Association of High-Density Lipoprotein Cholesterol With GFR Decline in a General Nondiabetic Population

Toralf Melsom; Jon Viljar Norvik; Inger Therese Enoksen; Vidar Stefansson; Renathe Rismo; Trond Jenssen; Marit D Solbu; Bjørn O Eriksen

doi:10.1016/j.ekir.2021.05.007

Association of High-Density Lipoprotein Cholesterol With GFR Decline in a General Nondiabetic Population

Kidney Int Rep. 2021 May 19;6(8):2084-2094. doi: 10.1016/j.ekir.2021.05.007. eCollection 2021 Aug.

Authors

Toralf Melsom^{1

2}, Jon Viljar Norvik^{1

2}, Inger Therese Enoksen¹, Vidar Stefansson¹, Renathe Rismo^{1

2}, Trond Jenssen^{1

3}, Marit D Solbu^{1

2}, Bjørn O Eriksen^{1

2}

Affiliations

¹ Metabolic and Renal Research Group, UiT Arctic University of Norway.
² Section of Nephrology, University Hospital of North Norway, Tromsø.
³ Department of Organ Transplantation, Oslo University Hospital and University of Oslo, Norway.

Abstract

Introduction: Although lower high-density lipoprotein cholesterol (HDL-C) levels are considered a risk factor for cardiovascular disease (CVD), experimental evidence suggest that aging, inflammation, and oxidative stress may remodel HDL-C, leading to dysfunctional HDL-C. Population studies on HDL-C and loss of the glomerular filtration rate (GFR) reported inconsistent results, but they used inaccurate estimates of the GFR and may have been confounded by comorbidity.

Methods: We investigated the association of HDL-C levels with risk of GFR loss in a general population cohort; the participants were aged 50-62 years and did not have diabetes, CVD, or chronic kidney disease (CKD) at baseline. The GFR was measured using iohexol-clearance at baseline (n=1627) and at the follow-up (n=1324) after a median of 5.6 years. We also investigated any possible effect modification by low-grade inflammation, physical activity, and sex.

Results: Higher HDL-C levels were associated with steeper GFR decline rates and increased risk of rapid GFR decline (>3 ml/min per 1.73 m² per year) in multivariable adjusted linear mixed models and logistic regression (-0.64 ml/min per 1.73 m² per year [95% CI -0.99, -0.29; P < 0.001] and odds ratio 2.7 [95% CI 1.4, 5.2; P < 0.001] per doubling in HDL-C). Effect modifications indicated a stronger association between high HDL-C and GFR loss in physically inactive persons, those with low-grade inflammation, and men.

Conclusion: Higher HDL-C levels were independently associated with accelerated GFR loss in a general middle-aged nondiabetic population.

Keywords: GFR; HDL cholesterol; aging; chronic kidney disease; glomerular filtration rate; high-density lipoprotein cholesterol.