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Serum lipoprotein (a) associates with a higher risk of reduced renal function: a prospective investigation.

ABSTRACT: Lipoprotein (a) [Lp(a)] is a well-known risk factor for cardiovascular disease, but analysis on Lp(a) and renal dysfunction is scarce. We aimed to investigate prospectively the association of serum Lp(a) with the risk of reduced renal function, and further investigated whether diabetic or hypertensive status modified such association. Six thousand two hundred and fifty-seven Chinese adults aged ≤40 years and free of reduced renal function at baseline were included in the study. Reduced renal function was defined as estimated glomerular filtration rate <60 ml/min/1.73 m² During a mean follow-up of 4.4 years, 158 participants developed reduced renal function. Each one-unit increase in log₁₀-Lp(a) (milligrams per deciliter) was associated with a 1.99-fold (95% CI 1.15-3.43) increased risk of incident reduced renal function; the multivariable-adjusted odds ratio (OR) for the highest tertile of Lp(a) was 1.61 (95% CI 1.03-2.52) compared with the lowest tertile (P for trend = 0.03). The stratified analysis showed the association of serum Lp(a) and incident reduced renal function was more prominent in participants with prevalent diabetes [OR 4.04, 95% CI (1.42-11.54)] or hypertension [OR 2.18, 95% CI (1.22-3.89)]. A stronger association was observed in the group with diabetes and high Lp(a) (>25 mg/dl), indicating a combined effect of diabetes and high Lp(a) on the reduced renal function risk. An elevated Lp(a) level was independently associated with risk of incident reduced renal function, especially in diabetic or hypertensive patients.

SUBMITTER: Xuan L

PROVIDER: S-EPMC7529054 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Serum lipoprotein (a) associates with a higher risk of reduced renal function: a prospective investigation.

Xuan Liping L Wang Tiange T Dai Huajie H Wang Bin B Xiang Jiali J Wang Shuangyuan S Lin Hong H Li Mian M Zhao Zhiyun Z Lu Jieli J Chen Yuhong Y Xu Yu Y Wang Weiqing W Xu Min M Bi Yufang Y Ning Guang G

Journal of lipid research 20200723 10

Lipoprotein (a) [Lp(a)] is a well-known risk factor for cardiovascular disease, but analysis on Lp(a) and renal dysfunction is scarce. We aimed to investigate prospectively the association of serum Lp(a) with the risk of reduced renal function, and further investigated whether diabetic or hypertensive status modified such association. Six thousand two hundred and fifty-seven Chinese adults aged ≤40 years and free of reduced renal function at baseline were included in the study. Reduced renal fun ...[more]

PMID: 32703886

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Project description:BackgroundEvidence regarding the effects of lipoprotein (a) [lp(a)] and renal function remains unclear. The present study aimed to explore the causal association of serum lp(a) with renal function damage in Chinese general adults.MethodsA total of 25343 individuals with available lp(a) data were selected from the baseline survey of the Cohort Study on Chronic Disease of Communities Natural Population in Beijing, Tianjin, and Hebei (CHCN-BTH). Five renal function indexes [estimated glomerular filtration rate (eGFR), serum creatinine (Scr), blood urea nitrogen (BUN), uric acid (UA), high-sensitivity C-reactive protein(CRPHS)] were analyzed. The restricted cubic spline (RCS) method, logistic regression, and linear regression were used to test the dose-response association between lp(a) and renal function. Stratified analyses related to demographic characteristics and disease status were performed. Two-sample Mendelian randomization (MR) analysis was used to obtain the causal association of lp(a) and renal function indexes. Genotyping was accomplished by MassARRAY System.ResultsLp(a) levels were independently associated with four renal function indexes (eGFR, Scr, BUN, CRPHS). Individuals with a higher lp(a) level had a lower eGFR level, and the association with Scr estimated GFR was stronger in individuals with a lower lp(a) level (under 14 mg/dL). . The association was similar in individuals regardless of diabetes or hypertension. MR analysis confirmed the causal association of two renal function indexes (Scr and BUN). For MR analysis, each one unit higher lp(a) was associated with 7.4% higher Scr (P=0.031) in the inverse-variance weighted method. But a causal effect of genetically increased lp(a) level with increased eGFR level which contrasted with our observational results was observed.ConclusionThe observational and causal effect of lp(a) on Scr and BUN were founded, suggesting the role of lp(a) on the risk of renal function damage in general Chinese adults.

Project description:ObjectiveProteinuria is the clinical expression of lupus nephritis and despite recent advances in the therapeutic armamentarium for lupus nephritis, morbidity and mortality rates remain high. Therefore, the identification of factors that predict lupus nephritis is paramount in preventing damage accrual and disease progression. Lipoprotein (a) (Lp[a]) is a primarily genetically inherited plasma lipoprotein with pro-thrombotic and pro-atherosclerotic effects. Elevated Lp(a) has been observed at early stages of renal impairment in the general population and is associated with the development of chronic kidney disease. However, little is known about renal implications of Lp(a) in SLE. Thus, we evaluated Lp(a) and atherosclerotic events, thrombotic events, renal disease, and disease activity in patients with SLE.MethodsSLE patients fulfilling the revised American College of Rheumatology (ACR) or SLICC classification criteria with a measurement of Lp(a) were included in the analysis. A cutoff of 125 nmol/L was chosen based on expert opinion. Chi-square test was used to compare the differences between patient characteristics and Lp(a) levels. Logistic regression or linear regression were used, where appropriate, to assess the association between Lp(a) values and the measured outcomes.ResultsLp(a) levels from 562 patients were analyzed. There was an association between elevated Lp(a) and a history of proteinuria (OR 1.58, p-value = 0.02). This association remained significant following adjustment for age, sex, race, low C3, and elevated anti-dsDNA (OR = 1.55, p-value = 0.04). There was also an association with eGFR < 60 (p = 0.02). Patients with elevated Lp(a) had higher physician global activity (p = 0.01) and erythrocyte sediment rate (p = 0.03).ConclusionElevated Lp(a) was associated with proteinuria, independent of known factors associated with lupus proteinuria, as well as reduced eGFR and physician global activity. Our findings highlight the potential role of Lp(a) as a noninvasive biomarker for early renal disease in SLE.

Project description:BackgroundChronic kidney disease (CKD) poses a significant global public health challenge. While lipoprotein(a) (Lp[a]) has been established as a significant factor in cardiovascular disease, its connection to CKD risk remains a topic of debate. Existing evidence indicates diverse risks of kidney disease among individuals with various renal function indicators, even when within the normal range.ObjectiveThis study aims to investigate the joint associations between different renal function indicators and Lp(a) regarding the risks of incident CKD in the general population.MethodsThe analysis involved a cohort of 329,415 participants without prior CKD who were enrolled in the UK Biobank between 2006 and 2010. The participants, with an average age of 56 (SD 8.1) years, included 154,298/329,415 (46.84%) males. At baseline, Lp(a) levels were measured using an immunoturbidimetric assay and classified into 2 groups: low (<75 nmol/L) and high (≥75 nmol/L). To assess participants' baseline renal function, we used the baseline urine albumin-to-creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR). The relationship between Lp(a), renal function indicators, and the risk of CKD was evaluated using multivariable Cox regression models. These models were adjusted for various factors, including sociodemographic variables, lifestyle factors, comorbidities, and laboratory measures.ResultsA total of 6003 incident CKD events were documented over a median follow-up period of 12.5 years. The association between elevated Lp(a) levels and CKD risk did not achieve statistical significance among all participants, with a hazard ratio (HR) of 1.05 and a 95% CI ranging from 0.98 to 1.13 (P=.16). However, a notable interaction was identified between Lp(a) and UACR in relation to CKD risk (P for interaction=.04), whereas no significant interaction was observed between Lp(a) and eGFR (P for interaction=.96). When compared with the reference group with low Lp(a) and low-normal UACR (<10 mg/g), the group with high Lp(a) and low-normal UACR exhibited a nonsignificant association with CKD risk (HR 0.98, 95% CI 0.90-1.08; P=.74). By contrast, both the low Lp(a) and high-normal UACR (≥10 mg/g) group (HR 1.16, 95% CI 1.08-1.24; P<.001) and the high Lp(a) and high-normal UACR group (HR 1.32, 95% CI 1.19-1.46; P<.001) demonstrated significant associations with increased CKD risks. In individuals with high-normal UACR, elevated Lp(a) was linked to a significant increase in CKD risk, with an HR of 1.14 and a 95% CI ranging from 1.03 to 1.26 (P=.01). Subgroup analyses and sensitivity analyses consistently produced results that were largely in line with the main findings.ConclusionsThe analysis revealed a significant interaction between Lp(a) and UACR in relation to CKD risk. This implies that Lp(a) may act as a risk factor for CKD even when considering UACR. Our findings have the potential to provide valuable insights into the assessment and prevention of CKD, emphasizing the combined impact of Lp(a) and UACR from a public health perspective within the general population. This could contribute to enhancing public awareness regarding the management of Lp(a) for the prevention of CKD.

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Serum lipoprotein (a) associates with a higher risk of reduced renal function: a prospective investigation.

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Serum lipoprotein (a) associates with a higher risk of reduced renal function: a prospective investigation.

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