Clonal hematopoiesis of indeterminate potential contributes to accelerated chronic kidney disease progression.

Background: Clonal hematopoiesis of indeterminate potential (CHIP) is a common inflammatory condition of aging that causes myriad end-organ damage. We have recently shown associations for CHIP with acute kidney injury and with kidney function decline in the general population, with stronger associations for CHIP driven by mutations in genes other than DNMT3A (non- DNMT3A CHIP). Longitudinal kidney function endpoints in individuals with pre-existing chronic kidney disease (CKD) and CHIP have been examined in two previous studies, which reported conflicting findings and were limited by small sample sizes. Methods: In this study, we examined the prospective associations between CHIP and CKD progression events in four cohorts of CKD patients (total N = 5,772). The primary outcome was a composite of 50% kidney function decline or kidney failure. The slope of eGFR decline was examined as a secondary outcome. Mendelian randomization techniques were then used to investigate potential causal effects of CHIP on eGFR decline. Finally, kidney function was assessed in adenine-fed CKD model mice having received a bone marrow transplant recapitulating Tet2 -CHIP compared to controls transplanted wild-type bone marrow. Results: Across all cohorts, the average age was 66.4 years, the average baseline eGFR was 42.6 ml/min/1.73m 2 , and 24% had CHIP. Upon meta-analysis, non- DNMT3A CHIP was associated with a 59% higher relative risk of incident CKD progression (HR 1.59, 95% CI: 1.02-2.47). This association was more pronounced among individuals with diabetes (HR 1.29, 95% CI: 1.03-1.62) and with baseline eGFR ≥ 30 ml/min/1.73m (HR 1.80, 95% CI: 1.11-2.90). Additionally, the annualized slope of eGFR decline was steeper among non- DNMT3A CHIP carriers, relative to non-carriers (ß -0.61 ± 0.31 ml/min/1.73m 2 , p = 0.04). Mendelian randomization analyses suggested a causal role for CHIP in eGFR decline among individuals with diabetes. In a dietary adenine mouse model of CKD, Tet2 -CHIP was associated with lower GFR as well as greater kidney inflammation, tubular injury, and tubulointerstitial fibrosis. Conclusion: Non- DNMT3A CHIP is a potentially targetable novel risk factor for CKD progression.

Incident heart failure in chronic kidney disease: proteomics informs biology and risk stratification.

BACKGROUND AND AIMS: Incident heart failure (HF) among individuals with chronic kidney disease (CKD) incurs hospitalizations that burden patients and health care systems. There are few preventative therapies, and the Pooled Cohort equations to Prevent Heart Failure (PCP-HF) perform poorly in the setting of CKD. New drug targets and better risk stratification are urgently needed. METHODS: In this analysis of incident HF, SomaScan V4.0 (4638 proteins) was analysed in 2906 participants of the Chronic Renal Insufficiency Cohort (CRIC) with validation in the Atherosclerosis Risk in Communities (ARIC) study. The primary outcome was 14-year incident HF (390 events); secondary outcomes included 4-year HF (183 events), HF with reduced ejection fraction (137 events), and HF with preserved ejection fraction (165 events). Mendelian randomization and Gene Ontology were applied to examine causality and pathways. The performance of novel multi-protein risk models was compared to the PCP-HF risk score. RESULTS: Over 200 proteins were associated with incident HF after adjustment for estimated glomerular filtration rate at P < 1 × 10-5. After adjustment for covariates including N-terminal pro-B-type natriuretic peptide, 17 proteins remained associated at P < 1 × 10-5. Mendelian randomization associations were found for six proteins, of which four are druggable targets: FCG2B, IGFBP3, CAH6, and ASGR1. For the primary outcome, the C-statistic (95% confidence interval [CI]) for the 48-protein model in CRIC was 0.790 (0.735, 0.844) vs. 0.703 (0.644, 0.762) for the PCP-HF model (P = .001). C-statistic (95% CI) for the protein model in ARIC was 0.747 (0.707, 0.787). CONCLUSIONS: Large-scale proteomics reveal novel circulating protein biomarkers and potential mediators of HF in CKD. Proteomic risk models improve upon the PCP-HF risk score in this population.

Salt-losing nephropathy associated with severe hypothyroidism.

Here, we present a case of an older man presenting with worsening confusion. Laboratory tests showed serum sodium of 120 mmol/L with severe hypothyroidism and renal salt wasting that improved with treatment of hypothyroidism, normalising the serum sodium.

Prognostic utility of rhythmic components in 24-h ambulatory blood pressure monitoring for the risk stratification of chronic kidney disease patients with cardiovascular co-morbidity.

Chronic kidney disease (CKD) represents a significant global burden. Hypertension is a modifiable risk factor for rapid progression of CKD. We extend the risk stratification by introducing the non-parametric determination of rhythmic components in 24-h profiles of ambulatory blood pressure monitoring (ABPM) in the Chronic Renal Insufficiency Cohort (CRIC) and the African American Study for Kidney Disease and Hypertension (AASK) cohort using Cox proportional hazards models. We find that rhythmic profiling of BP through JTK_CYCLE analysis identifies subgroups of CRIC participants that were more likely to die due to cardiovascular causes. While our fully adjusted model shows a trend towards a significant association between absent cyclic components and cardiovascular death in the full CRIC cohort (HR: 1.71,95% CI: 0.99-2.97, p = 0.056), CRIC participants with a history of cardiovascular disease (CVD) and absent cyclic components in their BP profile had at any time a 3.4-times higher risk of cardiovascular death than CVD patients with cyclic components present in their BP profile (HR: 3.37, 95% CI: 1.45-7.87, p = 0.005). This increased risk was not explained by the dipping or non-dipping pattern in ABPM. Due to the large differences in patient characteristics, the results do not replicate in the AASK cohort. This study suggests rhythmic blood pressure components as a potential novel biomarker to unmask excess risk among CKD patients with prior cardiovascular disease.

Intensive Care Admissions and Outcome of Cardiac Arrests; A National Cohort Study From the United States.

OBJECTIVE: Outcomes of cardiac arrest among patients who had cardiopulmonary resuscitation (CPR) in intensive care units (ICU) has limited data on the national level basis in the United States. We aimed to study the outcomes of ICU CPRs. METHODS: Data from the national readmissions database (NRD) sample that constitutes 49.1% of the stratified sample of all hospitals in the United States were analyzed for ICU-related hospitalizations for the years 2016 to 2019. ICU CPR was defined by procedure codes. RESULTS: A total of 4,610,154 ICU encounters were reported for the years 2016 to 2019 in the NRD. Of these patients, 426,729 (9.26%) had CPR procedure recorded during the hospital encounter (mean age 65 ± 17.81; female 42.4%). And 167,597 (39.29%) patients had CPR on the day of admission, of which 63.16% died; while 64,752 (15.18%) patients had CPR on the day of ICU admission, of which 72.85% died. And 36,002 (8.44%) had CPR among patients with length of stay 2 days, of which 73.34% died. A total of 1,222,799 (26.5%) admitted to ICU died, and patients who had ICU CPR had higher mortality, 291,391(68.3%). Higher complication rates were observed among ICU CPR patients, especially who died. Over the years from 2016 to 2019, ICU CPR rates increased from 8.18% (2016) to 8.66% (2019); p-trend = 0.001. The mortality rates among patients admitted to ICU increased from 22.1% (2016) to 24.1% (2019); p-trend = 0.005. CONCLUSION: The majority of ICU CPRs were done on the first day of ICU admission. The trend for ICU CPR was increasing. The mortality trend for overall ICU admissions has increased, which is concerning and would suggest further research to improve the high mortality rates in the CPR group.

Conversion from Intermittent Hemodialysis to Peritoneal Dialysis in Metastatic Catheter-Related Bloodstream Infection.

Of all complications from central venous catheters (CVC) in end-stage renal disease (ESRD) patients, catheter-related bloodstream infection (CRBSI) is one of the most devastating consequences. The option of catheter salvage is not an effective measure with metastatic infections. However, in patients with severe vasculopathy and/or near end-stage vascular disease, preservation of the venous access should be given utmost importance as the luxury of utilizing another vascular site is markedly limited. Providing adequate renal replacement therapy in this group of patients can be remarkably challenging for nephrologists. We are presenting an ESRD patient with advanced vascular disease who developed metastatic CRBSI with worsening uremia who was successfully converted from intermittent hemodialysis (IHD) to peritoneal dialysis (PD). Our rationale was to minimize repeated intravascular procedures coupled with the presence of another intravascular device. This has led to a complete resolution of persistent bacteremia, with a steady improvement in the uremic state. Conversion from IHD to PD for persistent bacteremia with metastatic complications was seldom addressed in literature. In the absence of a significant contraindication to PD, it can be considered as a valid alternative possibility in order to interrupt this viscous cycle, especially in vasculopathic patients.

Clustering-based spatial analysis (CluSA) framework through graph neural network for chronic kidney disease prediction using histopathology images.

Machine learning applied to digital pathology has been increasingly used to assess kidney function and diagnose the underlying cause of chronic kidney disease (CKD). We developed a novel computational framework, clustering-based spatial analysis (CluSA), that leverages unsupervised learning to learn spatial relationships between local visual patterns in kidney tissue. This framework minimizes the need for time-consuming and impractical expert annotations. 107,471 histopathology images obtained from 172 biopsy cores were used in the clustering and in the deep learning model. To incorporate spatial information over the clustered image patterns on the biopsy sample, we spatially encoded clustered patterns with colors and performed spatial analysis through graph neural network. A random forest classifier with various groups of features were used to predict CKD. For predicting eGFR at the biopsy, we achieved a sensitivity of 0.97, specificity of 0.90, and accuracy of 0.95. AUC was 0.96. For predicting eGFR changes in one-year, we achieved a sensitivity of 0.83, specificity of 0.85, and accuracy of 0.84. AUC was 0.85. This study presents the first spatial analysis based on unsupervised machine learning algorithms. Without expert annotation, CluSA framework can not only accurately classify and predict the degree of kidney function at the biopsy and in one year, but also identify novel predictors of kidney function and renal prognosis.

Prognostic utility of rhythmic components in 24-hour ambulatory blood pressure monitoring for the risk stratification of chronic kidney disease patients with cardiovascular co-morbidity.

Background: Chronic kidney disease (CKD) represents a significant global burden. Hypertension is a modifiable risk factor for rapid progression of CKD. Methods: We extend the risk stratification by introducing the non-parametric determination of rhythmic components in 24-hour profiles of ambulatory blood pressure monitoring (ABPM) in the African American Study for Kidney Disease and Hypertension (AASK) cohort and the Chronic Renal Insufficiency Cohort (CRIC) using Cox proportional hazards models. Results: We find that rhythmic profiling of BP through JTK_Cycle analysis identifies subgroups of CRIC participants at advanced risk of cardiovascular death. CRIC participants with a history of cardiovascular disease (CVD) and absent cyclic components in their BP profile had at any time a 3.4-times higher risk of cardiovascular death than CVD patients with cyclic components present in their BP profile (HR: 3.38, 95% CI: 1.45-7.88, p=0.005). This substantially increased risk was independent of whether ABPM followed a dipping or non-dipping pattern whereby non-dipping or reverse dipping were not significantly associated with cardiovascular death in patients with prior CVD (p>0.1). In the AASK cohort, unadjusted models demonstrate a higher risk in reaching end stage renal disease among participants without rhythmic ABPM components (HR:1.80, 95% CI: 1.10-2.96); however, full adjustment abolished this association. Conclusions: This study proposes rhythmic blood pressure components as a novel biomarker to unmask excess risk among CKD patients with prior cardiovascular disease.

Association of urine and plasma ADMA with atherosclerotic risk in DKD cardiovascular disease risk in diabetic kidney disease: findings from the Chronic Renal Insufficiency Cohort (CRIC) study.

BACKGROUND: Chronic kidney disease (CKD) is associated with atherosclerotic cardiovascular disease (ASCVD) risk, especially among those with diabetes. Altered metabolism of solutes that accumulate in CKD [asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA) and trimethylamine N-oxide (TMAO)] may reflect pathways linking CKD with ASCVD. METHODS: This case-cohort study included Chronic Renal Insufficiency Cohort participants with baseline diabetes, estimated glomerular filtration rate <60 mL/min/1.73 m2, and without prior history for each outcome. The primary outcome was incident ASCVD (time to first myocardial infarction, stroke or peripheral artery disease event) and secondary outcome was incident heart failure. The subcohort comprised randomly selected participants meeting entry criteria. Plasma and urine ADMA, SDMA and TMAO concentrations were determined by liquid chromatography-tandem mass spectrometry. Associations of uremic solute plasma concentrations and urinary fractional excretions with outcomes were evaluated by weighted multivariable Cox regression models, adjusted for confounding covariables. RESULTS: Higher plasma ADMA concentrations (per standard deviation) were associated with ASCVD risk [hazard ratio (HR) 1.30, 95% confidence interval (CI) 1.01-1.68]. Lower fractional excretion of ADMA (per standard deviation) was associated with ASCVD risk (HR 1.42, 95% CI 1.07-1.89). The lowest quartile of ADMA fractional excretion was associated with greater ASCVD risk (HR 2.25, 95% CI 1.08-4.69) compared with the highest quartile. Plasma SDMA and TMAO concentration and fractional excretion were not associated with ASCVD. Neither plasma nor fractional excretion of ADMA, SDMA and TMAO were associated with incident heart failure. CONCLUSION: These data suggest that decreased kidney excretion of ADMA leads to increased plasma concentrations and ASCVD risk.

Proteomic cardiovascular risk assessment in chronic kidney disease.

AIMS: Chronic kidney disease (CKD) is widely prevalent and independently increases cardiovascular risk. Cardiovascular risk prediction tools derived in the general population perform poorly in CKD. Through large-scale proteomics discovery, this study aimed to create more accurate cardiovascular risk models. METHODS AND RESULTS: Elastic net regression was used to derive a proteomic risk model for incident cardiovascular risk in 2182 participants from the Chronic Renal Insufficiency Cohort. The model was then validated in 485 participants from the Atherosclerosis Risk in Communities cohort. All participants had CKD and no history of cardiovascular disease at study baseline when ∼5000 proteins were measured. The proteomic risk model, which consisted of 32 proteins, was superior to both the 2013 ACC/AHA Pooled Cohort Equation and a modified Pooled Cohort Equation that included estimated glomerular filtrate rate. The Chronic Renal Insufficiency Cohort internal validation set demonstrated annualized receiver operating characteristic area under the curve values from 1 to 10 years ranging between 0.84 and 0.89 for the protein and 0.70 and 0.73 for the clinical models. Similar findings were observed in the Atherosclerosis Risk in Communities validation cohort. For nearly half of the individual proteins independently associated with cardiovascular risk, Mendelian randomization suggested a causal link to cardiovascular events or risk factors. Pathway analyses revealed enrichment of proteins involved in immunologic function, vascular and neuronal development, and hepatic fibrosis. CONCLUSION: In two sizeable populations with CKD, a proteomic risk model for incident cardiovascular disease surpassed clinical risk models recommended in clinical practice, even after including estimated glomerular filtration rate. New biological insights may prioritize the development of therapeutic strategies for cardiovascular risk reduction in the CKD population.

Cardiac Structure and Function and Subsequent Kidney Disease Progression in Adults With CKD: The Chronic Renal Insufficiency Cohort (CRIC) Study.

RATIONALE & OBJECTIVE: Heart-kidney crosstalk is recognized as the cardiorenal syndrome. We examined the association of cardiac function and structure with the risk of kidney failure with replacement therapy (KFRT) in a chronic kidney disease (CKD) population. STUDY DESIGN: Prospective observational cohort study. SETTING & PARTICIPANTS: 3,027 participants from the Chronic Renal Insufficiency Cohort Study. EXPOSURE: Five preselected variables that assess different aspects of cardiac structure and function: left ventricular mass index (LVMI), LV volume, left atrial (LA) area, peak tricuspid regurgitation (TR) velocity, and left ventricular ejection fraction (EF) as assessed by echocardiography. OUTCOME: Incident KFRT (primary outcome), and annual estimated glomerular filtration rate (eGFR) slope (secondary outcome). ANALYTICAL APPROACH: Multivariable Cox models and mixed-effects models. RESULTS: The mean age of the participants was 59±11 SD years, 54% were men, and mean eGFR was 43±17mL/min/1.73m2. Between 2003 and 2018 (median follow-up, 9.9 years), 883 participants developed KFRT. Higher LVMI, LV volume, LA area, peak TR velocity, and lower EF were each statistically significantly associated with an increased risk of KFRT, with corresponding HRs for the highest versus lowest quartiles (lowest vs highest for EF) of 1.70 (95% CI, 1.27-2.26), 1.50 (95% CI, 1.19-1.90), 1.43 (95% CI, 1.11-1.84), 1.45 (95% CI, 1.06-1.96), and 1.26 (95% CI, 1.03-1.56), respectively. For the secondary outcome, participants in the highest versus lowest quartiles (lowest vs highest for EF) had a statistically significantly faster eGFR decline, except for LA area (ΔeGFR slope per year, -0.57 [95% CI, -0.68 to-0.46] mL/min/1.73m2 for LVMI, -0.25 [95% CI, -0.35 to-0.15] mL/min/1.73m2 for LV volume, -0.01 [95% CI, -0.12 to-0.01] mL/min/1.73m2 for LA area, -0.42 [95% CI, -0.56 to-0.28] mL/min/1.73m2 for peak TR velocity, and -0.11 [95% CI, -0.20 to-0.01] mL/min/1.73m2 for EF, respectively). LIMITATIONS: The possibility of residual confounding. CONCLUSIONS: Multiple aspects of cardiac structure and function were statistically significantly associated with the risk of KFRT. These findings suggest that cardiac abnormalities and incidence of KFRT are potentially on the same causal pathway related to the interaction between hypertension, heart failure, and coronary artery diseases. PLAIN-LANGUAGE SUMMARY: Heart disease and kidney disease are known to interact with each other. In this study, we examined whether cardiac abnormalities, as assessed by echocardiography, were linked to the subsequent progression of kidney disease among people living with chronic kidney disease (CKD). We found that people with abnormalities in heart structure and function had a greater risk of progression to advanced CKD that required kidney replacement therapy and had a faster rate of decline in kidney function. Our study indicates the potential role of abnormal heart structure and function in the progression of kidney disease among people living with CKD.

Clinical outcomes and 30-day readmissions for heart failure with reduced ejection fraction with cardiorenal syndrome: A National Cohort Study.

BACKGROUND: Literature regarding outcomes of cardiorenal syndrome (CRS) among heart failure with reduced ejection fraction (HFrEF) is limited. OBJECTIVE: To study the clinical outcomes and 30-day readmission rates of CRS patients with HFrEF. METHODS: Data from the Nationwide Readmissions Database (NRD) that constitutes 49.1% of the stratified sample of all hospitals in the United States (US), representing >95% of the national population, was analyzed for the CRS with HFrEF visits from 2018 to 2019. CRS was defined by the ICD-10 codes. RESULTS: Out of the 1,530,749 index CRS-related hospitalizations (mean age:64.37 ± 13.30 years; 38.6%females) 73,126 (6.0%) CKD I-II, 883,119 (72.6%) CKD III-IV, and 258,835 (21.3%) CKD V-and-more related encounters were recorded. Mortality was higher among CKD stage V-and-more in comparison to other subgroups(7.6%vs5.73%;p < 0.001). AKI with underlying CKD was more common among stage III-IV compared to other subgroups (55.9%vs43.7%;p < 0.001). Respiratory failure, the second major complication, was more common among stage V-and-more compared to other subgroups (32.5%vs30%;p < 0.001). The overall CRS-related 30-day readmission rate was 22.7%, with CKD V-and-more accounting for highest rates(29.89%), followed by CKD stage III-IV(20.05%) and CKD I-II(12.99%). The primary etiology for 30-day readmission was cardiovascular among all subgroups (54.2%, 54.6%, and 41.80%, which corresponds to CKD I-II, CKD III-IV and CKD V-and-more, respectively). CONCLUSION: CRS among HFrEF accounts for substantial healthcare burden with high 30-day readmission rates. Higher all-cause mortality and 30-day readmissions were associated with worse renal disease. This would suggest that more vigilance is needed by physicians for discharge planning among this patient population.

Multi-Scalar Data Integration Links Glomerular Angiopoietin-Tie Signaling Pathway Activation With Progression of Diabetic Kidney Disease.

Diabetic kidney disease (DKD) is the leading cause of end-stage kidney disease (ESKD). Prognostic biomarkers reflective of underlying molecular mechanisms are critically needed for effective management of DKD. A three-marker panel was derived from a proteomics analysis of plasma samples by an unbiased machine learning approach from participants (N = 58) in the Clinical Phenotyping and Resource Biobank study. In combination with standard clinical parameters, this panel improved prediction of the composite outcome of ESKD or a 40% decline in glomerular filtration rate. The panel was validated in an independent group (N = 68), who also had kidney transcriptomic profiles. One marker, plasma angiopoietin 2 (ANGPT2), was significantly associated with outcomes in cohorts from the Cardiovascular Health Study (N = 3,183) and the Chinese Cohort Study of Chronic Kidney Disease (N = 210). Glomerular transcriptional angiopoietin/Tie (ANG-TIE) pathway scores, derived from the expression of 154 ANG-TIE signaling mediators, correlated positively with plasma ANGPT2 levels and kidney outcomes. Higher receptor expression in glomeruli and higher ANG-TIE pathway scores in endothelial cells corroborated potential functional effects in the kidney from elevated plasma ANGPT2 levels. Our work suggests that ANGPT2 is a promising prognostic endothelial biomarker with likely functional impact on glomerular pathogenesis in DKD.

Crescentic Glomerulonephritis and Membranous Nephropathy: A Rare Overlap.

Background: Membranous nephropathy (MN) is a disease that affects the basement membrane of the glomeruli of the kidney resulting in proteinuria. The concurrent incidence of vasculitic glomerulonephritis and MN in the same patient is unusual. Herein, we report a case with this unusual combination. Case: Our patient is a 53-year-old Hispanic male with a medical history of tobacco use, type 2 diabetes mellitus, and hypertension who presented with hematuria and was found to have nephrotic range proteinuria and renal impairment. Blood workup revealed positive ANCA serology, which led to a renal biopsy that showed crescentic vasculitis in addition to membranous nephropathy. The patient was started on intermittent hemodialysis (HD) and treated initially with intravenous (IV) pulse steroids; subsequently, oral prednisolone and IV cyclophosphamide were initiated. The patient remained HD dependent at the time of discharge with the resolution of hematuria. A follow-up with an outpatient nephrology clinic was arranged. Conclusion: Membranous nephropathy complicated by crescentic glomerulonephritis has a more aggressive clinical course and decline in renal function compared to MN alone which can lead to initiating renal replacement therapy. However, immunosuppressive drugs can result in significant improvement of renal function if started early enough.

Black and White Adults With CKD Hospitalized With Acute Kidney Injury: Findings From the Chronic Renal Insufficiency Cohort (CRIC) Study.

RATIONALE & OBJECTIVE: Few studies have investigated racial disparities in acute kidney injury (AKI), in contrast to the extensive literature on racial differences in the risk of kidney failure. We sought to study potential differences in risk in the setting of chronic kidney disease (CKD). STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: We studied 2,720 self-identified Black or White participants with CKD enrolled in the Chronic Renal Insufficiency Cohort (CRIC) Study from July 1, 2013, to December 31, 2017. EXPOSURE: Self-reported race (Black vs White). OUTCOME: Hospitalized AKI (≥50% increase from nadir to peak serum creatinine). ANALYTICAL APPROACH: Cox regression models adjusting for demographics (age and sex), prehospitalization clinical risk factors (diabetes, blood pressure, cardiovascular disease, estimated glomerular filtration rate, proteinuria, receipt of angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers), and socioeconomic status (insurance status and education level). In a subset of participants with genotype data, we adjusted for apolipoprotein L1 gene (APOL1) high-risk status and sickle cell trait. RESULTS: Black participants (n = 1,266) were younger but had a higher burden of prehospitalization clinical risk factors. The incidence rate of first AKI hospitalization among Black participants was 6.3 (95% CI, 5.5-7.2) per 100 person-years versus 5.3 (95% CI, 4.6-6.1) per 100 person-years among White participants. In an unadjusted Cox regression model, Black participants were at a modestly increased risk of incident AKI (HR, 1.22 [95% CI, 1.01-1.48]) compared with White participants. However, this risk was attenuated and no longer significant after adjusting for prehospitalization clinical risk factors (adjusted HR, 1.02 [95% CI, 0.83-1.25]). There were only 11 AKI hospitalizations among individuals with high-risk APOL1 risk status and 14 AKI hospitalizations among individuals with sickle cell trait. LIMITATIONS: Participants were limited to research volunteers and potentially not fully representative of all CKD patients. CONCLUSIONS: In this multicenter prospective cohort of CKD patients, racial disparities in AKI incidence were modest and were explained by differences in prehospitalization clinical risk factors.

Unsupervised machine learning for identifying important visual features through bag-of-words using histopathology data from chronic kidney disease.

Pathologists use visual classification to assess patient kidney biopsy samples when diagnosing the underlying cause of kidney disease. However, the assessment is qualitative, or semi-quantitative at best, and reproducibility is challenging. To discover previously unknown features which predict patient outcomes and overcome substantial interobserver variability, we developed an unsupervised bag-of-words model. Our study applied to the C-PROBE cohort of patients with chronic kidney disease (CKD). 107,471 histopathology images were obtained from 161 biopsy cores and identified important morphological features in biopsy tissue that are highly predictive of the presence of CKD both at the time of biopsy and in one year. To evaluate the performance of our model, we estimated the AUC and its 95% confidence interval. We show that this method is reliable and reproducible and can achieve 0.93 AUC at predicting glomerular filtration rate at the time of biopsy as well as predicting a loss of function at one year. Additionally, with this method, we ranked the identified morphological features according to their importance as diagnostic markers for chronic kidney disease. In this study, we have demonstrated the feasibility of using an unsupervised machine learning method without human input in order to predict the level of kidney function in CKD. The results from our study indicate that the visual dictionary, or visual image pattern, obtained from unsupervised machine learning can predict outcomes using machine-derived values that correspond to both known and unknown clinically relevant features.

Acute myocardial infarction and acute heart failure among renal transplant recipients: a national readmissions database study.

BACKGROUND: The literature on the mortality and 30-day readmissions for acute heart failure and for acute myocardial infarction among renal-transplant recipients is limited. OBJECTIVE: To study the in-hospital mortality, cardiovascular complications, and 30-day readmissions among renal transplant recipients (RTRs). METHODS: Data from the national readmissions database sample, which constitutes 49.1% of all hospitals in the United States and represents more than 95% of the stratified national population, was analyzed for the years 2012-2018 using billing codes. RESULTS: A total of 588,668 hospitalizations in renal transplant recipients (mean age 57.7 ± 14.2 years; 44.5% female) were recorded in the study years. A total of 15,788 (2.7%) patients had a diagnosis of acute heart failure; 11,320 (71.7%) had acute heart failure with preserved ejection fraction and 4468 (28.3%) had acute heart failure with reduced ejection fraction; 17,256 (3%) patients had myocardial infarction, 3496 (20%) had ST-Elevation myocardial infarction while 13,969 (80%) had non-ST-elevation myocardial infarction. Overall, 11,675 (2%) renal-transplant patients died, of whom 757 (6.5%) had acute heart failure, 330 (2.8%) had acute reduced and 427 (3.7%) had acute preserved ejection fraction failure. Among 1652 (14.1%) patient deaths with myocardial infarction, 465 (4%) were ST-elevation- and 1187 (10.1%) were non-ST-Elevation-related. The absolute yearly mortality rate due to acute heart failure increased over the years 2012-2018 (p-trend 0.0002, 0.001, 0.002, 0.05, respectively), while the mortality rate due to myocardial infarction with ST-elevation decreased (p-trend 0.002). CONCLUSION: Cardiovascular complications are significantly associated with hospitalizations among RTRs. The absolute yearly mortality, and rate of heart failure (with reduced or preserved ejection fraction) increased over the study years, suggesting that more research is needed to improve the management of these patients.

Scleroderma hypertensive renal crisis among systemic sclerosis patients: A national emergency department database study.

BACKGROUND: Literature regarding trends for incidence and mortality of scleroderma renal crisis (SRC) in systemic sclerosis (SSc) within the United States (US) emergency departments (EDs) is limited. OBJECTIVE: To study the mortality of SRC among SSc patient encounters within the US EDs. METHODS: Data from the National Emergency Department Sample (NEDS) constitutes 20% sample of hospital-owned EDs and inpatient sample in the US were analyzed for SSc with and without SRC using ICD-9 codes. A linear p-trend was used to assess the trends. RESULTS: Of the total 180,435 encounters with the diagnosis of SSc in NEDS for the years 2009 2014, 771 or 4.27/1000 patients (mean age 59.6 ± 15.5 years, 75.4% females) were recorded with SRC. The numerical differences in mortality among SRC (32 or 4.1%) and non-SRC subgroups (5487 or 3.1%) did not reach statistical significance (p = 0.3). Major complications among SRC in comparison to non-SRC subgroup include ischemic stroke (5.6% vs 0.98%, p = 0.001), new-onset AF (8% vs 6.9%, p = 0.001), new-onset congestive heart failure (24.1% vs 8.8%, p = 0.001), pulmonary arterial hypertension (15.8% vs 10.9%, p = 0.001), respiratory failure (27.5% vs 10.5%, p = 0.001), and deep vein thrombosis (4.7% vs 4.6%, p = 0.001). Congestive heart failure (CHF) was strongly associated with SRC among SSc (OR 4.3 95%CI 2.7-6.7; p < 0.001). The absolute yearly rate of SRC had increased over the study years from 2.11/1000 to 5.79/1000 (linear p-trend 0.002) while the mortality trend remained steady. CONCLUSION: SRC is a relatively rare medical emergency. Although there has been a significant rise in the rate of SRC among SSc patients over the study years, mortality rates had remained steady. SSc patients with CHF should be considered to have low threshold for admission to inpatient services from EDs.