Transplantology, Volume 2, Issue 1 (March 2021) – 9 articles

A six-year-old heart transplant recipient with additional significant co-morbidities, including severe hypoxic-ischemic injury, gastrostomy, tracheostomy, and mechanical ventilation dependency, encountered SARS-CoV-2 infection. The patient received tacrolimus and mycophenolate to prevent graft rejection, presented initially with SARS-CoV-2 positive and presumed pseudomonas aeruginosa pneumonia. Twenty-three days later, the patient presented with fever recurrence with evidence for systemic inflammation, which resolved rapidly with high-dose methylprednisolone. Interestingly, while IgM to SARS-CoV-2 was present, IgG was not detected even three months after his first positive test for SARS-CoV-2. The author discusses potential immune mechanisms that might have affected the course of multi-system inflammatory syndrome children (MIS-C) in this patient. Full article

Living kidney donation represents the best treatment for end stage renal disease patients, with the potentiality to pre-emptively address kidney failure and significantly expand the organ pool. Unfortunately, there is still limited knowledge about this underutilized resource. The present review aims to describe the general principles for the establishment, organization, and oversight of a successful living kidney transplantation program, highlighting recommendation for good practice and the work up of donor selection, in view of potential short- and long-terms risks, as well as the additional value of kidney paired exchange programs. The need for donor registries is also discussed, as well as the importance of lifelong follow up. Full article

Health-related quality of life (HRQOL) before and after liver transplant (LT) is an important outcome in LT candidates as, in these patients, HRQOL is commonly impaired. However, evidence regarding factors that influence HRQOL in patients with end-stage liver disease is inconclusive. The aim of the present study was to identify factors associated with poor HRQOL. An observational study was conducted over LT candidates. The 36-item Short Form Health Survey (widely used to assess HRQOL) and the Hospital Anxiety and Depression Scale were administered to 211 patients during the pre-transplant assessment. Baseline demographic and clinical data were also collected. Multiple regression analysis was performed to investigate risk factors for poor HRQOL. Female sex (lower B = 7.99 95%C = 0.07–15.92, higher B = 18.09 95%CI = 7.56–28.62), encephalopathy (lower B = −9.45, 95%CI = −14.59–−4.31, higher B = −6.69, 95%CI = −13.13 to −0.25), higher MELD scores (lower B = −1.14, 95%CI = −1.67 to −0.61, higher B = −0.33, 95%CI = −0.65 to −0.12), anxiety (lower B = −3.04 95%C = −4.71 to −1.36, higher B = −1.93 95%CI = −3.39 to −0.47)and depression (lower B = −3.27 95%C = −4.46 to −2.08, higher B = −1.02 95%CI = −1.90 to −0.13) symptoms were associated to poorer HRQOL. Psychosocial interventions should be addressed to liver transplant candidates, especially to women, patients with anxiety, depression or episodes of encephalopathy, in order to prevent the impact that these conditions can have on HRQOL. Full article

Rapid recovery after laparoscopic living donor nephrectomy (LLDN) for kidney donation is highly desirable for living kidney donors. To uphold rapid recovery, good analgesia with minimal adverse effects, including those related to opioid dependence, is essential. A pre-operative transversus abdominis plane (TAP) block with liposomal bupivacaine can effectively aid in perioperative pain management, while reducing opioid requirements. We conducted a single-center retrospective study involving patients 18 years and older who underwent LLDN to determine whether a TAP block with liposomal bupivacaine is efficacious in pain management after LLDN, while reducing opioid use. The study group comprised of patients who received a preoperative TAP block with liposomal bupivacaine in place of hydromorphone patient-controlled analgesia (PCA) and the control group included patients who received hydromorphone PCA post-operatively. Both groups were supplemented with oral and intravenous analgesics for breakthrough pain, as needed. The primary endpoint was reduction in post-operative opioid use in morphine milligram equivalents (MME). Secondary endpoints included: post-operative pain scores, postoperative length of stay, and re-hospitalizations within 7 days of discharge. Sixty-six patients were included in our study, with 33 in each group. Patients in both groups were well matched demographically. The study group who received TAP block demonstrated a significant reduction in post-operative opioid use (92.05 MME vs. 53.98 MME, p < 0.05) when compared to the control group who received hydromorphone PCA. Both groups achieved similar analgesia with comparable pain scores. There was no difference between postoperative hospital lengths of stay for both groups. Two patients in the control group were re-admitted due to small bowel obstruction within seven days of discharge. In conclusion, TAP block with liposomal bupivacaine significantly reduced postoperative opioid use, while also proving to be safe, efficacious and feasible in patients undergoing LLDN. Full article

The use of tacrolimus (Tac) may be involved in the development of new-onset diabetes after transplantation (NODAT) in a dose-related manner. This study aimed to evaluate the effects of a standard twice-daily formulation of Tac (TacBID) vs. the once-daily slow-release formulation (TacOD) on the basal insulin resistance indexes (Homa and McAuley), and related metabolic parameters, in a cohort of kidney transplant patients. We retrospectively evaluated 20 stable renal transplant recipients who were switched from TacBID to TacOD. Blood levels of Tac were analyzed at one-month intervals from 6 months before to 8 months after conversion. Moreover, Homa and McAuley indexes, C-peptide, insulin, HbA1c, uric acid, triglycerides, low-density lipoprotein (LDL) and high-density lipoprotein (HDL)-cholesterol serum levels and their associations with Tac levels were evaluated. We observed a significant decrease in Tac exposure (8.5 ± 2 ng/mL, CV 0.23 vs. 6.1 ± 1.9 ng/mL, CV 0.31, TacBID vs. TacOD periods, p < 0.001) and no significant changes in Homa (1.42 ± 0.4 vs. 1.8 ± 0.7, p > 0.05) and McAuley indexes (7.12 ± 1 vs. 7.58 ± 1.4, p > 0.05). Similarly, blood levels of glucose, insulin, HbA1c, lipids, and uric acid were unchanged between the two periods, while C-peptide resulted significantly lower after conversion to TacOD. These data suggest that in kidney transplant recipients, reduced Tac exposure has no significant effects on basal insulin sensitivity indexes and metabolic parameters. Full article

The JC polyomavirus (JCPyV/JCV) is a member of the Polyomaviridae family and is ubiquitious in the general population, infecting 50–80% of individuals globally. A primary infection with JCV usally results in an asymptomatic, persistent infection that establishes latency in the renourinary tract. Reactivation from latency via iatrogenic immununosuppression for allograft transplantation may result in organ pathology and a potential life-threatening neuropathological disease in the form of progressive multifocal leukoencephalopathy (PML). Currently, no treatment exists for PML, a rare complication that occurs after transplantation, with an incidence of 1.24 per 1000 persons a year among solid organ transplant patients. PML is also observed in HIV patients who are immununosuppressed and are not receiving antiretroviral therapy, as well as individuals treated with biologics to suppress chronic inflammatory responses due to multiple sclerosis, Crohn’s disease, non-Hodgkin’s lymphoma, rheumatoid arthritis, and other autoimmune-mediated hematological disorders. Here, we describe the proposed mechanisms of JCV reactivation as it relates to iatrogenic immunosuppression for graft survival and the treatment of proinflammatory disease, such as biologics, proposed trafficking of JCV from the renourinary tract, JCV central nervous system dissemination and the pathology of PML in immunosuppressed patients, and potential novel therapeutics for PML disease. Full article

Urological complications (UC) following kidney transplantation (KT) are associated with increased morbidity. The aim of this study is to evaluate the risk factors for UC in the era of “extended criteria donors” (ECD) and their impact on patient and graft survivals. A retrospective monocentric study of all patients undergoing KT from 2010 to 2019 with a follow-up ≥30 days was performed. Out of 459 patients (males: 296 (64.5%); age: 57 (19–77) years) enrolled, 228 (49.7%) received ECD organs, moreover, 166 (67.2%) grafts had a cold ischemia time ≥10 h. UCs were reported in 32 (7%) patients. In 21 (65.6%) cases UC occurred within 3 months post-KT and 24 (5.2%) were associated with early urinary tract infection (UTI). The overall 5 year patient and graft survival rates were 96.5% and 90.6%, respectively. UC decreased graft survival (UC-group: 75.0% vs. noUC-group: 91.8%, p < 0.001), especially if associated with early UTI (UC-group: 71.4% vs. noUC-group: 77.8%, p < 0.001). At multivariate analysis, early UTI after KT (OR: 9.975, 95%-IC: 2.934–33.909, p < 0.001) and delayed graft function (DGF) (OR: 3.844, 95%-IC: 1.328–11.131, p: 0.013) were significant risk factors for UC, while ECD graft did not increase the risk of post-transplant UC. ECD grafts are not associated with UC. DGF and early UTI post-KT increase the risks of UC and reduce graft survival in the long-term. Therefore, aggressive management of early post-transplant UTI and strategies to reduce DGF incidence, such as machine preservation, are essential to prevent UC after KT. Full article

Following primary infection, herpesviruses establish latency in infected individuals in the host cells and may reactivate upon external stimuli and during periods of immunosuppression. The objective of this paper was to the present current strategies on preventive and therapeutic management of infections with herpesviruses in recipients of hematopoietic cell transplantation. Strategies of antiviral management include prophylaxis, pre-emptive treatment and targeted treatment. Empirical therapy is not used in antiviral strategies. Prophylaxis can be done at universal (preventive strategy) and specific level. Universal prophylaxis includes non-pharmacologic methods of prevention of infection or reactivation. Risk-adapted specific prophylaxis includes use of specific antivirals or cellular therapy or other specific methods in order to prevent specific infection, in high-risk groups. Pre-emptive therapy means use of therapeutic approaches in asymptomatic infection, detected by a screening assay. Targeted therapy is used in established specific viral end-organ infections. The following sections of the paper refer to prophylaxis and treatment strategies, respectively, against CMV, EBV, HSV, VZV, HHV-6, HHV-7, and HHV-8 after allogeneic hematopoietic cell transplantation. Full article

Understanding the role of donor-specific antibodies (DSAs) in liver transplantation remains an investigative priority. Acute and chronic rejection associated with DSAs have been described. However, most transplant protocols did not consider the presence of DSAs at the moment of liver transplantation (LTx) or for the follow-up. A 65-year-old man received an ABO-compatible LTx for cirrhosis. Ten years after the LTx, he presented with a progressive elevation of liver enzymes and bilirubin. The single antigen Luminex bead assay showed the presence of DSAs against several DQ2, DQ7, and DQ8 alleles. The patient received several desensitization treatments regarding the persistence of DSAs. The anatomopathological study confirms chronic rejection. Although in this case the immunohistochemical deposits of C4d were negative, the data revealed morphological criteria of chronic graft injury and DSAs’ incompatibilities explained by structural analysis. These data support an antibody-mediated rejection (AMR). It could be reasonable to establish a protocol for human leukocyte antigen (HLA) typing of every LTx donor and recipient as well as a periodic follow-up to assess the presence of DSAs. This will make it possible to carry out studies of donor–recipient incompatibility and to confirm the existence of probable cases of AMR. Full article