Noninvasive biomarkers are needed to monitor stable patients after kidney transplant (KT), because subclinical acute rejection (subAR), currently detectable only with surveillance biopsies, can lead to chronic rejection and graft loss. We conducted a multicenter study to develop a blood-based molecular biomarker for subAR using peripheral blood paired with surveillance biopsies and strict clinical phenotyping algorithms for discovery and validation. At a predefined threshold, 72% to 75% of KT recipients achieved a negative biomarker test correlating with the absence of subAR (negative predictive value: 78%-88%), while a positive test was obtained in 25% to 28% correlating with the presence of subAR (positive predictive value: 47%-61%). The clinical phenotype and biomarker independently and statistically correlated with a composite clinical endpoint (renal function, biopsy-proved acute rejection, ≥grade 2 interstitial fibrosis, and tubular atrophy), as well as with de novo donor-specific antibodies. We also found that <50% showed histologic improvement of subAR on follow-up biopsies despite treatment and that the biomarker could predict this outcome. Our data suggest that a blood-based biomarker that reduces the need for the indiscriminate use of invasive surveillance biopsies and that correlates with transplant outcomes could be used to monitor KT recipients with stable renal function, including after treatment for subAR, potentially improving KT outcomes.

Transplantation of kidneys from selected deceased donors with ARF provides comparable survival and function compared to kidneys from non-ARF donors and may be considered for transplantation to expand the donor pool to overcome the current acute shortage of kidneys.

Background We recently reported that durable chimerism can be safely established in mismatched kidney recipients through nonmyeloablative conditioning followed by infusion of a facilitating cell (FC)-based hematopoietic stem cell transplant termed FCRx. Here we provide intermediate-term follow-up on this phase 2 trial. Methods Fifteen HLA mismatched living donor renal transplant recipients underwent low intensity conditioning (fludarabine, cyclophosphamide, 200cGyTBI), received a living donor kidney transplant on day 0, then infusion of cryopreserved FCRx on day +1. Maintenance immunosuppression(IS),consisting of tacrolimus and mycophenolate, was weaned over one year. Results All but one patient demonstrated peripheral blood macrochimerism post-transplantation. Engraftment failure occurred in a highly sensitized (PRA of52%) recipient. Chimerism was lost in 3patients at 2, 3, and 6 months post transplantation. Two of these subjects had received either a reduced cell dose or incomplete conditioning; the other 2 had PRA >20%. All demonstrated donor-specific hyporesponsiveness and were weaned from full dose immunosuppression. Complete immunosuppression withdrawal at one year post-transplant was successful in all patients with durable chimerism. There has been no GVHD or engraftment syndrome. Renal transplant loss occurred in 1 patient who developed sepsis following an atypical viral infection. Two subjects with only transient chimerism demonstrated subclinical rejection on protocol biopsy despite donor-specific hyporesponsiveness. Conclusions Low intensity conditioning plus FCRx safely achieved durable chimerism in mismatched allograft recipients. Sensitization represents an obstacle to successful induction of chimerism. Sustained T cell chimerism is a more robust biomarker of tolerance than donor-specific hyporeactivity.

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This paper reports a case of migrating intravascular bullet embolus that initially produced no symptoms but resulted in an above-knee amputation 14 months after its entry into a peripheral artery. The missile entered through a penetrating gunshot wound to the abdominal aorta and later became lodged in the left popliteal artery. However, the bullet fragment migrated further into the posterior tibial artery with consequent vascular insufficiency requiring a supracondylar amputation of the left lower extremity 14 months later. Emphasis is placed on the need for a high index of suspicion for bullet embolism, aggressive search for any bullets unaccounted for, and early surgical removal of all confirmed arterial emboli.