Long noncoding RNA from Betula platyphylla, BplncSIR1, confers salt tolerance by regulating BpNAC2 to mediate reactive oxygen species scavenging and stomatal movement.

Long noncoding RNAs (lncRNAs) play an important role in abiotic stress tolerance. However, their function in conferring abiotic stress tolerance is still unclear. Herein, we characterized the function of a salt-responsive nuclear lncRNA (BplncSIR1) from Betula platyphylla (birch). Birch plants overexpressing and knocking out for BplncSIR1 were generated. BplncSIR1 was found to improve salt tolerance by inducing antioxidant activity and stomatal closure, and also accelerate plant growth. Chromatin isolation by RNA purification (ChIRP) combined with RNA sequencing indicated that BplncSIR1 binds to the promoter of BpNAC2 (encoding NAC domain-containing protein 2) to activate its expression. Plants overexpressing and knocking out for BpNAC2 were generated. Consistent with that of BplncSIR1, overexpression of BpNAC2 also accelerated plant growth and conferred salt tolerance. In addition, BpNAC2 binds to different cis-acting elements, such as G-box and 'CCAAT' sequences, to regulate the genes involved in salt tolerance, resulting in reduced ROS accumulation and decreased water loss rate by stomatal closure. Taken together, BplncSIR1 serves as the regulator of BpNAC2 to induce its expression in response to salt stress, and activated BpNAC2 accelerates plant growth and improves salt tolerance. Therefore, BplncSIR1 might be a candidate gene for molecular breeding to cultivate plants with both a high growth rate and improved salt tolerance.

Genome-Wide Characterization of bHLH Family Genes and Expression Analysis in Response to Osmotic Stress in Betula platyphylla.

The bHLH family, as a superfamily of transcription factors (TFs), has special functional characteristics in plants and plays a crucial role in a plant's growth and development and helping the plant cope with various stresses. In this study, 128 bHLH family genes were screened in the birch (B. platyphylla) genome using conservative domain scan and blast analysis. These genes are clustered into 21 subfamilies based on the phylogenetic tree construction and are unevenly distributed among the 14 birch chromosomes. In all, 22 segmental duplication pairs with 27 BpbHLH genes were identified. The duplications were distributed on eight chromosomes. Analysis of gene structures and protein motifs revealed intra-group conservation of BpbHLHs. Of the BpbHLH family genes, 16 contain only one intron each. The BPChr14G06667 gene contains the most introns, that is, 19. The cis-elements, which respond to plant hormones, light, defense, and stress, were found on the promoter of BHLH family genes. As per RNA-seq data analysis, under PEG osmotic stress, most BpbHLH genes were differentially expressed, and eight were highly differentially expressed. The qRT-PCR analysis results further indicated that BPChr06G09475 was the gene with the highest expression level in leaves, roots, and stems, and that the expression of these eight genes was higher in leaves than in roots and stems and upregulated in all three tissues under osmotic stress compared to the controls. The above analysis suggests that the BpbHLH family genes have a certain biological effect under drought stress that provides a basis for molecular breeding for stress resistance in birch.

Impact of Easing COVID-19 Restrictions on Fear of COVID-19 and Social Support Among Chinese Students: A Longitudinal Analysis.

Introduction: This longitudinal study aims to investigate the relationship between fear of COVID-19, support-seeking behaviors, and perceived social support among Chinese college students during two distinct periods of the COVID-19 pandemic: the period of strict control (time 1) and the period following a relaxation of restrictions (time 2). Methods: A total of 408 Chinese college students participated in this study. Data collection included demographic information, measures of fear of COVID-19, support-seeking behaviors, and perceived social support. Results: Fear of COVID-19 at time 1 showed a significant positive association with fear of COVID-19 at time 2. The relationship between support-seeking behavior at time 1 and fear of COVID-19 at time 2 was significantly mediated through a chain mediation effect of support-seeking behavior at time 1 and perceived social support at time 2. Discussion: This study contributes to the growing body of evidence on the psychological impacts of the COVID-19 pandemic and underscores the significance of social support in mitigating fear of COVID-19. It calls for a re-evaluation of public health policies considering their potential psychological effects and introduces new opportunities for developing psychosocial interventions.

Effects of the dipeptides comprising leucine and lysine on lifespan and age-related stress in Caenorhabditis elegans.

The aging process is affected by various stressors. An increase in oxidative stress is related to the impairment of physiological functions and enhancement of glycative stress. Food-derived bioactive peptides have various physiological functions, including antioxidant activities. Dipeptides comprising Leu and Lys (LK and KL, respectively) have been isolated from foods; however, their physiological properties remain unclear. In this study, we investigated the antioxidant/antiglycation activity of dipeptides and their antiaging effects using Caenorhabditis elegans (C. elegans). Both dipeptides showed antioxidant activities against several reactive oxygen species (ROS) in vitro. In particular, the scavenging activity of LK against superoxide radicals was higher than KL did. Moreover, dipeptides suppressed advanced glycation end products (AGEs) formation in the BSA-glucose model. In the lifespan assays using wild-type C. elegans, both LK and KL significantly prolonged the mean lifespan by 20.9% and 11.7%, respectively. In addition, LK decreased intracellular ROS and superoxide radical levels in C. elegans. Blue autofluorescence, an indicator of glycation in C. elegans with age, was also suppressed by LK. These results suggest that dipeptides, notably LK, show an antiaging effect by suppressing oxidative and glycative stress. Our findings suggest that such dipeptides can be used as a novel functional food ingredient. Food-derived dipeptide Leu-Lys (LK) and Lys-Leu (KL) exert antioxidant and antiglycation activity in vitro. Treatment with LK prolonged the mean lifespan and maximum lifespan of C. elegans more than that of KL. Intracellular ROS and blue autofluorescence levels (indicator of aging) were suppressed by LK.

Complete mitochondrial genome of the little-known regional endemic Aporia hastata (Oberthür, 1892) (Lepidoptera: Pieridae).

The present study reports the mitochondrial genome of A. hastata (Oberthür, 1892), a little-known Aporia species endemic to the southern margin of the Hengduan Mountains in Yunnan Province. This genome is circular, 15,148 bp in length, and consists of 13 PCGs, 22 tRNAs, and two rRNAs. The Bayesian phylogenetic tree clusters A. hastata with other Aporia taxa inside tribe Pierini Duponchel, [1835]. The findings of this study add valuable new information to the genus Aporia and are beneficial to a better understanding of phylogeography of these butterflies.

Identification of birch lncRNAs and mRNAs responding to salt stress and characterization of functions of lncRNA.

Long noncoding RNAs (lncRNAs) are important in abiotic stress tolerance. Here, we identified salt-responsive genes and lncRNAs in the roots and leaves of Betula platyphylla Suk. (birch), and characterized their lncRNAs functions. In total, 2660 mRNAs and 539 lncRNAs responding to salt treatment were identified using RNA-seq. The salt-responsive genes were substantially enriched in 'cell wall biogenesis' and 'wood development' in the roots and were enriched in 'photosynthesis' and 'response to stimulus' in the leaves. Meanwhile, the potential target genes of the salt-responsive lncRNAs in roots and leaves were both enriched in 'nitrogen compound metabolic process' and 'response to stimulus'. We further built a method for quickly identifying abiotic stress tolerance of lncRNAs, which employed transient transformation for overexpression and knock-down of the lncRNA, enabling gain- and loss-of-function analysis. Using this method, 11 randomly selected salt-responsive lncRNAs were characterized. Among them, six lncRNAs confer salt tolerance, two lncRNAs confer salt sensitivity, and the other three lncRNAs are not involved in salt tolerance. In addition, a lncRNA, LncY1, was further characterized, which improves salt tolerance by regulating two transcription factors, BpMYB96 and BpCDF3. Taken together, our results suggested that lncRNAs play important roles in the salt response of birch plants.

Biomarkers of eGFR decline after cardiac surgery in children: findings from the ASSESS-AKI study.

BACKGROUND: Children who require surgery for congenital heart disease have increased risk for long-term chronic kidney disease (CKD). Clinical factors as well as urine biomarkers of tubular health and injury may help improve the prognostication of estimated glomerular filtration rate (eGFR) decline. METHODS: We enrolled children from 1 month to 18 years old undergoing cardiac surgery in the ASSESS-AKI cohort. We used mixed-effect models to assess the association between urinary biomarkers (log2-transformed uromodulin, NGAL, KIM-1, IL-18, L-FABP) measured 3 months after cardiac surgery and cyanotic heart disease with the rate of eGFR decline at annual in-person visits over 4 years. RESULTS: Of the 117 children enrolled, 30 (24%) had cyanotic heart disease. During 48 months of follow-up, the median eGFR in the subgroup of children with cyanotic heart disease was lower at all study visits as compared with children with acyanotic heart disease (p = 0.01). In the overall cohort, lower levels of both urine uromodulin and IL-18 after discharge were associated with eGFR decline. After adjustment for age, RACHS-1 surgical complexity score, proteinuria, and eGFR at the 3-month study visit, lower concentrations of urine uromodulin and IL-18 were associated with a monthly decline in eGFR (uromodulin ß = 0.04 (95% CI: 0.00-0.09; p = 0.07) IL-18 ß = 0.07 (95% CI: 0.01-0.13; p = 0.04), ml/min/1.73 m2 per month). CONCLUSIONS: At 3 months after cardiac surgery, children with lower urine uromodulin and IL-18 concentrations experienced a significantly faster decline in eGFR. Children with cyanotic heart disease had a lower median eGFR at all time points but did not experience faster eGFR decline. A higher-resolution version of the Graphical abstract is available as Supplementary information.

Deceased-Donor Acute Kidney Injury and Acute Rejection in Kidney Transplant Recipients: A Multicenter Cohort.

RATIONALE & OBJECTIVE: Donor acute kidney injury (AKI) activates innate immunity, enhances HLA expression in the kidney allograft, and provokes recipient alloimmune responses. We hypothesized that injury and inflammation that manifested in deceased-donor urine biomarkers would be associated with higher rates of biopsy-proven acute rejection (BPAR) and allograft failure after transplantation. STUDY DESIGN: Prospective cohort. SETTING & PARTICIPANTS: 862 deceased donors for 1,137 kidney recipients at 13 centers. EXPOSURES: We measured concentrations of interleukin 18 (IL-18), kidney injury molecule 1 (KIM-1), and neutrophil gelatinase-associated lipocalin (NGAL) in deceased donor urine. We also used the Acute Kidney Injury Network (AKIN) criteria to assess donor clinical AKI. OUTCOMES: The primary outcome was a composite of BPAR and graft failure (not from death). A secondary outcome was the composite of BPAR, graft failure, and/or de novo donor-specific antibody (DSA). Outcomes were ascertained in the first posttransplant year. ANALYTICAL APPROACH: Multivariable Fine-Gray models with death as a competing risk. RESULTS: Mean recipient age was 54 ± 13 (SD) years, and 82% received antithymocyte globulin. We found no significant associations between donor urinary IL-18, KIM-1, and NGAL and the primary outcome (subdistribution hazard ratio [HR] for highest vs lowest tertile of 0.76 [95% CI, 0.45-1.28], 1.20 [95% CI, 0.69-2.07], and 1.14 [95% CI, 0.71-1.84], respectively). In secondary analyses, we detected no significant associations between clinically defined AKI and the primary outcome or between donor biomarkers and the composite outcome of BPAR, graft failure, and/or de novo DSA. LIMITATIONS: BPAR was ascertained through for-cause biopsies, not surveillance biopsies. CONCLUSIONS: In a large cohort of kidney recipients who almost all received induction with thymoglobulin, donor injury biomarkers were associated with neither graft failure and rejection nor a secondary outcome that included de novo DSA. These findings provide some reassurance that centers can successfully manage immunological complications using deceased-donor kidneys with AKI.

Pre-operative kidney biomarkers and risks for death, cardiovascular and chronic kidney disease events after cardiac surgery: the TRIBE-AKI study.

BACKGROUND: Soluble tumor necrosis factor receptor (sTNFR)1, sTNFR2, and plasma kidney injury molecule-1 (KIM-1) are associated with kidney events in patients with and without diabetes. However, their associations with clinical outcomes when obtained pre-operatively have not been explored. METHODS: The TRIBE-AKI cohort study is a prospective, multicenter, cohort study of high-risk adults undergoing cardiac surgery. We assessed the associations between pre-operative concentrations of plasma sTNFR1, sTNFR2, and KIM-1 and post-operative long-term outcomes including mortality, cardiovascular events, and chronic kidney disease (CKD) incidence or progression after discharge. RESULTS: Among 1378 participants included in the analysis with a median follow-up period of 6.7 (IQR 4.0-7.9) years, 434 (31%) patients died, 256 (19%) experienced cardiovascular events and out of 837 with available long-term kidney function data, 30% developed CKD. After adjustment for clinical covariates, each log increase in biomarker concentration was independently associated with mortality with 95% CI adjusted hazard ratios (aHRs) of 3.0 (2.3-4.0), 2.3 (1.8-2.9), and 2.0 (1.6-2.4) for sTNFR1, sTNFR2, and KIM-1, respectively. For cardiovascular events, the 95% CI aHRs were 2.1 (1.5-3.1), 1.9 (1.4-2.6) and 1.6 (1.2-2.1) for sTNFR1, sTNFR2 and KIM-1, respectively. For CKD events, the aHRs were 2.2 (1.5-3.1) for sTNFR1, 1.9 (1.3-2.7) for sTNFR2, and 1.7 (1.3-2.3) for KIM-1. Despite the associations, each of the biomarkers alone or in combination failed to result in robust discrimination on an absolute basis or compared to a clinical model. CONCLUSION: sTNFR1, sTNFR2, and KIM-1 were independently associated with longitudinal outcomes after discharge from a cardiac surgery hospitalization including death, cardiovascular, and CKD events when obtained pre-operatively in high-risk individuals. Pre-operative plasma biomarkers could serve to assist during the evaluation of patients in whom cardiac surgery is planned.

Clinically adjudicated deceased donor acute kidney injury and graft outcomes.

BACKGROUND: Acute kidney injury (AKI) in deceased donors is not associated with graft failure (GF). We hypothesize that hemodynamic AKI (hAKI) comprises the majority of donor AKI and may explain this lack of association. METHODS: In this ancillary analysis of the Deceased Donor Study, 428 donors with available charts were selected to identify those with and without AKI. AKI cases were classified as hAKI, intrinsic (iAKI), or mixed (mAKI) based on majority adjudication by three nephrologists. We evaluated the associations between AKI phenotypes and delayed graft function (DGF), 1-year eGFR and GF. We also evaluated differences in urine biomarkers among AKI phenotypes. RESULTS: Of the 291 (68%) donors with AKI, 106 (36%) were adjudicated as hAKI, 84 (29%) as iAKI and 101 (35%) as mAKI. Of the 856 potential kidneys, 669 were transplanted with 32% developing DGF and 5% experiencing GF. Median 1-year eGFR was 53 (IQR: 41-70) ml/min/1.73m2. Compared to non-AKI, donors with iAKI had higher odds DGF [aOR (95%CI); 4.83 (2.29, 10.22)] and had lower 1-year eGFR [adjusted B coefficient (95% CI): -11 (-19, -3) mL/min/1.73 m2]. hAKI and mAKI were not associated with DGF or 1-year eGFR. Rates of GF were not different among AKI phenotypes and non-AKI. Urine biomarkers such as NGAL, LFABP, MCP-1, YKL-40, cystatin-C and albumin were higher in iAKI. CONCLUSION: iAKI was associated with higher DGF and lower 1-year eGFR but not with GF. Clinically phenotyped donor AKI is biologically different based on biomarkers and may help inform decisions regarding organ utilization.

Hierarchical transcription factor and regulatory network for drought response in Betula platyphylla.

Although many genes and biological processes involved in abiotic stress response have been identified, how they are regulated remains largely unclear. Here, to study the regulatory mechanism of birch (Betula platyphylla) responding to drought induced by polyethylene glycol (PEG) 6000 (20%, w/v), a partial correlation coefficient-based algorithm for constructing gene regulatory network (GRN) was proposed, and a three-layer hierarchical GRN was constructed, including 68 transcription factors (TFs), and 252 structural genes. Totally, 1448 predicted regulatory relationships are included, and most of them are novel. The reliability of GRN was verified by ChIP-PCR and qRT-PCR based on transient transformation. About 55% of genes in the bottom layer of GRN could confer drought tolerance. We selected the two TFs, BpMADS11 and BpNAC090, from the up layer and characterized their function in drought tolerance. Overexpression of BpMADS11 and BpNAC090 both reduces electrolyte leakage, ROS and MDA contents, displaying increased drought tolerance than wild-type birch. According to this GRN, the important biological processes involved in drought were identified, including "signaling hormone pathways", "water transport", "regulation of stomatal movement" and "response to oxidative stress". This work indicated that BpERF017, BpAGL61 and BpNAC090 are the key upstream regulators in birch drought tolerance. Our data clearly revealed the upstream regulators and TF-DNA interaction regulate different biological processes to adapt drought stress.

Angiopoietins as Prognostic Markers for Future Kidney Disease and Heart Failure Events after Acute Kidney Injury.

BACKGROUND: The mechanisms underlying long-term sequelae after AKI remain unclear. Vessel instability, an early response to endothelial injury, may reflect a shared mechanism and early trigger for CKD and heart failure. METHODS: To investigate whether plasma angiopoietins, markers of vessel homeostasis, are associated with CKD progression and heart failure admissions after hospitalization in patients with and without AKI, we conducted a prospective cohort study to analyze the balance between angiopoietin-1 (Angpt-1), which maintains vessel stability, and angiopoietin-2 (Angpt-2), which increases vessel destabilization. Three months after discharge, we evaluated the associations between angiopoietins and development of the primary outcomes of CKD progression and heart failure and the secondary outcome of all-cause mortality 3 months after discharge or later. RESULTS: Median age for the 1503 participants was 65.8 years; 746 (50%) had AKI. Compared with the lowest quartile, the highest quartile of the Angpt-1:Angpt-2 ratio was associated with 72% lower risk of CKD progression (adjusted hazard ratio [aHR], 0.28; 95% confidence interval [CI], 0.15 to 0.51), 94% lower risk of heart failure (aHR, 0.06; 95% CI, 0.02 to 0.15), and 82% lower risk of mortality (aHR, 0.18; 95% CI, 0.09 to 0.35) for those with AKI. Among those without AKI, the highest quartile of Angpt-1:Angpt-2 ratio was associated with 71% lower risk of heart failure (aHR, 0.29; 95% CI, 0.12 to 0.69) and 68% less mortality (aHR, 0.32; 95% CI, 0.15 to 0.68). There were no associations with CKD progression. CONCLUSIONS: A higher Angpt-1:Angpt-2 ratio was strongly associated with less CKD progression, heart failure, and mortality in the setting of AKI.

Trends in the procurement and discard of kidneys from deceased donors with acute kidney injury.

Kidney allocation trends from deceased donors with acute kidney injury (AKI) have not been characterized since initial Kidney Donor Profile Index reporting in 2012 and its use under the revised Kidney Allocation System (KAS) in 2014. We conducted a retrospective analysis of US registry data to characterize kidney procurement and discard trends in deceased donors with AKI, defined by ≥50% or ≥0.3 mg/dl (≥4.0 mg/dl or ≥200% for stage 3) increase in terminal serum creatinine from admission. From 2010 to 2020, 172 410 kidneys were procured from 93 341 deceased donors 16 years or older; 34 984 kidneys were discarded (17 559 from AKI donors). The proportion of stage 3 AKI donors doubled from 6% (412/6841) in 2010 to 12% (1365/11493) in 2020. Procurement of stage 3 AKI kidneys increased from 51% (423/824) to 80% (2183/2730). While discard of stage 3 AKI kidneys increased from 41% (175/423) in 2010 to 44% (960/2183) in 2020, this increase was not statistically significant in interrupted time-series analysis following KAS implementation (slope difference -0.41 [-3.22, 2.4], and level change 3.09 [-6.4, 12.6]). In conclusion, the absolute number of stage 3 AKI kidneys transplanted has increased. Ongoing high discard rates of these kidneys suggest opportunities for improved utilization.

Characterization of the Function of Two S1Fa-Like Family Genes From Populus trichocarpa.

S1Fa-like transcription factors (TFs) are small molecular weight proteins that contain both nuclear localization and DNA binding domains. However, the functions of S1Fa-like TFs are poorly understood. In the present study, we identified the S1Fa-like TFs from the Populus trichocarpa genome, which revealed two S1Fa-like TF genes, PtS1Fa1 and PtS1Fa2. PtS1Fa1 and PtS1Fa2 expression was suppressed by drought and salt stress, and was also significantly altered by ABA, MeJA, or SA treatment. Both PtS1Fa1 and PtS1Fa2 are nuclear proteins. Transgenic P. trichocarpa plants overexpressing PtS1Fa1 and PtS1Fa2, respectively, were generated. The plants overexpressing PtS1Fa2 showed increased fresh weight, chlorophyll content, and root length and weight compared with those in wild-type (WT) P. trichocarpa under drought conditions. Meanwhile, these phenotype traits of plants overexpressing PtS1Fa1 were similar to those of WT plants. Furthermore, overexpression of PtS1Fa2 reduced the malondialdehyde (MDA) content, electrolyte leakage, H2O2 and O2- contents, and increased superoxide dismutase (SOD) and peroxidase (POD) activities. The expression of SOD and POD was also induced by PtS1Fa2. However, overexpression of PtS1Fa1 failed to affect any of these physiological parameters or SOD and POD gene expression. These results suggested that PtS1Fa2 plays a role in drought tolerance, and confers drought tolerance by increase antioxidant activity to reduce reactive oxygen species (ROS) accumulation.

Donor-derived Cell-free DNA Kinetics Post-kidney Transplant Biopsy.

BACKGROUND: Donor-derived cell-free DNA (dd-cfDNA) has generated interest as a biomarker for kidney injury including transplant (KT) rejection. It is possible that the KT biopsy procedure can cause the release of dd-cfDNA, therefore affecting the reliability of this assay in the postbiopsy period. We evaluated the effect of KT biopsy on the kinetics of dd-cfDNA. METHODS: We conducted a single-arm prospective study. Samples were collected from 16 adult KT recipients undergoing KT biopsy. All participants had samples drawn within 8 h before the biopsy (prebiopsy), within 20 min (hour 0), 2 h (hour 2), and 24-48 h (hours 24-48) after the biopsy. We evaluated the change in dd-cfDNA from the prebiopsy time point to the following 3 time points after the biopsy. RESULTS: At hour 0 and hour 2, there was a significantly larger log dd-cfDNA mean score compared with the prebiopsy score (least square mean estimate 0.4 [0.17-0.63] and 0.39 [0.09-0.68], respectively). By 24-28 h postbiopsy, there was no significant difference in log dd-cfDNA mean score compared with the prebiopsy score (least square mean estimate -0.21 [-0.6 to 0.19]). CONCLUSIONS: Mechanical injury from a KT biopsy can transiently increase circulating dd-cfDNA. The increase resolves by 24-48 h after the biopsy. Providers should wait 48 h postbiopsy to obtain dd-cfDNA levels to establish the correct baseline to be used for monitoring.

Overview of Antabuse® (Disulfiram) in Radiation and Cancer Biology.

Antabuse®, generic name disulfiram, has been extensively used in daily clinical practice to treat alcohol abuse. In vivo and in vitro experiments have demonstrated that disulfiram was capable of inhibiting tumor cell proliferation; clinical studies have indicated that the administration of this drug was associated with favorable survival, whilst in vitro experiments have elucidated the anticancer mechanism of disulfiram. In addition, radiation and cancer biology studies have shown that disulfiram can protect normal cells and sensitize tumor cells during radiotherapy. This review aims at describing the antitumor activity of disulfiram in both preclinical studies and clinical trials, whilst focusing on the advances of this drug in radiation and cancer biology, and the promise of repurposing it as a novel sensitizer to, and protector against, radiation on the incoming clinical studies.

Urinary EGF and MCP-1 and risk of CKD after cardiac surgery.

BACKGROUNDAssessment of chronic kidney disease (CKD) risk after acute kidney injury (AKI) is based on limited markers primarily reflecting glomerular function. We evaluated markers of cell integrity (EGF) and inflammation (monocyte chemoattractant protein-1, MCP-1) for predicting long-term kidney outcomes after cardiac surgery.METHODSWe measured EGF and MCP-1 in postoperative urine samples from 865 adults who underwent cardiac surgery at 2 sites in Canada and the United States and assessed EGF and MCP-1's associations with the composite outcome of CKD incidence or progression. We used single-cell RNA-Seq (scRNA-Seq) of AKI patient biopsies to perform transcriptomic analysis of programs corregulated with the associated genes.RESULTSOver a median (IQR) follow-up of 5.8 (4.2-7.1) years, 266 (30.8%) patients developed the composite CKD outcome. Postoperatively, higher levels of urinary EGF were protective and higher levels of MCP-1 were associated with the composite CKD outcome (adjusted HR 0.83, 95% CI 0.73-0.95 and 1.10, 95% CI 1.00-1.21, respectively). Intrarenal scRNA-Seq transcriptomes in patients with AKI-defined cell populations revealed concordant changes in EGF and MCP-1 levels and underlying molecular processes associated with loss of EGF expression and gain of CCL2 (encoding MCP-1) expression.CONCLUSIONUrinary EGF and MCP-1 were each independently associated with CKD after cardiac surgery. These markers may serve as noninvasive indicators of tubular damage, supported by tissue transcriptomes, and provide an opportunity for novel interventions in cardiac surgery.TRIAL REGISTRATIONClinicalTrials.gov NCT00774137.FUNDINGThe NIH funded the TRIBE-AKI Consortium and Kidney Precision Medicine Project. Yale O'Brien Kidney Center, American Heart Association, Patterson Trust Fund, Dr. Adam Linton Chair in Kidney Health Analytics, Canadian Institutes of Health Research, ICES, Ontario Ministry of Health and Long-Term Care, Academic Medical Organization of Southwestern Ontario, Schulich School of Medicine & Dentistry, Western University, Lawson Health Research Institute, Chan Zuckerberg Initiative Human Cell Atlas Kidney Seed Network.

Deceased-Donor Acute Kidney Injury and BK Polyomavirus in Kidney Transplant Recipients.

BACKGROUND AND OBJECTIVES: BK polyomavirus (BKV) infection commonly complicates kidney transplantation, contributing to morbidity and allograft failure. The virus is often donor-derived and influenced by ischemia-reperfusion processes and disruption of structural allograft integrity. We hypothesized that deceased-donor AKI associates with BKV infection in recipients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We studied 1025 kidney recipients from 801 deceased donors transplanted between 2010 and 2013, at 13 academic centers. We fitted Cox proportional-hazards models for BKV DNAemia (detectable in recipient blood by clinical PCR testing) within 1 year post-transplantation, adjusting for donor AKI and other donor- and recipient-related factors. We validated findings from this prospective cohort with analyses for graft failure attributed to BKV within the Organ Procurement and Transplantation Network (OPTN) database. RESULTS: The multicenter cohort mean kidney donor profile index was 49±27%, and 26% of donors had AKI. Mean recipient age was 54±13 years, and 25% developed BKV DNAemia. Donor AKI was associated with lower risk for BKV DNAemia (adjusted hazard ratio, 0.53; 95% confidence interval, 0.36 to 0.79). In the OPTN database, 22,537 (25%) patients received donor AKI kidneys, and 272 (0.3%) developed graft failure from BKV. The adjusted hazard ratio for the outcome with donor AKI was 0.7 (95% confidence interval, 0.52 to 0.95). CONCLUSIONS: In a well-characterized, multicenter cohort, contrary to our hypothesis, deceased-donor AKI independently associated with lower risk for BKV DNAemia. Within the OPTN database, donor AKI was also associated with lower risk for graft failure attributed to BKV. PODCAST: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2021_03_10_CJN18101120_final.mp3.

24-hour ambulatory blood pressure monitoring 9 years after pediatric cardiac surgery: a pilot and feasibility study.

BACKGROUND: Children undergoing cardiac surgery are at risk of high blood pressure (BP), a risk factor for cardiovascular and kidney disease. Twenty-four-hour ambulatory BP monitoring (ABPM) is a reference standard hypertension (HTN) test. Little data exist on ABPM abnormalities in children several years post cardiac surgery. This study aimed to (a) determine ABPM feasibility; (b) describe and compare ABPM measures and abnormalities (percent load, masked HTN [MH]; non-dipping, mean systolic/diastolic BP > 95th percentile; pre-HTN (ABPM); white-coat HTN [WCH]) to casual BP; and (c) compare BP in patients with and without acute kidney injury (AKI). METHODS: Prospective, follow-up pilot study of children (0-18 years) who underwent cardiac surgery from 2007 to 2009 at Montreal Children's Hospital. We recorded if participants had post-operative AKI and assessed the following outcomes at 9-year follow-up: casual BP classified by three single-visit measures (normal; elevated BP [eBPSingleVisit]; HTNSingleVisit); ABPM. Bivariable analyses were used to compare characteristics between groups. RESULTS: Twenty-three patients (median [interquartile range], 8.6 [8.0, 9.0] years post cardiac surgery) were included; 16 (70%) male. Six participants (26%) had eBPSingleVisit or higher. On ABPM, 11 (48%) had ≥ 1 abnormality: 9 (39%) had non-dipping; 3 (13%) had pre-HTN; 3 (13%) had WCH; none had HTN or MH. There were no differences in ABPM according to AKI status. CONCLUSION: Our pilot study determined that ABPM was feasible in children years after cardiac surgery and frequently identified ABPM abnormalities. Future research in larger populations is needed to define specific risk factors for HTN in children after cardiac surgery.

Contemporary incidence and risk factors of post transplant Erythrocytosis in deceased donor kidney transplantation.

BACKGROUND: Post-Transplant erythrocytosis (PTE) has not been studied in large recent cohorts. In this study, we evaluated the incidence, risk factors, and outcome of PTE with current transplant practices using the present World Health Organization criteria to define erythrocytosis. We also tested the hypothesis that the risk of PTE is greater with higher-quality kidneys. METHODS: We utilized the Deceased Donor Study which is an ongoing, multicenter, observational study of deceased donors and their kidney recipients that were transplanted between 2010 and 2013 across 13 centers. Eryrthocytosis is defined by hemoglobin> 16.5 g/dL in men and> 16 g/dL in women. Kidney quality is measured by Kidney Donor Profile Index (KDPI). RESULTS: Of the 1123 recipients qualified to be in this study, PTE was observed at a median of 18 months in 75 (6.6%) recipients. Compared to recipients without PTE, those with PTE were younger [mean 48±11 vs 54±13 years, p < 0.001], more likely to have polycystic kidney disease [17% vs 6%, p < 0.001], have received kidneys from younger donors [36 ±13 vs 41±15 years], and be on RAAS inhibitors [35% vs 22%, p < 0.001]. Recipients with PTE were less likely to have received kidneys from donors with hypertension [16% vs 32%, p = 0.004], diabetes [1% vs 11%, p = 0.008], and cerebrovascular event (24% vs 36%, p = 0.036). Higher KDPI was associated with decreased PTE risk [HR 0.98 (95% CI: 0.97-0.99)]. Over 60 months of follow-up, only 17 (36%) recipients had sustained PTE. There was no association between PTE and graft failure or mortality, CONCLUSIONS: The incidence of PTE was low in our study and PTE resolved in majority of patients. Lower KDPI increases risk of PTE. The underutilization of RAAS inhibitors in PTE patients raises the possibility of under-recognition of this phenomenon and should be explored in future studies.