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

Abstract

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.

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

“… 20 Regarding this, recent studies have shown that the levels of inflammatory biomarkers such as CRP, TNF-α, IL-1, and IL-6 are elevated in CKD and ESRD patients. 21 , 22 Furthermore, this elevation has also been shown to be associated with the progression of CKD to ESRD with higher rates of cardiovascular complications and mortality in this patient group. 23 In vivo experiments showed a significant increase of serum levels of proinflammatory cytokines in patients with type 1 CRS compared to those with acute HF without renal insufficiency which included IL-6, IL-18, MPO, and neutrophil gelatinase-associated lipocalin (NGAL).…”

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

“… 16 , 17 Furthermore, this elevation has also shown to be associated with the progression of CKD to ESRD with higher rates of cardiovascular complications and mortality in this patient group. 17 – 20 Interestingly, major improvements were observed at the levels of inflammatory biomarkers after kidney transplantation; this has indicated that inflammation is not only a cause but also a consequence in the development of a kidney disease and its associated complications. 21 Regarding this, several dialysis-related factors have been associated with persistent and low-grade inflammation in ESRD.…”