Chronic kidney disease on hemodialysis is associated with decreased serum PCSK9 levels

Abujrad, Hussein; Mayne, Janice; Ruzicka, Marcel; Cousins, Marion; Raymond, Angela; Cheesman, Judy O.; Taljaard, Monica; Sorisky, Alexander; Burns, Kevin D.; Ooi, Teik Chye

doi:10.1016/j.atherosclerosis.2013.12.030

Cited by 40 publications

(40 citation statements)

References 34 publications

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“…1). Recently, the other authors have also indicated the lack of increase in PCSK9 serum concentration in patients on hemodialysis treatment; thus, our results seem to be consistent to that extent [16,17]. These facts allow us to suggest that serum PCSK9 concentration is at least partly dependent on the glomerular filtration rate and its elevated level noted in renal failure may be fully corrected by the applied methods of renal replacement therapy.…”

Section: Discussionsupporting

confidence: 73%

“…Abujrad et al . reported that the mean plasma PCSK9 level was 38% higher in hemodialysed patients receiving statins than in patients without this therapy [16]. In our study, a comparable percentage of patients of both groups was treated with statins, admittedly with more effective ones and in slightly higher doses in patients with CKD, but the mean PCSK9 plasma level was more than 120% higher in CKD patients than in controls.…”

Section: Discussionmentioning

confidence: 56%

“…Abujrad et al showed similar results. The correlation between serum concentrations of PCSK9 and TCh and LDL-Ch was observed only in patients not treated with statins [16]. …”

Section: Discussionmentioning

confidence: 99%

“…Recently, Abujrad et al [16] reported the decreased plasma level in patients on maintenance hemodialysis treatment and Jin et al [17] indicated enhanced plasma PCSK9 concentration in nephrotic syndrome and peritoneal dialysis. So far, to our knowledge, circulating PCSK9 level has not been evaluated in patients with conservatively treated CKD.…”

Section: Introductionmentioning

confidence: 99%

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Elevated Circulating PCSK-9 Concentration in Renal Failure Patients is Corrected by Renal Replacement Therapy

Konarzewski¹,

Szołkiewicz

Sucajtys-Szulc

et al. 2014

Am J Nephrol

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Background: A high level of circulating PCSK9 binds to the LDL receptor, reduces its cell's surface density and leads to hypercholesterolemia. The aim of this study was to examine the circulating PCSK9 level in patients with kidney disease. Methods: Out of the patients treated in our Departments we selected: (a) 44 patients with CKD stage 3 and 4 (b) 29 patients with CKD stage 5 on maintenance hemodialysis treatment; and (c) 20 patients after successful renal transplantation. Thirty-four subjects, without CKD formed the control group. Serum biochemical parameters' concentrations were assayed by a certified laboratory. Serum PCSK9 concentration was estimated by a commercially available ELISA kit. Results: The mean serum concentration of PCSK9 in patients with kidney disease was higher than in the control group (238.7 ± 64.5 vs. 536.7 ± 190.4; p < 0.001). A strong negative correlation between serum PCSK9 concentration and eGFR was found (r = -0.66; p < 0.001), as well as between serum concentrations of PCSK9 and total- (r = 0.482; p < 0.05) or LDL-cholesterol (r = 0.533; p < 0.05), but exclusively in patients not receiving statins. The elevated serum concentration of PCSK9 in patients before hemodialysis session declined afterwards, reaching the values observed in patients after kidney transplantation and in the control group. Conclusion: The circulating PCSK9 concentration is increased in patients with CKD; however, this is not accompanied by hypercholesterolemia. The positive correlations between PCSK9/TCh and PCSK9/LDL-Ch have been found only in patients not treated with statins. The elevated circulating PCSK9 level is corrected by maintenance hemodialysis treatment and normalized by a successful kidney transplantation.

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Section: Discussionsupporting

confidence: 73%

Section: Discussionmentioning

confidence: 56%

“…Abujrad et al showed similar results. The correlation between serum concentrations of PCSK9 and TCh and LDL-Ch was observed only in patients not treated with statins [16]. …”

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Elevated Circulating PCSK-9 Concentration in Renal Failure Patients is Corrected by Renal Replacement Therapy

Konarzewski¹,

Szołkiewicz

Sucajtys-Szulc

et al. 2014

Am J Nephrol

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“…PCSK9 levels were found to be almost 2 times higher in CKD patients compared with subjects with normal kidney function [46]. In contrast, Rogacev et al [47] found no correlation between eGFR and PCSK9 levels in CKD patients.…”

Section: Proprotein Convertase Subtilisin/kexin Type 9 Effect On Lipimentioning

confidence: 99%

Disorders of Lipid Metabolism in Chronic Kidney Disease

et al. 2018

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Cardiovascular disease (CVD) is the leading cause of death in chronic kidney disease (CKD). One of the most important pathophysiological mechanisms for CVD in patients with CKD is the widespread and possibly accelerated formation of atherosclerotic plaques due to hyperlipidemia, uremic toxins, inflammation, oxidative stress, and endothelial dysfunction. Recent studies showed that the level of oxidized low-density lipoprotein cholesterol increases, and that high-density lipoprotein cholesterol dysfunction occurs as kidney function declines and inflammation becomes more prevalent. In this review, we aimed to discuss the effect of kidney dysfunction, oxidative stress, and inflammation on lipid profile.

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Beyond cholesterol metabolism: The pleiotropic effects of proprotein convertase subtilisin/kexin type 9 (PCSK9). Genetics, mutations, expression, and perspective for long‐term inhibition

et al. 2020

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Proprotein convertase subtilisin/kexin type 9 (PCSK9) has a crucial role in lipid metabolism, particularly due to its function in low‐density lipoprotein receptor degradation. Gain‐of‐function genetic mutations of PCSK9 result in autosomal dominant familial hypercholesterolemia, characterized by high levels of low‐density lipoprotein cholesterol (LDL‐C) and clinical signs of early atherosclerosis. In recent years, PCSK9 has become an important therapeutic target for cholesterol‐lowering therapy. Particularly, its inhibition with monoclonal antibodies has shown excellent efficacy in decreasing LDL‐C and reducing cardiovascular events. However, PCSK9, first identified in the brain, seems to be a ubiquitous protein with different tissue‐specific functions also independent of cholesterol metabolism. Accordingly, it appears to be involved in the immune response, haemostasis, glucose metabolism, neuronal survival, and several other biological functions. This review provides a comprehensive overview of the genetics, biochemical structure, expression, and function of PCSK9 and discusses the potential implications of its long‐term pharmacological inhibition.

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Chronic kidney disease on hemodialysis is associated with decreased serum PCSK9 levels

Cited by 40 publications

References 34 publications

Elevated Circulating PCSK-9 Concentration in Renal Failure Patients is Corrected by Renal Replacement Therapy

Elevated Circulating PCSK-9 Concentration in Renal Failure Patients is Corrected by Renal Replacement Therapy

Disorders of Lipid Metabolism in Chronic Kidney Disease

Beyond cholesterol metabolism: The pleiotropic effects of proprotein convertase subtilisin/kexin type 9 (PCSK9). Genetics, mutations, expression, and perspective for long‐term inhibition

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