A deeper dive into the impact of multiple‐organ transplant policy on kidney transplant candidate prognoses

Author(s):  
Jesse D. Schold ◽  
Sumit Mohan
Author(s):  
Scott G. Westphal ◽  
Eric D. Langewisch ◽  
Amanda M. Robinson ◽  
Amber R. Wilk ◽  
Jianghu J. Dong ◽  
...  

2021 ◽  
Vol 10 (9) ◽  
pp. 1934
Author(s):  
Domingo Hernández ◽  
Teresa Vázquez ◽  
Juana Alonso-Titos ◽  
Myriam León ◽  
Abelardo Caballero ◽  
...  

The impact of human leukocyte antigen (HLA)-mismatching on the early appearance of subclinical inflammation (SCI) in low-immunological-risk kidney transplant (KT) recipients is undetermined. We aimed to assess whether HLA-mismatching (A-B-C-DR-DQ) is a risk factor for early SCI. As part of a clinical trial (Clinicaltrials.gov, number NCT02284464), a total of 105 low-immunological-risk KT patients underwent a protocol biopsy on the third month post-KT. As a result, 54 presented SCI, showing a greater number of total HLA-mismatches (p = 0.008) and worse allograft function compared with the no inflammation group (48.5 ± 13.6 vs. 60 ± 23.4 mL/min; p = 0.003). Multiple logistic regression showed that the only risk factor associated with SCI was the total HLA-mismatch score (OR 1.32, 95%CI 1.06–1.64, p = 0.013) or class II HLA mismatching (OR 1.51; 95%CI 1.04–2.19, p = 0.032) after adjusting for confounder variables (recipient age, delayed graft function, transfusion prior KT, and tacrolimus levels). The ROC curve illustrated that the HLA mismatching of six antigens was the optimal value in terms of sensitivity and specificity for predicting the SCI. Finally, a significantly higher proportion of SCI was seen in patients with >6 vs. ≤6 HLA-mismatches (62.3 vs. 37.7%; p = 0.008). HLA compatibility is an independent risk factor associated with early SCI. Thus, transplant physicians should perhaps be more aware of HLA mismatching to reduce these early harmful lesions.


2017 ◽  
Vol 101 (9) ◽  
pp. 2213-2217 ◽  
Author(s):  
Lucy Chen ◽  
Lisa Liberatore ◽  
Tom Chin ◽  
Scott Walker ◽  
Helen Fanous ◽  
...  

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Thomas Duflot ◽  
Charlotte Laurent ◽  
Anne Soudey ◽  
Xavier Fonrose ◽  
Mouad Hamzaoui ◽  
...  

AbstractThis study addressed the hypothesis that epoxyeicosatrienoic acids (EETs) synthesized by CYP450 and catabolized by soluble epoxide hydrolase (sEH) are involved in the maintenance of renal allograft function, either directly or through modulation of cardiovascular function. The impact of single nucleotide polymorphisms (SNPs) in the sEH gene EPHX2 and CYP450 on renal and vascular function, plasma levels of EETs and peripheral blood monuclear cell sEH activity was assessed in 79 kidney transplant recipients explored at least one year after transplantation. Additional experiments in a mouse model mimicking the ischemia–reperfusion (I/R) injury suffered by the transplanted kidney evaluated the cardiovascular and renal effects of the sEH inhibitor t-AUCB administered in drinking water (10 mg/l) during 28 days after surgery. There was a long-term protective effect of the sEH SNP rs6558004, which increased EET plasma levels, on renal allograft function and a deleterious effect of K55R, which increased sEH activity. Surprisingly, the loss-of-function CYP2C9*3 was associated with a better renal function without affecting EET levels. R287Q SNP, which decreased sEH activity, was protective against vascular dysfunction while CYP2C8*3 and 2C9*2 loss-of-function SNP, altered endothelial function by reducing flow-induced EET release. In I/R mice, sEH inhibition reduced kidney lesions, prevented cardiac fibrosis and dysfunction as well as preserved endothelial function. The preservation of EET bioavailability may prevent allograft dysfunction and improve cardiovascular disease in kidney transplant recipients. Inhibition of sEH appears thus as a novel therapeutic option but its impact on other epoxyfatty acids should be carefully evaluated.


2021 ◽  
Vol 10 (8) ◽  
pp. 1551
Author(s):  
Marta Bodro ◽  
Frederic Cofan ◽  
Jose Ríos ◽  
Sabina Herrera ◽  
Laura Linares ◽  
...  

In the context of the coronavirus disease 2019 (COVID-19) pandemic, we aimed to evaluate the impact of anti-cytokine therapies (AT) in kidney transplant recipients requiring hospitalization due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. This is an observational retrospective study, which included patients from March to May 2020. An inverse probability of treatment weighting from a propensity score to receive AT was used in all statistical analyses, and we applied a bootstrap procedure in order to calculate an estimation of the 2.5th and 97.5th percentiles of odds ratio (OR). outcomes were measured using an ordinal scale determination (OSD). A total of 33 kidney recipients required hospitalization and 54% of them received at least one AT, mainly tocilizumab (42%), followed by anakinra (12%). There was no statistical effect in terms of intensive care unit (ICU) admission, respiratory secondary infections (35% vs. 7%) or mortality (16% vs. 13%) comparing patients that received AT with those who did not. Nevertheless, patients who received AT presented better outcomes during hospitalization in terms of OSD ≥5 ((OR 0.31; 2.5th, 97.5th percentiles (0.10; 0.72)). These analyses indicate, as a plausible hypothesis, that the use of AT in kidney transplant recipients presenting with COVID-19 could be beneficial, even though multicenter randomized control trials using these therapies in transplanted patients are needed.


2021 ◽  
Vol 10 (9) ◽  
pp. 2005
Author(s):  
Domingo Hernández ◽  
Juana Alonso-Titos ◽  
Teresa Vázquez ◽  
Myriam León ◽  
Abelardo Caballero ◽  
...  

The impact of corticosteroid withdrawal on medium-term graft histological changes in kidney transplant (KT) recipients under standard immunosuppression is uncertain. As part of an open-label, multicenter, prospective, phase IV, 24-month clinical trial (ClinicalTrials.gov, NCT02284464) in low-immunological-risk KT recipients, 105 patients were randomized, after a protocol-biopsy at 3 months, to corticosteroid continuation (CSC, n = 52) or corticosteroid withdrawal (CSW, n = 53). Both groups received tacrolimus and MMF and had another protocol-biopsy at 24 months. The acute rejection rate, including subclinical inflammation (SCI), was comparable between groups (21.2 vs. 24.5%). No patients developed dnDSA. Inflammatory and chronicity scores increased from 3 to 24 months in patients with, at baseline, no inflammation (NI) or SCI, regardless of treatment. CSW patients with SCI at 3 months had a significantly increased chronicity score at 24 months. HbA1c levels were lower in CSW patients (6.4 ± 1.2 vs. 5.7 ± 0.6%; p = 0.013) at 24 months, as was systolic blood pressure (134.2 ± 14.9 vs. 125.7 ± 15.3 mmHg; p = 0.016). Allograft function was comparable between groups and no patients died or lost their graft. An increase in chronicity scores at 2-years post-transplantation was observed in low-immunological-risk KT recipients with initial NI or SCI, but CSW may accelerate chronicity changes, especially in patients with early SCI. This strategy did, however, improve the cardiovascular profiles of patients.


2020 ◽  
Vol 10 (3) ◽  
pp. 174-179
Author(s):  
Flaviu Tosa ◽  
Roxana Manaila ◽  
Alina Elec ◽  
Tudor Moisoiu ◽  
Liviu Ghervan ◽  
...  

As coronavirus disease 2019 (COVID-19) caused by the novel virus SARS-CoV-2 is expanding worldwide, kidney involvement seems to be part of the spectrum of its effects. Moreover, the prognosis of the disease seems to be worse in immunocompromised patients when compared to the general population, with 4–5 times higher mortality rates. However, the overall impact on long-term function of the kidney graft is unknown. We report on a case of a 46-year-old kidney transplant recipient who was successfully treated for severe COVID-19 pneumonia. The clinical course was complicated by transient acute kidney injury, most likely due to tubulo-interstitial involvement, with return to the baseline of the creatinine level by the time of discharge. We discuss the characteristics and differential diagnosis of acute kidney injury, as well as management of immunosuppression in connection with overall clinical status and evolution of kidney function. The case is illustrative for dilemmas that transplant professionals may face in the absence of evidence-based, efficient COVID-19 therapy. The risk-benefit balance of the yet to be approved treatment strategies may be weighed differently in organ transplant recipients owing to their immunocompromised status and potential drug interactions with immunosuppressive therapy.


2021 ◽  
Vol 7 (5) ◽  
pp. 327
Author(s):  
Nipat Chuleerarux ◽  
Achitpol Thongkam ◽  
Kasama Manothummetha ◽  
Saman Nematollahi ◽  
Veronica Dioverti-Prono ◽  
...  

Background: Cytomegalovirus (CMV) and invasive aspergillosis (IA) cause high morbidity and mortality in solid organ transplant (SOT) recipients. There are conflicting data with respect to the impact of CMV on IA development in SOT recipients. Methods: A literature search was conducted from existence through to 2 April 2021 using MEDLINE, Embase, and ISI Web of Science databases. This review contained observational studies including cross-sectional, prospective cohort, retrospective cohort, and case-control studies that reported SOT recipients with post-transplant CMV (exposure) and without post-transplant CMV (non-exposure) who developed or did not develop subsequent IA. A random-effects model was used to calculate the pooled effect estimate. Results: A total of 16 studies were included for systematic review and meta-analysis. There were 5437 SOT patients included in the study, with 449 SOT recipients developing post-transplant IA. Post-transplant CMV significantly increased the risk of subsequent IA with pORs of 3.31 (2.34, 4.69), I2 = 30%. Subgroup analyses showed that CMV increased the risk of IA development regardless of the study period (before and after 2003), types of organ transplantation (intra-thoracic and intra-abdominal transplantation), and timing after transplant (early vs. late IA development). Further analyses by CMV definitions showed CMV disease/syndrome increased the risk of IA development, but asymptomatic CMV viremia/infection did not increase the risk of IA. Conclusions: Post-transplant CMV, particularly CMV disease/syndrome, significantly increased the risks of IA, which highlights the importance of CMV prevention strategies in SOT recipients. Further studies are needed to understand the impact of programmatic fungal surveillance or antifungal prophylaxis to prevent this fungal-after-viral phenomenon.


Author(s):  
Zana Stanic ◽  
Marko Vulic ◽  
Zlatko Hrgovic ◽  
Rajko Fureš ◽  
Milvija Plazibat ◽  
...  

AbstractThe majority of patients with simultaneous pancreas and kidney transplant (SPKT) required transplantation owing to a long-standing history of insulin-dependent diabetes mellitus (IDDM). The disease causes multiple organ damage, impairs fertility, and affects quality of life. A successful kidney and pancreas transplant can improve health, ameliorate the consequences of pre-existent diabetes, and restore fertility. Good graft function, without any sign of rejection, and stable doses of immunosuppressant drugs are of utmost importance prior to the planned pregnancy. SPKT recipients who become pregnant may be at an increased risk for an adverse outcome and require meticulous multidisciplinary surveillance. We present experiences with SPKT pregnancies, traditional approaches, and recent considerations. In light of complex interactions between new anatomic relations and the impact of developing pregnancy and immunosuppressive medications, special stress is put on the risk of graft rejection, development of pregnancy complications, and potential harmful effects on fetal development. Recent recommendations in management of SPKT recipients who wish to commence pregnancy are presented as well. Key words: transplantation, pregnancy, pancreas, kidney, simultaneous pancreas and kidney transplantation (SPKT)


2019 ◽  
Vol 103 (6) ◽  
pp. 1267-1271 ◽  
Author(s):  
Jessica M. Ruck ◽  
Annette M. Jackson ◽  
Allan B. Massie ◽  
Dorry L. Segev ◽  
Niraj Desai ◽  
...  

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