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Nephrotic syndrome

PCSK9: a target for hypercholesterolaemia in nephrotic syndrome

Nature Reviews Nephrology volume 12, page 510 (2016)Cite this article

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To examine the association between PCSK9 and hypercholesterolaemia in nephrotic syndrome, Biddinger and colleagues first assessed PCSK9 levels in plasma from affected patients and mouse models of nephrotic syndrome. “PCSK9 is known in other contexts to disrupt the clearance of LDL particles by degrading the LDL receptor,” explains Mary Haas, a researcher involved in the study. “We therefore hypothesized that it could be playing a similar role in nephrotic syndrome–associated hypercholesterolaemia.” The researchers found that plasma PCSK9 levels were increased 7–24-fold in two mouse models of acute nephrotic syndrome — one induced by nephrotoxic serum and the other induced by podocyte apoptosis — compared to levels in control mice, and that PCSK9 levels were associated with increased levels of LDL cholesterol.

The findings in mice corresponded to findings from an analysis of PCSK9 and cholesterol levels in 50 patients with nephrotic syndrome. “We measured plasma PCSK9 levels in patients with nephrotic syndrome at two distinct time points: during the disease state and during remission,” explains Haas. “We found decreases in PCSK9 upon remission of the disease, suggesting that the findings elucidated from the mouse studies are conserved in humans.”

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References

  1. Haas, M. E. et al. The role of proprotein convertase subtilisin/kexin type 9 in nephrotic syndrome-associated hypercholesterolemia. Circulation http://dx.doi.org/10.1161/CIRCULATIONAHA.115.020912 (2016)

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Authors
  1. Alan W. J. Morris
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Morris, A. PCSK9: a target for hypercholesterolaemia in nephrotic syndrome. Nat Rev Nephrol 12, 510 (2016). https://doi.org/10.1038/nrneph.2016.111

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