Serum lipoprotein (a) associates with the risk of renal function damage in the CHCN-BTH Study: Cross-sectional and Mendelian randomization analyses

Abstract

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.

Lipoprotein(a) and the Risk for Recurrent Atherosclerotic Cardiovascular Events Among Adults With CKD: The Chronic Renal Insufficiency Cohort (CRIC) Study

“…This hypothesis is supported by a prior analysis of the Cohort Study on Chronic Disease of Communities Natural Population in Beijing, Tianjin, and Hebei study. 41 In this analysis, higher Lp(a) mass concentration was associated with lower eGFR in a cross-sectional analysis. However, higher genetically predicted Lp(a) was associated with higher eGFR in a Mendelian randomization analysis conducted in the same study population, suggesting that Lp(a) may not cause low kidney function.…”

Tafolecimab in Chinese patients with non-familial hypercholesterolemia (CREDIT-1): a 48-week randomized, double-blind, placebo-controlled phase 3 trial

“… 11 In our study, tafolecimab treatment reduced the Lp(a) levels in Chinese hypercholesterolemia and a significant correlation was observed between reductions in Lp(a) and LDL-C, consistent with the findings of evolocumab. 24 Given the lower Lp(a) levels in Chinese population and skewed distribution of Lp(a) levels, together with elevations of Lp(a) levels observed in placebo group which was possibly due to the use of statins and concomitant chronic kidney disease of enrolled patients, 25 , 26 the potential Lp(a) lowering effects of tafolecimab still warrant further investigation.…”

Association between lipoprotein(a) plasma levels and diabetic nephropathy in Han Chinese patients with type 2 diabetes mellitus

“…On one hand, the kidney is thought to be a site of Lp(a) catabolism, and pathological alterations in the kidney, such as those occurring in end-stage renal disease, might lead to decreased excretion of Lp(a) and thus increased Lp(a) levels [ 30 ]. A study involving a large sample of Chinese adults found that Lp(a) levels were independently associated with several renal function indicators, including estimated glomerular filtration rate (eGFR), serum creatinine (Scr), and blood urea nitrogen (BUN) [ 31 ]. However, the relationship between renal function and Lp(a) levels is a subject of ongoing debate, with some studies reporting conflicting results [ 32 ].…”