Abstract
Cardiovascular disease (CVD) is the leading cause of death in hemodialysis patients. This comes about because of a lack of predicted biomarkers in the risk analysis of CVD events in chronic kidney disease (CKD) patients. The present study aimed to determine the clinical utility of independent, predictable biomarkers such as serum creatinine, estimated Glomerular Filtration Rate (eGFR), high sensitive C-Reactive protein (hsCRP), fibrinogen and lipid profile as early predictors of CVD in CKD at stage III/IV.
Methods. This is a case-control study that includes a sample size of 100 patients of cases and 100 patients of controls who were recruited from November 2020 to April 2021, from the Nephrology department of the Visakhapatnam tertiary care teaching hospital, and present with chronic kidney disease – stage III/IV. The subjects’ general conditions (age, gender, height, weight, systolic blood pressure, diastolic blood pressure, and smoking history); underlying diseases (coronary heart disease and diabetes mellitus) were recorded. Fasting venous blood samples were collected under aseptic conditions from the study group after taking informed consent. The measurement of serum creatinine was performed by modification of kinetic Jaffe reaction. The Cockcroft-Gault equation was used to calculate eGFR in both cases and controls. CRP testing was done with a Cobas C311 analyzer, using immunoturbidimetric assay. The Fibroquant kit from Tulip was employed to measure fibrinogen levels in blood samples, and enzymatic methods were applied for lipid profile analysis.
Results. In this study, higher mean values of hsCRP (34.28 mg/dl), increased serum creatinine levels (2.876 mg/dl), reduced eGFR (28.37 mls/min), high levels of serum fibrinogen (291.6 mg/dl), and cholesterol (214.5 mg/dl), HDL (28.34 mg/dl), TG (162.1 mg/dl), VLDL (32.41 mg/dl) and LDL (153.77 mg/dl) were found to be independent predictors of assessment of CV events in patients with CKD stages III and IV as determined by Chi-square test.
Conclusion. A prompt and accurate assessment of cardiovascular risk in CKD patients would enable more aggressive and focused treatment of the individuals who are most in need of preventive interventions to decrease incident rates.
References
1. Abraham G, Moorthy AV, Aggarwal V. Chronic Kidney Disease: a silent epidemic in Indian subcontinent-strategies for management. J Ind Med Assoc. 2006;104(12):689-91.
2. Muntner P, Jiang He, Hamm L, Loria C, Whelton PK. Renal insufficiency and subsequent death from cardiovascular disease. J Am Soc Nephrolgy. 2002;13:745-53.
3. Kuhn A, van der Giet M, Kuhlmann MK, Mielke N, Ebert N, Schaeffner ES, et al. Kidney function as risk factor and predictor of cardiovascular outcomes and mortality among older adults. Am J Kidney Dis. 2021;77(3):386-96.
4. Fu EL, Franko MA, Obergfell A, Dekker FW, Gabrielsen A, Jernberg T, Carrero JJ. High-sensitivity C-reactive protein and the risk of chronic kidney disease progression or acute kidney injury in post-myocardial infarction patients. Am Heart J. 2019;216:20-9.
5. Go AS, Chertow GM, Fan D, McCulloch CE, Hsu CY. Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. N Engl J Med. 2004;351(13):1296-305.
6. National Kidney Foundation. K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis. 2002;39(2 Suppl 1):S1-266.
7. Inker LA, Astor BC, Fox CH, Isakova T, Lash JP, Peralta CA, et al. K/DOQI US commentary on the 2012 KDIGO clinical practice guideline for the evaluation and management of CKD. Am J Kidney Dis. 2014;63(5):713-35.
8. Roberts WL. CDC/AHA workshop on markers of inflammation and cardiovascular disease: Application to Clinical and Public Health Practice: laboratory tests available to assess inflammation – performance and standardization: a background paper. Circulation. 2004;110(25):572-6.
9. Fraser SD, Roderick PJ, Aitken G, Roth M, Mindell JS, Moon G, et al. Chronic kidney disease, albuminuria and socioeconomic status in the Health Surveys for England 2009 and 2010. J Public Health (Oxf.) 2014;36(4):577-86.
10. Tonelli M, Wiebe N, Guthrie B, James MT, Quan H, Fortin M, et al. Comorbidity as a driver of adverse outcomes in people with chronic kidney disease. Kidney Int. 2015;88(4):859-66.
11. Jankowski J, Floege J, Fliser D, Bohm M, Marx N. Cardiovascular disease in chronic Kidney Disease. Circulation. 2021;143(11):1157-72.
12. Balagopal PB, De Ferranti SD, Cook S, Daniels SR, Gidding SS, Hayman LL, et al. Nontraditional risk factors and biomarkers for cardiovascular disease: mechanistic, research, and clinical considerations for youth: a scientific statement from the American Heart Association. Circulation. 2011;123:2749-69.
13. Atkinson AJ, Colburn WA, DeGruttola VG, DeMets DL, Downing GJ, Hoth DF, et al. Biomarkers and surrogate endpoints: Preferred definitions and conceptual framework. Clin Pharmacol Ther. 2001; 69:89-95.
14. Manolio T. Novel risk markers and clinical practice. N Engl J Med. 2003;349:1587-9.
15. Bash LD, Erlinger TP, Coresh J, Marsh-Manzi J, Folsom AR, Astor BC. Inflammation, hemostasis, and the risk of kidney function decline in the Atherosclerosis Risk in Communities (ARIC) Study. Am J Kidney Dis. 2009;53:596-605.
16. Erlinger TP, Tarver-Carr ME, Powe NR, Appel LJ, Coresh J, Eberhardt MS. Leukocytosis, hypoalbuminemia, and the risk for chronic kidney disease in US adults. Am J Kidney Dis. 2003; 42:256-63.
17. Fried L, Solomon C, Shlipak M, Seliger S, Stehman-Breen C, Bleyer AJ, et al. Inflammatory and prothrombotic markers and the progression of renal disease in elderly individuals. J Am Soc Nephrol. 2004;15:3184-91.
18. Langston RD, Presley R, Flanders WD, McClellan WM. Renal insufficiency and anaemia are independent risk factors for death among patients with acute myocardial infarction. Kidney Int. 2003;64:1398-405.
19. Keeley EC, Kadakia R, Soman S, Borzak S, McCullough PA. Analysis of long-term survival after revascularization in patients with chronic kidney disease presenting with acute coronary syndromes. Am J Cardiol. 2003;92:509-14.
20. Matthew J. Tunbridge, Alan G. Jardine. Atherosclerotic Vascular Disease associated with chronic kidney disease. Cardiology Clinics. 2021;39(3):403-14.
21. Hak AE, Stehouwer CD, Bots ML, Polderman KH, Schalkwijk CG, Westenorp IC, et al. Associations of C-reactive protein with measures of obesity, insulin resistance, and subclinical atherosclerosis in healthy, middle-aged women. Arterioscler Thromb Vasc Biol. 1999; 19:1986-91.
22. Elkind MS, Tai W, Coates K, Paik MC, Sacco RL. High-sensitivity C-reactive protein, lipoprotein-associated phospholipase A2, and outcome after ischemic stroke. Arch Intern Med. 2006;166: 2073-80.
23. Arici M, Walls J. End stage renal disease, atherosclerosis, and cardiovascular mortality: Is C-reactive protein the missing link? Kidney Int. 2001;59:407-17.
24. Menon V, Greene T, Wang X, Pereira AA, Marcovina SC, Beck GJ, et al. C-reactive protein and albumin as predictors of all-cause and cardiovascular mortality in chronic kidney disease. Kidney Int. 2005; 68:766-72.
25. Mullens W, Abrahams Z, Francis GS, Sokos G, Taylor DO, Starling RC, et al. Importance of venous congestion for worsening of renal function in advanced decompensated heart failure. J Am Coll Cardiol. 2009;53:589-96.
26. Dries DL, Exner DV, Domanski MJ, Greenberg B, Stevenson LW. The prognostic implications of renal insufficiency in asymptomatic and symptomatic patients with left ventricular systolic dysfunction. J Am Coll Cardiol. 2000;35:681-9.
27. Iseki K, Yamazato M, Tozawa M, Takishita S. Hypocholesterolemiais a significant predictor of death in a cohort of chronic hemodialysis patients. Kidney Int. 2002;61:1887-93.
28. Kaysen GA. New insights into lipid metabolism in chronic kidney disease. J Ren Nutr. 2011;21:120-3.
29. Goldstein JL, Kita T, Brown MS. Defective lipoprotein receptors and atherosclerosis. N Engl J Med. 1983;309:288-96.
30. Gordon T, Castelli WP, Hjortland MC, Kannel WB, Dawber TR. High density lipoprotein as a protective factor against coronary heart disease. Am J Med. 1977;62:707-14.
31. Rifkind BM, Segal P. Lipid Research Clinics Program reference values for hyperlipidemia and hypolipidemia. JAMA. 1983;250:1869-72.
32. Attman PO, Alaupovic P. Lipid and apolipoprotein profiles of uremic dyslipoproteinemia: Relation to renal function and dialysis. Nephron. 1991;57:401-10.
33. Shlipak MG, Simon JA, Grady D, Lin F, Wenger NK, Furberg CD. Renal insufficiency and cardiovascular events in postmenopausal women with coronary heart disease. J Am Coll Cardiol. 2001;38: 705-11.
34. Modi ZJ, Lu Y, Ji N, et al. Risk of Cardiovascular Disease and Mortality in Young Adults With End-stage Renal Disease: An Analysis of the US Renal Data System. JAMA Cardiol. 2019;4(4): 353-62.
35. Zoccali C, Mallamaci F, Tripepi G, Kapke A, Selewski DT, Dietrich X, et al. Fibrinogen, mortality and incident cardiovascular complications in endstagerenal failure. J Intern Med. 2003;254(2): 132-9.
36. Undas A, Nycz K, Pastuszczak M, Stompor T, Zmudka K. The effect of chronic kidney disease on fibrin clot properties in patients with acute coronary syndrome. Blood Coagul Fibrinolysis. 2010;21(6):522-7.
37. Collet JP, Allali Y, Lesty C, Tanguy ML, Silvain J, Ankri A, et al. Altered fibrin architecture is associated with hypofibrinolysis and premature coronary atherothrombosis. Arterioscler Thromb Vasc Biol. 2006;26(11):2567-73.
38. Kearney K, Tomlinson D, Smith K, Ajjan R. Hypofibrinolysis in diabetes: a therapeutic target for the reduction of cardiovascular risk. Cardiovasc Diabetol. 2017;16:34.
39. Parastatidis I, Thomson L, Burke A, Chenysh J, Nagaswami C, Visser J, et al. Fibrinogen beta-chain tyrosine nitration is a prothrombotic risk factor. J Biol Chem. 2008;283(49):33846-53.
40. Lee SJ, Hong JM, Lee, SE, Kang DR, Ovbiagele B, Dermchuk AM, et al. Association of fibrinogen level with early neurological deterioration among acute ischemic stroke patients with diabetes. BMC Neurol. 2017;17:101.
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 Unported License.
Copyright (c) 2022 Authors