Relationship of serum lipid parameters with kidney function decline accompanied by systemic arterial stiffness: a retrospective cohort study

Q: What are the key findings of this study?

Elevated triglycerides (>=82 mg/dL) independently increased kidney function decline risk (HR 1.267, 95% CI 1.146-1.401), partially mediated by systemic arterial stiffness (2.9%).

Q: What is the clinical evidence from this study?

Study design: Cohort. Population: Kidney function decline and dyslipidemia (n=27864). Intervention: Baseline serum lipid parameters (specifically elevated triglycerides >= 82 mg/dL, TG/HDL-C ratio >= 1.28, and HDL-C < 65 mg/dL) vs. Reference lipid levels below cut-off thresholds (e.g., triglycerides < 82 mg/dL). Primary outcome: Kidney function decline (KFD), defined as development of eGFR < 60 mL/min/1.73 m2 (HR 1.267, 95% CI 1.146-1.401).

Q: What does this research mean for the field?

Elevated triglycerides (>=82 mg/dL) independently increase the risk of kidney function decline, an association partially mediated by systemic arterial stiffness. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

Daiji Nagayama; Yasuhiro Watanabe; Takashi Yamaguchi; Kentaro Fujishiro; Kenji Suzuki; Kohji Shirai; Atsuhito Saiki

doi:10.1093/ckj/sfad131

May 26, 2023Clinical Kidney JournalOpen Access

Relationship of serum lipid parameters with kidney function decline accompanied by systemic arterial stiffness: a retrospective cohort study

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Key result

Elevated triglycerides linked to ~27% higher risk of kidney function decline.

HR 1.267
95% CI 1.146-1.401
n=27,864

Figures

Graphical abstract published by Clinical Kidney Journal — Graphical abstract · Published by Clinical Kidney Journal · CC BY

Why the study?

Although dyslipidemia is linked to kidney function decline, the non-linear relationship between lipid parameters and decline, including the potential mediating role of arterial stiffness, has not been fully elucidated.

Do baseline serum lipid parameters (LDL-C, HDL-C, TG, and TG/HDL-C ratio) linearly or non-linearly predict kidney function decline in urban residents with preserved baseline kidney function, and is this relationship mediated by systemic arterial stiffness (CAVI)?

Key Points

To determine the relationship between baseline serum lipid parameters and kidney function decline, including the mediating role of arterial stiffness.
Retrospective cohort study of 27 864 urban residents with baseline eGFR ≥60 mL/min/1.73 m2 who attended a median of three consecutive annual health examinations between 2010 and 2018.
Arterial stiffness was measured via the cardio-ankle vascular index (CAVI), and kidney function decline was defined as the development of eGFR <60 mL/min/1.73 m2.
Predictive cut-offs and risk associations were evaluated using ROC curve analysis, multivariable Cox proportional hazards models, and mediation analysis adjusting for age, sex, BMI, blood pressure, fasting glucose, proteinuria, and smoking.
Over the study period, 1837 participants (6.6%) developed kidney function decline.
Independent associations with kidney function decline were observed for TG ≥82 mg/dL (adjusted HR 1.267, 95% CI 1.146–1.401), TG/HDL-C ratio ≥1.28 (adjusted HR 1.253, 95% CI 1.133–1.387), and HDL-C <65 mg/dL (adjusted HR 1.135, 95% CI 1.027–1.254), whereas LDL-C ≥123 mg/dL showed no significant association (adjusted HR 1.091, 95% CI 0.992–1.201).
Risk increased linearly with TG and TG/HDL-C ratio and displayed a U-shaped relationship with HDL-C, with CAVI partially mediating the effect of TG (mediating rate: 2.9%) and TG/HDL-C ratio (mediating rate: 2.5%) on kidney function decline.

Study Design

Type

Cohort (n=27,864)

Multicenter

Yes

Structured PICO

Do baseline serum lipid parameters (LDL-C, HDL-C, TG, and TG/HDL-C ratio) linearly or non-linearly predict kidney function decline in urban residents with preserved baseline kidney function, and is this relationship mediated by systemic arterial stiffness (CAVI)?

P

Population

27,864 Japanese urban residents (median age 46 years, 55.6% female) with baseline eGFR >= 60 mL/min/1.73 m2 and no prior kidney disease, followed across a median of 3 consecutive annual health examinations between 2010 and 2018.

E

Exposure

Baseline serum lipid abnormalities: triglycerides (TG) >=82 mg/dL, TG/HDL-C ratio >=1.28, HDL-C <65 mg/dL, and LDL-C >=123 mg/dL, with mediation analysis via cardio-ankle vascular index (CAVI).

C

Comparator

Lipid levels below the ROC-derived cut-off values (TG <82 mg/dL, TG/HDL-C ratio <1.28, HDL-C >=65 mg/dL, LDL-C <123 mg/dL) or lowest lipid stratum.

O

Outcome

Development of kidney function decline (KFD), defined as eGFR <60 mL/min/1.73 m2 at any subsequent annual health examination during the study period.surrogate

Main Result

Hazard Ratio: 1.267 (95% CI 1.146–1.401)

Limitations

Cut-off values of lipid parameters may only apply to the middle-aged Japanese population.
The Japanese Society of Nephrology eGFR formula may deviate from conventional MDRD or CKD-EPI equations.
Serum creatinine was used instead of the more precise indicator cystatin C.
Urinary protein was assessed by the less precise dipstick method.
Fasting plasma glucose was used instead of HbA1c because only 34% of subjects had HbA1c measured.
Potential selection bias as participants undergoing regular health screenings may be more health-conscious.
Lipid cut-off values may only be applicable to the middle-aged Japanese population.
Use of the Japanese Society of Nephrology eGFR formula may deviate from conventional MDRD/CKD-EPI equations.
Serum creatinine was used rather than cystatin C to estimate kidney function.
Proteinuria was determined using the dipstick method, which lacks precision.
Only 34% of subjects had HbA1c measured, necessitating the use of fasting plasma glucose as the glucose metabolism parameter.
Potential selection bias due to healthy volunteer effect among regular health screening participants.

Implication

Triglycerides and TG/HDL-C ratio show a linear positive association with kidney function decline that is partially mediated by systemic arterial stiffness (CAVI), whereas HDL-C exhibits a U-shaped relationship and LDL-C shows no independent association.

Abstract

Background Dyslipidemia is associated with kidney function decline (KFD), although the non-linear relationship of lipid parameters to KFD has not been fully elucidated. We aimed to determine the detailed relationship of baseline lipid parameters with KFD, considering the mediation of arterial stiffness. Methods A total of 27 864 urban residents with estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2 at baseline, who participated in a median of three (range two to eight) consecutive annual health examinations were studied. Arterial stiffness was assessed by cardio-ankle vascular index (CAVI). KFD was defined as development of eGFR <60 mL/min/1.73 m2. Results During the study period, 1837 participants (6.6%) developed KFD. Receiver operating characteristic analysis determined that the cutoff values independently associated with KFD are 123 mg/dL for low-density lipoprotein cholesterol (LDL-C) [area under the curve (95% confidence interval) 0.570 (0.557–0.583)], 65 mg/dL for high-density lipoprotein cholesterol (HDL-C) [0.552 (0.539–0.566)], 82 mg/dL for triglycerides (TG) [0.606 (0.593–0.618)] and 1.28 for TG/HDL-C ratio [0.600 (0.587–0.612)]. These cut-offs were independently associated with KFD in Cox analysis. Regarding the contribution of each lipid parameter to KFD, a linear relationship was observed for both TG and TG/HDL-C, and a U-shaped relationship for HDL-C. A adjusted mediating effect of CAVI on the relationship of TG or TG/HDL-C ratio with KFD was observed (mediating rate: 2.9% in TG, 2.5% in TG/HDL-C ratio). Regarding the association to KFD, a linear relationship was observed for both TG and TG/HDL-C, and a U-shaped relationship for HDL-C. A mediating effect of CAVI on the relationship of TG or TG/HDL-C ratio with KFD was observed after adjustment for confounders. Conclusions TG and TG/HDL-C ratio related linearly to KFD and this was partially mediated by CAVI. A U-shaped relationship was observed between HDL-C and KFD risk. LDL-C showed no significant association. Further study should investigate whether intensive TG-lowering treatment prevents KFD via decreasing CAVI.

Discussion

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Cite This Study

Nagayama et al. (2023) conducted a cohort in Kidney function decline and dyslipidemia (n=27,864). Baseline serum lipid parameters (specifically elevated triglycerides >= 82 mg/dL, TG/HDL-C ratio >= 1.28, and HDL-C < 65 mg/dL) vs. Reference lipid levels below cut-off thresholds (e.g., triglycerides < 82 mg/dL) was evaluated on Kidney function decline (KFD), defined as development of eGFR < 60 mL/min/1.73 m2 (HR 1.267, 95% CI 1.146-1.401). Elevated triglycerides (>=82 mg/dL) independently increased kidney function decline risk (HR 1.267, 95% CI 1.146-1.401), partially mediated by systemic arterial stiffness (2.9%).

synapsesocial.com/papers/6a71b7d96ceb2bbd16e037cd https://doi.org/10.1093/ckj/sfad131

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Relationship of serum lipid parameters with kidney function decline accompanied by systemic arterial stiffness: a retrospective cohort study

Figures

Key Points

Study Design

Structured PICO

Main Result

Limitations

Implication

Abstract

Discussion

Cite This Study

Relationship of serum lipid parameters with kidney function decline accompanied by systemic arterial stiffness: a retrospective cohort study

Figures

Key Points

Study Design

Structured PICO

Main Result

Limitations

Implication

Abstract

Discussion

Cite This Study

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