Increased serum PCSK9 levels are associated with renal function impairment in patients with type 2 diabetes mellitus

Zhicai Feng; Xiangyu Liao; Hao Zhang; Juan Peng; Zhijun Huang; Bin Yi

doi:10.1080/0886022X.2023.2215880

Increased serum PCSK9 levels are associated with renal function impairment in patients with type 2 diabetes mellitus

Ren Fail. 2023 Dec;45(1):2215880. doi: 10.1080/0886022X.2023.2215880.

Authors

Zhicai Feng^{1

2}, Xiangyu Liao^{1

2}, Hao Zhang^{1

2}, Juan Peng^{1

2}, Zhijun Huang^{1

2

3}, Bin Yi^{1

2}

Affiliations

¹ Department of Nephrology, The Third Xiangya Hospital, Central South University, Changsha, P.R. China.
² The Critical Kidney Disease Research Center of Central South University, Changsha, P.R. China.
³ Center for Clinical Pharmacology, The Third Xiangya Hospital, Central South University, Changsha, P.R. China.

Abstract

Purpose: The purpose of this study was to investigate the association between serum proprotein convertase subtilisin/kexin type 9 (PCSK9) levels and renal function impairment in type 2 diabetes mellitus (T2DM) patients.

Methods: PCSK9 levels were measured in T2DM patients, streptozotocin plus high-fat diet (STZ + HFD) mice, human proximal tubular epithelial (HK-2) cells treated with high glucose plus palmitic acid (HGPA) and the corresponding control groups. The T2DM patients were further divided into three groups according to serum PCSK9 levels. An analysis of clinical data was conducted, and a binary logistic regression model was used to test the relationship between potential predictors and urine albumin/urine creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR).

Results: PCSK9 levels were higher in the DM group than in the control group in humans, mice and HK-2 cells. The systolic blood pressure (SBP), serum creatinine (Scr), blood urea nitrogen (BUN), triglyceride (TG), and urine α1-MG/urine creatinine ratio (UαCR) values in PCSK9 tertile 3 were significantly higher than those in PCSK9 tertile 1 (p < 0.05). The DBP and UACR values were significantly higher in PCSK9 tertile 3 than in PCSK9 tertile 1 and PCSK9 tertile 2 (both p < 0.05). In addition, URCR values were significantly higher in PCSK9 tertile 3 and PCSK9 tertile 2 than in PCSK9 tertile 1 (both p < 0.05). Serum PCSK9 levels were positively correlated with SBP, Scr, BUN, TG, URCR, UαCR and UACR but inversely correlated with eGFR. In STZ + HFD mice, serum PCSK9 levels were positively correlated with Scr, BUN and UACR, which was consistent with the findings in the patients. A logistic regression model revealed that serum PCSK9 is an independent risk factor for UACR ≥30 mg/g and eGFR <60 mL/min/1.73 m². The ROC curve showed that 170.53 ng/mL and 337.26 ng/mL PCSK9 were the best cutoff values for UACR ≥30 mg/g and eGFR <60 mL/min/1.73 m², respectively.

Conclusion: Serum PCSK9 levels are associated with renal function impairment in T2DM patients and in some patients lower PCSK9 may be helpful to decrease chronic kidney disease.

Keywords: Proprotein convertase subtilisin/kexin type 9; Type 2 diabetes mellitus; estimated glomerular filtration rate; urine albumin/urine creatinine ratio.

MeSH terms

Adult
Aged
Albumins
Animals
Cell Line
Diabetes Mellitus, Type 2* / blood
Diabetic Nephropathies* / blood
Disease Models, Animal
Glomerular Filtration Rate
Humans
Kidney / physiopathology
Mice
Mice, Inbred C57BL
Middle Aged
Proprotein Convertase 9* / blood
Young Adult

Substances

PCSK9 protein, human
Proprotein Convertase 9
Albumins

Grants and funding

The study was supported by grants from the National Natural Science Foundation of China [82070759] and Natural Science Foundation of Hunan Province [2021JJ31016].