ABSTRACT
Importance: Recipient outcomes after kidney transplant from deceased donors who received dialysis prior to kidney donation are not well described. Objective: To compare outcomes of transplant recipients who received kidneys from deceased donors who underwent dialysis prior to kidney donation vs recipients of kidneys from deceased donors who did not undergo dialysis. Design, Setting, and Participants: A retrospective cohort study was conducted including data from 58 US organ procurement organizations on deceased kidney donors and kidney transplant recipients. From 2010 to 2018, 805 donors who underwent dialysis prior to kidney donation were identified. The donors who underwent dialysis prior to kidney donation were matched 1:1 with donors who did not undergo dialysis using a rank-based distance matrix algorithm; 1944 kidney transplant recipients were evaluated. Exposure: Kidney transplants from deceased donors who underwent dialysis prior to kidney donation compared with kidney transplants from deceased donors who did not undergo dialysis. Main Outcomes and Measures: The 4 study outcomes were delayed graft function (defined as receipt of dialysis by the kidney recipient ≤1 week after transplant), all-cause graft failure, death-censored graft failure, and death. Results: From 2010 to 2018, 1.4% of deceased kidney donors (805 of 58â¯155) underwent dialysis prior to kidney donation. Of these 805 individuals, 523 (65%) donated at least 1 kidney. A total of 969 kidneys (60%) were transplanted and 641 kidneys (40%) were discarded. Among the donors with kidneys transplanted, 514 (mean age, 33 years [SD, 10.8 years]; 98 had hypertension [19.1%] and 36 had diabetes [7%]) underwent dialysis prior to donation and were matched with 514 (mean age, 33 years [SD, 10.9 years]; 98 had hypertension [19.1%] and 36 had diabetes [7%]) who did not undergo dialysis. Kidney transplants from donors who received dialysis prior to donation (n = 954 kidney recipients) were associated with a higher risk of delayed graft function compared with kidney transplants from donors who did not receive dialysis (n = 990 kidney recipients) (59.2% vs 24.6%, respectively; adjusted odds ratio, 4.17 [95% CI, 3.28-5.29]). The incidence rates did not significantly differ at a median follow-up of 34.1 months for all-cause graft failure (43.1 kidney transplants per 1000 person-years from donors who received dialysis prior to donation vs 46.9 kidney transplants per 1000 person-years from donors who did not receive dialysis; adjusted hazard ratio [HR], 0.90 [95% CI, 0.70-1.15]), for death-censored graft failure (22.5 vs 20.6 per 1000 person-years, respectively; adjusted HR, 1.18 [95% CI, 0.83-1.69]), or for death (24.6 vs 30.8 per 1000 person-years; adjusted HR, 0.76 [95% CI, 0.55-1.04]). Conclusions and Relevance: Compared with receiving a kidney from a deceased donor who did not undergo dialysis, receiving a kidney from a deceased donor who underwent dialysis prior to kidney donation was associated with a significantly higher incidence of delayed graft function, but no significant difference in graft failure or death at follow-up.
Subject(s)
Delayed Graft Function , Kidney Transplantation , Renal Dialysis , Tissue Donors , Humans , Retrospective Studies , Female , Male , Adult , Middle Aged , Delayed Graft Function/epidemiology , Tissue and Organ ProcurementABSTRACT
Serum creatinine levels are insensitive to real-time changes in kidney function or injury. There is a growing interest in assessing kidney injury by measuring biomarkers in body fluid. From our previous studies, we identified and reported three urinary biomarkers namely Uromodulin (UMOD), Osteopontin (OPN), and Interleukin-9 (IL-9) to be associated with kidney health. The availability of a rapid point-of-care test for these urinary biomarkers will potentially accelerate its applicability and accessibility. In this study, we aimed to develop novel lateral flow device (LFD) for UMOD, OPN and IL-9. We tested paired antibodies using Enzyme Linked Immunosorbent Assay wherein we observed functionality only for UMOD and OPN and not for IL-9. A conjugation buffer pH of 7.8 and 8.5 was found suitable at a detection antibody concentration of 15 µg/mL for LFD development. The developed LFDs were found to quantitatively measure UMOD standard (LLOD of 80,000 pg/mL) and OPN standard (LLOD of 8600 pg/mL) respectively. The LFD was also able to measure human urinary UMOD and OPN with a percent CV of 12.12 and 5.23 respectively.
Subject(s)
Interleukin-9 , Urinary Tract , Humans , Kidney , Antibodies , Biomarkers , UromodulinABSTRACT
Acute kidney injury (AKI) is a major risk factor for long-term adverse outcomes, including chronic kidney disease. In mouse models of AKI, maladaptive repair of the injured proximal tubule (PT) prevents complete tissue recovery. However, evidence for PT maladaptation and its etiological relationship with complications of AKI is lacking in humans. We performed single-nucleus RNA sequencing of 120,985 nuclei in kidneys from 17 participants with AKI and seven healthy controls from the Kidney Precision Medicine Project. Maladaptive PT cells, which exhibited transcriptomic features of dedifferentiation and enrichment in pro-inflammatory and profibrotic pathways, were present in participants with AKI of diverse etiologies. To develop plasma markers of PT maladaptation, we analyzed the plasma proteome in two independent cohorts of patients undergoing cardiac surgery and a cohort of marathon runners, linked it to the transcriptomic signatures associated with maladaptive PT, and identified nine proteins whose genes were specifically up- or down-regulated by maladaptive PT. After cardiac surgery, both cohorts of patients had increased transforming growth factor-ß2 (TGFB2), collagen type XXIII-α1 (COL23A1), and X-linked neuroligin 4 (NLGN4X) and had decreased plasminogen (PLG), ectonucleotide pyrophosphatase/phosphodiesterase 6 (ENPP6), and protein C (PROC). Similar changes were observed in marathon runners with exercise-associated kidney injury. Postoperative changes in these markers were associated with AKI progression in adults after cardiac surgery and post-AKI kidney atrophy in mouse models of ischemia-reperfusion injury and toxic injury. Our results demonstrate the feasibility of a multiomics approach to discovering noninvasive markers and associating PT maladaptation with adverse clinical outcomes.
Subject(s)
Acute Kidney Injury , Reperfusion Injury , Mice , Adult , Animals , Humans , Proteome/metabolism , Transcriptome/genetics , Kidney/metabolism , Kidney Tubules, Proximal , Acute Kidney Injury/genetics , Reperfusion Injury/metabolism , Disease Models, AnimalABSTRACT
Biomarkers of tubular function such as epidermal growth factor (EGF) may improve prognostication of participants at highest risk for chronic kidney disease (CKD) after hospitalization. To examine this, we measured urinary EGF (uEGF) from samples collected in the Assessment, Serial Evaluation, and Subsequent Sequelae of Acute Kidney Injury (ASSESS-AKI) Study, a multi-center, prospective, observational cohort of hospitalized participants with and without AKI. Cox proportional hazards regression was used to investigate the association of uEGF/Cr at hospitalization, three months post-discharge, and the change between these time points with major adverse kidney events (MAKE): CKD incidence, progression, or development of kidney failure. Clinical findings were paired with mechanistic studies comparing relative Egf expression in mouse models of kidney atrophy or repair after ischemia-reperfusion injury. MAKE was observed in 20% of 1,509 participants over 4.3 years of follow-up. Each 2-fold higher level of uEGF/Cr at three months was associated with decreased risk of MAKE (adjusted hazards ratio 0.46, 95% confidence interval: 0.39-0.55). Participants with the highest increase in uEGF/Cr from hospitalization to three-month follow-up had a lower risk of MAKE (adjusted hazards ratio 0.52; 95% confidence interval: 0.36-0.74) compared to those with the least change in uEGF/Cr. A model using uEGF/Cr at three months combined with clinical variables yielded moderate discrimination for MAKE (area under the curve 0.73; 95% confidence interval: 0.69-0.77) and strong discrimination for kidney failure at four years (area under the curve 0.96; 95% confidence interval: 0.92-1.00). Accelerated restoration of Egf expression in mice was seen in the model of adaptive repair after injury, compared to a model of progressive atrophy. Thus, urinary EGF/Cr may be a biomarker of distal tubular health, with higher concentrations and increased uEGF/Cr post-discharge independently associated with reduced risk of MAKE in hospitalized patients.
Subject(s)
Acute Kidney Injury , Renal Insufficiency, Chronic , Humans , Animals , Mice , Epidermal Growth Factor , Prospective Studies , Aftercare , Glomerular Filtration Rate , Patient Discharge , Kidney , Renal Insufficiency, Chronic/diagnosis , Biomarkers , Acute Kidney Injury/diagnosis , Acute Kidney Injury/epidemiology , AtrophyABSTRACT
RATIONALE & OBJECTIVE: Patients hospitalized with COVID-19 are at increased risk for major adverse kidney events (MAKE). We sought to identify plasma biomarkers predictive of MAKE in patients hospitalized with COVID-19. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: A total of 576 patients hospitalized with COVID-19 between March 2020 and January 2021 across 3 academic medical centers. EXPOSURE: Twenty-six plasma biomarkers of injury, inflammation, and repair from first available blood samples collected during hospitalization. OUTCOME: MAKE, defined as KDIGO stage 3 acute kidney injury (AKI), dialysis-requiring AKI, or mortality up to 60 days. ANALYTICAL APPROACH: Cox proportional hazards regression to associate biomarker level with MAKE. We additionally applied the least absolute shrinkage and selection operator (LASSO) and random forest regression for prediction modeling and estimated model discrimination with time-varying C index. RESULTS: The median length of stay for COVID-19 hospitalization was 9 (IQR, 5-16) days. In total, 95 patients (16%) experienced MAKE. Each 1 SD increase in soluble tumor necrosis factor receptor 1 (sTNFR1) and sTNFR2 was significantly associated with an increased risk of MAKE (adjusted HR [AHR], 2.30 [95% CI, 1.86-2.85], and AHR, 2.26 [95% CI, 1.73-2.95], respectively). The C index of sTNFR1 alone was 0.80 (95% CI, 0.78-0.84), and the C index of sTNFR2 was 0.81 (95% CI, 0.77-0.84). LASSO and random forest regression modeling using all biomarkers yielded C indexes of 0.86 (95% CI, 0.83-0.89) and 0.84 (95% CI, 0.78-0.91), respectively. LIMITATIONS: No control group of hospitalized patients without COVID-19. CONCLUSIONS: We found that sTNFR1 and sTNFR2 are independently associated with MAKE in patients hospitalized with COVID-19 and can both also serve as predictors for adverse kidney outcomes. PLAIN-LANGUAGE SUMMARY: Patients hospitalized with COVID-19 are at increased risk for long-term adverse health outcomes, but not all patients suffer long-term kidney dysfunction. Identification of patients with COVID-19 who are at high risk for adverse kidney events may have important implications in terms of nephrology follow-up and patient counseling. In this study, we found that the plasma biomarkers soluble tumor necrosis factor receptor 1 (sTNFR1) and sTNFR2 measured in hospitalized patients with COVID-19 were associated with a greater risk of adverse kidney outcomes. Along with clinical variables previously shown to predict adverse kidney events in patients with COVID-19, both sTNFR1 and sTNFR2 are also strong predictors of adverse kidney outcomes.
Subject(s)
Acute Kidney Injury , COVID-19 , Humans , Prospective Studies , COVID-19/complications , Kidney , Biomarkers , Acute Kidney Injury/epidemiology , Risk FactorsABSTRACT
OBJECTIVE: Treatment regimens combining glucocorticoids with cyclophosphamide or rituximab or both are used to induce remission in ANCA-associated glomerulonephritis (ANCA-GN). There is a paucity of data on the efficacy and safety of these regimens in elderly patients with ANCA-GN. This study aimed to examine outcomes and adverse events in elderly AAV patients with three induction regimens: cyclophosphamide (CYC), cyclophosphamide and rituximab (CYC + RTX), and rituximab (RTX). METHODS: This single-center retrospective cohort study included patients 60 years and older diagnosed with ANCA-GN. Baseline characteristics and outcomes across several clinical parameters were recorded and compared for significance using Kruskal-Wallis test, Chi-squared test, Fisher exact test, univariate, and multivariate logistic regression as appropriate. Cox proportional hazard regression model was used for survival analysis. RESULTS: Seventy-five patients were included. The mean (SD) age at diagnosis was 70 (± 6) years. The mean (SD) follow-up duration was 5.17 (± 3.47) years. Remission induction therapy with glucocorticoids plus CYC was used in 25 patients, glucocorticoids plus CYC and RTX in 12 patients, and glucocorticoids plus RTX in 38 patients. RTX-treated patients had a higher baseline estimated glomerular filtration ratio (eGFR) (p = 0.00009). High remission rates were achieved in all groups (100% vs. 100% vs. 94.6% respectively, p = 0.368). The incidence of end-stage renal disease (ESRD) at one year was 8% among all groups (p = 0.999). There was no difference in the number of infections requiring hospitalization (p = 0.822), but a statistical difference in leukopenia was noted (32% vs. 25% vs. 3% respectively, p = 0.005). The use of RTX only was associated with reduced leukopenia (aOR = 0.1, 95% CI = 0.005-0.8) after adjusting for other variables. CONCLUSIONS: CYC, CYC + RTX, and RTX are equally effective for remission induction in elderly patients with ANCA-GN. Induction therapy with RTX only was associated with a lower risk of leukopenia compared to CYC-containing regimens. Infections requiring hospitalization were similar among all groups. End-stage kidney disease at one year was comparable among the 3 groups. Key Points ⢠Cyclophosphamide, Rituximab, and Cyclophosphamide+Rituximab are equally effective in remission induction in elderly patients with ANCA glomerulonephritis. ⢠The use of Rituximab only was associated with a lower risk of bone marrow suppression compared to Cyclophosphamide only. ⢠More information is needed on the comparative safety of induction therapy strategies in elderly ANCA glomerulonephritis patients.
Subject(s)
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis , Glomerulonephritis , Kidney Failure, Chronic , Humans , Aged , Middle Aged , Rituximab/therapeutic use , Glucocorticoids/therapeutic use , Antibodies, Antineutrophil Cytoplasmic , Retrospective Studies , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/diagnosis , Cyclophosphamide , Glomerulonephritis/drug therapy , Remission Induction , Treatment Outcome , Immunosuppressive AgentsABSTRACT
BACKGROUNDLongitudinal investigations of murine acute kidney injury (AKI) suggest that injury and inflammation may persist long after the initial insult. However, the evolution of these processes and their prognostic values are unknown in patients with AKI.METHODSIn a prospective cohort of 656 participants hospitalized with AKI, we measured 7 urine and 2 plasma biomarkers of kidney injury, inflammation, and tubular health at multiple time points from the diagnosis to 12 months after AKI. We used linear mixed-effect models to estimate biomarker changes over time, and we used Cox proportional hazard regressions to determine their associations with a composite outcome of chronic kidney disease (CKD) incidence and progression. We compared the gene expression kinetics of biomarkers in murine models of repair and atrophy after ischemic reperfusion injury (IRI).RESULTSAfter 4.3 years, 106 and 52 participants developed incident CKD and CKD progression, respectively. Each SD increase in the change of urine KIM-1, MCP-1, and plasma TNFR1 from baseline to 12 months was associated with 2- to 3-fold increased risk for CKD, while the increase in urine uromodulin was associated with 40% reduced risk for CKD. The trajectories of these biological processes were associated with progression to kidney atrophy in mice after IRI.CONCLUSIONSustained tissue injury and inflammation, and slower restoration of tubular health, are associated with higher risk of kidney disease progression. Further investigation into these ongoing biological processes may help researchers understand and prevent the AKI-to-CKD transition.FUNDINGNIH and NIDDK (grants U01DK082223, U01DK082185, U01DK082192, U01DK082183, R01DK098233, R01DK101507, R01DK114014, K23DK100468, R03DK111881, K01DK120783, and R01DK093771).
Subject(s)
Acute Kidney Injury , Renal Insufficiency, Chronic , Mice , Animals , Prospective Studies , Kidney/metabolism , Acute Kidney Injury/metabolism , Renal Insufficiency, Chronic/metabolism , Biomarkers/metabolism , Inflammation/complications , Disease ProgressionABSTRACT
Introduction: Biomarkers of acute kidney injury (AKI) are often indexed to urine creatinine (UCr) or urine osmolarity (UOsm) to control for urine concentration. We evaluated how these approaches affect the biomarker-outcome association in patients with AKI. Methods: The Assessment, Serial Evaluation, and Subsequent Sequelae in Acute Kidney Injury Study was a cohort of hospitalized patients with and without AKI between 2009 and 2015. Using Cox proportional hazards regression, we assessed the associations and predictions (C-statistics) of urine biomarkers with a composite outcome of incident chronic kidney disease (CKD) and CKD progression. We used 4 approaches to account for urine concentration: indexing and adjusting for UCr and UOsm. Results: Among 1538 participants, 769 (50%) had AKI and 300 (19.5%) developed composite CKD outcome at median follow-up of 4.7 years. UCr and UOsm during hospitalization were inversely associated with the composite CKD outcome. The associations and predictions with CKD were significantly strengthened after indexing or adjusting for UCr or UOsm for urine kidney injury molecule-1 (KIM-1), interleukin-18 (IL-18), and monocyte chemoattractant protein-1 (MCP-1) in patients with AKI. There was no significant improvement with indexing or adjusting UCr or UOsm for albumin, neutrophil gelatinase-associated lipocalin (NGAL), and chitinase 3-like 1 (YKL-40). Uromodulin's (UMOD) inverse association with the outcome was significantly blunted after indexing but not adjusting for UCr or UOsm. Conclusion: UCr and UOsm during hospitalization are inversely associated with development and progression of CKD. Indexing or adjusting for UCr or UOsm strengthened associations and improved predictions for CKD for only some biomarkers. Incorporating urinary concentration should be individualized for each biomarker in research and clinical applications.
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BACKGROUND: Cancer survivors develop other chronic medical conditions because of shared risk factors and delayed effects of cancer treatment. This study investigated trends in the prevalence of chronic diseases and estimated their population sizes among adult cancer survivors in the United States from 2002 to 2018. METHODS: Using 2002-2018 National Health Interview Survey data, this study calculated the age-sex-race/ethnicity-adjusted prevalences and estimated the population sizes for the following chronic conditions among cancer survivors: hypertension, diabetes, stroke, heart disease, chronic obstructive pulmonary disease (COPD)/asthma, hepatitis, arthritis, liver disease, kidney disease, and morbid obesity. This study also examined multiple chronic conditions (MCC; 3 or more health conditions). MCC trends were further examined by sociodemographic factors to identify high-risk populations. Parallel analyses were performed for participants without a cancer history to provide a reference. RESULTS: Among 30,728 cancers survivors, increasing trends were observed in the prevalence of hypertension, diabetes, kidney disease, liver disease, and morbid obesity, whereas decreasing prevalence trends were observed for ischemic heart disease, COPD, and hepatitis. Cancer survivors with MCC increased from 4.7 million in 2002 to 8.1 million in 2018 (the prevalence increased from 43.7% to 46.6%). The increase was more pronounced among survivors aged 18 to 44 years. Among adults without a cancer history, the MCC prevalence also increased, although more slowly than among survivors. CONCLUSIONS: The number of adult cancer survivors in the United States with comorbid illnesses has increased substantially over the past 2 decades. Optimal management of comorbid conditions and aggressive interventions for risk reduction may benefit the cancer survivor population.
Subject(s)
Cancer Survivors , Neoplasms , Adolescent , Adult , Chronic Disease , Comorbidity , Humans , Neoplasms/epidemiology , Prevalence , Survivors , United States/epidemiology , Young AdultABSTRACT
Study objective: Oral anticoagulants (direct oral anticoagulants [DOACs] or warfarin) prevent stroke in patients with atrial fibrillation (AF), but their use may be associated with acute kidney injury (AKI). We aimed to compare AKI risk across individual oral anticoagulants in patients with AF. Design: Systematic review and network meta-analysis. Setting: Randomized trials and population-based studies. Participants: Patients with AF. Interventions: Oral anticoagulants. Main outcome measures: AKI. Results: A systematic literature search in Medline and Embase databases performed on December 17, 2021 identified ten randomized trials and eight population-based longitudinal studies based on prespecified inclusion criteria for systematic review. Clinical trials had short follow-ups and reported only low event rates of serious AKI. Retrospective longitudinal studies were assessed to be at higher risk for bias from confounding and outcome ascertainment, but follow-up was longer (1.5 to 8 years), with AKI incidence ranging from 2 to 29/100 person-years. Eight longitudinal studies that met transitivity assumption were included in a random-effects network meta-analysis within a Bayesian framework. All DOACs were associated with significantly lower risk of AKI compared to warfarin. Dabigatran was associated with lower risk of AKI compared to apixaban (hazard ratio [HR] = 0.82; 95% confidence interval [CI]: 0.68-0.99), rivaroxaban (HR = 0.84; 95%CI: 0.72-0.98), and warfarin (HR = 0.68; 95%CI: 0.59-0.77). Effect size estimates varied by chronic kidney disease status and study geographic locations. Conclusion: Apixaban, rivaroxaban, and dabigatran were associated with lower long-term risk of AKI compared to warfarin among patients with AF, with dabigatran potentially associated with the lowest risk.
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OBJECTIVE: To identify redundant clinical trials evaluating statin treatment in patients with coronary artery disease from mainland China, and to estimate the number of extra major adverse cardiac events (MACEs) experienced by participants not treated with statins in those trials. DESIGN: Cross sectional study. SETTING: 2577 randomized clinical trials comparing statin treatment with placebo or no treatment in patients with coronary artery disease from mainland China, searched from bibliographic databases to December 2019. PARTICIPANTS: 250 810 patients with any type of coronary artery disease who were enrolled in the 2577 randomized clinical trials. MAIN OUTCOME MEASURES: Redundant clinical trials were defined as randomized clinical trials that initiated or continued recruiting after 2008 (ie, one year after statin treatment was strongly recommended by clinical practice guidelines). The primary outcome is the number of extra MACEs that were attributable to the deprivation of statins among patients in the control groups of redundant clinical trials-that is, the number of extra MACEs that could have been prevented if patients were given statins. Cumulative meta-analyses were also conducted to establish the time points when statins were shown to have a statistically significant effect on coronary artery disease. RESULTS: 2045 redundant clinical trials were identified published between 2008 and 2019, comprising 101 486 patients in the control groups not treated with statins for 24 638 person years. 3470 (95% confidence interval 3230 to 3619) extra MACEs were reported, including 559 (95% confidence interval 506 to 612) deaths, 973 (95% confidence interval 897 to 1052) patients with new or recurrent myocardial infarction, 161 (132 to 190) patients with stroke, 83 (58 to 105) patients requiring revascularization, 398 (352 to 448) patients with heart failure, 1197 (1110 to 1282) patients with recurrent or deteriorated angina pectoris, and 99 (95% confidence interval 69 to 129) unspecified MACEs. CONCLUSIONS: Of more than 2000 redundant clinical trials on statins in patients with coronary artery disease identified from mainland China, an extra 3000 MACEs, including nearly 600 deaths, were experienced by participants not treated with statins in these trials. The scale of redundancy necessitates urgent reform to protect patients.
Subject(s)
Coronary Artery Disease/drug therapy , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Randomized Controlled Trials as Topic/standards , China , Coronary Artery Disease/mortality , Cross-Sectional Studies , Humans , Randomized Controlled Trials as Topic/statistics & numerical data , Research Design/standards , Systematic Reviews as TopicABSTRACT
Despite advancements in standardizing the criteria for acute kidney injury (AKI), its definition remains based on changes in serum creatinine and urinary output that do not specifically represent tubular function or injury and that have significant limitations in the acute hospital setting. Much effort in nephrology has centered on identifying biomarkers of AKI to address these limitations. This review summarizes recent advances in our knowledge of biomarkers involved in pathophysiological processes during AKI and describes their potential clinical implications. Blood and urine biomarkers are released via various mechanisms during renal tubular injury. Urinary kidney injury molecule-1 (KIM-1), liver-type fatty acid binding protein (L-FABP), insulin-like growth factor-binding protein-7 (IGFBP-7), and tissue inhibitor of metalloprotease-2 (TIMP-2) are released from the proximal tubule while uromodulin (UMOD) is secreted from the loop of Henle and neutrophil gelatinase-associated lipocalin (NGAL) is released from the distal tubule. These biomarkers could therefore be used to localize specific segments of injured tubules. Biomarkers also have diverse roles in pathophysiological processes in AKI, including inflammation, repair, and fibrosis. Current evidence suggests that these biomarkers could be used to predict the transition to chronic kidney disease (CKD), decrease discard of AKI kidneys, differentiate between kidney dysfunction and injury, guide AKI management, and improve diagnosis of diseases such as acute interstitial nephritis (AIN). They could differentiate between disease phenotypes, facilitate the inclusion of a homogenous patient population in future trials of AKI, and shed light on therapeutic pathways to prevent the transition from AKI to CKD. However, a major limitation of current biomarker research in AKI is the lack of tissue correlation. The Kidney Precision Medicine Project, a large-scale national effort, is currently underway to construct a kidney tissue atlas and expand the use of biomarkers to assess nephron health. Numerous biomarkers are involved in distinct pathophysiological processes after kidney injury and have demonstrated potential to improve diagnosis and risk stratification as well as provide a prognosis for patients with AKI. Some biomarkers are ready for use in clinical trials of AKI and could guide management in various clinical settings. Further investigation of these biomarkers will provide insight that can be applied to develop novel therapeutic agents for AKI.
Subject(s)
Acute Kidney Injury , Acute Kidney Injury/diagnosis , Biomarkers , Creatinine , Humans , Kidney , Kidney Function TestsABSTRACT
BACKGROUND: Interstitial fibrosis, tubular atrophy (IFTA), and glomerulosclerosis are indicators of irrecoverable kidney injury. Modern machine learning (ML) tools have enabled robust, automated identification of image structures that can be comparable with analysis by human experts. ML algorithms were developed and tested for the ability to replicate the detection and quantification of IFTA and glomerulosclerosis that renal pathologists perform. METHODS: A renal pathologist annotated renal biopsy specimens from 116 whole-slide images (WSIs) for IFTA and glomerulosclerosis. A total of 79 WSIs were used for training different configurations of a convolutional neural network (CNN), and 17 and 20 WSIs were used as internal and external testing cases, respectively. The best model was compared against the input of four renal pathologists on 20 new testing slides. Further, for 87 testing biopsy specimens, IFTA and glomerulosclerosis measurements made by pathologists and the CNN were correlated to patient outcome using classic statistical tools. RESULTS: The best average performance across all image classes came from a DeepLab version 2 network trained at 40× magnification. IFTA and glomerulosclerosis percentages derived from this CNN achieved high levels of agreement with four renal pathologists. The pathologist- and CNN-based analyses of IFTA and glomerulosclerosis showed statistically significant and equivalent correlation with all patient-outcome variables. CONCLUSIONS: ML algorithms can be trained to replicate the IFTA and glomerulosclerosis assessment performed by renal pathologists. This suggests computational methods may be able to provide a standardized approach to evaluate the extent of chronic kidney injury in situations in which renal-pathologist time is restricted or unavailable.
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BACKGROUND: Previous study reported shared decision making was underused in PSA-based prostate cancer screening. In mid-2018, the US Preventive Service Task Force recommended shared decision making (SDM) before PSA-based prostate cancer screening among men aged 55-69 year while remained against PSA testing in men aged 70 or older. The objective of this study is to examine recent changes in SDM and prostate cancer screening following recent USPSTF recommendations. METHODS: A retrospective cross-sectional study among men aged 50 years or older were conducted using 2015 and 2018 National Health Interview Survey data (n = 10,926). Outcomes included self-reported PSA testing for prostate cancer screening last year, and if yes, whether respondent ever had a discussion with the healthcare provider about its advantages and disadvantages. Analyses were stratified by respondent's age (50-54 vs. 55-69 vs. 70+). RESULTS: Routine PSA screening rates remained stable from 34.3% in 2015 to 35.4% in first half of 2018, and 36.0% in second half of 2018 (p trend = 0.57). A similar pattern was found in men ≥70 years (p trend = 0.98). Receipt of SDM increased in men aged ≥50 years from 30.5% in 2015 to 33.6% in first half of 2018, and 36.7% in second half of 2018 (p trend = 0.002). The increase was most prominent in men aged 55 to 69 years (31.6, 36.9, and 40.2% in 2015, first half of 2018 and second half of 2018 respectively; p trend = 0.001). CONCLUSIONS: Between 2015 and 2018, there was no significant increase in the PSA-based prostate cancer screening. However, a significant increasing trend in SDM was observed, especially in men aged 55-69 years.
Subject(s)
Decision Making, Shared , Early Detection of Cancer/methods , Guidelines as Topic , Mass Screening/methods , Prostatic Neoplasms/diagnosis , Age Factors , Aged , Biomarkers, Tumor/blood , Cross-Sectional Studies , Humans , Male , Middle Aged , Prognosis , Prostate-Specific Antigen , Prostatic Neoplasms/blood , Retrospective Studies , Risk Factors , Self ReportABSTRACT
INTRODUCTION: The term "acute tubular injury" (ATI) represents histopathologic renal tubular injury and often manifests clinically as acute kidney injury (AKI). Studies systematically summarizing the clinical presentation and histological changes in human ATI are limited. METHODS: We used a comprehensive search strategy to search human studies of ATI from 1936 to July 2019. We extracted study characteristics, clinical characteristics, and histologic descriptions of ATI by bright field, immunofluorescence, electron microscopy, and immunohistochemistry. We compared ATI histology as a function of tissue procurement type, timing, and etiologies. RESULTS: We included 292 studies comprising a total of 1987 patients. The majority of studies (222 of 292, 76%) were single-center case reports. The mean age of included patients was 47 years. In native kidney biopsy cases, baseline, peak, and latest creatinine were 1.3 mg/dl, 7.19 mg/dl, and 1.85 mg/dl respectively, and biopsy was performed mostly after peak creatinine (86.7%, 391 of 451). We identified 16 histologic descriptions of tubular injury, including tubular cell sloughing (115 of 292, 39.4%), tubular epithelial flattening/simplification (110 of 292, 37.7%), tubular dilatation (109 of 292, 37.3%), and tubular cell necrosis (93 of 292, 31.8%). There was no difference in tubular injury histology among different tissue procurement types (native kidney biopsy, transplant kidney biopsy, and autopsy), among different etiologies, or between different tissue procurement timing (before or after creatinine peaks in native kidneys). Electron microscopy and immunohistochemistry were used in a minority of studies. CONCLUSION: ATI manifests with diverse histologic changes. Efforts to establish protocols to harmonize biopsy practices, to handle kidney biopsy for tissue interrogation, and to report results across clinical practice are needed to improve our understanding of this complex disease.
ABSTRACT
Electrophysiology (EP) procedures carry the risk of kidney injury due to contrast/hemodynamic fluctuations. We aim to evaluate the national epidemiology of acute kidney injury requiring dialysis (AKI-D) in patients undergoing EP procedures. Using the National Inpatient Sample, we included 2,747,605 adult hospitalizations undergoing invasive diagnostic EP procedures, ablation and implantable device placement from 2006 to 2014. We examined the temporal trend of AKI-D and outcomes associated with AKI-D. The rate of AKI-D increased significantly in both diagnostic/ablation group (8-21/10,000 hospitalizations from 2006 to 2014, P = 0.02) and implanted device group (19-44/10,000 hospitalizations from 2006 to 2014, P < 0.01), but it was explained by temporal changes in demographics and comorbidities. Cardiac resynchronization therapy and pacemaker placement had higher risk of AKI-D compared to implantable cardioverter-defibrillator placement (23 vs. 31 vs. 14/10,000 hospitalizations in cardiac resynchronization therapy, pacemaker placement, and implantable cardioverter-defibrillator group, respectively). Development of AKI-D was associated with significant increase in in-hospital mortality (adjusted odds ratio, 9.6 in diagnostic/ablation group, P < 0.01; adjusted odds ratio, 5.1 in device implantation group, P < 0.01) and with longer length of stay (22.5 vs. 4.5 days in diagnostic/ablation group, 21.1 vs. 5.7 days in implanted device group) and higher cost (282,775 vs. 94,076 USD in diagnostic/ablation group, 295,660 vs. 102,007 USD in implanted device group). The incidence of AKI-D after EP procedures increased over time but largely explained by the change of demographics and comorbidities. This increasing trend, however, was associated with significant increase in resource utilization and in-hospital mortality in these patients.
Subject(s)
Acute Kidney Injury/epidemiology , Arrhythmias, Cardiac/therapy , Catheter Ablation , Electrophysiologic Techniques, Cardiac , Hospital Mortality , Postoperative Complications/epidemiology , Prosthesis Implantation , Acute Kidney Injury/physiopathology , Acute Kidney Injury/therapy , Aged , Arrhythmias, Cardiac/diagnosis , Cardiac Resynchronization Therapy Devices , Defibrillators, Implantable , Female , Hospital Charges , Hospitalization , Humans , Incidence , Length of Stay , Male , Middle Aged , Pacemaker, Artificial , Postoperative Complications/therapy , Renal Dialysis/trends , Respiration, Artificial/statistics & numerical data , Retrospective Studies , Risk Factors , Sepsis/epidemiology , Severity of Illness IndexABSTRACT
OBJECTIVE: This study aimed to investigate the association between age and the risk of 30-day unplanned readmission among adult patients with acute myocardial infarction (AMI) undergoing percutaneous coronary intervention (PCI). METHODS: This retrospective analysis included patients from the Nationwide Readmissions Database with AMI who underwent PCI during 2013-2014. We used multivariable logistic regression model to calculate adjusted odds ratios (AORs) for risk of readmission. To examine potential non-linear association, we performed logistic regression with restricted cubic splines (RCS). RESULTS: Of the 492 550 patients with AMI aged above 18 years undergoing PCI during the index hospitalisation, 48 630 (9.87%) were readmitted within 30 days. Although the crude readmission rate of younger patients (aged 18-54 years) was the lowest (7.27%), younger patients had higher risk of readmission compared with patients aged 55-64 years for all-causes (AOR 1.06 (1.01 to 1.11), p=0.0129) and specific causes, such as AMI and chest pain (both cardiac and non-specific) after adjusted for covariates. Patients aged 65-74 years were at lower risk of all-cause readmission. Older patients (age ≥75 years) had higher risk of readmission for heart failure (AOR 1.50 (1.29 to 1.74)) and infection (AOR 1.44 (1.16 to 1.79)), but lower risk for chest pain. RCS analyses showed a U-shaped relationship between age and readmission risk. CONCLUSIONS: Our results suggest higher risk of readmission in younger patients for all-cause unplanned readmission after adjusted for covariates. The trends of readmission risk along with age were different for specific causes. Age-targeted initiatives are warranted to reduce preventable readmissions in patients with AMI undergoing PCI.
Subject(s)
Myocardial Infarction/therapy , Patient Readmission , Percutaneous Coronary Intervention/adverse effects , Adolescent , Adult , Age Factors , Aged , Databases, Factual , Female , Humans , Male , Middle Aged , Myocardial Infarction/diagnosis , Myocardial Infarction/epidemiology , Retrospective Studies , Risk Assessment , Risk Factors , Time Factors , Treatment Outcome , United States , Young AdultSubject(s)
Eligibility Determination , Kidney Diseases/complications , Patient Selection , Peripheral Arterial Disease/therapy , Humans , Kidney Diseases/diagnosis , Kidney Function Tests , Peripheral Arterial Disease/complications , Peripheral Arterial Disease/diagnosis , Randomized Controlled Trials as Topic , Reproducibility of Results , Severity of Illness IndexABSTRACT
Objectives: This cross-sectional study aims to investigate the odds of developing angioedema (AE) in systemic lupus erythematosus (SLE) populations compared to non-SLE populations in hospital settings in the United States using a nationwide database. Materials and methods: We used the data from the National Inpatient Sample for the years 2012 to 2014. We constructed two models for multivariate logistic regression analysis. Model 1 was designed to adjust demographic information, while model 2 included each factor in model 1 and additionally accounted for AE-related comorbidities. Results: A total of 90,485 hospitalizations with an AE diagnosis were identified for the years 2012 to 2014, among which 1,505 hospitalizations had both SLE and AE. Compared to those without SLE, AE patients with SLE were younger and included more females. In AE hospitalizations, SLE was associated with higher odds of AE-related comorbidities including atopic disorder, leukocytoclastic vasculitis, eosinophilia, and infections. SLE was associated with higher odds of AE both as all inpatient diagnosis and as principal diagnosis (unadjusted odds ratio [OR] 3.24, 95% confidence interval [CI] 2.87-3.63, p<0.001, model 1 adjusted OR 2.54, 95% CI 2.26-2.86, p<0.001, model 2 adjusted OR 1.71, 95% CI 1.51-1.93, p<0.001). Conclusion: Our study demonstrates that SLE is associated with higher odds of having AE, including severe AE as the principal reason for inpatient admission. SLE is possibly an independent risk factor for AE.