Increased risk of interstitial fibrosis and tubular atrophy in controlled donation after circulatory death kidney transplantation

Introduction: Comparable transplant outcomes between controlled donation after circulatory death (cDCD) and donation after brain death (DBD) kidney transplantation (KT) have been confirmed. However, few data describes the histology of cDCD-KT which is subjected to prolonged procurement warm ischemia. This study aimed to evaluate the rate of interstitial fibrosis (IF) and tubular atrophy (TA) on the surveillance biopsy performed in our unit between the 2 and 6 months post KT. Acute rejection was considered as secondary endpoint. Patients and Methods: 330 KT (226 DBD and 104 DCD) have been performed between 2008 and 2014. Surveillance or per-cause biopsy was performed in 272 recipients. Among them, the rate of adequate (≥8 glomeruli and ≥1 large-sized artery) was 76.8%. Results: IFTA was found in 11.5% and 25.7% of DBD and cDCD-KT, respectively (p = 0.004). Considering IF and TA separately, the corresponding rates were 20.4% vs 32% (p = 0.04) and 23% vs 36% (p = 0.03), respectively. If acute rejection before routine biopsy was excluded, either IF or TA rate was significantly higher in cDCD- than DBD-KT (12.6% vs 27.1%, p = 0.006; 17.6% vs 31.4%, p = 0.016; and 20.9% vs 35.7%, p = 0.015 in case of IF-TA, IF, and TA, respectively). A cDCD-KT compared to a DBD-KT was 3.11 (95%CI 1.51– 6.43, p = 0.002), 2.34 (95%CI 1.21–4.53, p = 0.011) and 2.29 (95%CI 1.23– 4.27, p = 0.009) times more likely to have IFTA, IF, and TA, respectively. Extended criteria donor (ECD) vs standard criteria donor (SCD) was also an independent risk factor for IFTA (OR = 3.11, 95%CI 1.51–6.43, p = 0.002), IF (OR = 4.86, 95%CI 1.96–12.05, p = 0.001), and TA (OR = 4.09, 95%CI 1.68– 9.93, p = 0.002). The rate of acute rejection diagnosed by SB was 7.1% and 8.9% in DBD and cDCD kidney grafts (p = ns), respectively.Conclusion: KT from cDCD increased the risk of IF-TA between 3 and 6 months post-transplant. Further studies are warranted to investigate the evolution of this phenomenon over time and its effect on graft function

HOME BLOOD PRESSURE IN KIDNEY TRANSPLANT RECIPIENTS (Ktr)-VALIDITY OF DIFFERENT SCHEDULES OF SELF-MONITORING

Office blood pressure (OBP) coupled with 24-h ambulatory monitoring (24-h ABPM) or home self-monitoring (HBPM) allow a more accurate assessment of BP control in treated hypertensive patients and identification of different phenotypes of BP. ESH/ESC guidelines (2013) recommended 7 days of home measurements (3 days at least) but that duration is questioned. The present study examined if we can reduce, and to what extent, the 7-days schedule for home measurements in treated hypertensive kidney transplant recipients (ktr) while keeping a reliable assessment of their BP status

Administration of Third-Party Mesenchymal Stromal Cells at the Time of Kidney Transplantation: Interim Safety Analysis at One-Year Follow-Up

Mesenchymal stromal cells (MSC)-based therapy has been proposed in kidney transplantation (KTx). We report on the 1-year follow-up of an open-label phase I trial using MSC in KTx. On postoperative day 3, third-party MSC (~2.0x106/kg) were administered to 7 non-immunized first-transplant recip- ients from deceased donors, under standard immunosuppression (Basiliximab, Tacrolimus, MMF and steroids). No HLA matching was required for MSC donors. Seven comparable KTx recipients were included as controls. Informed consent was obtained. No side-effect was noted at the time of MSC injection. Still, 1 patient with a history of ischemic heart disease had a NSTEMI ~3h after MSC infusion. Ten months after KTx, 1 MSC patient had type B aortic dissection and STEMI. Four MSC patients had at least 1 opportunistic infection, whereas 3 controls had polyoma-BK viremia. At day 14, eGFR in MSC and control groups was 47.1 ± 6.8 and 39.7 ± 5.9 ml/min, respectively (p, 0.05). At 1 year, eGFR in MSC and control groups was 46.5 ± 18.6 and 54.2 ± 16.3 ml/min, respectively (p, 0.42). Per-cause biopsies evidenced 1 bor- derline and 1 acute rejections in MSC group, whereas no AR was biopsy-proven in controls. Three patients developed anti-HLA antibodies against MSC (n=1) or shared kidney/MSC (n=2) mismatches.MSC infusion was safe in all patients except one. Incidence of opportunist infections was similar in both groups. No difference in eGFR was found at 1-year post KTx. Putative immunization against MSC was observed in 3 patients

Mesenchymal Stromal Cell Therapy in Ischemia/Reperfusion Injury.

Ischemia/reperfusion injury (IRI) represents a worldwide public health issue of increasing incidence. IRI may virtually affect all organs and tissues and is associated with significant morbidity and mortality. Particularly, the duration of blood supply deprivation has been recognized as a critical factor in stroke, hemorrhagic shock, or myocardial infarction, as well as in solid organ transplantation (SOT). Pathophysiologically, IRI causes multiple cellular and tissular metabolic and architectural changes. Furthermore, the reperfusion of ischemic tissues induces both local and systemic inflammation. In the particular field of SOT, IRI is an unavoidable event, which conditions both short- and long-term outcomes of graft function and survival. Clinically, the treatment of patients with IRI mostly relies on supportive maneuvers since no specific target-oriented therapy has been validated thus far. In the present review, we summarize the current literature on mesenchymal stromal cells (MSC) and their potential use as cell therapy in IRI. MSC have demonstrated immunomodulatory, anti-inflammatory, and tissue repair properties in rodent studies and in preliminary clinical trials, which may open novel avenues in the management of IRI and SOT