Emerging New Approaches in Desensitization: Targeted Therapies for HLA Sensitization

There is an urgent need for therapeutic interventions for desensitization and antibody-mediated rejection (AMR) in sensitized patients with preformed or de novo donor-specific HLA antibodies (DSA). The risk of AMR and allograft loss in sensitized patients is increased due to preformed DSA detected at time of transplant or the reactivation of HLA memory after transplantation, causing acute and chronic AMR. Alternatively, de novo DSA that develops post-transplant due to inadequate immunosuppression and again may lead to acute and chronic AMR or even allograft loss. Circulating antibody, the final product of the humoral immune response, has been the primary target of desensitization and AMR treatment. However, in many cases these protocols fail to achieve efficient removal of all DSA and long-term outcomes of patients with persistent DSA are far worse when compared to non-sensitized patients. We believe that targeting multiple components of humoral immunity will lead to improved outcomes for such patients. In this review, we will briefly discuss conventional desensitization methods targeting antibody or B cell removal and then present a mechanistically designed desensitization regimen targeting plasma cells and the humoral response

Early changes in scores of chronic damage on transplant kidney protocol biopsies reflect donor characteristics, but not future graft function.

The amount of irreversible injury on renal allograft biopsy predicts function, but little is known about the early evolution of this damage. In a single-center cohort, we examined the relationship between donor-, recipient-, and transplantation-associated factors and change in a morphometric index of chronic damage (ICD) between protocol biopsies performed at implantation and at 2-3 months. We then investigated whether early delta ICD predicted subsequent biochemical outcomes. We found little evidence to support differences between the study group, who had undergone serial biopsies, and a contemporaneous control group, who had not. In allografts with serial biopsies (n = 162), there was an increase in ICD between implantation (median: 2%, IQR:0-8) and 2-3 months post-transplant (median 8% IQR:4-15; p < 0.0001). Donation from younger or live donors was independently associated with smaller early post-transplant increases in ICD. There was no evidence for a difference in delta ICD between donation after cardiac death vs. donation after brain death, nor association with length of cold ischemia. After adjustment for GFR at the time of the second biopsy, delta ICD after three months did not predict allograft function at one yr. These findings suggest that graft damage develops shortly after transplantation and reflects donor factors, but does not predict future biochemical outcomes

Passenger donor lymphocytes: To affinity and beyond

Graft-versus-host recognition by passenger donor lymphocytes within organ transplants can trigger host alloantibody production (Charmetant et al .)

Optimal Immunosuppression Strategy in the Sensitized Kidney Transplant Recipient

Patients with previous sensitization events against anti-human leukocyte antigens (HLA) often have circulating anti-HLA antibodies. Following organ transplantation, sensitized patients have higher rates of antibody-mediated rejection (AMR) compared to those who are non-sensitized. More stringent donor matching is required for these patients, which results in a reduced donor pool and increased time on the waitlist. Current approaches for sensitized patients focus on reducing preformed antibodies that preclude transplantation; however, this type of desensitization does not modulate the primed immune response in sensitized patients. Thus, an optimized maintenance immunosuppressive regimen is necessary for highly sensitized patients, which may be distinct from non-sensitized patients. In this review, we will discuss the currently available therapeutic options for induction, maintenance, and adjuvant immunosuppression for sensitized patients

Biological Mesh Repair of a Large Incisional Hernia Containing a Kidney Transplant in the Presence of Inflammation

The incidence of incisional hernia after kidney transplantation varies between 1.1% and 3.8%. These are usually repaired electively using polypropylene mesh. We present here a case where a patient presented as an emergency, with a large painful incisional hernia over his kidney transplant, and evidence of local erythema and systemic inflammation. As this could have represented either infection or rejection, the patient was started on antibiotics and subsequently underwent graft nephrectomy and hernia repair using a biological (porcine-derived) acellular dermal matrix, Strattice™, with a satisfactory outcome. In addition, histology showed evidence of allograft rejection. This is the first reported case of an incisional hernia containing a rejecting kidney allograft, managed with nephrectomy and biological mesh repair