‐mediated rejection (AMR) occurred at a median follow‐up of 12 months. ABO antibody titers have remained below pretreatment levels. The absence of AMR and stable allograft function in this series show the potential of this preconditioning protocol to increase ABOi renal transplantation. The use of rituximab, allowing avoidance of splenectomy, may further remove one of the significant disincentives to ABOi transplantation, and eliminate the risk of post‐splenectomy infections.

Pretransplant donor-specific antibodies detected by single-antigen bead flow cytometry are associated with inferior kidney transplant outcomes.

Background. The clinical significance of pretransplant donor-specific antibodies (pre-Tx DSAs) detected by single-antigen bead flow cytometry (SAB-FC) remains unclear. Methods. To investigate the impact that pre-Tx DSAs detected by SAB-FC have on early clinical outcomes, we tested pre-Tx sera from all consecutive deceased-donor kidney transplants performed between January 2005 and July 2006 (n=237). Results. In the study population of which 66% had a high-immunologic risk, mean fluorescence intensity (MFI) more than or equal to 100 for class I and more than or equal to 200 for class II were the lowest DSA thresholds associated with inferior antibody-mediated rejection-free graft survival (75% vs. 90%, P=0.004 and 76% vs. 87%, P=0.017, respectively). The hazard ratio for antibody-mediated rejection increased linearly with higher class II DSA from MFI 100 to 800 (1.7[0.8–3.2], P=0.1 for MFI≥100 vs. 4.7[2.4–8.8], P<0.001 for MFI ≥800). Differences in graft function were only evident in patients with class II MFI more than or equal to 500 (estimated glomerular filtration rate: 47.6 vs. 54.3, P=0.02 and proteinuria: 0.6±0.6 vs. 0.4±0.3, P=0.03). A difference in death-censored graft survival was detected in patients with class II MFI more than or equal to 1000 (75% vs. 91.9%, P=0.055). Conclusion. High-pre-Tx DSAs detected by SAB-FC are associated with incrementally poor graft outcomes in deceased-donor kidney transplant with high-immunologic risk.

Shorter waiting times for hepatitis C virus seropositive recipients of cadaveric renal allografts from hepatitis C virus seropositive donors

Introduction. The purposes of this study were: 1) to analyze the early results of cadaveric renal transplantation from either hepatitis C virus seropositive (HCV+) or hepatitis C virus seronegative (HCV−) donors into HCV+ recipients; and 2) to determine whether HCV+ patients with end‐stage renal disease (ESRD) might benefit from receiving renal allografts from HCV+ donors. 
Methods. From January 1997 to June 1999, 28 patients with ESRD and HCV infection underwent 29 cadaveric renal transplants. The data were reviewed retrospectively. Nineteen of the renal transplants were performed with allografts obtained from 15 HCV+ donors and 10 with allografts obtained from 10 HCV− donors. The median follow‐up was 16.2 months, with an average of 15.4±2 months. 
Results. Recipients of HCV+ renal allografts had shorter waiting times for transplantation. On average, patients who received a kidney from HCV+ donors were transplanted 9±3 months after being placed on the transplant list, compared to 29±3 months for patients who received a kidney from a HCV− donor. Shorter waiting times were noted in every blood type group. There were no significant differences in rejection episodes, infectious complications, renal function, liver function, graft survival, or patient survival. 
Conclusions. The use of renal allografts from HCV+ donors for HCV+ recipients shortens the waiting time for these patients, with no short‐term differences in renal and liver function, graft loss, or patient survival.

Combined percutaneous mechanical and chemical thrombectomy for renal vein thrombosis in kidney transplant recipients.

Renal vein thrombosis occurring after the immediate post‐transplant period often leads to loss of the transplant organ. We report two cases of renal vein thrombosis in the setting of de novo membranous nephropathy occurring 5 and 26 months post‐transplantation. Both cases were treated with percutaneous mechanical thrombectomy and localized catheter‐directed thrombolysis with resolution of clot burden, and regained kidney function after thrombolysis without subsequent thromboses. Percutaneous mechanical thrombolysis can be safely done in renal transplant recipients and should be considered in patients with renal vein thrombosis beyond the immediate post‐operative period in order to minimize exposure to systemic thrombolysis.

Outcomes of simultaneous liver/kidney transplants are equivalent to kidney transplant alone: a preliminary report.

Background. With adoption of Model for End-Stage Liver Disease, the number of simultaneous liver-kidney transplants (SLK) has greatly increased. A recent registry study questioned the equity of allocating kidney transplants (KTx) simultaneously with liver transplantation due to poor outcomes (Locke et al., Transplantation 2008; 85: 935). Methods. To investigate outcome of KTx in SLK, all SLK (n=36) performed at our center from January 2000 to December 2007 were reviewed and KTx outcomes compared with those of kidney transplant alone (KTA) performed during that period (n=1283). We also reviewed whether pretransplant panel reactive antibody and donor-specific antibody affected KTx outcome in SLK. Results. One- and 3-year KTx and patient survival were not different between KTA and SLK regardless of sensitization level. There were 348 (27%) KTx failures in KTA vs. 6 (17%) in SLK (NS). Overall freedom from acute cellular rejection (ACR) and antibody-mediated rejection (AMR) in SLK was 93 and 96% at 3 years, compared with 72 and 78% in KTA (P=0.0105 and P=0.0744, respectively). Sensitized KTx recipients had more ACR and AMR (32 and 38%) at 3 years compared with nonsensitized recipients (28 and 20%) (P=0.23 and 0.0001, respectively). No differences in ACR and AMR were observed when SLK was divided and level of sensitization compared (P=0.17 and 0.65, respectively). Conclusion. SLK is a life-saving procedure with excellent patient and graft survival. AMR incidence in the KTx appears reduced in SLK compared with KTA regardless of level of preoperative panel reactive antibody. A high level of donor-specific antibody should not preclude simultaneous transplantation when clinically indicated.

West Nile virus encephalitis in a kidney transplant recipient.

We describe a case of West Nile virus encephalitis in a 54‐year‐old kidney transplant recipient. The clinical course was rapid and fatal. Serial CSF samples showed an evolving mononuclear pleiocytosis and serial MRIs showed increasing signs of cytotoxic edema in her basal ganglia. Seroepidemiological testing indicated that the infection was most likely acquired from transfusion of fresh frozen plasma at the time of transplantation.

High-Dose Mycophenolate Mofetil in the Treatment of Posttransplant Glomerular Disease in the Allograft: A Case Series

Background: Glomerular disease is an important cause of allograft loss. Treatment regimens for posttransplant glomerular disease are not well defined. Several reports have demonstrated that mycophenolate mofetil (MMF) is effective in treating native kidney glomerular disease. The effects of MMF are dose related. Therefore, we hypothesized that high-dose MMF (3 g/day) would be effective in treating glomerular disease in the allograft, minimizing the need for intravenous steroids and/or cyclophosphamide. This case series describes the results of the use of high-dose MMF in 6 patients. Methods: High-dose MMF (3 g/day) was used to treat biopsy-proven glomerular disease (focal segmental glomerulosclerosis, membranoproliferative glomerulonephritis, proliferative lupus nephritis, and perinuclear antineutrophil cytoplasmic antibodies glomerulonephritis) in 6 renal transplant recipients. Patients were offered this treatment if they had failed or did not tolerate standard treatment regimens. Remission was defined by a decrease or stabilization of serum creatinine, decrease in proteinuria and, where applicable, improvement in immunological markers of disease. Results: All 6 patients had disease remission after starting MMF with the most common side effect being leukopenia, which responded to dose reduction. Conclusions: High-dose MMF may be an effective agent in treating glomerular disease in the allograft.

Donor horseshoe kidneys for transplantation.

BACKGROUND Experience with donor horseshoe kidneys for transplantation is very limited. Currently, horseshoe kidneys may be underutilized for transplantation because of the greater incidence of vascular anomalies, associated renal anomalies, and predisposition to renal disease. METHODS In this report, we review five transplantations using horseshoe kidneys: the largest reported institutional experience. In addition, a review of all published cases in the English literature is performed. RESULTS All five patients underwent successful renal transplantations with a median follow-up of 35 months. One patient lost his kidney from recurrent disease soon after transplantation. CONCLUSION With appropriate reconstruction of the vessels, careful division of the isthmus, and avoidance of ureteral obstruction, long-term data revealed good graft survival of donor horseshoe kidneys in renal transplantation.

Complement as a mediator of allograft injury: an inflammatory view

Complement regulates many of the mediators of inflammation, immunity, and repair. As a result, complement is an important link between antigen-independent and antigen-dependent immune responses to transplanted organs. This review discusses the role of complement in activating platelets, granulocytes, monocytes, macrophages, lymphocytes, endothelial cells, and vascular smooth muscle cells at different stages after organ transplantation.