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.

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.

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.