Thromboinflammatory Biomarkers of Cardiorenal Syndrome in Patients With End-Stage Renal Disease.

Cardiovascular disease is a prevalent complication in patients with end-stage renal disease (ESRD) on maintenance hemodialysis. In the ESRD patient population, cardiovascular mortality is 20 times higher compared to the general population. The strong relationship between both illnesses can be explained through cardiorenal syndrome (CRS). CRS encompasses a spectrum of disorders involving both the heart and kidneys in which acute or chronic dysfunction in one organ may induce a similar effect in the other organ. Current literature reveals that inflammation and thrombosis are integral to CRS development. Hence, this study aims to demonstrate whether thromboinflammatory biomarkers and laboratory parameters correlate with ESRD progression and the development of CRS. Ninety-five ESRD patients were recruited at Loyola University Medical Center hemodialysis unit. Epic chart analysis was used to determine patients with CRS. Biomarkers (C-reactive protein, tumor necrosis factor alpha, interleukin-6, Annexin V, L-fatty acid binding protein, monocyte chemoattractant protein 1, nitric oxide, von Willebrand factor, D-dimer, and plasminogen activator inhibitor-1) were profiled using the enzyme-linked immunosorbent assay method in patients with and without CRS in the ESRD cohort. All biomarkers were significantly elevated in ESRD patients compared to normal controls (P < .05) and laboratory parameters, ferritin (521.99 ± 289.33) and PTH (442.91 ± 1.50). Through EPIC chart analysis 47% of ESRD patients have CRS. D-dimer and TNF-α were significantly elevated in patients with CRS compared to patients without CRS. This study suggests that biomarkers, D-dimer, and TNF-α, can be good predictors of CRS in ESRD patients.

The Relevance of Thrombo-Inflammatory Biomarkers and Their Relationship with Circulating Glycosaminoglycans in End-Stage Renal Disease Patients.

En-stage renal disease (ESRD) is a growing public health problem. The atherosclerotic cardiovascular complications are the leading causes of mortality and morbidity in the ESRD. In this study, we sought to quantify the levels of thrombo-inflammatory biomarkers in an ESRD patients in comparison to healthy controls to determine their relevance in thrombo-inflammation and adverse outcomes. The levels of D-Dimer, C-reactive protein (CRP), plasminogen activator inhibitor 1 (PAI-1) antigen, functional PAI-1, thrombin activatable fibrinolysis inhibitor, tissue plasminogen activator, von Willebrand factor, and anti-PF4 IgG and microparticle (MP) activity were quantified by using commercially available ELISA immunoassays for each of the ESRD (n = 73) and control plasma samples (n = 10). The levels of endogenous glycosaminoglycans (GAGs) were quantified by utilizing a Heparin Red Probe (Redprobes UG, Germany). The collected data were analyzed to demonstrate the relationship between various parameters. All the tested biomarkers were increased in ESRD patients in comparison to healthy controls (p < 0.05). These biomarkers have shown significant correlations within each other except for anti-PF4 Ig G and MPs. The CRP levels were significantly higher in patients who had coronary artery disease (CAD) (p < 0.05), but there was no significant difference in other biomarkers according to the cardiovascular outcomes. In the multivariate analysis, the CRP (odds ratio: 1.19; 95% confidence interval: 1.01-1.41; p: 0.03) value was an independent predictor of CAD. In this study, we demonstrated increased levels of 10 different biomarkers in ESRD patients. The CRP levels can be a good predictor of CAD in ESRD patients.

Endogenous Glycosaminoglycans in Various Pathologic Plasma Samples as Measured by a Fluorescent Quenching Method.

Endogenous glycosaminoglycans (GAGs) with a similar structure to heparin are widely distributed in various tissues. A fluorescence probe, namely Heparin Red, can detect polyanionic GAGs in plasma samples. The purpose of this study is to measure endogenous GAGs in various plasma samples obtained from different pathologic states in comparison to healthy controls utilizing this method. Plasma samples were obtained from patient groups including atrial fibrillation (AF), end-stage-renal-disease (ESRD), diabetes mellitus (DM), sepsis, cancer, liver disease (LD), and pulmonary embolism (PE). Normal human plasma (NHP) was used as healthy controls. The Heparin Red kit from Red Probes (Münster, Germany) was used for the quantification of endogenous GAGs in each sample before and after heparinase I degradation. All results were compiled as group means ± SD for comparison. NHP was found to have relatively low levels of endogenous GAGs with a mean concentration of 0.06 µg/mL. The AF, ESRD, DM, and sepsis patient samples had a mean endogenous GAG concentration of 0.55, 0.72, 0.92, and 0.94 µg/mL, respectively. The levels of endogenous GAGs were highest in cancer, LD, and PE patient plasma samples with a mean concentration of 1.95, 2.78, and 2.83 µg/mL, respectively. Heparinase I degradation resulted in a decline in GAG levels in plasma samples. These results clearly show that detectable Heparin Red sensitive endogenous GAGs are present in circulating plasma at varying levels in various patient groups. Additional studies are necessary to understand this complex pathophysiology.

Arterial-renal Syndrome in Patients with ESRD, a New Disease Paradigm.

BACKGROUND: Patients with end-stage renal disease (ESRD) often present with an increased risk of cardiovascular disease. Conditions of compromised cardiovascular health such as atrial fibrillation (AFIB) and peripheral arterial disease (PAD) may alter biomarker levels in a way that reflects worsening ESRD. This study profiled biomarkers and laboratory parameters of endothelium dysfunction in patients with ESRD, categorized by additional AFIB and PAD conditions. METHODS: Citrated blood samples were collected from 95 patients with ESRD. Biomarker levels were measured from plasma samples using sandwich ELISAs, including tissue plasminogen activator (tPA), D-dimer, and nitrotyrosine. Lab parameters, including BUN, calcium, creatinine, parathyroid hormone, phosphate, alkaline phosphatase, ferritin, transferrin, and total iron capacity, and patient comorbidities were obtained from patient medical records. The comorbidities were determined through provider notes, and evidence of applicable testing. RESULTS: 14.89% of patients were found to have atrial fibrillation (n = 14), 30.85% of patients were found to have peripheral arterial disease (n = 29), and 6.38% of patients were found to have both peripheral arterial disease and atrial fibrillation (n = 6). When compared to patients with only ESRD, patients with ESRD and PAD showed elevated levels of D-Dimer (p = .0314) and nitrotyrosine (p = .0330). When compared to patients with only ESRD, patients with atrial fibrillation showed elevated levels of D-Dimer (p = .0372), nitrotyrosine (p = .0322), and tPA (p = .0198). CONCLUSION: When compared to patients with just ESRD, patients with concomitant PAD had elevated levels of Nitrotyrosine and D-dimer; while patients with concomitant Afib had elevated levels of nitrotyrosine, D-dimer, as well as tPA.

Procalcitonin as a Marker of Comorbid Atrial Fibrillation in Chronic Kidney Disease and History of Sepsis.

Cardiovascular disease and infection are the leading causes of mortality in patients with stage 5 chronic kidney disease on hemodialysis (CKD5-HD). Inflammation is a large component in the pathogenesis of both atrial fibrillation (AF) and sepsis and may link these conditions in CKD5-HD. Procalcitonin (PCT) is an inflammatory biomarker elevated in systemic infection and CKD5-HD, yet its value with regard to comorbid AF has not been thoroughly investigated. The aim of this study sought to evaluate circulating inflammatory markers, including PCT, Angiopoietin-1, Angiopoetin-2, CD40-L, C-reactive protein, d-dimer, and von Willebrand factor in relation to these conditions. Plasma levels of inflammatory markers were measured by enzyme linked immunosorbent assay method in CKD5-HD (n = 97) patients and controls (n = 50). Procalcitonin levels were significantly elevated (P = .0270) in CKD5-HD with comorbid AF compared to those without AF. Further analysis of patients with a history of sepsis demonstrated significantly elevated levels of PCT (P = .0405) in those with comorbid AF (160.7 ± 39.5 pg/mL) compared to those without AF (117.4 ± 25.3 pg/mL). This study demonstrates that the inflammatory biomarker PCT is further elevated in the presence of both AF and a history of sepsis in hemodialysis patients and suggests that underlying chronic inflammation following sepsis resolution may place these patients at greater risk of developing AF.

Relationship Between 25-Hydroxyvitamin D, Renin, and Collagen Remodeling Biomarkers in Atrial Fibrillation.

The interplay between vitamin D, the renin-angiotensin system (RAS), and collagen remodeling has been implicated in the pathogenesis of various cardiovascular diseases. This study sought to explore this relationship in atrial fibrillation (AF) by profiling plasma levels of 25-hydroxyvitamin D, RAS biomarkers, and collagen remodeling biomarkers using the enzyme-linked immunosorbent assay method. We hypothesized that 25-hydroxyvitamin D levels would inversely correlate with RAS biomarkers and that levels of RAS and collagen remodeling biomarkers would positively correlate with each other. Although our AF cohort (n = 37) did not exhibit decreased 25-hydroxyvitamin D levels compared to normal controls (n = 26), these levels inversely correlated with renin (Spearman r = -0.57, P = 0.005). Renin levels were elevated in patients with AF compared to normal controls (1233 ± 238 ng/mL vs 401 ± 27 ng/mL, P = 0.0002) and positively correlated with levels of matrix metalloproteinase 1 (MMP-1; Spearman r = 0.89, P = 0.01) and MMP-2 (Spearman r = 0.82, P = 0.03). These data suggest that 25-hydroxyvitamin D may influence RAS activation, and renin may help mediate the collagen remodeling process in AF. Understanding mediators of RAS dysregulation in AF may elucidate targets for therapeutic intervention to prevent collagen remodeling.

Osteopontin Levels in Patients With Chronic Kidney Disease Stage 5 on Hemodialysis Directly Correlate With Intact Parathyroid Hormone and Alkaline Phosphatase.

Chronic kidney disease stage 5 (CKD5) marks the fifth stage of renal failure, frequently causing dysregulation of bone and mineral metabolism. Challenges exist in evaluating and managing chronic kidney disease-mineral bone disorder (CKD-MBD) with the standard panel of biomarkers. Our objective was to profile osteopontin (OPN) in patients with CKD5 on maintenance hemodialysis (CKD5-HD) and elucidate its relationship to phosphorus (P), calcium (Ca2+), alkaline phosphatase (AP), and intact parathyroid hormone (iPTH) to improve understanding of the present model of CKD-MBD. Elevation of plasma OPN was seen in the CKD5-HD cohort (n = 92; median: 240.25 ng/mL, interquartile range [IQR]: 169.85 ng/mL) compared to a normal group (n = 49; median: 63.30 ng/mL, IQR: 19.20 ng/mL; p < .0001). Spearman correlation tests revealed significant positive correlations of OPN with iPTH (p < .0001; r = 0.561, 95% confidence interval = 0.397-0.690) and OPN with AP (p < .0001; r = 0.444, 95% confidence interval = 0.245-0.590) in CKD5-HD patients. Ultimately, OPN may play an integral role in the MBD axis, suggesting that it may be important to actively monitor OPN when managing CKD5-HD.

Circulating Biomarker Levels in Patients With Stage 5 Chronic Kidney Disease With Respect to Neurovascular Diseases.

The prevalence of neurocognitive deficits remains high in patients with stage 5 chronic kidney disease (CKD5D). Major contributors to such deficits include stroke, cervical carotid artery disease (CCAD), and intracranial atherosclerotic disease (ICAD). The risk of developing these dysfunctional vascular processes is facilitated by the chronic inflammation associated with renal failure. Plasma levels of 10 circulating biomarkers in patients with CKD5D (n = 78-90) were quantified using the sandwich enzyme linked immune sorbent assay method. Biomarkers for this study included kidney injury molecule-1, N-terminal prohormone of brain natriuretic peptide (NT-proBNP), neutrophil gelatinase-associated lipocalin, interleukin-18, endothelin 1, calcifediol, parathyroid hormone, platelet-derived growth factor, microparticles-expressing tissue factor, and lipoprotein(a) (Lp(a)). Of the 90 patients with CKD5D, 30 had CCAD, 24 had ICAD, and 22 had stroke. Lp(a) level was significantly elevated in patients with CKD5D with comorbid ICAD compared to those without (125.70 ± 10.03 ng/mL vs 97.16 ± 5.97 ng/mL; P = .0065). NT-proBNP level was also significantly elevated in patients with CKD5D with comorbid stroke diagnosis compared to those without stroke history, once patients with a diagnosis of heart failure (HF) were excluded (14.84 ± 2.80 ng/mL vs 9.06 ± 1.27 ng/mL; P = .0283). Profiling levels of Lp(a) and NT-ProBNP could thus be useful in the risk stratification of ICAD and stroke, respectively, in the CKD5D population.

Biomarker Profiling in Stage 5 Chronic Kidney Disease Identifies the Relationship between Angiopoietin-2 and Atrial Fibrillation.

Atrial fibrillation (AF) is prevalent in nearly 27% of patients with stage 5 chronic kidney disease on hemodialysis (CKD5-HD), suggesting a strong association between these 2 pathologies. It is hypothesized that the relationship between these 2 diseases may be mediated by inflammation. Angiopoietin-2 (Ang-2), a pro-inflammatory biomarker of endothelial instability, inflammation, and vascular remodeling, is elevated in CKD5-HD and AF, yet has not been evaluated in patients with concomitant AF and CKD5-HD. The aim of this study is to analyze circulating levels of inflammatory and thrombotic biomarkers in patients with concomitant AF and CKD5-HD. Plasma levels of Ang-2 were measured via sandwich enzyme-linked immunosorbent assay method in CKD5-HD patients (n = 96), patients with AF (n = 38), and controls (n = 50). Angiopoietin-2 was markedly elevated in CKD5-HD with comorbid AF as compared to CKD5-HD alone, and AF alone, respectively (13.05 ± 1.56 vs 9.57 ± 0.71 ng/mL; P = .00169; vs 2.48 ± 0.57 ng/mL; P < .0001). The results of this study suggest an additive effect of Ang-2 with coexistence of AF and CKD5-HD, which may be useful in the detection of AF within this patient population.

Biomarker Profiling of Neurovascular Diseases in Patients with Stage 5 Chronic Kidney Disease.

Patients with stage 5 chronic kidney disease (CKD5D) have a higher risk of developing neurocognitive deficits. Stroke, cervical carotid artery disease (CCAD), and intracranial atherosclerotic disease (ICAD) are causes of such deficits in CKD5D. Chronic inflammation from renal failure elevates risk for these diseases through oxidative stress and vascular dysfunction. The adverse impact on the carotid and intracranial vasculatures contributes to the multifactorial pathophysiology of stroke. Eleven plasma biomarker levels in patients with CKD5D (n = 97) and healthy controls (n = 17-50) were measured using sandwich enzyme-linked immunosorbent assay (ELISA) method. Of the 97 patients with CKD5D, 24 had CCAD, 19 had ICAD, and 23 had acute stroke. Elevations in NACHT, LRR, and PYD domains-containing protein 3 (NALP3) levels in patients with CKD5D (+)CCAD (1.80 ± 0.11 ng/mL) compared to patients with (-)CCAD (1.55 ± 0.08 ng/mL) were statistically significant (P = .0299). Differences in D-dimer levels were also found to be statistically significant (P = .0258) between CKD5D (+)stroke (1.83 ± 0.42 µg/mL) and (-)stroke (0.89 ± 0.13 µg/mL) groups. The ages of the (+) neurovascular disease groups were found to be significantly elevated compared to the (-) neurovascular disease groups (P = .0002 carotid AD; P < .0001 ICAD; P = .0157 stroke). D-dimer levels were positively correlated with age in CKD5D (P = .0375). With the possible exception of NALP3 for CCAD, profiling levels of specific biomarkers for risk stratification of neurovascular diseases in the CKD5D population warrants further investigation.

Elevated extracellular nucleosomes and their relevance to inflammation in stage 5 chronic kidney disease.

BACKGROUND: Chronic kidney disease is a disorder characterized by a pro-inflammatory state that is associated with increased morbidity and mortality. Endogenous damage-associated molecular patterns, including nucleosomes, may contribute to this persistent inflammation. The aim of this study was to profile and evaluate the clinical significance of circulating nucleosomes in patients with Stage 5 chronic kidney disease (CKD5) on hemodialysis (HD). METHODS: Under institutional review board approval, plasma samples were collected from 90 CKD5-HD patients (45 male and 45 female) prior to hemodialysis. Normal human plasma samples (25 male and 25 female) were used as a control group. Commercial enzyme-linked immunosorbent and colorimetric assays were used to profile nucleosome levels and biochemical markers of kidney injury, inflammation, thrombosis, and renal function in CKD5-HD and control groups. Clinical laboratory parameters were documented from the electronical medical record and correlated to nucleosome levels in the CKD5-HD cohort. RESULTS: In comparison to healthy volunteers, the plasma from CKD5-HD patients exhibited markedly elevated nucleosomes (P<0.0001). Furthermore, nucleosome levels correlated with WBC count (P=0.025, R=0.243) and CRP (P=0.019, R=0.266) levels. No correlation was found between nucleosomes and the other parameters studied. CONCLUSIONS: Our findings indicate extracellular nucleosomes are significantly elevated in CKD5-HD, suggesting increased cell death and/or inflammation. The observed correlations between nucleosomes and parameters of inflammation is suggestive of a complex, systemic inflammatory process underlying renal deterioration, consistent with the literature. Thus, nucleosomes may play a role in the pathogenesis and outcome of CKD5-HD.

Diversity of the midstream urine microbiome in adults with chronic kidney disease.

PURPOSE: To examine the characteristics of the midstream urine microbiome in adults with stage 3-5 non-dialysis-dependent chronic kidney disease (CKD). METHODS: Patients with non-dialysis-dependent CKD (estimated glomerular filtration rate [eGFR] < 60 ml/min/1.73 m2) and diuretic use were recruited from outpatient nephrology clinics. Midstream voided urine specimens were collected using the clean-catch method. The bacterial composition was determined by sequencing the hypervariable (V4) region of the bacterial 16S ribosomal RNA gene. Extraction negative controls (no urine) were included to assess the contribution of extraneous DNA from possible sources of contamination. Midstream urine microbiome diversity was assessed with the inverse Simpson, Chao and Shannon indices. The diversity measures were further examined by demographic characteristics and by comorbidities. RESULTS: The cohort of 41 women and 36 men with detectable bacterial DNA in their urine samples had a mean age of 71.5 years (standard deviation [SD] 7.9) years (range 60-91 years). The majority were white (68.0%) and a substantial minority were African-American (29.3%) The mean eGFR was 27.2 (SD 13.6) ml/min/1.73 m2. Most men (72.2%) were circumcised and 16.6% reported a remote history of prostate cancer. Many midstream voided urine specimens were dominated (> 50% reads) by the genera Corynebacterium (n = 11), Staphylococcus (n = 9), Streptococcus (n = 7), Lactobacillus (n = 7), Gardnerella (n = 7), Prevotella (n = 4), Escherichia_Shigella (n = 3), and Enterobacteriaceae (n = 2); the rest lacked a dominant genus. The samples had high levels of diversity, as measured by the inverse Simpson [7.24 (95% CI 6.76, 7.81)], Chao [558.24 (95% CI 381.70, 879.35)], and Shannon indices [2.60 (95% CI 2.51, 2.69)]. Diversity measures were generally higher in participants with urgency urinary incontinence and higher estimated glomerular filtration rate (eGFR). After controlling for demographics and diabetes status, microbiome diversity was significantly associated with estimated eGFR (P < 0.05). CONCLUSIONS: The midstream voided urine microbiome of older adults with stage 3-5 non-dialysis-dependent CKD is diverse. Greater microbiome diversity is associated with higher eGFR.

Biomarkers of Endothelial, Renal, and Platelet Dysfunction in Stage 5 Chronic Kidney Disease Hemodialysis Patients With Heart Failure.

The aim of this study was to determine the role of endothelial, renal, and inflammatory biomarkers in the pathogenesis of heart failure (HF) in patients with stage 5 chronic kidney disease (CKD5) undergoing maintenance hemodialysis (HD). Plasma levels of biomarkers-kidney injury molecule 1 (KIM-1), N-terminal pro brain natriuretic peptide (NT-proBNP), glycated hemoglobin, neutrophil gelatinase-associated lipocalin, interleukin-18,platelet-derived growth factor, platelet factor 4 (PF4), 25-OH vitamin D, parathyroid hormone (PTH), endothelin, and endocan-were measured in CKD5-HD patients at the Loyola University Ambulatory Dialysis facility. The HF (+) CKD5-HD patients, as compared to HF (-) CKD5-HD patients, exhibited significantly elevated NT-proBNP ( P = .0194) and KIM-1 ( P = .0485). The NT-proBNP in HF (+) CKD5-HD patients was found to correlate with the levels of serum potassium ( P = .023, R = -.39), calcium ( P = .029, R = -.38), and PF4 ( P = .045, R = -.35). The KIM-1 in HF (+) CKD5-HD patients was found to correlate with PTH ( P = .043, R = -.36) and 25-OH vitamin D ( P = .037, R = .36). Elevated plasma NT-proBNP and KIM-1 in CKD5-HD and HF (+) CKD5-HD patients suggest that natriuretic peptides and KIM-1 may contribute to the pathogenesis of HF in CKD5-HD patients.

Oral Anticoagulants to Prevent Stroke in Nonvalvular Atrial Fibrillation in Patients With CKD Stage 5D: An NKF-KDOQI Controversies Report.

Stroke risk may be more than 3-fold higher among patients with chronic kidney disease stage 5D (CKD-5D) compared to the general population, with the highest stroke rates noted among those 85 years and older. Atrial fibrillation (AF), a strong risk factor for stroke, is the most common arrhythmia and affects >7% of the population with CKD-5D. Warfarin use is widely acknowledged as an important intervention for stroke prevention with nonvalvular AF in the general population. However, use of oral anticoagulants for stroke prevention in patients with CKD-5D and nonvalvular AF continues to be debated by the nephrology community. In this National Kidney Foundation-Kidney Disease Outcomes Quality Initiative (NKF-KDOQI) controversies report, we discuss the existing observational studies that examine warfarin use and associated stroke and bleeding risks in adults with CKD-5D and AF. Non-vitamin K-dependent oral anticoagulants and their potential use for stroke prevention in patients with CKD-5D and nonvalvular AF are also discussed. Data from randomized clinical trials are urgently needed to determine the benefits and risks of oral anticoagulant use for stroke prevention in the setting of AF among patients with CKD-5D.

KDOQI US Commentary on the 2017 KDIGO Clinical Practice Guideline Update for the Diagnosis, Evaluation, Prevention, and Treatment of Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD).

Chronic kidney disease-mineral and bone disorder (CKD-MBD) encompasses laboratory and bone abnormalities and vascular calcification and has deleterious effects on clinical outcomes. KDOQI (Kidney Disease Outcomes Quality Initiative), an initiative of the National Kidney Foundation, addressed this issue with the publication of a clinical practice guideline for bone metabolism and disease in CKD in 2003, and 2 years later, a new definition and classification scheme for CKD-MBD was developed following a KDIGO (Kidney Disease: Improving Global Outcomes) Controversies Conference. The initial KDIGO guideline on CKD-MBD was then published in 2009. New evidence was subsequently reviewed at the 2013 KDIGO Controversies Conference, and in 2017, KDIGO issued a clinical practice guideline update for the diagnosis, evaluation, prevention, and treatment of CKD-MBD. This commentary presents the views of the KDOQI CKD-MBD work group convened by the National Kidney Foundation. The KDOQI work group agrees with most of the KDIGO guideline update recommendations, particularly the suggestions regarding bone mineral density testing, joint assessments of longitudinal trends in mineral metabolism markers, and dietary phosphate counseling focused on phosphate additives. However, the KDOQI work group has some concerns about the suggestions related to hypocalcemia and hypercalcemia, phosphate-binder choice, and treatment of abnormal parathyroid hormone concentrations. The overall goal of this commentary is to provide a broad discussion for the US nephrology community regarding CKD-MBD and its diagnosis, prevention, and treatment.

Biomarker profiling of plasma samples utilizing RANDOX biochip array technology.

RANDOX Biochip Array Technology offers an efficient, cost-effective method of measuring multiple analytes on a large number of samples in biologic fluids. This innovative technology has proven extremely useful in the profiling of markers in a number of different disease states. Biochip arrays have also shown promise in clinical trials, offering rapid evaluation of multiple markers and circulating levels of the analyte with only a small sample. This biochip technology has broad applications in clinical, pharmaceutical, toxicological, immunologic and microbiologic areas. This technique offers parallel profiling and will have great value in personalized and precision medicine. The aim of this manuscript is to explore the recent and future utility of biochips for profiling marker levels in different diseased populations using RANDOX's Biochip Array Technology.

Inflammatory and Metabolic Syndrome Biomarker Analysis of Vascular Outcomes in End-stage Renal Disease.

End-stage renal disease (ESRD) presents a complex syndrome in which inflammatory and metabolic processes contribute to disease progression and development of comorbid conditions. Over $1 trillion is spent globally on ESRD care. Plasma samples collected from 83 ESRD patients prior to hemodialysis were profiled for metabolic and inflammatory biomarker concentrations. Concentrations were compared between groups with and without history of stroke, acute coronary syndrome (ACS), congestive heart failure (CHF), and coronary artery disease (CAD). The 25 patients (30.1%) with history of stroke demonstrated decreased plasma interferon-γ levels (p = 0.042) and elevated plasma resistin, interleukin (IL)-1α, and leptin levels (p = 0.008, 0.021, 0.026, respectively) when compared with ESRD patients without history of stroke. The 14 patients (16.9%) with history of ACS demonstrated elevated plasma IL-6 levels (p = 0.040) when compared with ESRD patients without history of ACS. The 30 patients (36.1%) with history of CHF demonstrated decreased plasma leptin levels (p = 0.031) and elevated plasma IL-1ß levels (p = 0.042) when compared with ESRD patients without history of CHF. Finally, the 39 patients (47.0%) with history of CAD demonstrated elevated plasma IL-1α levels (p = 0.049) when compared with ESRD patients without history of CAD. Plasma biomarker concentration disturbances were observed in ESRD patients with history of stroke, ACS, CHF, and CAD when compared with ESRD patients without such history. Proinflammatory biomarker elevations were seen in stroke, ACS, CHF and CAD, while adipocytokine aberrations were observed in both stroke and CHF. These studies demonstrate that biomarker profiling of vascular comorbidities in ESRD may provide useful diagnostic and prognostic information in the management of ESRD patients.

Potential Deaths Averted and Serious Adverse Events Incurred From Adoption of the SPRINT (Systolic Blood Pressure Intervention Trial) Intensive Blood Pressure Regimen in the United States: Projections From NHANES (National Health and Nutrition Examination Survey).

BACKGROUND: SPRINT (Systolic Blood Pressure Intervention Trial) demonstrated a 27% reduction in all-cause mortality with a systolic blood pressure (SBP) goal of <120 versus <140 mm Hg among US adults at high cardiovascular disease risk but without diabetes mellitus, stroke, or heart failure. To quantify the potential benefits and risks of SPRINT intensive goal implementation, we estimated the deaths prevented and excess serious adverse events incurred if the SPRINT intensive SBP treatment goal were implemented in all eligible US adults. METHODS: SPRINT eligibility criteria were applied to the 1999 to 2006 National Health and Nutrition Examination Survey and linked with the National Death Index through December 2011. SPRINT eligibility included age ≥50 years, SBP of 130 to 180 mm Hg (depending on the number of antihypertensive medications being taken), and high cardiovascular disease risk. Exclusion criteria were diabetes mellitus, history of stroke, >1 g proteinuria, heart failure, estimated glomerular filtration rate <20 mL·min-1·1.73 m-2, or dialysis. Annual mortality rates were calculated by dividing the Kaplan-Meier 5-year mortality by 5. Hazard ratios for all-cause mortality and heart failure and absolute risks for serious adverse events in SPRINT were used to estimate the number of potential deaths and heart failure cases prevented and serious adverse events incurred with intensive SBP treatment. RESULTS: The mean age was 68.6 years, and 83.2% and 7.4% were non-Hispanic white and non-Hispanic black, respectively. The annual mortality rate was 2.20% (95% confidence interval [CI], 1.91-2.48), and intensive SBP treatment was projected to prevent ≈107 500 deaths per year (95% CI, 93 300-121 200) and give rise to 56 100 (95% CI, 50 800-61 400) episodes of hypotension, 34 400 (95% CI, 31 200-37 600) episodes of syncope, 43 400 (95% CI, 39 400-47 500) serious electrolyte disorders, and 88 700 (95% CI, 80 400-97 000) cases of acute kidney injury per year. The analysis-of-extremes approach indicated that the range of estimated lower- and upper-bound number of deaths prevented per year with intensive SBP control was 34 600 to 179 600. Intensive SBP control was projected to prevent 46 100 (95% CI, 41 800-50 400) cases of heart failure annually. CONCLUSIONS: If fully implemented in eligible US adults, intensive SBP treatment could prevent ≈107 500 deaths per year. A consequence of this treatment strategy, however, could be an increase in serious adverse events.

Non-dialysis dependent chronic kidney disease is associated with high total and out-of-pocket healthcare expenditures.

BACKGROUND: Previous studies have documented the high costs of non-dialysis dependent chronic kidney disease (CKD) but out-of-pocket healthcare expenditures remain poorly explored. This study described total direct and out-of-pocket expenditures for adults with non-dialysis dependent CKD and compared expenditures with those for cancer or stroke. METHODS: This study used data from the 2011-2013 Medical Expenditure Panel Survey, a national survey of healthcare expenditures in the U.S. POPULATION: Expenditures were determined for adults with the following chronic diseases: CKD defined by 585 ICD9 codes (n = 52), cancer (colon, breast or bronchus/lung) (n = 870), or stroke (n = 1104). These represent adults who were aware of their conditions or visited a healthcare provider for the condition during the study period. Generalized linear models were used to estimate the marginal effects of CKD, cancer or stroke on adjusted expenditures compared to adults without CKD, cancer or stroke (n = 72,241) while controlling for demographics and co-morbidities and incorporating the sample weights of the complex survey design. RESULTS: The mean age for group with CKD, cancer or stroke was 65.5, 66.1, and 68.2 years, respectively, while mean age for group without CKD, cancer or stroke was 47.8 years. Median values of total direct and out of pocket healthcare expenditures ranged from as high as $12,877 (Interquartile Range [IQR] $5031-$19,710) and $1439 ($688-$2732), respectively, with CKD, to as low as $1189 (IQR $196-$4388) and $226 (IQR $20-$764) in the group without CKD, cancer or stroke. After adjusting for demographics and comorbidities, the adjusted difference in total direct healthcare expenditures was $4746 (95% CI $1775-$7718) for CKD, $8608 (95% CI $6167-$11,049) for cancer and $5992 (95% CI $4208-$7775) for stroke vs. group without CKD, cancer or stroke. Adjusted difference in out-of-pocket healthcare expenditures was highest for adults with CKD ($760; 95% CI 0-$1745) and was larger than difference noted for cancer ($419; 95% CI 158-679) or stroke ($246; 95% CI 87-406) relative to group without CKD, cancer or stroke. CONCLUSIONS: Total and out of pocket health expenditures for adults with non-dialysis dependent CKD are high and may be equal to or higher than expenditures incurred by adults with cancer or stroke.