Mortality In Kidney Transplant Recipients Research Articles

Increased Mortality in Kidney Transplant Recipients During the Delta/Omicron Era of the COVID-19 Pandemic Despite Widespread Vaccination.

The incidence of mortality late in the pandemic, particularly after widespread vaccine availability, is not well understood. Herein, we elucidate the effect of this impact of the COVID pandemic as well as risk factors for mortality during it. The primary end point was death with a functioning graft with secondary endpoints of mortality rates in subgroups and at different time intervals during the pandemic. Despite widespread vaccination, mortality rates for kidney transplant (KTx) recipients almost doubled during the COVID-19 era (6.40 deaths per 100 person years vs. 3.54 pre-COVID). Mortality increased in all racial/ethnic groups but increased more in Native Americans, Hispanics, and African Americans compared to non-Hispanic Caucasians. The highest mortality rate occurred during the Delta and Omicron time frames. In contrast to the general population, mortality was more evenly spread across age groups in KTx recipients. Mortality rates during the COVID-19 era were extremely high, more than doubling in some racial/ethnic groups. We conclude that the KTx population was a particularly vulnerable group during the COVID-19 era and suggests the need for further research into the management of variants in the future.

Low 25-Hydroxyvitamin D Post-Kidney Transplant Is Associated with Increased Risk of BK Polyomavirus-Associated Nephropathy.

BK viremia (BKPyV-DNAemia) and nephropathy (BKPyVAN) are significant causes of morbidity and mortality in kidney transplant recipients (KTRs). Vitamin D supports immune function, yet low 25-hydroxyvitamin D [25(OH)D] is common among KTRs. The association between serum 25(OH)D, measured 61 days to 2 years post-transplant, and subsequent incident BKPyV-DNAemia and BKPyVAN was examined in KTRs without previous BKPyV-DNAemia or BKPyVAN, respectively. Out of 3308 KTRs, 399 (12%) were vitamin D deficient [25(OH)D ≤ 20 ng/mL], and 916 (27.7%) were insufficient [25(OH)D 21-29 ng/mL]. A total of 184 KTRs developed BKPyV-DNAemia and 44 developed BKPyVAN. The incidence rate (/100 person-years) for BKPyV-DNAemia was 2.88 in the 25(OH)D sufficient group, 2.22 in the insufficient group, and 2.37 in the deficient group. The incidence rate (/100 person-years) for BKPyVAN was 0.30 in the 25(OH)D sufficient group, 0.75 in the insufficient group, and 1.28 in the deficient group. Vitamin D deficiency (adjusted hazard ratio [aHR] compared to 25(OH)D sufficiency: 3.92; 95% CI: 1.66-9.23) and insufficiency (aHR: 2.22; 95% CI: 1.11-4.45) remained significantly associated with the incidence of BKPyVAN after adjustment for baseline characteristics. Low serum 25(OH)D was associated with an increased risk of BKPyVAN but not BKPyV-DNAemia.

Continuous Glucose Monitoring for the Diagnosis of Post-Transplantation Diabetes Mellitus and Impaired Glucose Tolerance From Years One to Five After Kidney Transplantation-A Prospective Pilot Study.

Post-transplantation diabetes mellitus (PTDM) and prediabetes are associated with increased cardiovascular morbidity and mortality in kidney transplant recipients (KTR), when diagnosed by an oral glucose tolerance test (oGTT). Hemoglobin A1c (HbA1c) and fasting plasma glucose (FPG) display low concordance with the oGTT in the early phase posttransplant. For this prospective cross-sectional pilot study, 41 KTR from years one to five after transplantation without known preexisting PTDM (defined by HbA1c ≥ 6.5% (NGSP) or 48mmol/mol (IFCC) at last visit or glucose-lowering therapy) were recruited at the Charité Transplant Outpatient Clinic. For each study participant HbA1c, FPG and an oGTT were followed by CGM. 38 of the 41 patients recruited had sufficient CGM-recordings (≥10days). PTDM and impaired glucose tolerance (IGT), as defined by the gold standard oral glucose tolerance test (oGTT)-derived 2-h plasma glucose (2hPG), were diagnosed in one (3%) and twelve (32%) patients, respectively. HbA1c exhibited good test characteristics regarding IGT (ROC-AUC: 0.87); sensitivity/specificity of HbA1c-threshold 5.7% (NGSP) or 39mmol/mol (IFCC) were 1.0/0.64, respectively. Best performing CGM-readouts mean sensor glucose and percent of time >140mg/dL (%TAR (140mg/dL)) displayed acceptable diagnostic performance (ROC-AUC: 0.78 for both). Thus, HbA1c can aid in timely diagnosis of IGT in the stable phase after kidney transplantation.

The use of myocardial perfusion scintigraphy to screen for asymptomatic coronary artery disease prior to kidney transplantation

Abstract Background and Objectives Advanced chronic kidney disease (CKD) is associated with an increased risk of cardiovascular disease (CVD), including significant asymptomatic coronary artery disease (CAD) [1], compared to the general general public. Additionally, CVD is the leading cause of mortality in kidney transplant recipients [2]. Given the relative scarcity of available organs, individuals are commonly screened for CAD with non-invasive cardiac testing such as Myocardial Perfusion Scintigraphy (MPS). However, the benefits of screening for asymptomatic CAD are unproven and in the absence of an established screening protocol, investigations vary centre to centre and can result in uncertain interpretation of results and unnecessary delays in transplantation. The objective of this study was to assess the benefits of asymptomatic CVD screening of potential kidney transplant recipients, and its impact on transplantation outcomes. Methods This retrospective analysis included all MPS requested by the transplant team during patients’ assessment process between 2015 and 2023. Any resultant coronary angiograms (CA) were reviewed for evidence of significant CAD. Transplant decisions were reviewed to assess the impact of CVD screening on individuals’ transplant status. Results 689 individuals underwent MPS. Of these, 90% required no further cardiovascular investigations. 6% (42 individuals) had subsequent CA. <1% (5) required percutaneous intervention (PCI) whilst the rest (37) were deemed to have no significant CAD. A further 4% (29) required coronary angiography at a later date (>2 years after their MPS), with similar rates of PCI (1%). All three outcome groups (negative MPS, CA referral, CA in the future) had similar rates of diabetes (40%) and previous diagnoses of CAD (14%). The average wait for CA was 283 days post-MPS. Transplant decisions took a further 286 days after CA, which in combination with the delays associated with CA resulted in average delays of 1.5 years. Conclusions The use of MPS to screen for significant asymptomatic CAD identifies only a small proportion of individuals requiring intervention prior to kidney transplantation and significantly delays transplant decisions. These results suggest transplant centres should review their use of CVD screening prior to listing.

Analysis of the Correlation between Hypercholesterolemia and Increased Cardiovascular Morbidity and Mortality among Adult Kidney Transplant Recipients

Introduction: The correlation between hypercholesterolemia and cardiovascular disease in kidney transplant recipients (KTRs) remains uncertain. We sought to characterize the association between abnormal cholesterol profiles and cardiovascular morbidity and mortality in this unique population. Methods: This retrospective cohort study was conducted at a single center and included all adult KTR, transplanted between January 2005 and April 2014. The primary outcome was major adverse cardiovascular events (MACE) while the secondary outcome was the composite outcome of MACE and all-cause mortality. Exposure to abnormal cholesterol levels was calculated using a time-weighted average calculation. MACE and mortality risk were analyzed using a multivariate time-varying Cox model. Results: The final cohort comprised 737 KTR, with a median follow-up of 2,920 days. A total of 126 patients (17.1%) experienced MACE. High LDL-C levels and MACE risk were correlated by multivariate analysis (HR 1.008 per mg/dL, 95% CI: 1.001–1.016), while low HDL-C levels were not significantly associated with MACE (HR 0.992 per mg/dL, 95% CI: 0.976–1.009). A higher LDL-C/HDL-C ratio was significantly associated with an increased risk of MACE in multivariate analyses (HR 1.502 per unit, 95% CI: 1.147–1.968), and also correlated with the composite outcome (HR 1.35 per unit, 95% CI: 1.06–1.71). Conclusions: A high LDL-C/HDL-C ratio is predictive of an increased risk of cardiovascular morbidity and mortality in KTRs. These findings emphasize the significance of the LDL-C/HDL-C ratio as a valuable marker of cardiovascular risk and support current recommendations to improve hypercholesterolemia in this high-risk group.

The effectiveness of nirmatrelvir/ritonavir regimen in hospitalized renal transplant patients with prolonged COVID-19 infection: a multicenter clinical experience

Objectives Effectiveness of nirmatrelvir/ritonavir (NR) in kidney transplant recipients (KTRs) infected COVID-19 for more than 5 days has not been evaluated. Methods In this multicenter retrospective study, 85 KTRs with COVID-19 were enrolled, including 50 moderate, 21 severe, and 14 critical patients. Results The median time from onset to starting NR treatment was 14 (IQR, 11–19) days. Before NR treatment, 96.5% patients reduced use of antimetabolites. They also stopped using calcineurin inhibitors (CNI) 12–24 hours before NR treatment, with CNI concentrations well-controlled during NR treatment. The use of intravenous corticosteroids increased with COVID-19 severity. The median time to reach viral negative conversion was 5 (IQR, 4–8) days for all patients. For moderate and severe COVID-19 patients, they had a low rate of ICU admission (1.4%), exacerbation requiring upgraded oxygen therapy (5.6%), and dialysis (2.8%); no intubation and mechanical ventilation, and no deaths were observed. Patients with critical COVID-19 had a low mortality rate (7.1%). Conclusions A regimen including NR for clearing SARS-CoV-2 along with reducing immunosuppressants and using intravenous corticosteroids is associated with lower rates of exacerbation and mortality in KTRs who have moderate to critical SARS-CoV-2 infection and the virus still present after 5 days.

P.237: Association between estimated glomerular filtration rates at initiation of dialysis and all-cause mortality in kidney transplant recipients with a failing kidney allograft.

P.237: Association between estimated glomerular filtration rates at initiation of dialysis and all-cause mortality in kidney transplant recipients with a failing kidney allograft.

Sarcopenia as a predictor of mortality in kidney transplant recipients: A 5-year prospective cohort study with propensity score matching.

Sarcopenia is known to bring about adverse outcomes in elderly populations and dialysis patients. However, whether it is a risk factor in kidney transplant recipients (KTRs) has not yet been established. In the present study, the association of sarcopenia with mortality was investigated in KTRs. We conducted a single-center prospective cohort study and recruited KTRs who were more than 1-year posttransplant from August 2017 to January 2018. The participants were followed for 5 years, and the Kaplan-Meier method and Cox proportional hazards model were used to assess patient survival. A total of 212 KTRs with a median age of 54 years and median transplant vintage of 79 months were enrolled in this study. Among them, 33 (16%) had sarcopenia according to the Asia Working Group for Sarcopenia 2019 at baseline. During the 5-year follow-up period, 20 (9.4%) died, 5 returned to dialysis after graft loss, and 4 were lost to follow-up. The 5-year overall survival rate was 90%. After 1:1 propensity score matching, a matched cohort with 60 KTRs was generated. The overall survival rate was significantly lower in the sarcopenia group compared to the non-sarcopenia group (p = 0.025, log-rank test). Furthermore, mortality risk was significantly higher in the sarcopenia group compared to the non-sarcopenia group (hazard ratio = 7.57, 95% confidence interval = 0.94-62). Sarcopenia was a predictor of mortality in KTRs. KTRs with suboptimal muscle status who were at risk for poor survival could have a clinical benefit by interventions for sarcopenia.

Establishing targets for goal-directed anesthesia in renal transplantation: A cohort analysis of high-saliency surgical time courses

Delayed graft function (DGF) increases morbidity and mortality in kidney transplant recipients. Operative parameters, including hemodynamic manipulation through vasopressors and fluids, can impact perfusion to the newly transplanted kidney and influence DGF incidence. We analyzed intraoperative time-series data in 5-minute intervals from kidney transplant recipient operations (N = 545) in conjunction with pretransplant characteristics and postsurgical outcomes, including DGF incidence, 60-day creatinine, and graft survival. Of the operations, 127 DGF events were captured in our cohort from a single academic transplant center (57/278 donations after brainstem death [DBDs], 65/150 donations after circulatory/cardiac death [DCDs], 5/117 live donations). In multiple regression, postanastomosis hypotension defined as mean arterial pressure (MAP) <75 mmHg was a risk factor for DGF independent of conventional predictors of DGF in DCD and DBD kidneys. DCD recipients with DGF had lower average postanastomosis MAP (DGF: 80.1 ± 8.1 mmHg vs no DGF: 76.4 ± 6.7 mmHg, P = .004). Interaction analysis demonstrated above-average doses of vasopressors and crystalloids were associated with improved outcomes when used at MAPs ≤75 mmHg, but they were associated with increased DGF at MAPs >75 mmHg, suggesting that the incidence of DGF can be highly influenced by intraoperative hemodynamic controls. This analysis of surgical time courses has identified potential new strategies for goal-directed anesthesia in renal transplantation.

Vitamin C deficiency after kidney transplantation: a cohort and cross-sectional study of the TransplantLines biobank

PurposeVitamin C deficiency is associated with excess mortality in kidney transplant recipients (KTR). We aim to evaluate plasma vitamin C status at different post-transplantation moments and assess the main characteristics associated with vitamin C deficiency in KTR.MethodsPlasma vitamin C was assessed in 598 KTR at 3-, 6-, 12-, 24-, and 60-months post-transplantation, 374 late KTR with a functioning graft ≥ 1 year, and 395 potential donors. Vitamin C deficiency was defined as plasma vitamin C ≤ 28 µmol/L. Diet was assessed by a 177-item food frequency questionnaire. Data on vitamin C-containing supplements use were extracted from patient records and verified with the patients.ResultsVitamin C deficiency ranged from 46% (6-months post-transplantation) to 30% (≥ 1 year post-transplantation). At all time points, KTR had lower plasma vitamin C than potential donors (30–41 µmol/L vs 58 µmol/L). In cross-sectional analyses of the 953 KTR at their first visit ≥ 12 months after transplantation (55 ± 14 years, 62% male, eGFR 55 ± 19 mL/min/1.73 m2), the characteristics with the strongest association with vitamin C deficiency were diabetes and smoking (OR 2.67 [95% CI 1.84–3.87] and OR 1.84 [95% CI 1.16–2.91], respectively). Dietary vitamin C intake and vitamin C supplementation were associated with lower odds (OR per 100 mg/day 0.38, 95% CI 0.24–0.61 and OR 0.21, 95% CI 0.09–0.44, respectively).ConclusionVitamin C deficiency is frequent among KTR regardless of the time after transplantation, especially among those with diabetes and active smokers. The prevalence of vitamin C deficiency was lower among KTR with higher vitamin C intake, both dietary and supplemented. Further research is warranted to assess whether correcting this modifiable risk factor could improve survival in KTR.

#2913 The malignancy in transplant recipients exposed to immunosuppressive therapy prior kidney transplantation

Abstract Background and Aims Post-transplant malignancy has a negative effect on morbidity and mortality of kidney transplant recipients (KTR). Pre-transplant exposure to immunosuppression (PTI) might increase the risk for post-transplant malignancy. Method In a single-center, retrospective study of 3874 KTR transplanted between January 2000 and December 2019 with follow-up until 2020 the cancer incidence and outcome were compared between KTR with glomerulonephritis as primary kidney disease treated with PTI (GN group) and KTR with polycystic kidney disease as non-PTI-receiving controls (PKD group). Results In both groups, the average time from transplantation to cancer manifestation was similar (p=0.947) as well as from cancer diagnosis to death (p=0.856). Depending on cancer type we observed no difference between time of onset (p=0.351) but in incidence rate for death. The worst survival probability was in lung (0.041 years, 95% confidence interval (CI) [0.014-0.301]) and gastrointestinal (0.350 years, 95% CI [0.022-1.558]) cancer. The risk of cancer increased with age (hazard ratio (HR)=1.05, 95% CI [1.03, 1.07], p&amp;lt;0.001). After adjustment, GN increased the risk for post-transplant cancer (HR=1.72, 95% CI [1.12, 2.63], p=0.013). PTI exposure had adjusted increase of risk of cancer (HR=1.76, 95% CI [1.07, 2.89], p=0.027). Posttransplant malignancy was associated with higher risk of death (HR=8.29, 95% CI [5.46, 12.59], p&amp;lt;0.001) together with patient's age at the time of transplant surgery (HR=1.09, 95% CI [1.06, 1.11], p&amp;lt;0.001) while neither gender (p=0.633) nor PTI (=0.0639). Patient's adjusted probability of remaining cancer-free posttransplant had decreasing tendency over time. Conclusion Patients with GN exposed to PTI showed higher adjusted risk of development of post-transplant malignancy.

#801 Impact of delayed graft function on cardiovascular events in kidney transplant recipients

Abstract Background and Aims Acute kidney injury (AKI) increases long-term cardiovascular risk in non-transplanted patients. Delayed graft function (DGF) mimics AKI in kidney transplant recipients, yet its impact on their cardiovascular risk remains unclear. Method We investigated the impact of DGF on cardiovascular morbidity and mortality in kidney transplant recipients using data from patients across 17 French centres from the Astre and Divat cohorts. Included patients were aged 18 years or older, transplanted between 2008 and 2022, with follow-up until 31/03/2023. DGF was defined as the need for hemodialysis within the first week following renal transplantation. The primary outcome was the impact of DGF on the occurrence of a cardiovascular event (composite endpoint including cardiovascular death, coronary artery disease, stroke, heart failure), adjusted for conventional cardiovascular risk factors and glomerular filtration rate at 3 months. Analyses were performed using univariate and multivariate Cox models. Results Among the 19, 837 patients transplanted during the inclusion period, 3, 794 experienced DGF (19.1%). In the multivariate Cox model, DGF was strongly associated with cardiovascular risk (adjusted Hazard Ratio [HR] = 1.37, P &amp;lt; .0001), independently of renal function. Other significantly associated variables included age, duration of dialysis, expanded criteria donors, diabetes, dyslipidemia, smoking, initial nephropathy, and various cardiovascular comorbidities. The effect of DGF was predominantly observed in men, patients over 40, and those at lower cardiovascular risk. DGF was associated with independent cardiac outcomes, such as cardiovascular death (HR 1.31), coronaropathy (HR 1.51), heart failure (HR 1.61 and arrhythmia (HR 1.38), but not with stroke (HR 0.99) nor peripheral artery disease (HR 0.97). Conclusion DGF is an independent risk factor for the occurrence of cardiovascular events in kidney transplant recipients. Strategies aimed at minimizing DGF could potentially reduce cardiovascular complications in these patients.

Post-Transplant Cardiovascular Disease in Kidney Transplant Recipients: Incidence, Risk Factors, and Outcomes in the Era of Modern Immunosuppression.

Introduction: Post-transplant cardiovascular disease (PTCVD) poses a significant challenge in kidney transplantation, potentially impacting graft outcomes and patient survival. This retrospective study aimed to investigate the incidence, risk factors, and consequential impact of PTCVD in kidney transplant recipients (KTRs) devoid of pre-existing cardiovascular disease (CVD). Method: The cohort comprised 1114 KTRs, with 749 individuals included after excluding those with pre-existing CVD and early graft loss. PTCVD encompasses ischemic heart disease, myocardial infarction, arrhythmias, heart failure, stroke, peripheral vascular disease, and valvular heart disease. Competing risk regression analysis was performed to identify predictors of PTCVD, while Cox proportional hazards analysis assessed the impact of PTCVD on graft and recipient survival. Results: The cumulative incidence of PTCVD at 5, 10, and 20 years was 5.4%, 14.3%, and 22.5%, respectively. Competing risk regression identified increased age (sub-hazard ratio [SHR], 1.22; p = 0.036) per decade, duration of dialysis (SHR, 1.07; p = 0.048) per year on dialysis, and the slope of the estimated glomerular filtration rate (SHR, 1.08; p = 0.008) mL/min/year decline as independent predictors of higher-risk PTCVD. A higher baseline estimated glomerular filtration rate (eGFR) was protective (SHR, 0.98; p = 0.032). PTCVD was not significantly associated with death-censored graft loss (adjusted hazard ratio [aHR] 1.31; p = 0.48) but was correlated with higher all-cause graft loss (aHR, 1.71; p = 0.011) and recipient mortality (aHR, 1.97; p = 0.004). Conclusion: This study provides insights into PTCVD predictors. Although not directly associated with graft loss, PTCVD significantly correlates with heightened mortality in kidney transplant recipients, emphasizing the need for enhanced clinical management and surveillance strategies.

Developing a genetic testing panel for evaluation of morbidities in kidney transplant recipients

Cardiovascular disease, infection, malignancy, and thromboembolism are major causes of morbidity and mortality in kidney transplant recipients (KTR). Prospectively identifying monogenic conditions associated with post-transplant complications may enable personalized management. Therefore, we developed a transplant morbidity panel (355 genes) associated with major post-transplant complications including cardiometabolic disorders, immunodeficiency, malignancy, and thrombophilia. This gene panel was then evaluated using exome sequencing data from 1590 KTR. Additionally, genes associated with monogenic kidney and genitourinary disorders along with American College of Medical Genetics (ACMG) secondary findings v3.2 were annotated. Altogether, diagnostic variants in 37 genes associated with Mendelian kidney and genitourinary disorders were detected in 9.9% (158/1590) of KTR; 25.9% (41/158) had not been clinically diagnosed. Moreover, the transplant morbidity gene panel detected diagnostic variants for 56 monogenic disorders in 9.1% KTRs (144/1590). Cardiovascular disease, malignancy, immunodeficiency, and thrombophilia variants were detected in 5.1% (81), 2.1% (34), 1.8% (29) and 0.2% (3) among 1590 KTRs, respectively. Concordant phenotypes were present in half of these cases. Reviewing implications for transplant care, these genetic findings would have allowed physicians to set specific risk factor targets in 6.3% (9/144), arrange intensive surveillance in 97.2% (140/144), utilize preventive measures in 13.2% (19/144), guide disease-specific therapy in 63.9% (92/144), initiate specialty referral in 90.3% (130/144) and alter immunosuppression in 56.9% (82/144). Thus, beyond diagnostic testing for kidney disorders, sequence annotation identified monogenic disorders associated with common post-transplant complications in 9.1% of KTR, with important clinical implications. Incorporating genetic diagnostics for transplant morbidities would enable personalized management in pre- and post-transplant care.

Antibody Response after 3-Dose Booster against SARS-CoV-2 mRNA Vaccine in Kidney Transplant Recipients.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is associated with a high rate of mortality in kidney transplant recipients (KTRs). Current vaccine strategies for KTRs seem to be unable to provide effective protection against coronavirus disease 2019 (COVID-19), and the occurrence of severe disease in some vaccinated KTRs suggested a lack of immunity. We initially analyzed the antibody response in a group of 32 kidney transplant recipients (KTRs) followed at the nephrology and dialysis unit of the Hospital Pio XI of Desio, ASST-Brianza, Italy. Thus, we studied the differences in antibody levels between subjects who contracted SARS-CoV-2 after the booster (8 individuals) and those who did not contract it (24 individuals). Furthermore, we verified if the antibody response was in any way associated with creatinine and eGFR levels. We observed a significant increase in the antibody response pre-booster compared to post-booster using both a Roche assay and DIAPRO assay. In the latter, through immunotyping, we highlight that the major contribution to this increase is specifically due to IgG S1 IgM S2. We observed a significant increase in IgA S1 and IgA NCP (p = 0.045, 0.02) in the subjects who contracted SARS-CoV-2. We did not find significant associations for the p-value corrected for false discovery rate (FDR) between the antibody response to all assays and creatinine levels. This observation allows us to confirm that patients require additional vaccine boosters due to their immunocompromised status and therapy in order to protect them from infections related to viral variants. This is in line with the data reported in the literature, and it could be worthwhile to deeply explore these phenomena to better understand the role of IgA S1 and IgA NCP antibodies in SARS-CoV-2 infection.

Urinary Endotrophin and Long-term Outcomes in Kidney Transplant Recipients

Background. Kidney fibrosis is a suggested cause of kidney failure and premature mortality. Because collagen type VI is closely linked to kidney fibrosis, we aimed to evaluate whether urinary endotrophin, a collagen type VI fragment, is associated with graft failure and mortality among kidney transplant recipients (KTR). Methods. In this prospective cohort study, KTR with a functioning graft ≥1-y posttransplantation were recruited; 24-h urinary endotrophin excretion was measured using an ELISA method. Multivariate Cox regression analyses were performed. Results. A total of 621 KTR (mean age 53 y old, 43% female) at a median of 5.2 y posttransplantation were included. Median 24-h urinary endotrophin excretion was 5.6 (3.1–13.6) µg/24h. During a median follow-up of 7.5 y, 87 KTR (14%) developed graft failure and 185 KTR (30%) died; 24-h urinary endotrophin excretion was associated with increased risk of graft failure (hazard ratio [95% confidence interva] per doubling = 1.24 [1.08-1.42]) and all-cause mortality (hazard ratio [95% confidence intervals] per doubling = 1.14 [1.03-1.25]) independent of potential confounders including plasma endotrophin concentration. Twenty-four-hour urinary protein excretion was a significant effect modifier for the association with mortality (Pinteraction = 0.002). Twenty-four-hour urinary endotrophin excretion was only significantly associated with mortality in KTR with low levels of proteinuria. Conclusions. Urinary endotrophin is independently associated with an increased risk of graft failure in all KTR and mortality only in KTR with low levels of proteinuria. Further studies with different KTR populations are needed to confirm these findings.

Allograft function predicts mortality in kidney transplant recipients with severe COVID-19: a paradoxical risk factor.

Kidney transplant recipients (KTRs) are at a higher risk of severe coronavirus disease (COVID-19) because of their immunocompromised status. However, the effect of allograft function on the prognosis of severe COVID-19 in KTRs is unclear. In this study, we aimed to analyze the correlation between pre-infection allograft function and the prognosis of severe COVID-19 in KTRs. This retrospective cohort study included 82 patients who underwent kidney transplantation at the Sichuan Provincial Peoples Hospital between October 1, 2014 and December 1, 2022 and were diagnosed with severe COVID-19. The patients were divided into decreased eGFR and normal eGFR groups based on the allograft function before COVID-19 diagnosis (n=32 [decreased eGFR group], mean age: 43.00 years; n=50 [normal eGFR group, mean age: 41.88 years). We performed logistic regression analysis to identify risk factors for death in patients with severe COVID-19. The nomogram was used to visualize the logistic regression model results. The mortality rate of KTRs with pre-infection allograft function insufficiency in the decreased eGFR group was significantly higher than that of KTRs in the normal eGFR group (31.25% [10/32] vs. 8.00% [4/50], P=0.006). Pre-infection allograft function insufficiency (OR=6.96, 95% CI: 1.4633.18, P=0.015) and maintenance of a mycophenolic acid dose >1500 mg/day before infection (OR=7.59, 95% CI: 1.0853.20, P=0.041) were independent risk factors, and the use of nirmatrelvir/ritonavir before severe COVID-19 (OR=0.15, 95% CI: 0.030.72, P=0.018) was a protective factor against death in severe COVID-19. Pre-infection allograft function is a good predictor of death in patients with severe COVID-19. Allograft function was improved after treatment for severe COVID-19, which was not observed in patients with non-severe COVID-19.

Age and Epstein-Barr viral load at diagnosis of post-transplant lymphoproliferative disease are associated with patient survival in kidney transplant recipients.

This study investigated variables associated with mortality in kidney transplant recipients (KTRs) diagnosed with post-transplant lymphoproliferative disease (PTLD) and a simultaneous Epstein-Barr virus (EBV) viremia. This was a retrospective cohort study enrolling KTRs diagnosed with PTLD between 2018 and 2020. Outcome: death within two years after diagnosis. Among 1,625 KTRs who collected EBV viremia (by PCR, 2018-2020) for any reason, 238 (14.6%) had a positive viral load and 41 (17.2%) simultaneous PTLD. These 41 patients were 40.1 years old at diagnosis and 8.6 years after transplantation; 26.8% were induced with rATG and 92.7% were maintained on tacrolimus and azathioprine (TAC/AZA) as immunosuppressive regimen. Lymph nodes (75.6%) was the most common site of PTLD, followed by the gastrointestinal tract (48.8%), with 61.0% at Lugano stage IV and 80.5% monomorphic PTLD. The mean EBV viral load was 12,198 IU/mL. One- and two-year patient survival post-diagnosis was 60.4% and 46.8%, respectively. In the Cox regression analysis, age at PTLD diagnosis (HR for each year = 1.039; p < 0.001) and EBV viral load (HR for each log = 1.695; p = 0.026) were associated with risk of death. This study suggests that in patients predominantly on TAC/AZA, PTLD with simultaneous EBV positive viral load is a late event, and worse survival is associated with older age and EBV viral load at diagnosis.

The impact of hepatitis B and C positive serologies on the outcomes of non-hepatic solid organ transplantation in the United States.

Chronic viral hepatitis B (HBV) and C (HCV) infection could negatively affect outcomes of non-hepatic solid organ transplantations due to the risk of viral reactivation in the presence of immunosuppression. This study aimed to determine post-transplant outcomes in patients with HBV or HCV positivity receiving non-hepatic solid-state organ transplant. Data was collected from the Scientific Registry of Transplant Recipients (SRTR) 2006-2021 for patients (≥18) who received a lung, heart, or kidney single organ transplant in the U.S. Hepatitis C positivity (HCV+) was determined as positive HCV Ab and hepatitis B positivity (HBV+) as positive HBsAg. We included N = 30,872 lung, N = 36,990 heart and N = 280,162 kidney transplant recipients. The prevalence of HBV+ was 1.3% in lung, 1.5% in heart and 1.7% in kidney patients, HCV+ was 2.2%, 2.2% and 5.0%, respectively. Post-transplant survival of patients with vs. without HBV+ was similar in all solid organ transplants (all p > .05). Similarly, there was no difference in post-transplant survival between lung transplant recipients with vs. without anti-HCV (all p > .05). Heart transplant recipients with HCV+ had higher crude post-transplant mortality (all p < .01). Similarly, there was higher post-transplant mortality in kidney transplant recipients with HCV+ (1-year: 6% vs. 3%; 5-year: 21% vs. 13%; 10-year: 47% vs. 31%; all p < .0001). In multivariate analysis controlling for confounders, only the association of HCV+ with higher post-kidney transplant mortality remained significant: adjusted hazard ratio (aHR) (95% CI) = 1.16 (1.12-1.20), p < .0001. There was no association of viral hepatitis seropositivity with the risk of graft failure in all groups (p > .05). In most cases, the presence of HBV or HCV serologies is not associated with adverse post-transplant outcomes in non-hepatic solid organ transplants. However, kidney transplant recipients who are positive for HCV serology have an increased risk for post-transplant mortality.

High diet quality indices associated with lower risk of lipid profile abnormalities in Taiwanese kidney transplant recipients

Cardiovascular disease (CVD) and its risk factors seem to be linked with deteriorated graft function and persists as the major cause of mortality in kidney transplant recipients (KTRs). Diet quality is associated with CVD prevention in the healthy population, however, less study focuses on KTRs. The study aimed to determine the association between diet quality indices and lipid profile abnormalities as risk factors for CVD in KTRs. This prospective study enrolled 106 KTRs who had functioning allografts from September 2016. Lipid profiles included low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC), and triglyceride (TG) and were based on the National Cholesterol Education Program Adult Treatment Panel III recommendations. Three-day dietary data were collected by a well-trained registered dietitian. The Alternative Healthy Eating Index-Taiwan (AHEI-Taiwan), Alternative Healthy Eating Index-2010 (AHEI-2010), and Healthy Eating Index-2015 (HEI-2015) scores were calculated and divided into quartiles and compared accordingly. KTRs’ mean LDL-C, HDL-C, TC, and TG levels were 119.8 ± 36.6 mg/dL, 52.0 ± 17.9 mg/dL, 205.8 ± 43.9 mg/dL, and 160.2 ± 121.6 mg/dL, respectively. Compared with the lowest quartile, only the highest quartile of AHEI-Taiwan had lower TC and LDL-C levels. After adjustment for age, gender, energy, Charlson comorbidity index, transplant duration, and dialysis duration, logistic regression analysis revealed that the highest quartile of AHEI-Taiwan had 82% (odds ratio [OR], 0.18; 95% confidence interval [CI] 0.04–0.72, p < 0.05) lower odds of high TC and 88% (OR 0.12; 95% CI 0.03–0.58, p < 0.05) lower odds of high LDL-C, and the highest quartile of HEI-2015 had 77% (OR 0.23; 95% CI 0.05–0.95, p < 0.05) lower odds of high LDL-C. Higher adherence to a healthy diet as per AHEI-Taiwan and HEI-2015 guidelines associated with lower risk of lipid profile abnormalities in KTRs.