Vitamin K Dependent Proteins in Kidney Disease

Abstract

Patients with chronic kidney disease (CKD) have an increased risk of developing vascular calcifications, as well as bone dynamics impairment, leading to a poor quality of life and increased mortality. Certain vitamin K dependent proteins (VKDPs) act mainly as calcification inhibitors, but their involvement in the onset and progression of CKD are not completely elucidated. This review is an update of the current state of knowledge about the relationship between CKD and four extrahepatic VKDPs: matrix Gla protein, osteocalcin, growth-arrest specific protein 6 and Gla-rich protein. Based on published literature in the last ten years, the purpose of this review is to address fundamental aspects about the link between CKD and circulating VKDPs levels as well as to raise new topics about how the interplay between molecular weight and charge could influence the modifications of circulating VKDPs at the glomerular level, or whether distinct renal etiologies have effect on VKDPs. This review is the output of a systematic literature search and may open future research avenues in this niche domain.

Sclerostin as Regulatory Molecule in Vascular Media Calcification and the Bone–Vascular Axis

“…In this context, it is worth mentioning that renal elimination of sclerostin increases with declining renal function [13]. Moreover, sclerostin is a positively charged molecule which is easily filtered by the negatively charged glomerular membrane [14]. Taken together, this allows us to put forward the hypothesis that sclerostin, originating from excessive local production in calcified vessels, may spill over to the serum by which it may prevent further progression of (vascular) calcifications and contribute to the high incidence of low bone turnover in CKD patients [15].…”

Role of emerging vitamin K‑dependent proteins: Growth arrest‑specific protein 6, Gla‑rich protein and periostin (Review)

“…More specifically, Gas 6 and albumin (approximately 66 kDa) have a similar molecular weight and a net negative charge repelled the glomerular membrane. complex interactions eventually lead Gas 6 to filter through the glomerular membrane and be excreted from the body (100). Therefore, the concentration of plasma Gas 6 changes in different stages of diabetes.…”

Vitamin K and Kidney Transplantation

“…Vitamin K acts at least in two ways. First, as the coenzyme of a carboxylase, determining the carboxylation of glutamic acid residues with a resulting formation of the amino acid γ-carboxy-glutamic acid (Gla: active form) [ 13 , 14 ]. Second, as a ligand of the steroid and xenobiotic receptor (SXR) and pregnane X receptor (PXR, murine ortholog) [ 15 ].…”