The Association Between Cystatin C and Arterial Stiffness in Non-Chronic Kidney Disease Patients - European Medical Journal

The Association Between Cystatin C and Arterial Stiffness in Non-Chronic Kidney Disease Patients

3 Mins
*Nejc Piko,1,2 Robert Ekart,2,3 Radovan Hojs,1,3 Tadej Petreski,1,3 Sebastjan Bevc1,3

The authors have declared no conflicts of interest.

EMJ Nephrol. ;8[1]:31-32. Abstract Review No. AR1.
Arterial stiffness, atherosclerosis, cystatin C (cysC).

Each article is made available under the terms of the Creative Commons Attribution-Non Commercial 4.0 License.


Serum cystatin C (cysC) is a protease inhibitor with a low molecular weight, which is produced by all nucleated cells at a constant rate. It is freely filtered by the glomerulus, then reabsorbed and metabolised in the proximal tubule. Extrarenal clearance of cysC is low.1 Compared to serum creatinine, it is influenced less by age, sex, and muscle mass; additionally, it is not affected by inflammation or fever. However, thyroid dysfunction, certain malignancies, and corticosteroid therapy can alter cysC levels.2 Despite some of its drawbacks, it is an important marker in detecting renal impairment, especially in early stages of chronic kidney disease (CKD).3,4

Increased arterial stiffness is a hallmark of atherosclerosis and is associated with increased morbidity and mortality because of cardiovascular causes. It is a consequence of structural and functional vascular changes.5,6 Studies have shown that in patients with CKD, cysC correlates with increased arterial stiffness.7 However, the data on the connection between cysC and arterial stiffness in patients without CKD are sparse.


The study was a cross-section, single-centre evaluation of arterial stiffness parameters in patients without CKD. It was performed at the University Medical Centre Maribor, Maribor, Slovenia, between 1st October 2018 and 1st January 2020. Basic demographic and laboratory data of enrolled patients were recorded. The CKD Epidemiology (CKD-EPI) creatinine-based equation was used to estimate glomerular filtration rate (eGFR). Patients with active malignancies, previously diagnosed CKD, and/or eGFR ≤60 mL/min/1.73m2 at the time of admission were excluded from the study. None of the included patients had a history of thyroid disease and none of them were treated with corticosteroids at the time of inclusion in the study. Arterial stiffness was measured with applanation tonometry (SphygmoCor®, AtCor Medical, Sydney, Australia). Carotid-femoral pulse wave velocity (cfPWV) was used as the gold standard of central arterial stiffness8 and subendocardial viability ratio (SEVR) was used as the marker of myocardial perfusion.9 SPSS® (IBM, Armonk, New York, USA) version 22 was used for statistical analysis and results with p<0.05 were deemed as statistically significant.


In the study, 111 patients (65.8% male; median age: 64.3±9.4 years) were included. The most common comorbidities were arterial hypertension (n=86; 77.5%), hyperlipidaemia (n=64; 57.7%), and diabetes  (n=22; 19.8%). Mean creatinine value was 77.7±13.8 μmol/L (range: 49–108 μmol/L), mean eGFR was 81.3±9.4 mL/min/1.73m2 (range: 62–90 mL/min/1.73m2), and mean value of cysC was 0.94±0.18 mg/L (range: 0.67–1.63 mg/L). Mean cfPWV value was 10.1±2.4 m/s (range: 6.2–16.8 m/s) and mean SEVR value was 165.7±36.1% (range: 92.0–299.0%). Significant correlation was found between cysC and SEVR (Pearson’s correlation coefficient [r]=-0.316; p<0.001) and between cysC and cfPWV (r=0.472; p<0.001). Multiple regression analysis, with SEVR and cfPWV as dependent variables and cysC, age, sex, diabetes, arterial hypertension, eGFR, and hyperlipidaemia as independent variables, showed statistically significant association between cysC and SEVR (β coefficient [β]=-0.278; p=0.017) and between cysC and cfPWV (β=0.220; p=0.038).


Serum cysC was independently associated with increased arterial stiffness, reduced myocardial perfusion, and increased cardiovascular risk in the cohort of patients without CKD. This research shows the potentially important role of cysC in cardiovascular risk assessment in all patients, even in those with normal kidney function.

Hojs R et al. Serum cystatin C as an endogenous marker of renal function in patients with mild to moderate impairment of kidney function. Nephrol Dial Transplant. 2006;21(7):1855-62. Jones M et al. Evaluation of cystatin C in malignancy and comparability of estimates of GFR in oncology patients. Pract Lab Med. 2017;8:95-104. Levey AS, Eckfeldt JH. Using glomerular filtration rate estimating equations: clinical and laboratory considerations. Clin Chem. 2015;61(10):1226-9. Randers E, Erlandsen EJ. Serum cystatin C as an endogenous marker of the renal function--a review. Clin Chem Lab Med. 1999;37(4):389-95. Catalano M et al. Aortic augmentation index in patients with peripheral arterial disease. J Clin Hypertens (Greenwich). 2014;16(11):782-7. Laurent S et al. Expert consensus document on arterial stiffness: methodological issues and clinical applications. Eur Heart J. 2006;27(21):2588-605. Madero M et al. Cystatin C associates with arterial stiffness in older adults. J Am Soc Nephrol. 2009;20(5):1086-93. Van Bortel LM et al. Expert consensus document on the measurement of aortic stiffness in daily practice using carotid-femoral pulse wave velocity. J Hypertens. 2012;30(3):445-8. Anyfanti P et al. Noninvasive assessment of myocardial perfusion in different blood pressure phenotypes and its association with arterial stiffness indices. Am J Hypertens. 2019;32(6):557-63.

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