Multicenter study of lipoprotein(a) and apolipoprotein(a) phenotypes in patients with end-stage renal disease treated by hemodialysis or continuous ambulatory peritoneal dialysis.

Abstract

Numerous studies have investigated lipoprotein(a) (Lp(a)) plasma concentrations in patients with ESRD, a patient group with an enormous risk for atherosclerosis. The reported differences in Lp(a) between controls and patients vary from a decrease of 49% to an increase of more than 1,000%. However, data are not consistent, mostly because of problems with statistical analysis, and only limited data are available for patients treated by continuous ambulatory peritoneal dialysis (CAPD). To estimate the significance of Lp(a) in ESRD and to demonstrate the statistical pitfalls concerning Lp(a) in case-control studies, a large multicenter study including 702 patients treated by either hemodialysis (HD) (N = 534) or CAPD (N = 168) was conducted, and results were compared with results from 256 healthy controls. Both patient groups showed significantly elevated Lp(a) levels in comparison with controls: 23.4 +/- 25.0 mg/dL (P < 0.005; HD) and 34.6 +/- 38.4 mg/dL (P < 0.0001; CAPD) versus 18.4 +/- 22.8 mg/dL (controls). CAPD patients showed significantly higher Lp(a) values than did patients treated by HD (P < 0.001). The difference between the two treatment groups possibly reflects an overproduction of Lp(a) to compensate for protein losses in CAPD patients. Both treatment groups included significantly more patients with Lp(a) values greater than the 75th percentile (25.6 mg/dL) of the control group (33.9 and 41.7% for HD and CAPD, respectively; P < 0.005). The higher Lp(a) values in patients were not explained by differences in isoform frequencies and the increase in Lp(a) was apolipoprotein(a) type specific: only patients with high-molecular-weight apolipoprotein(a) isoforms showed a significant elevation in Lp(a) levels. The increased plasma concentrations of Lp(a) may contribute to the high risk for atherosclerosis in ESRD, especially in patients treated by CAPD. Finally, it is believed that small sample sizes are responsible for the diverging results in Lp(a) literature.

Non-genetic influences on lipoprotein(a) concentrations

“…Of note, the median Lp(a) levels increased as the kidney function impaired (11.0 at GFR >90, 18.4 at GFR 45–90 and 24.4 mg/dL at GFR <45 mL/min/1.73 m 2 ). These findings suggested that Lp(a) levels begin to increase even in early stages of kidney impairment [ 124 , 125 ] and showed an inverse association between Lp(a) levels and kidney function [ 125 , 126 ].…”

“…Other studies have shown that the Lp(a) response was dependent on apo(a) sizes also during dialysis treatment. Apo(a) size specific increases in Lp(a) levels were seen among patients with NNKD or ESRD patients treated with HD [ 121 , 126 , 127 ]. Thus, Lp(a) levels were higher in HD patients compared with healthy controls (13.6 versus 9.2 mg/dL) as was the prevalence of a high Lp(a) level (23% versus 12%), despite a similar distribution of apo(a) isoforms in both groups [ 127 ].…”

Apolipoprotein A‐IV concentrations and clinical outcomes in a large chronic kidney disease cohort: Results from the GCKD study

“…The average apoA‐IV concentrations in the general population are between 15 and 18 mg/dl [ 30 ]. We know from studies in the general population that apoA‐IV concentrations are an early marker of kidney impairment: concentrations start to increase early when eGFR decreases and albuminuria increases [ 30 ] and reach concentrations between 30 and 50 mg/dl in patients with kidney failure [ 33 , 34 ]. Immunohistochemical studies suggested that apoA‐IV is filtered by the glomerulus and is reabsorbed by tubular cells.…”

“…In case of the rare situation of very low or very high concentrations outside of the linear range, samples were repeated using a lower or higher dilution, respectively. The intra‐ and inter‐assay coefficients of variation were 2.7% and 6%, respectively [ 31 , 33 , 34 , 37 ].…”

“…Furthermore, higher concentrations predicted the progression of CKD [ 31 ]. ApoA‐IV concentrations in dialysis patients have been reported to be twice as high compared to controls without CKD [ 32 , 33 ]. In a study including more than 1200 haemodialysis patients with type‐2 diabetes mellitus, we reported that low apoA‐IV concentrations were strongly associated with a higher risk for all‐cause mortality, congestive heart failure and sudden cardiac death [ 34 ].…”