Arylesterase activity but not PCSK9 levels is associated with chronic kidney disease in type 2 diabetes
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NEPHROLOGY - ORIGINAL PAPER
Arylesterase activity but not PCSK9 levels is associated with chronic kidney disease in type 2 diabetes Nutsiwat Didas1 · Witsawat Thitisopee2 · Sureerut Porntadavity3 · Nutjaree Jeenduang1 Received: 20 March 2020 / Accepted: 16 June 2020 © Springer Nature B.V. 2020
Abstract Purpose Oxidative stress and dyslipidemia have been found to be associated with the progression of chronic kidney disease (CKD) in type 2 diabetes mellitus (T2DM) patients. Paraoxonase 1 (PON-1) activity, and proprotein convertase subtilisin kexin type 9 (PCSK9) levels play an important role regarding anti-oxidants, and lipid metabolism, respectively. The aim of this study was to investigate the association of PON-1 activity, and PCSK9 levels with CKD in T2DM. Methods A total of 180 T2DM (87 CKD, and 93 non-CKD) with age-, and gender-matched subjects were recruited in this study. PON-1 activity was measured with two kinds of substrate: paraoxon for paraoxonase (PONase) activity and phenylacetate for arylesterase (AREase) activity. PCSK9 levels were measured by enzyme-linked immunosorbent assay (ELISA). Results AREase activity was significantly lower in CKD compared with non-CKD (225.53 ± 108.73 vs. 257.45 ± 106.12 kU/L, p = 0.044) in T2DM, whereas there was no significant difference in PONase activity and PCSK9 levels between CKD and non-CKD groups. In addition, multivariate logistic regression analysis showed that the lowest tertile of AREase increased the risk for CKD in T2DM (OR 3.251; 95% CI 1.333–7.926, p = 0.010), whereas PONase activity and PCSK9 levels were not associated with CKD in T2DM. Conclusion Reduced AREase activity can increase the risk for CKD in T2DM patients. AREase activity, but not PONase activity and PCSK9 levels, may be used as the biomarker for predicting the progression of CKD in T2DM. Keywords Paraoxonase 1 · PCSK9 · Type 2 diabetes · CKD · Non-CKD
Introduction Chronic kidney disease (CKD) is one of common complications of type 2 diabetes mellitus (T2DM) [1]. According to the Kidney Disease Outcomes Quality Initiative (K/ DOQI), CKD is characterized by an estimated glomerular filtration rate (eGFR) below 60 ml/min/1.73 m2 lasting for at least 3 months [1]. The pathogenesis of CKD in T2DM patients results from renal hemodynamics changes, oxidative stress, inflammation, hypoxia, and overactive renin–angiotensin–aldosterone system (RAAS) [2]. In * Nutjaree Jeenduang [email protected] 1
School of Allied Health Sciences, Walailak University, 222 Thaiburi, Thasala, Nakhon Si Thammarat, Thailand
2
Department of Medicine, Thasala Hospital, Nakhon Si Thammarat, Thailand
3
Department of Clinical Chemistry, Faculty of Medical Technology, Mahidol University, Bangkok, Thailand
addition, dyslipidemia which is developed by CKD, is in turn, also associated with the progression of CKD [3]. Paraoxonase 1 (PON-1), which is an HDL-associated enzyme esterase, possesses anti-oxidant and anti-atherosclerotic properties [4]. The anti-atherogenic functions of HDL-C by PON-1 included the p
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