Chronic Renal Dysfunction Research Articles

2116. Long-term (2-year) outcomes and complications of COVID-19 in solid organ transplant (SOT) recipients

Abstract Background The long-term complications of COVID-19 infection in the general population include mortality, re-infection, secondary infection, persistent organ dysfunction, and symptoms of long-COVID. The prevalence of these outcomes and impact on graft function in solid organ transplant (SOT) remain uncertain. We aim to describe these complications in a large series of SOT with COVID-19 with 2 years of long-term follow up. Methods We retrospectively studied all adult (age >18) SOT from a single center hospitalized with SARS-CoV-2 diagnosed by nasopharyngeal swab between 3/10-5/30/2020. Patients with early mortality within 28 days were excluded. Outcomes including mortality, allograft rejection, allograft failure, secondary infections, COVID-19 re-infections, post-COVID complications (oxygen requirement, chronic renal or cardiac dysfunction), and symptoms of long-COVID were analyzed. Re-infections were characterized by severity and likely variant based on local variant predominance. Results 117 SOT recipients were hospitalized with COVID-19 in the study period. 94 survived the first 28 days and were followed for a median of 751 (742-760) days post-infection. 9 (9.57%) died within 1 year of infection and 14 (14.9%) within 2 years. 21 (22.3%) had ≥1 episode of allograft rejection and 21 (22.3%) had allograft failure. 11 (9.4%) were re-infected with COVID-19 at a median of 603 (389-642) days following initial infection, of whom 2 (18.2%) were hospitalized and 0 died. 43 (45.7%) had secondary infections and 18 (19.1%) with multi-drug resistant organisms. 32 (34.0%) developed new chronic kidney disease or end-stage renal disease, 25 (26.6%) had new cardiovascular disease, and 8 (8.51%) had a prolonged oxygen requirement following infection. Of reported long-COVID symptoms, fatigue (26, 27.7%), dyspnea (18, 19.1%), and cough (11, 11.7%) predominated with 25 (26.6%) having >1 symptom. Conclusion In this large cohort of SOT recipients hospitalized during the first wave of the COVID-19 pandemic, long-term 2-year follow-up showed high rates of mortality, allograft rejection, allograft failure, secondary infection, organ dysfunction, and symptoms consistent with long-COVID. Ongoing study of the impact of these complications will be crucial to improving outcomes in SOT recipients. Disclosures Marcus R. Pereira, MD, Hologic: Grant/Research Support|Merck: Grant/Research Support|Moderna: Grant/Research Support|Shire/Takeda: Grant/Research Support|Takeda: Advisor/Consultant|Union Therapeutics: Advisor/Consultant Elizabeth Verna, MD, Salix: Grant/Research Support.

Human serum lipidomics analysis revealed glyphosate may lead to lipid metabolism disorders and health risks

Glyphosate-based herbicides (GBH) are one of the most widely used pesticides worldwide. Industrial workers in glyphosate-based herbicides manufacture are the populations who experience long-term exposure to high glyphosate levels. The impacts of glyphosate on human health are the important public health problem of great concern. Up to date, the potential adverse effects of glyphosate on humans or other mammals have been reported in multiple studies. However, limited research is available on lipid alternations related to human exposure to glyphosate. In fact, the perturbations in some lipid metabolisms have been found in industrial workers in previous work. This study aims to explore the serum lipidomic characterization and to understand the underlying mechanisms of health risks associated with glyphosate exposure. A nontargeted lipidomics study was conducted to investigate the 391 serum samples from the general population and chemical factory workers. It was demonstrated that glyphosate caused significant perturbations of 115 differentially expressed lipids. The main manifestations were the elevation of circulating diacylglycerols (DG), cholesteryl esters (CE), ceramides (Cer), sphingomyelins (SM), lysophosphatidylethanolamines (LPE) and phosphatidylcholines (PC), and the decrease of ysophosphatidylcholines (LPC), triacylglycerols (TG), fatty acids (FA) and phosphatidylethanolamines (PE). A total of 88 lipids were further screened as potential lipid biomarkers associated closely with glyphosate using partial correlation analysis, and five of which (including PC 16:0/18:2; O, PC 18:0/18:2; O, PC 18:0/20:4; O, PC O-40:9 and CE 18:3) showed excellent superior performance (AUC = 1) to evaluate and monitor health risks due to glyphosate exposure. The present work discovered glyphosate-induced potential health risks, including chronic hepatic and renal dysfunction, atherosclerosis, cardiovascular disease and neurodegenerative diseases from a lipidomic perspective, and could inform the identification of early indicators and interpretation of biological mechanisms to detect health risks of the glyphosate-exposed populations as early as possible.

Hypothyroidism predicts worsened prognosis in patients undergoing percutaneous coronary intervention.

The link between thyroid dysfunction and cardiovascular disease is well established. Hypothyroidism has been significantly associated with increased risk of dyslipidemia, atherosclerosis and heart failure. However, little is known regarding its effect on patients undergoing percutaneous coronary intervention (PCI). The aim of study was to examine the impact of concomitant hypothyroidism on mortality and major adverse cardiac event (MACE) in patients undergoing PCI. The Rabin Medical Center PCI registry includes all consecutive patients who have undergone PCI between 2004 and 2020. We identified patients with prior diagnosis of hypothyroidism, and compared rates of mortality and MACE (comprising death, myocardial infarction, target vessel revascularization and/or coronary bypass surgery). Among 28,274 patients, 1,922 (6.8%) were found to have hypothryoidism. These patients were older (70.3 ± 10.4 vs. 66.0 ± 11.8 y.o, P < 0.001) and more likely to be women (34.2% vs. 26.1%, P < 0.001). They had a higher prevalence of atrial fibrillation (10.8% vs. 7.7%, P < 0.001), chronic renal dysfunction (25.1% vs. 18.7%, P = 0.04) and dementia (2.9% vs. 1.8%, P = 0.004). PCI was performed on ACS setting in 52-54% of patients in both groups (p = 0.569). Unadjusted 5-year rates of all-cause mortality (26.9% vs. 20.3%, P < 0.001) and MACE (40.3% vs. 29.4%, P < 0.001) were higher for hypothyroid patients. A propensity match score was able to form 672 matched pairs of HT and control patients, showing similar results. Moreover, following multivariate analysis, TSH as a continuous parameter was associated with a higher risk of mortality and MACE (HR, 1.06 per additional 1 mIU/L; CI, 1.02-1.11; P < 0.001 and HR, 1.07; CI, 1.02-1.12; P < 0.001, respectively) at 5-year follow up. In our study, hypothyroidism confers worse outcomes in patients undergoing PCI. Further research is needed to establish effective ways to mitigate this augmented risk.

Serum cystatin C is an early renal dysfunction biomarker in patients with hepatitis C virus

BackgroundHepatitis C virus (HCV) may induce extrahepatic manifestations as acute or chronic renal dysfunction. The aim was to evaluate the diagnostic role of some biomarkers as cystatin C, cryoglobulins, rheumatoid factor (RF), and complement C3 for extrahepatic renal affection in newly diagnosed patients with HCV infection.MethodsBlood and urine were collected from randomized individuals screened for new HCV infection (n=400). The studied populations were divided into 3 groups: control group I: thirty healthy individuals not suffering from either liver or kidney diseases, group IIa: thirty HCV patients who have positive HCV antibody test but showed negative PCR test, and group IIb: thirty HCV patients who showed positive results for both HCV antibody and PCR tests.ResultsIn HCV group IIb, levels of serum total bilirubin, AST and ALT, and urine albumin/creatinine ratio were increased whereas serum albumin and creatinine clearance were decreased versus other groups. However, the levels of blood urea nitrogen and serum creatinine were still within the normal range in all groups. In HCV group IIb, cystatin C, cryoglobulins, and RF levels were increased; meanwhile, serum creatinine/cystatin C ratio and complement 3 levels were decreased compared to the other groups. HCV-infected patients significantly had higher serum cystatin C (>1.24 mg/L, P<0.001) and lower creatinine/cystatin C ratio (<70.1μMol/mg, P=0.002), and cystatin C was significantly correlated with liver and kidney parameters.ConclusionHigh serum cystatin C and low creatinine/cystatin C ratio may be early indicators of mild renal dysfunction with normal serum levels of creatinine in HCV-infected individuals.

Cladribine with Low Dose Cytarabine for Unfit Patients: A Safe and Effective Approach with Low Early Mortality in a Population Ineligible for Clinical Trials

Background Patients with newly diagnosed AML can often present with debilitating medical conditions, active infection, concurrent malignancies, significant cardiovascular disease, and poor performance status. There is a lack of trial options for these patients. Such patients would have been excluded from the VIALE-A trial, that studied HMA + venetoclax in older and unfit patients. Frontline cladribine (Clad) with low dose cytarabine (LDAC) alternating with decitabine yielded an overall response rate (ORR) of 68%, a median overall survival (OS) 13.8 months, and was well-tolerated, with a 4-week mortality of 1% in an older patient population. This combination potentially provides an avenue for therapy in an unfit patient population with significant comorbidities. Here we present the results of this phase II study in unfit patients, ineligible for other clinical trials. Methods Pts over 18 with newly diagnosed AML found to be ineligible for clinical trials due to severe comorbidity, active infection/malignancy, or poor PS were enrolled. To be eligible, pts must have at least 1 of the following: Cr ≥2mg/dL, Bilirubin ≥2 mg/dL, ECOG of 3 or 4, active infection, concurrent active malignancy, or ineligibility for a higher priority protocol. Induction consisted of Clad 5mg/m2 on D1-5 and LDAC 20mg SQ BID on D1-10. Consolidation consisted of Clad 5mg/m2 on D1-3 and LDAC 20mg SQ BID on D1-10 with pts receiving decitabine 20mg/m2 IV monotherapy on D1-5 on alternate cycles. The primary objective was 60-day mortality. Results Between 04/2020 and 05/2022, 33 pts have been enrolled. Baseline characteristics are in Table 1. The median age is 72 yrs (range: 44-82). Fulfilled eligibility criteria for study entry included: comorbidities [acute or chronic renal dysfunction in 7 (21%) pts, cardiac in 2 (6%) , hepatic in 2 (6%), and morbid obesity with advanced PS in 1 (3%) pt] in 12 pts (36%) concomitant (active) malignancy in 9 (27%), poor PS in 6 (18%) pts , active infection in 5 pts (15%), and numerous prior treatments for MDS in 1 pt (3%), making them ineligible for other trials. 15 (45%) had history of ongoing cardiovascular or renal disease. 14 (42%) pts had history of other malignancies. 11 (33%) pts had therapy-related disease. The median blast percent was 31% (range: 12-88). Adverse risk disease based on ELN 2017 criteria was overrepresented in the cohort, occurring in 70% of pts. Complex karyotype and TP53 mutations occurred in 18% and 21% of pts, respectively. The overall response rate (CR/CRi/PR) was 66% (22 pts) with a CR/CRi rate of 63% (21) and a CR rate of 33% (11). 30% (10) attained an MRD negative remission. The median cycles to response was 1 (range: 1-4). Of the pts that responded, 3 (9%) remain on-trial, 2 (6%) went on to allogeneic SCT, 5 (15%) proceeded to post-remission maintenance strategies, 5 (15%) relapsed, 5 (15%) died after infections, 1 (3%) died after falling and developing a subdural hematoma, and 1 (3) was taken off trial due to prolonged myelosuppression. At a median follow up of 14 months, the median OS and median RFS were 8.3 months (95% CI: 0.19-15.7) and 7.9 months (95% CI: 0.45-15.3) respectively. The OS for pts with ECOG 1, 2 and >3 PS was 8.3, 7.6 and 8.8 months respectively. Pts with significant cardiac or renal disease had worse OS at 3.03 months compared to 12.5 months (p = 0.03) in pts without this history. Grade ≥3 adverse events possibly related to this combination occurred in 2 patients: one with Grade 3 nausea and the second with Grade 3 tumor lysis syndrome. The 30-day and 60-day survival were 91% and 82%% respectively. Of the 6 patients (18%) that experienced 60-day mortality, 4 (12%) died from infection (2 with pneumonia and 2 with bacteremia), 1 (3%) patient died due to a heart failure exacerbation with a critical coronary artery stenosis, and 1 (3%) pt died after transitioning to another trial, developing a medullary lesion, and opting for hospice. Conclusions In an unfit patient population with numerous comorbidities, the combination of Clad and LDAC was well tolerated with a 60-day survival of 82%, an ORR of 66%, and a median OS of 8.3 months. Once in remission, patients were able to move onto maintenance therapy or SCT in an improved condition. This combination represents a potential option for treatment in a high-risk, unfit, and undertreated patient population and demonstrates the feasibility of safely expanding trial inclusion criteria for select populations of patients. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Haematological and renal toxicity of radiation therapy in neuroblastoma paediatric patients.

The objective of this study was to evaluate the renal and hematologic toxicity in paediatric patients with adrenal high-risk neuroblastoma who have received radiation therapy (RT) as part of radical treatment. Pediatric patients diagnosed with high-risk adrenal neuroblastoma who received RT as part of the definitive treatment between January 2004 and May 2020 in a single institution were selected. Complete blood counts (CBC) and creatinine clearance (CrCl) pre-RT and post-RT were compared through the Wilcoxon signed-rank test and correlated with survival analysis by Cox regression. Forty-two children with a median age of 3years at diagnosis and 2.8years of follow-up were selected. A significant and acute decrease in lymphocytes was found (p = 0.002) 1month from RT. Patients with a drop higher than 50% of the previous value experimented a significant reduction in overall survival (55 vs 10%; p = 0.031). At the end of the follow-up, a significant increase in all blood counts was observed. With respect to renal function, an acute and significant decrease in CrCl was observed tin patients younger than 4years who received RT (p = 0.013). However, it was not clinically relevant. Our data suggest that acute lymphopenia occurs after RT and could be associated with a poorer prognosis. Other blood counts are reduced after RT and all of them are in physiological range at the end of follow-up. Our cohort presented excellent renal outcomes without any case of chronic renal dysfunction.

IRF1/ZNF350/GPX4-mediated ferroptosis of renal tubular epithelial cells promote chronic renal allograft interstitial fibrosis.

Renal interstitial fibrosis and tubular atrophy are essential pathological characteristics of chronic renal allograft dysfunction (CAD). Herein, we revealed that ferroptosis of renal tubular epithelial cells (RTECs) might contribute to renal tubular injury in CAD. Mechanistically, TNF-α induced ferroptosis by inhibiting GPX4 transcription through upregulating IRF1 in RTECs. IRF1 could bind with ZNF350 to form a transcription factor complex, which directly binds to the GPX4 promoter region to inhibit GPX4 transcription. Ferroptotic RTECs might secrete profibrotic factors, including PDGF-BB and IL-6, to activate neighboring fibroblasts to transform into myofibroblasts or induce EMT in adjacent RTECs. In conclusion, our results confirmed a novel role of ferroptosis in renal tubular injury and interstitial fibrosis, thereby providing insights into the pathogenesis of chronic renal allograft interstitial fibrosis during CAD.

Systemic immune-inflammation index as a prognostic marker for advanced chronic heart failure with renal dysfunction.

We aim to investigate the correlation between high levels of the systemic immune-inflammation index (SII) and long-term mortality and major cardiovascular adverse events in advanced chronic heart failure patients with renal dysfunction. Seven hundred seventeen advanced chronic heart failure patients with renal dysfunction, who visited the First affiliated hospital of Zhengzhou University from September 2019 to December 2020, were included. All-cause mortalities (ACM) were selected as primary endpoints and major cardiovascular adverse events (MACEs) as the secondary endpoints. Based on the receiver operating characteristic (ROC) curve and the Youden index, the optimal cut-off values of SII for ACM and MACEs were 1228 and 1406. In the group where ACM were the primary endpoint, patients were categorized into the low-SII group (n=479) and the high-SII group (n=238). Patients in the group using MACEs as the secondary endpoint were also categorized into the low-SII groups (n=514) and the high-SII groups (n=203). Univariate and multivariate COX regression were used to screen the independent predictors for ACM and MACEs, revealing the relationship between SII levels and endpoints. According to the univariate COX analysis, SII was the risk factor (hazard ratio [HR]=2.144, 95% confidence interval [CI]: 1.565-2.938, P<0.001) for the ACM subgroup. It was also the risk factor (HR=1.625, CI: 1.261-2.905, P<0.001) for the MACEs subgroup. Multivariate COX regression analysis indicated that the occurrence of ACM and MACEs in high-level SII and low-level SII patients had statistical differences. The incidence of ACM increased by 70.3% (HR=1.703; 95% CI: 1.200-2.337; P=0.002) in patients of the high SII level group, the incidence of MACEs increased by 58.3% (HR=1.583, 95% CI: 1.213-2.065, P=0.001). Kaplan-Meier (K-M) survival analysis further suggested that patients with a high SII level had an increased risk of having ACM (log-rank P<0.001) and MACEs (log-rank P<0.001) within 30months. SII could be considered as a novel predictor of the occurrence of ACM and MACEs for patients with advanced chronic heart failure and renal dysfunction. This study suggested that SII is a novel independent predictor of mortality in advanced chronic heart failure patients with renal dysfunction, and it should be considered in current clinical management.

POS-028 RENAL INVOLVEMENT AND OUTCOMES IN PATIENTS WITH COVID DURING THIRD WAVE IN INDIA

SARS-CoV-2, a respiratory virus, can involve the kidneys and cause acute kidney injury (AKI) by both direct and indirect mechanisms. Patients with renal dysfunction form a special group with special needs. Chronic kidney disease (CKD) is a state of impaired innate and adaptive immunity, co-existing with chronic inflammation; their clinical manifestations can be mild, while progress rapidly giving physicians shorter window period to intervene. Many CKD patients are on immunosuppressive medications for glomerulonephritis or as transplant recipients. Kidney being the excretory organ for most drugs and its metabolites, acute or chronic renal dysfunction calls for dose modification. It is important to look for nephrotoxicity of medications especially in those with CKD. Trials involving new medications exclude patients with renal dysfunction, hence experience with such medications arrives late. This was a prospective study intended to analyze the renal involvement and outcomes in patients who were infected by COVID infection during the third wave. This study was conducted in India, across multiple hospitals. All adult patients who were seen by Nephrologist either as outpatient or as an inpatient between 12-01-2022 and 18-02-2022 were included. Data was collected in a repository in a software developed by Bloom Value Corporation, extracted to excel sheet and analyzed. 159 patients, 67.9% males, aged 59.5 ± 14.98 years, who were diagnosed to have COVID infection during third wave in India studied [figure - 1]. 45 (47.87%) out of 94, who were admitted did not need any oxygen supplementation; 9 (24.3%) of those admitted in ICU / HDU needed ventilatory support. Steroids was prescribed or dosage escalated in 36.48%; Remdesivir was used in 34.59%. Other than 54 patients, who were on maintenance hemodialysis, 23 (14.47%) needed dialysis.Previous COVID infection was noted in 12.58%; 86.79% were vaccinated with at least 1 dose. 18 (11.32%) were renal transplant recipients, 54 (33.96%) were hemodialysis patients; 30 (18.87%) were on immunosuppressive medications. Presenting complaints were fever 99 (62.26%) cough 81 (50.94%), breathlessness 43 (27.04%) diarrhea 5 (3.14%) and vomiting 15 (9.43%). 65 (40.88%) were treated as Outpatient, 57 (35.85%) in wards while 30 (18.87%) needed either ICU or HDU admission [figure - 2]. 16 new patients became dialysis dependent, they had CKD, with a mean eGFR of 14.52 ml/min. 6 (3.77%) patients died, all had been vaccinated against COVID with 2 doses of vaccine; needed ICU care; 2 were ventilated. Among those who died, 3 had CKD, one each were patient on dialysis, transplant and AKI. 4 (66.7%) had needed dialysis.View Large Image Figure ViewerDownload Hi-res image Download (PPT) None of those with normal renal functions developed AKI [figure - 3]. Renal involvement in the form of AKI or acute worsening of renal functions was seen among COVID patients. Vaccination did not prevent infection. Mortality was higher among CKD patients.

Soluble (Pro)Renin Receptor Levels Are Regulated by Plasma Renin Activity and Correlated with Edema in Mice and Humans with HFrEF

Symptomatic heart failure with reduced ejection fraction (HFrEF) is characterized by edema and chronic pathological activation of the classical renin–angiotensin–aldosterone system (RAAS). The soluble (pro)renin receptor (s(P)RR) is released into circulation by proteolytic cleavage of tissue expressed (P)RR and is a candidate biomarker of RAAS activation. However, previous studies linked elevated levels of s(P)RR in patients with HFrEF to renal dysfunction. Utilizing prospectively enrolled patients with comparable rEF, we show that increased plasma levels of s(P)RR are associated with symptomatic HF (characterized by edema), independent of chronic renal dysfunction. We also found that s(P)RR levels were positively correlated with patient plasma renin activity (PRA). Normotensive mice with dilated cardiomyopathy (DCM) and HFrEF, without renal dysfunction, showed plasma s(P)RR and PRA patterns similar to human HFrEF patients. Plasma s(P)RR levels positively correlated with PRA and systemic edema, but not with EF, resembling findings in patients with HFrEF without chronic kidney dysfunction. In female DCM mice with elevated PRA levels and plasma s(P)RR levels, a randomized, blinded trial comparing the direct renin inhibitor, aliskiren vs. vehicle control, showed that direct renin inhibition normalized PRA, lowered s(P)RR, and prevented symptomatic HFrEF. Considered in light of previous findings, these data suggest that, in HFrEF, in the absence of renal dysfunction, elevation of plasma s(P)RR levels is caused by increased PRA and associated with the development of systemic edema.

Liver Transplantation in Sexagenarian Patients Using Grafts From Uncontrolled Circulatory Death Versus Grafts From Brain Death Donation

An increased number of older recipients underwent liver transplantation in recent years, and consequently needing to obtain more liver grafts. In order to increase this pool, in 2006, we initiated the use of livers from uncontrolled circulatory death (uDCD). We analyzed the use of uDCD livers in sexagenarian recipients and their effect on overall survival. A retrospective and comparative study was performed among 4 groups according to recipient age (less or greater than 60 years) and donor type (donor brain death [DBD] or uDCD): Group A: DBD livers in recipients aged <60 years (n=169); Group B: uDCD livers in recipients aged <60 years (n=36); Group C: DBD livers in recipients aged >60 years (n=96); and Group D: uDCD livers in recipients aged >60 years(n=39). Intraoperative transfusion, biliary complications, primary non-function, acute rejection, chronic renal dysfunction, retransplantation, and mortality during follow-up (cardiovascular diseases in 3 patients, hepatitis C virus recurrence in 4 patients, and de novo malignancies in 3 patients) were significantly higher, and 5-year patient and graft survival was significantly lower in sexagenarian recipients. Bilirubin and packed red blood cells transfusion were risk factors for patient survival, whereas hepatocelular carcinoma, creatinine, and packed red blood cells transfusion were risk factors for patient survival. Recipient age (<60 years) was confirmed as protective factor for patient and graft survival, whereas the use of uDCD was not a risk factor for patient or graft survival. Use of a uDCD liver did not demonstrate as a risk factor for patient and graft survival, and recipient age (<60 years) was a protective factor for patient and graft survival.

Nephrogenic Systemic Fibrosis in Patients with Chronic Kidney Disease after the Use of Gadolinium-Based Contrast Agents: A Review for the Cardiovascular Imager.

Gadolinium-enhanced cardiac magnetic resonance has revolutionized cardiac imaging in the last two decades and has emerged as an essential and powerful tool for the characterization and treatment guidance of a wide range of cardiovascular diseases. However, due to the high prevalence of chronic renal dysfunction in patients with cardiovascular conditions, the risk of nephrogenic systemic fibrosis (NSF) after gadolinium exposure has been a permanent concern. Even though the newer macrocyclic agents have proven to be much safer in patients with chronic kidney disease and end-stage renal failure, clinicians must fully understand the clinical characteristics and risk factors of this devastating pathology and maintain a high degree of suspicion to prevent and recognize it. This review aimed to summarize the existing evidence regarding the physiopathology, clinical manifestations, diagnosis, and prevention of NSF related to the use of gadolinium-based contrast agents.

Correlation Between Bioelectrical Impedance Analysis and Chest CT-Measured Erector Spinae Muscle Area: A Cross-Sectional Study.

BackgroundSkeletal muscle mass (SMM) plays an important part in diverse health and disease states. Bioelectrical impedance analysis (BIA) and computed tomography (CT) are available for its assessment. However, muscle mass assessed by BIA may be influenced by multiple factors. The erector spinae muscle area (ESA) on chest CT is recently presumed to be representative of SMM. This study aimed to derive BIA from the ESA and evaluate the magnitude of association (between ESA measured from chest CT) and BIA.MethodsSubjects hospitalized for health checkups between December 2020 and December 2021, having undergone both BIA (50 kHz, 0.8 mA) and chest CT, were included. ESA was quantified at the level of the 12th thoracic vertebra (T12-ESA) by a standardized semi-automated segmentation algorithm. Low SMM was defined using the Asian Working Group for Sarcopenia criteria. The association between T12-ESA and BIA was then evaluated. Stratified analyses by sex and BMI were also performed.ResultsAmong 606 included subjects (59.7 ± 16.6 years, 63.5% male), 110 (18.2%) had low SMM. BMI in low and normal SMM groups was 20.1 and 24.7 kg/m2, respectively. Current smoking, drinking, chronic obstructive pulmonary disease, and chronic renal dysfunction were more frequently seen in the low SMM group than in the normal SMM group. The final regression model included T12-ESA, weight, BMI, and age, and had an adjusted R 2 of 0.806 with BIA. In the validation group, the correlation between T12-ESA-derived BIA and BIA remained high (Pearson correlation = 0.899). Stratified analysis disclosed a stronger correlation between T12-ESA and BIA in male subjects than in female subjects (adjusted R 2 = 0.790 vs. adjusted R 2 = 0.711, p < 0.05), and a better correlation was observed in obese (BMI ≥ 30 kg/m2) compared with underweight (BMI < 18.5 kg/m2) subjects (adjusted R 2 = 0.852 vs. adjusted R 2 = 0.723, p < 0.05). Additional analysis revealed a significant correlation between T12-ESA and skeletal muscle cross-sectional area at the 3rd lumbar vertebra (L3-CSA) (adjusted R 2 = 0.935, p < 0.001).ConclusionsCT-based assessment of ESA at the T12 level is feasible and correlated well with BIA, especially in male subjects and obese subjects.

Mild and moderate to severe early acute kidney injury following cardiac surgery among patients with heart failure and preserved vs. mid-range vs. reduced ejection fraction: A retrospective cohort study.

Patients with heart failure who undergo cardiac surgery have increased long-term mortality in which acute kidney injury (AKI) plays a role. However, little is known about whether the incidence of AKI differs according to stratified left ventricular ejection fraction (LVEF). To assess the risks of mild AKI and moderate to severe AKI postcardiac surgery among patients with heart failure. Retrospective cohort analysis of patient data. Ejection fractions were categorised as LVEF less than 40%, heart failure with reduced ejection fraction (HFrEF); LVEF 40 to 49%, heart failure with mid-range ejection fraction (HFmrEF); and LVEF at least 50%, heart failure with preserved ejection fraction (HFpEF). Patients who underwent cardiac surgery from 2012 to 2019 in Fuwai Hospital, Beijing, China, were consecutively enrolled. The primary endpoint was postoperative AKI staged either as mild AKI or moderate to severe AKI. The secondary outcome was the peri-operative composite adverse event of dialysis support, tracheotomy, intrasurgical and postsurgical mechanical cardiac support and in-hospital mortality. This study also assessed chronic renal dysfunction at follow-up. Of the 54 696 included patients, 18.9% presented with heart failure. Among these with HFpEF, HFmrEF and HFrEF, the incidence of postoperative mild AKI was 37.0, 33.4 and 37.6%, respectively. Patients with HFpEF and HFmrEF were characterised by numerically greater prevalence of moderate to severe AKI than HFrEF (8.5 vs. 9.1 vs. 5.8%). HFrEF and HFmrEF patients had comparable risks for mild AKI relative to HFpEF patients, odds ratio (OR) 0.885; 95% confidence interval CI 0.763 to 1.027 for HFmrEF vs. HFpEF; OR 1.083; 95% CI 0.933 to 1.256 for HFrEF vs. HFpEF. Patients with HFmrEF were more at risk for moderate to severe AKI than patients with HFpEF (OR, 1.368; 95% CI 1.066 to 1.742), but HFrEF and HFpEF did not differ significantly (OR 1.012; 95% CI 0.752 to 1.346). An increasing number of noncardiac comorbidities led to a higher risk of mild AKI and moderate to severe AKI in patients with heart failure; and its effect on AKI was almost equal among the three heart failure strata. The incidence of postoperative composite adverse outcome increased in a graded manner from HFpEF to HFmrEF to HFrEF. Information on the creatine concentrations at 3 months postoperatively and longer were retained for 5200 out of 10 347 (50.6%) heart failure patients in our charts.The AKI severity and the presence of HFmrEF contributed substantially to the development of renal dysfunction over a median [IQR] follow-up of 10 months [4.0 to 21.0]. Initiative programmes aimed at patients with HFrEF to prevent moderate to severe AKI and chronic kidney dysfunction should also include patients with HFmrEF.

Clinical course of patients with rheumatoid arthritis who continue or discontinue biologic therapy after hospitalization for infection: a retrospective observational study

BackgroundTo analyse the subsequent clinical course of patients with rheumatoid arthritis (RA) who either continued or discontinued biologic agents after hospitalization for infections.MethodsWe retrospectively reviewed the clinical records of 230 RA patients with 307 hospitalizations for infections under biologic therapy between September 2008 and May 2014 in 15 institutions for up to 18 months after discharge. The risks of RA flares and subsequent hospitalizations for infections from 61 days to 18 months after discharge were evaluated.ResultsSurvival analyses indicated that patients who continued biologic therapy had a significantly lower risk of RA flares (31.4% vs. 60.6%, P < 0.01) and a slightly lower risk of subsequent infections (28.7% vs. 34.5%, P = 0.37). Multivariate analysis showed that discontinuation of biologic therapy, diabetes, and a history of hospitalization for infection under biologic therapy were associated with RA flares. Oral steroid therapy equivalent to prednisolone 5 mg/day or more and chronic renal dysfunction were independent risk factors for subsequent hospitalizations for infections.ConclusionsDiscontinuation of biologic therapy after hospitalization for infections may result in RA flares. Continuation of biologic therapy is preferable, particularly in patients without immunodeficiency.

Early recovery status and outcomes after sepsis-associated acute kidney injury in critically ill patients.

Acute kidney injury (AKI) is one of the common complications in critically ill septic patients, which is associated with increased risks of death, cardiovascular events, and chronic renal dysfunction. The duration of AKI and the renal function recovery status after AKI onset can affect the patient prognosis. Nevertheless, it remains controversial whether early recovery status after AKI is closely related to the prognosis in patients with sepsis-associated AKI (SA-AKI). In addition, early prediction of renal function recovery after AKI is beneficial to individualized treatment decision-making and prevention of severe complications, thus improving the prognosis. At present, there is limited clinical information on how to identify SA-AKI patients at high risk of unrecovered renal function at an early stage. The study aims to investigate the association between early recovery status after SA-AKI, identify risk factors for unrecovered renal function, and to improve patients' quality of life. We retrospectively analyzed clinical data of septic patients who were admitted to the intensive care unit (ICU) and developed AKI within the first 48 hours after ICU admission in the Second Xiangya Hospital and the Third Xiangya Hospital of Central South University from January 2015 to March 2017. Sepsis was defined based on the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). AKI was diagnosed and staged according to the 2012 Kidney Disease: Improving Global Outcomes (KDIGO) guideline. SA-AKI patients were assigned into 3 groups including a complete recovery group, a partial recovery group, and an unrecovered group based on recovery status at Day 7 after the diagnosis of AKI. Patients' baseline characteristics were collected, including demographics, comorbidities, clinical and laboratory examination information at ICU admission, and treatment within the first 24 hours. The primary outcome of the study was the composite of death and chronic dialysis at 90 days, and secondary outcomes included length of stay in the ICU, length of stay in the hospital, and persistent renal dysfunction. Multivariate regression analysis was performed to evaluate the prognostic value of early recovery status after AKI and to determine the risk factors for unrecovered renal function after AKI. Sensitivity analysis was conducted in patients who still stayed in hospital on Day 7 after AKI diagnosis, patients without premorbid chronic kidney disease, and patients with AKI Stage 2 to 3. A total of 553 SA-AKI patients were enrolled, of whom 251 (45.4%), 73 (13.2%), and 229 (41.4%) were categorized as the complete recovery group, the partial recovery group, and the unrecovered group, respectively. Compared with the complete or partial recovery group, the unrecovered group had a higher incidence of 90-day mortality (unrecovered vs partial recovery or complete recovery: 64.2% vs 26.0% or 22.7%; P<0.001) and 90-day composite outcome (unrecovered vs partial recovery or complete recovery: 65.1% vs 27.4% or 22.7%; P<0.001). The unrecovered group also had a shorter length of stay in the hospital and a larger proportion of progression into persistent renal dysfunction than the other 2 groups. After adjustment for potential confounders, patients in the unrecovered group were at an increased risk of 90-day mortality (HR=3.50, 95% CI 2.47 to 4.96, P<0.001) and 90-day composite outcome (OR=5.55, 95% CI 3.43 to 8.98, P<0.001) when compared with patients in the complete recovery group, but patients in the partial recovery group had no significant difference (P>0.05). Male sex, congestive heart failure, pneumonia, respiratory rate >20 beats per minute, anemia, hyperbilirubinemia, need for mechanical ventilation, and AKI Stage 3 were identified as independent risk factors for unrecovered renal function after AKI. The sensitivity analysis further supported that unrecovered renal function after AKI remained an independent predictor for 90-day mortality and composite outcome in the subgroups. The early recovery status after AKI is closely associated with poor prognosis in critically ill patients with SA-AKI. Unrecovered renal function within the first 7 days after AKI diagnosis is an independent predictor for 90-day mortality and composite outcome. Male sex, congestive heart failure, pneumonia, tachypnea, anemia, hyperbilirubinemia, respiratory failure, and severe AKI are risk factors for unrecovered renal function after AKI. Therefore, timely assessment for the renal function in the early phase after AKI diagnosis is essential for SA-AKI patients. Furthermore, patients with unrecovered renal function after AKI need additional management in the hospital, including rigorous monitoring, avoidance of nephrotoxin, and continuous assessment for the renal function, and after discharge, including more frequent follow-up, regular outpatient consultation, and prevention of long-term adverse events.

Multimorbidity, guideline‐directed medical therapies, and associated outcomes among hospitalized heart failure patients

AimsMultimorbidity is common among heart failure (HF) patients and may attenuate guideline‐directed medical therapy (GDMT). Multimorbid patients are under‐represented in clinical trials; therefore, the effect of multimorbidity clustering on the prognosis of HF patients remains unknown. We evaluated the prevalence of multimorbidity clusters among consecutively registered hospitalized HF patients and assessed whether GDMT attenuated outcomes.Methods and resultsWe examined 1924 hospitalized HF patients with reduced left ventricular ejection fraction (<50%) in a multicentre registry (West Tokyo HF Registry: WET‐HF). Ten comorbid conditions in the WET‐HF were abstracted: coronary artery disease, atrial fibrillation, stroke, anaemia, chronic obstructive pulmonary disease, renal dysfunction, obesity, hypertension, dyslipidaemia, and diabetes. Patients were divided into three groups (0–2: n = 451; 3–4: n = 787; and ≥5: n = 686) based on the number of comorbid conditions. The primary composite endpoint was all‐cause mortality and HF rehospitalization. The most prevalent comorbidities were renal dysfunction (67.9%), hypertension (66.0%), and anaemia (53.8%). Increased comorbidity was associated with increased adverse outcomes [3–4: hazard ratio (HR) 1.42, 95% confidence interval (CI) 1.13–1.77, P = 0.003; ≥5: HR 2.12, 95%CI 1.69–2.65, P < 0.001; and reference: 0–2] and lower GDMT prescription rate (0–2: 69.2%; 3–4: 57.7%; and ≥5: 57.6%). GDMT was associated with decreased adverse outcomes; this association was maintained even as the comorbidity burden increased but tended to weaken (0–2: HR 0.53, 95%CI 0.35–0.78; P = 0.001; 3–4: HR 0.82, 95%CI 0.65–1.04, P = 0.095; and ≥5: HR 0.81, 95%CI 0.65–1.00, P = 0.053; P for interaction = 0.156).ConclusionsComorbidity clusters were prevalent and associated with poorer outcomes. GDMT remained beneficial regardless of the comorbidity burden but tended to weaken with increasing comorbidity burden. Further research is required to optimize medical care in these patients.

High-Frequency US for BK Polyomavirus-associated Nephropathy after Kidney Transplant.

Background BK polyomavirus-associated nephropathy (BKPyVAN) is an important cause of chronic renal allograft dysfunction. However, US features indicative of BKPyVAN have not been fully evaluated. Purpose To assess the value of high-frequency US for the diagnosis of BKPyVAN in kidney transplant recipients. Materials and Methods In this prospective cohort study, participants who tested positive for BK viruria after kidney transplant from September 2019 to January 2021 were evaluated with high-frequency US 1 day before biopsy. Clinical characteristics and US features were compared between participants with and without BKPyVAN. Significant predictors associated with BKPyVAN were determined using logistic regression analyses. The area under the receiver operating characteristic curve (AUC) was used to evaluate diagnostic performance. Results A total of 105 participants who underwent kidney transplant (mean age, 38 years ± 11 [SD]; 63 men) were evaluated; 45 participants were diagnosed with BKPyVAN. Multivariable analysis demonstrated that eccentric hydronephrosis and subcapsular hypoechoic areas were independent factors for BKPyVAN. The AUC for predicting BKPyVAN according to subcapsular hypoechoic areas was 0.66 (95% CI: 0.55, 0.77), with a specificity of 92% (55 of 60 participants). The AUC of combined US (eccentric hydronephrosis plus subcapsular hypoechoic area) and clinical (urine BKPyV DNA load [BKPyV-DNA] plus BK viremia) features was 0.90, with a specificity of 92% (55 of 60 participants). Parenchymal hyperechoic and subcapsular hypoechoic areas were independent factors for differentiating BKPyVAN from transplant rejection. The pooled specificity of subcapsular hypoechoic areas was 96% (21 of 22 participants), with an AUC of 0.67 (95% CI: 0.54, 0.80). For the combination of US (parenchymal echogenicity plus subcapsular hypoechoic area) and clinical (urine BKPyV-DNA plus time since transplant) features, the AUC reached 0.92 and specificity was 82% (18 of 22 participants). Conclusion High-frequency US characteristics are valuable for diagnosing BK polyomavirus-associated nephropathy (BKPyVAN) and distinguishing BKPyVAN from rejection in kidney transplant recipients. © RSNA, 2022 Online supplemental material is available for this article.

MO458: Superb Micro-Vascular Imaging: An Innovative Ultrasound Technique for Early Detecting of Renal Damage

Abstract BACKGROUND AND AIMS Novel ultrasound (US) methods are required to assess qualitative alterations in renal tissue. Superb microvascular imaging (SMI) is an innovative US technique designed for imaging and better visualization of micro-vascularization unseen with color Doppler US. We assume that SMI will provide sufficient information regarding the severity of chronic kidney disease (CKD) and reflect renal histological alterations. To assess the early detection of kidney dysfunction and renal fibrosis capabilities of SMI imaging in comparison to the reference standard renal biopsy, in order to determine the usefulness of this approach in the early diagnosis of kidney dysfunction and renal fibrosis. METHOD The SMI was performed in patients (n = 52) with CKD stage 2–5, where some of them underwent biopsy-proven chronic renal dysfunction and fibrosis as part of the diagnosis and therapeutic judgment as needed. In addition, biochemical tests were performed in order to determine kidney function (BUN, Serum Creatinine), a urine collection test for the assessment of proteinuria and estimation of GFR by MDRD formula in patients with CKD of various severity and healthy controls (n = 17). In addition, all subjects underwent SMI US imaging, where vascularity is expressed as SMI index (low index reflects low vascularity/fibrosis and vice versa). RESULTS As expected, SMI vascular index was significantly lower in CKD patients as compared with healthy control (72.2 ± 12.9 versus 49.9 ± 16.7 %, P &amp;lt; 0.01). Interestingly, significant correlation between the SMI index and eGFR was found among the CKD patients (r = 0.56, P &amp;lt; 0.001). Similarly, a keen correlation was found between the SCr and SMI index of the diseased subjects (r = −0.54, P &amp;lt; 0.001). Among those who underwent renal biopsy, SMI index corresponds with the histological alterations such as fibrosis and CKD staging. CONCLUSION These findings show that SMI technique could be used due to its diagnostic capacity as a simple and practical method for evaluation of chronic renal histological changes and for the differentiation between CKD grades.

Plication Of A High-flow Arteriovenous Fistula Resulting In Improvement Of High-output Heart Failure

<h3>Introduction</h3> High-output heart failure (HOF) is characterized by a state of congestion resulting from high cardiac output (CO) and decreased systemic vascular resistance (SVR). Arteriovenous fistulae (AVF) are durable vascular access used for renal replacement therapy (RRT). They are an important and perhaps under-recognized etiology of HOF. We present a case where plication of a high-flow AVF resulted in clinical improvement of HOF. <h3>Case Presentation</h3> A 54-year-old woman with end-stage renal disease underwent renal transplant eighteen years ago after receiving RRT through an AVF for eleven months. Currently, she has developed chronic renal allograft dysfunction and congestive heart failure. Her baseline ejection fraction (EF) and estimated glomerular filtration rate (eGFR) were 50-55% and 25-30 mL/min/1.7m². On this hospital admission, she had marked volume overload (20 kg over her dry weight), poor response to continuous rate infusion bumetanide, and newly depressed EF of 25-30%. Right heart catheterization showed elevated CO (9.8 L/min) and elevated filling pressures (right atrial pressure 17 mmHg; pulmonary capillary wedge pressure 27 mmHg). Doppler ultrasound of the AVF measured its flow to be 4.9 L/min. Temporary occlusion of the AVF resulted in a 35% decrease in CO and 21% increase in SVR, suggesting HOF due to AVF. Due to ongoing concern for renal allograft failure, the decision was made to plicate the AVF to preserve its potential future use in RRT. A 10cm length of the AVF was plicated. Repeat echocardiography ten days after plication revealed recovery of EF to baseline. Following the plication, her response to diuresis improved and she eventually achieved euvolemia over a period of three weeks. She was discharged home on oral bumetanide 3mg twice daily. <h3>Conclusion</h3> AVF-related HOF is associated with detrimental ventricular remodeling that may be reversed with attenuation of the shunt. In our case, plication was used in a novel manner to preserve AVF function. There are no guidelines that suggest how AVF should be managed following renal transplant. Further work in this field may be useful in exploring the role of plication in the management of HOF.