Thrombo-inflammatory biomarkers of cardiorenal syndrome in patients undergoing maintenance hemodialysis in end stage renal disease

Abstract Background and Aims Cardiovascular disease is a highly common 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 of 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 similar effect in the other organ. The diagnosis, prognosis and risk stratification of CRS is poorly understood. Current literature reveals that inflammation and thrombosis are integral to CRS development and key cardiac and renal biomarkers are elevated in CRS patients. Hence, this study aims to demonstrate that thrombo-inflammatory biomarkers and laboratory parameters give a telling narrative of ESRD progression to CRS. Method Plasma samples were collected from 95 ESRD patients which were recruited with an approved IRB protocol at Loyola University Medical Center hemodialysis unit. Normal human plasma (NHP) was obtained from a commercial source (George King Biomedical, Overland Park, KS). Thrombo-inflammatory biomarkers, including Annexin V, MPO, Troponin, L-FABP, VEGF, D-dimer, TNF-alpha, IL-6, CRP, eNOS, Nitrotyrosine, MDA, NEFA, NO, vWF and MCP-1 were measured using commercially available ELISA methods. Cardiovascular comorbidities and laboratory parameters were obtained from EPIC chart analysis. Results were then statistically analyzed using GraphPad Prism v.9; the results were compiled into mean ± SEM, percent change comparison to NHP, analyzed for significance. Results Several cardiovascular comorbidities were seen in the 95 ESRD patient samples including AF (22%), PAD (29%), HF (24%), CAD (22%), DVT (15%), COPD (6.5%), and PE (5.3%). Overall, 25% of the ESRD patients have CRS. Laboratory parameters, ferratin (521.99 ±289.33) and PTH (442.91 ± 1.50) were elevated in ESRD patients. Most of the thrombo-inflammatory CRS biomarkers were elevated in ESRD patients. Biomarkers including Annexin V (ESRD 7.57 ± 5.24, 23.64% vs. 6.125 ± 8.29, p< 0.001), L-FABP (106599.43 ± 176728.97, 1983% vs. 5116.33 ± 1767.88, p<0.0001), D-dimer (ESRD 1447.01 ± 2103, 650.53% vs. 192.8 ± 212.9, p<0.0001), TNF-alpha (ESRD 2.52 ± 1.06, 35.87% vs. 1.85 ± 1.20, p<0.0001), IL-6 (ESRD 5.211 ± 10.36, 317.21% vs. 1.25 ± 1.24, p <0.0001), CRP (ESRD 14.53 ± 14.11, 2214.43% vs. 0.63 ± 0.99, p< 0.0001), NO (ESRD 34.74 ± 19.74, 151.74% vs. 13.8 ± 5.60, p<0.0001), vWF (ESRD 200.7 ± 25.89, 183.03% vs. 70.91 ± 23.13 p< 0.0001) and MCP-1 (148.4 ± 56.09, 67.49% vs. 88.6 ± 27.25, p<0.0001) showed significant increase when compared to NHP. Conclusion This study suggests that thrombo-inflammatory biomarkers and laboratory parameters may be helpful in indicating CRS in ESRD patients. Ultimately, these biomarkers can now be readily used to correlate against other biomarker findings and studied further to determine their accuracy in prognosis and diagnosis of CRS.