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. 6,257 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 (eGFR) < 60 ml/min/1.73 m2. During a mean follow-up of 4.4 years, 158 participants developed reduced renal function. Each 1-unit increase in log10-Lp (a) (mg/dl) was associated with 1.99-folds (95% confidence interval [CI] 1.15-3.43) increased risk of incident reduced renal function; multivariable-adjusted odds ratio (OR) for the highest tertile of Lp (a) was 1.61 (95% CI 1.03–2.52) compared to 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 among 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. Elevated Lp (a) level was independently associated with risk of incident reduced renal function, especially in diabetic or hypertensive patients.

Association Between Lipoprotein (A) and Diabetic Nephropathy in Patients With Type 2 Diabetes Mellitus: A Meta-Analysis

“…Of these, 16 were further excluded for the reasons listed in Figure 1 . Finally, eleven observational studies, including six prospective cohort studies ( 12 , 15 , 17 , 19 , 21 , 22 ), three cross-sectional studies ( 13 , 14 , 18 ), and two nested case-control studies ( 16 , 20 ), were included into the meta-analysis.…”

“…Overall, eleven studies with 9304 T2DM patients were included. The studies were performed in Korea ( 12 , 15 ), China ( 17 , 18 ), Japan ( 14 ), Iran ( 16 , 20 ), the United States ( 13 , 19 ), Denmark ( 21 ), and the Netherlands ( 22 ). The mean ages of the patients varied from 53 to 69 years.…”

“…The follow-up duration of the cohort studies varied from 2 to 11 years. In two studies, diabetic nephropathy was defined as the presence of microalbuminuria or macroalbuminuria ( 18 , 22 ); in seven studies, diabetic nephropathy was defined as the decline of renal function as evidenced by reduced eGFR or elevated SCr ( 12 , 13 , 15 – 17 , 19 , 21 ); while in the other two studies, a combined outcome of albuminuria and/or decline of renal function was used ( 14 , 20 ). Potential confounding factors, such as age, sex, smoking, body mass index, exercise, comorbidities, and use of antihypertensive medications, antidiabetic drugs, and lipid-lowering medications were adjusted to a varying degree.…”

“…Eight studies ( 13 – 17 , 19 , 20 , 22 ) evaluated the odds of diabetic nephropathy in T2DM patients with highest versus lowest serum Lp (a) levels. Pooled results with a random-effect model showed that patients with the highest Lp (a) level had higher odds of diabetic nephropathy (adjusted odds ratio [OR]: 1.63, 95% confidence interval [CI]: 1.25–2.14, I 2 = 54%, P <0.001; Figure 2A ).…”

“…Although early study has proposed that higher serum Lp (a) may also be associated with renal dysfunction in diabetic patients, subsequent studies evaluating the association between Lp (a) and diabetic nephropathy showed inconsistent results (10,11). Some studies suggested that serum Lp (a) is related to higher odds of diabetic nephropathy in T2DM patients (12)(13)(14)(15)(16)(17), while others did not (18)(19)(20)(21)(22). Therefore, relationship between Lp (a) level and diabetic nephropathy remains undetermined.…”