世界移植杂志(英文版)最新文献

The second half of the previous century witnessed a tremendous rise in the number of clinical kidney transplants worldwide. This activity was, however, accompanied by many issues and challenges. An accurate diagnosis and appropriate management of causes of graft dysfunction were and still are, a big challenge. Kidney allograft biopsy played a vital role in addressing the above challenge. However, its interpretation was not standardized for many years until, in 1991, the Banff process was started to fill this void. Thereafter, regular Banff meetings took place every 2 years for the past 30 years. Marked changes have taken place in the interpretation of kidney allograft biopsies, diagnosis, and classification of rejection and other non-rejection pathologies from the original Banff 93 classification. This review attempts to summarize those changes for increasing the awareness and understanding of kidney allograft pathology through the eyes of the Banff process. It will interest the transplant surgeons, physicians, pathologists, and allied professionals associated with the care of kidney transplant patients.

Renal transplantation is the treatment of choice for end stage kidney disease. However, despite all the efforts to expand the donor pool, the shortage of donors is increasing and as a consequence, there has been a significant increase in the number of patients on transplant waiting lists globally. Societies worldwide have employed different methods to address this, each with specific ethical concerns surrounding them. Over three decades ago, a governmentally regulated program of kidney transplantation from living unrelated donors was introduced in Iran and since practiced which has been the subject of hot debate in the literature. Nevertheless, despite all these extensive discussions and publications, several key aspects of the program have still not been properly elucidated and addressed. In this article, the author aims to illuminate some dark corners related to this issue that have largely escaped the notice of ethicists.

Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are novel oral hypoglycemic agents garnering much attention for their substantial benefits. These recent data have positioned SGLT2i at the forefront of diabetic chronic kidney disease (CKD) and heart failure management. SGLT2i use post-kidney transplant is an emerging area of research. Highlights from this mini review include the following: Empagliflozin is the most prescribed SGLT2i in kidney transplant recipients (KTRs), median time from transplant to initiation was 3 years (range: 0.88-9.6 years). Median baseline estimated glomerular filtration rate (eGFR) was 66.7 mL/min/1.73 m² (range: 50.4-75.8). Median glycohemoglobin (HgbA1c) at initiation was 7.7% (range: 6.9-9.3). SGLT2i were demonstrated to be effective short-term impacting HgbA1c, eGFR, hemoglobin/hematocrit, serum uric acid, and serum magnesium levels. They are shown to be safe in KTRs with low rates of infections, hypoglycemia, euglycemic diabetic ketoacidosis, and stable tacrolimus levels. More data is needed to demonstrate long-term outcomes. SGLT2i appear to be safe, effective medications for select KTRs. Our present literature, though limited, is founded on precedent robust research in CKD patients with diabetes. Concurrent research/utilization of SGLT2i is vital to not only identify long-term patient, graft and cardiovascular outcomes of these agents, but also to augment management in KTRs.

Background: Although the availability of related living donors (LDs) provides a better chance for receiving kidney transplantation (KT), the evaluation protocols for LD selection remain a safeguard for the LD's safety. These protocols are variable from one center to another, resulting in variable rates of decline of the potential LDs (PLDs). The decline of willing PLDs may occur at any stage of evaluation, starting from the initial contact and counseling to the day of operation.

Aim: To identify the causes of the decline of PLDs, the predictors of PLD candidacy, and the effect on achieving LDKT.

Methods: A retrospective study was performed on the willing PLDs who attended our outpatient clinic for kidney donation to their related potential recipients between October 2015 and December 2022. The variables influencing their candidacy rate and the fate of their potential recipients were studied. Two groups of PLDs were compared: Candidate PLDs after a completed evaluation vs non-candidate PLDs with a complete or incomplete evaluation. A multivariate logistic regression was performed to assess the factors contributing to the achievement of PLD candidacy.

Results: Of 321 willing PLDs, 257 PLDs (80.1%) accessed the evaluation to variable extents for 212 potential recipients, with a mean age (range) of 40.5 ± 10.4 (18-65) years, including 169 females (65.8%). The remaining 64 PLDs (19.9%) did not access the evaluation. Only 58 PLDs (18.1%) succeeded in donating, but 199 PDLs (62.0%) were declined; exclusion occurred in 144 PLDs (56.0%) for immunological causes (37.5%), medical causes (54.9%), combined causes (9.7%), and financial causes (2.1%). Regression and release occurred in 55 PLDs (17.1%). The potential recipients with candidate PLDs were not significantly different from those with non-candidate PLDs, except in age (P = 0.041), rates of completed evaluation, and exclusion of PLDs (P < 0.001). There were no factors that independently influenced the rate of PLD candidacy. Most patients who failed to have KT after the decline of their PLDs remained on hemodialysis for 6 mo to 6 years.

Conclusion: The rate of decline of willing related PLDs was high due to medical or immunological contraindications, release, or regression of PLDs. It reduced the chances of high percentages of potential recipients in LDKT.

Background: Infections, including invasive fungal infections (IFIs), are among the leading causes of mortality in liver transplant recipients during the first year post-transplantation.

Aim: To investigate the epidemiology, clinical manifestations, risk factors, treatment outcomes, and mortality rate of post-liver transplantation invasive aspergillosis (IA).

Methods: In this case-control study, 22 patients with IA were identified by reviewing the archived and electronic medical records of 850 patients who received liver transplants at the Imam Khomeini Hospital complex in Tehran, Iran, between 2014 and 2019. The control group comprised 38 patients without IA infection matched for age and sex. The information obtained included the baseline characteristics of liver transplant patients, operative reports, post-transplantation characteristics of both groups and information about the fungal infection of the patient group.

Results: The prevalence rate of IA among liver transplant recipients at Imam Khomeini Hospital was 2.7%. The risk factors of IA among studied patients included high serum creatinine levels before and post-transplant, renal replacement therapy, antithymocyte globulin induction therapy, post-transplant bile leakage, post-transplant hepatic artery thrombosis, repeated surgery within 30 d after the transplant, bacterial pneumonia before the aspergillosis diagnosis, receiving systemic antibiotics before the aspergillus infection, cytomegalovirus infection, and duration of post-transplant hospitalization in the intensive care unit. The most prevalent form of infection was invasive pulmonary aspergillosis, and the most common chest computed tomography scan findings were nodules, pleural effusion, and the halo sign. In the case group, prophylactic antifungal therapy was administered more frequently than in the control group. The antifungal therapy response rate at 12 wk was 63.7%. The 3- and 12- mo mortality rates of the patients with IA were 36.4% and 45.4%, respectively (compared with the mortality rate of the control group in 12 mo, which was zero).

Conclusion: In this study, the prevalence of IA among liver transplant recipients was relatively low. However, it was one of the leading causes of mortality following liver transplantation. Targeted antifungal therapy may be a factor in the low incidence of infections at our facility. Identifying the risk factors of IFIs, maintaining an elevated level of clinical suspicion, and initiating early antifungal treatment may significantly improve the prognosis and reduce the mortality rate of liver transplant recipients.

Background: Blood transfusion is common during the peri-transplantation period. The incidence of immunological reactions to blood transfusion after kidney tran splantation and their consequences on graft outcomes have not been extensively studied.

Aim: To examine the risk of graft rejection and loss in patients who received blood transfusion in the immediate peri-transplantation period.

Methods: We conducted a single-center retrospective cohort study of 105 kidney recipients, among them 54 patients received leukodepleted blood transfusion at our center between January 2017 and March 2020.

Results: This study included 105 kidney recipients, of which 80% kidneys were from living-related donors, 14% from living-unrelated donors, and 6% from deceased donors. Living-related donors were mostly first-degree relatives (74.5%), while the rest were second-degree relatives. The patients were divided into transfusion (n = 54) and non-transfusion (n = 51) groups. The average hemoglobin level at which blood transfusion was commenced was 7.4 ± 0.9 mg/dL. There were no differences between the groups in terms of rejection rates, graft loss, or death. During the study period, there was no significant difference in creatinine level progression between the two groups. Delayed graft function was higher in the transfusion group; however, this finding was not statistically significant. A high number of transfused packed red blood cells was significantly associated with increased creatinine levels at the end of the study.

Conclusion: Leukodepleted blood transfusion was not associated with a higher risk of rejection, graft loss, or death in kidney transplant recipients.

Background: Gastroesophageal reflux (GER) has been associated with poor outcomes after lung transplantation for chronic lung disease, including increased risk of chronic rejection. GER is common in cystic fibrosis (CF), but factors influencing the likelihood of pre-transplant pH testing, and the impact of testing on clinical management and transplant outcomes in patients with CF are unknown.

Aim: To evaluate the role of pre-transplant reflux testing in the evaluation of lung transplant candidates with CF.

Methods: This was a retrospective study from 2007-2019 at a tertiary medical center that included all patients with CF undergoing lung transplant. Patients with pre-transplant anti-reflux surgery were excluded. Baseline characteristics (age at transplantation, gender, race, body mass index), self-reported GER symptoms prior to transplantation, and pre-transplant cardiopulmonary testing results, were recorded. Reflux testing consisted of either 24-h pH- or combined multichannel intraluminal impedance and pH monitoring. Post-transplant care included a standard immunosuppressive regimen, and regular surveillance bronchoscopy and pulmonary spirometry in accordance with institutional practice as well as in symptomatic patients. The primary outcome of chronic lung allograft dysfunction (CLAD) was defined clinically and histologically per International Society of Heart and Lung Transplantation criteria. Statistical analysis was performed with Fisher's exact test to assess differences between cohorts, and time-to-event Cox proportional hazards modeling.

Results: After applying inclusion and exclusion criteria, a total of 60 patients were included in the study. Among all CF patients, 41 (68.3%) completed reflux monitoring as part of pre-lung transplant evaluation. Objective evidence of pathologic reflux, defined as acid exposure time > 4%, was found in 24 subjects, representing 58% of the tested group. CF patients with pre-transplant reflux testing were older (35.8 vs 30.1 years, P = 0.01) and more commonly reported typical esophageal reflux symptoms (53.7% vs 26.3%, P = 0.06) compared to those without reflux testing. Other patient demographics and baseline cardiopulmonary function did not significantly differ between CF subjects with and without pre-transplant reflux testing. Patients with CF were less likely to undergo pre-transplant reflux testing compared to other pulmonary diagnoses (68% vs 85%, P = 0.003). There was a decreased risk of CLAD in patients with CF who underwent reflux testing compared to those who did not, after controlling for confounders (Cox Hazard Ratio 0.26; 95%CI: 0.08-0.92).

Conclusion: Pre-transplant reflux testing revealed high prevalence of pathologic reflux in CF patients and was associated with decreased risk of CLAD. Systematic reflux testing may enhance outcomes in this

Background: Indications to refer patients with cirrhosis for liver transplant evaluation (LTE) include hepatic decompensation or a model for end stage liver disease (MELD-Na) score ≥ 15. Few studies have evaluated how delaying referral beyond these criteria affects patient outcomes.

Aim: To evaluate clinical characteristics of patients undergoing inpatient LTE and to assess the effects of delayed LTE on patient outcomes (death, transplantation).

Methods: This is a single center retrospective cohort study assessing all patients undergoing inpatient LTE (n = 159) at a large quaternary care and liver transplant center between 10/23/2017-7/31/2021. Delayed referral was defined as having prior indication (decompensation, MELD-Na ≥ 15) for LTE without referral. Early referral was defined as referrals made within 3 mo of having an indication based on practice guidelines. Logistic regression and Cox Hazard Regression were used to evaluate the relationship between delayed referral and patient outcomes.

Results: Many patients who require expedited inpatient LTE had delayed referrals. Misconceptions regarding transplant candidacy were a leading cause of delayed referral. Ultimately, delayed referrals negatively affected overall patient outcome and an independent predictor of both death and not receiving a transplant. Delayed referral was associated with a 2.5 hazard risk of death.

Conclusion: Beyond initial access to an liver transplant (LT) center, delaying LTE increases risk of death and reduces risk of LT in patients with chronic liver disease. There is substantial opportunity to increase the percentage of patients undergoing LTE when first clinically indicated. It is crucial for providers to remain informed about the latest guidelines on liver transplant candidacy and the transplant referral process.

Background: Warts are common in recipients of kidney transplantation (KT). Resistant warts which are not amenable to conventional therapies may lead to significant mor bidity. Limited data exists on safety and efficacy of local immunotherapy among immunocompromised KT recipients.

Case summary: We report a seven-year-old child who presented with recalcitrant plantar per iungual warts in the early KT period. Immunosuppression consisted of tacrolimus, mycophenolate and steroid. Due to failure of conventional anti-wart therapies, he was treated with two sessions of intralesional (IL) candida immunotherapy along with liquid nitrogen cryotherapy leading to complete resolution of the warts. Interestingly, de novo BK viremia was seen about three weeks following the last candida immunotherapy. This required reduction of immu nosuppression and other anti-BK viral therapies. Allograft function remained stable but there were donor specific antibodies detected. There also was elevated level of plasma donor derived cell-free DNA. A pneumocystis jirovecii pneumonia occurred ten months following completion of immunotherapy that was successfully treated with trimethoprim-sulfamethoxazole. During this ten-month follow-up period, there have been no recurrence of warts, and transplant kidney function has remained stable.

Conclusion: Stimulation of cell-mediated immunity against the human papilloma virus induced by the IL candida immunotherapy is thought to be a cause for wart resolution. With this therapy, whether it is necessary to augment the immunosuppression to prevent rejection is unclear as that may come with a risk of infectious complications. Larger, prospective studies in pediatric KT recipients are needed to explore these important issues.

Background: In brain death donors (BDDs), donor management is the key in the complex donation process. Donor management goals, which are standards of care or clinical parameters, have been considered an acceptable barometer of successful donor management.

Aim: To test the hypothesis that aetiology of brain death could influence haemody namic management in BDDs.

Methods: Haemodynamic data (blood pressure, heart rate, central venous pressure, lactate, urine output, and vasoactive drugs) of BDDs were recorded on intensive care unit (ICU) admission and during the 6-h observation period (Time 1 at the beginning; Time 2 at the end).

Results: The study population was divided into three groups according to the aetiology of brain death: Stroke (n = 71), traumatic brain injury (n = 48), and postanoxic encephalopathy (n = 19). On ICU admission, BDDs with postanoxic encephalopathy showed the lowest values of systolic and diastolic blood pressure associated with higher values of heart rate and lactate and a higher need of norepinephrine and other vasoactive drugs. At the beginning of the 6-h period (Time 1), BDDs with postanoxic encephalopathy showed higher values of heart rate, lactate, and central venous pressure together with a higher need of other vasoactive drugs.

Conclusion: According to our data, haemodynamic management of BDDs is affected by the aetiology of brain death. BDDs with postanoxic encephalopathy have higher requirements for norepinephrine and other vasoactive drugs.