Serum sulfatides as a novel biomarker for cardiovascular disease in patients with end-stage renal failure

Abstract

Sulfatides, normal components of serum lipoproteins, may play an important role in cardiovascular disease due to their various modulatory functions in haemostasis. The incidence of cardiovascular disease in patients with end-stage renal failure undergoing maintenance hemodialysis has been reported to be approximately 10 to 30 times higher than that in the general population. To elucidate the possible roles of serum sulfatides in this high incidence, we measured the level of sulfatides in 59 such patients, by converting them to lysosulfatides according to a recently developed quantitative, qualitative, high-throughput technique using matrix-assisted laser desorption ionization-time of flight mass spectrometry. The mean level of sulfatides in patients 3.58 +/- 1.18 nmol/ml was significantly lower than that in age-matched normal subjects (8.21 +/- 1.50 nmol/ml; P < 0.001). Patients receiving maintenance hemodialysis over a longer period had lower levels of sulfatides. When the mean levels of sulfatides were compared between patients with cardiovascular disease (N = 22) and those without the disease (N = 37), the level in the former group 2.85 +/- 0.67 nmol/ml was found to be significantly lower than that in the latter group 4.01 +/- 1.22 nmol/ml (P < 0.001). These findings reveal a close correlation between low levels of serum sulfatides and a high risk of cardiovascular disease in these patients. Determination of the level of serum sulfatides can contribute to predictions of the incidence of cardiovascular disease in patients with end-stage renal failure undergoing maintenance hemodialysis.

Acute kidney injury induced by protein-overload nephropathy down-regulates gene expression of hepatic cerebroside sulfotransferase in mice, resulting in reduction of liver and serum sulfatides

“…Further investigation about the precise molecular mechanism of CST gene-regulation is necessary. We previously found that the level of serum sulfatides was significantly decreased in human hemodialysis patients via an unknown mechanism [9]. The results obtained by the present study indicate that the reduction in serum sulfatide levels in these patients would be caused by down-regulation of hepatic CST gene expression.…”

“…However, their physiological functions in blood are not fully understood. We have reported the antithrombotic potential of sulfatides in some experimental studies [4][5][6][7][8] and recently showed that the level of serum sulfatides might be a novel biomarker for cardiovascular diseases in human hemodialysis patients [9]. These findings suggest that the investigation of the in vivo kinetics of sulfatides affected by kidney dysfunction would be important.…”

“…Our clinical research demonstrated that the serum sulfatide level was significantly lower in human hemodialysis patients than that in normal subjects, suggesting a relationship between the serum level and kidney function [9]. To clarify the relationship, we investigated the influence of kidney dysfunction on sulfatide metabolism using an established murine model of acute kidney injury, protein-overload nephropathy in peroxisome proliferator-activated receptor α (Ppara)-null mice [10].…”

Peroxisome proliferator-activated receptor α mediates enhancement of gene expression of cerebroside sulfotransferase in several murine organs

“…In fact, the sphingoid base composition of serum sulfatides is similar to those of liver [34]. Recent clinical studies have revealed a significant reduction in serum sulfatide levels in the final stage of chronic kidney disease, which is strongly correlated with a high incidence of cardiovascular disease at this stage [51][52][53]. Other studies using a kidney dysfunction mouse model have demonstrated that kidney injuries cause simultaneous reductions in the levels of sulfatides in serum and liver, which is associated with the down-regulation of hepatic CST expression [4,5].…”

Kidney transplantation recovers the reduction level of serum sulfatide in ESRD patients via processes correlated to oxidative stress and platelet count

“…Recently, we reported that the serum level of sulfatide in end-stage renal disease (ESRD) patients undergoing hemodialysis therapy (HD) was significantly lower than that in age-matched normal subjects [9]. This earlier study demonstrated that the reduction of the serum sulfatide level in ESRD patients was detected prior to the induction of HD treatment, and that the reduction level linearly decreased according to HD duration.…”