Transplantology, Volume 4, Issue 2 (June 2023) – 5 articles

Background: Despite great progress in graft survival and complication rates, pronounced inflammatory responses are common after pancreas transplantation (PT). Subsequent to the first postoperative increase in inflammatory markers, we have frequently observed a second peak of C-reactive protein (CRP) and white blood cells (WBCs) following PT. This analysis is to assess the incidence and clinical relevance of late-onset increases in inflammatory markers following PT. Materials and methods: We analyzed all consecutive PTs over a 20-year period. The second peak of CRP (SCP) and WBCs (SWP) was defined as an increase >3 days after PT subsequent to a relevant initial decrease. Results: Of 116 patients, 60 (51.7%) developed SCP. SCP was not associated with pancreas graft loss or with thrombosis at discharge or at 90 days after PT (6.7% vs. 0.0%, p = 0.1; 8.3% vs. 1.8%, p = 0.2; and 15.0% vs. 3.6%, p = 0.06, respectively). Patients with SCP had more complications overall at discharge and at 90 days (85.0% vs. 50.0%, p < 0.001 and 93.3% vs. 76.8%, p = 0.02). In multivariable analysis, SCP was significantly associated with pre-transplant HbA1c (OR 2.1 (95% CI: 1.3–3.8); p = 0.005) and female gender (OR 0.03 (95% CI: 0.004–0.14); p ≤ 0.001). No significant association was found between SCP and pancreas cold ischemia time (OR 1.0 (95% CI: 1.0–1.0); p = 0.1), donor age (OR 1.01 (95% CI: 0.96–1.06); p = 0.7), recipient age (OR 0.9 (95% CI: 0.9–1.0); p = 0.1), or recipient BMI (OR 0.9 (95% CI: 0.9–1.4); p = 0.3). SWP did not differ in patients with or without SCP (p = 0.07) and there was no correlation with pancreas graft loss or relaparotomy (p = 0.3 and p = 0.6, respectively). Insulin-free graft survival after 1, 5, and 10 years did not differ between patients with SCP and those without SCP (95.0%, 90.2%, 90.2% vs. 96.1%, 91.2%, 88.7%, respectively; p = 0.964). Conclusion: Late-onset inflammatory reactions are frequently seen in PT and are correlated with higher overall complication rates. They are not correlated, however, with graft-specific complications or insulin-free graft survival. Full article

One of the major challenges in developing programs for kidney transplantation is represented by the presence of antibodies targeting the HLA of the donor in the recipients and, in particular cases, the incompatibility of the ABO blood groups among donor and recipient for living donors [...] Full article

Chronic liver injury and subsequent liver fibrosis are usually a slow process without any specific or no clinical signs, resulting in pathological conditions with a poor chance of improvement through medical and surgical treatment, which if not promptly recognized, often lead to a liver transplant as the only therapeutic option. On the other hand, screening and follow-up are hard to establish in large populations using regularly invasive methods such as biopsies and other expensive diagnostic tools due to cost and a lack of adequate specificity and sensibility. In the last few years, a large variety of serological and radiological tests have been proposed to assess liver fibrosis. In this review, we will consider the most commonly used scores to evaluate liver fibrosis, with a special focus on the NAFLD pathogenesis. We will try to answer the question: can we rely on them? Full article

Circulatory death donor (DCD) kidneys are increasingly used to enlarge the donor pool. These kidneys undergo ischemia-reperfusion injury, frequently leading to renal fibrosis. Transforming growth factor beta 1 (TGF-β1) and matrix metalloproteases have been identified as central mediators of fibrosis and inhibition of these targets could attenuate fibrosis. We studied whether galunisertib, doxycycline, taurine, and febuxostat alleviated fibrosis in precision-cut kidney slices (PCKS). PCKS were prepared from porcine kidneys that were exposed to 30 min of warm ischemia followed by 3 h of oxygenated hypothermic machine perfusion. We subsequently incubated PCKS for 48 h at 37 °C with the described compounds. To further elucidate the antifibrotic effects of galunisertib, we cultured PCKS with TGF-β1. We first screened the effects of the compounds without TGF-β1. Most significant effects were observed for galunisertib which lowered the expression of ACTA2, TGFB1, FN2, and SERPINE1. We then investigated the effects of galunisertib in fibrotic PCKS incubated with TGF-β1. TGF-β1 significantly increased expression of TGFB1, FN1, SERPINE1, and SERPINH1. Galunisertib, however, attenuated the expression of all fibrosis-related genes. Galunisertib appears to be a promising antifibrotic compound requiring further research in a preclinical model and may ultimately be administered during machine perfusion as an antifibrotic treatment in a transplant setting. Full article

Background: When a partial liver graft is transplanted into a recipient with portal hypertension, it is subject to sinusoidal shear stress, which, in good measure, is essential for regeneration. However, portal hyperperfusion which exceeds the capacity of the graft results in the small-for-size syndrome manifested by ascites, cholestasis and coagulopathy. This review discusses intraoperative hemodynamic variables that have been described in the literature, and inflow modulation strategies and their outcomes. Apart from using donor grafts which are of adequate size for the recipient weight, portal hemodynamics are an important consideration to prevent early allograft dysfunction, graft failure and mortality. Summary: Understanding normal portal hemodynamics, how they change with the progression of cirrhosis, portal hypertension and changes after the implantation of a partial liver graft is key to managing patients with living-donor liver transplantation. If the intraoperative measurement of portal flow or pressure suggests graft portal hyperperfusion, inflow modulation strategies can be adopted. Splenic artery ligation, splenectomy and hemiportocaval shunts are well described in the literature. The proper selection of a donor to match the recipient’s anatomic, metabolic and hemodynamic environment and deciding which modulation strategy to use in which patient is an exercise in sound clinical judgement. Key message: The intraoperative assessment of portal hemodynamics in living-donor liver transplant should be standard practice. Inflow modulation in properly selected patients offers a point-of-care solution to alter portal inflow to the graft with a view to improve recipient outcomes. In patients with small (anatomically/metabolically) grafts, using inflow modulation can result in outcomes equivalent to those in patients in whom larger grafts are used. Full article