Cardiovascular risk in chronic kidney disease (CKD): the CKD-mineral bone disorder (CKD-MBD)

Abstract

Recent advances in our understanding of the excess mortality of chronic kidney disease (CKD) due to cardiovascular complications demonstrate through observational studies that vascular calcification and hyperphosphatemia are major cardiovascular risk factors. Mechanistic studies demonstrate that these two risk factors are related, and that hyperphosphatemia directly stimulates vascular calcification. The role of hyperphosphatemia in stimulating vascular calcification in CKD is associated with a block to the skeletal reservoir function in phosphate balance due to excess bone resorption. This has lead to the realization that renal osteodystrophy is linked to vascular calcification by disordered mineral homeostasis (phosphate), and that a multiorgan system fails in CKD leading to cardiovascular mortality. In children with renal disease the multiorgan system fails just as in adults, but the outcomes have been less well studied and perceptions of differences from adults are possibly incorrect. Vascular calcification and cardiovascular mortality are less prevalent but present. However, CKD induced vascular disease causes stiffness of the arterial tree causing systolic hypertension and left ventricular hypertrophy as early manifestations of the same pathology in the adult. Because of the role of the skeleton in these outcomes, renal osteodystrophy has been renamed as the CKD-mineral bone disorder (CKD-MBD). This review adapted to children describes our current state of knowledge with regards to the pathophysiology of the CKD-MBD, including the new discoveries related to early stages of CKD. As a new necessity, cardiovascular function issues are incorporated into the CKD-MBD, and new advances in our knowledge of this critical component of the disorder will lead to improved outcomes in CKD.

Inorganic phosphate homeostasis in sodium-dependent phosphate cotransporter Npt2b+/−mice

“…Hyperphosphatemia is an important consequence of chronic kidney disease (CKD) (13,14,25). Decreasing plasma P i concentrations is believed to be critical in the management of patients with CKD, especially those on dialysis (13,14,25).…”

“…Decreasing plasma P i concentrations is believed to be critical in the management of patients with CKD, especially those on dialysis (13,14,25). Recently, Marks et al (23) used an in situ intestinal loop technique to determine intestinal phosphate absorption in the 5 ⁄6 nephrectomy rat model of chronic renal failure (CRF) under disease conditions and reported that P i absorption in the duodenum and jejunum is not significantly altered, regardless of dietary P i intake level.…”

“…In chronic renal failure, P i retention leads to secondary hyperparathyroidism and uremic bone disease and progression to end-stage renal disease (13,14,25). The current therapy for hyperphosphatemia in patients with chronic renal failure consists of dietary P i restriction in combination with administration of P i binders, but each therapy has practical problems (8,24).…”

Effect of parathyroid hormone on serum magnesium levels: the neglected relationship in hemodialysis patients with secondary hyperparathyroidism

“…20,21 However, compared to the wide attention in the derangement of calcium/phosphate metabolism and the vascular/valvular calcification, the magnesium metabolism is usually neglected and is still among the less well understood clinical problems encountered by nephrologists until now. 22,23 Recently, since numerous studies suggested an association between hypomagnesaemia and risk factors of cardiovascular disease, such as diabetes mellitus, metabolic syndrome, coronary artery disease and atherosclerosis risk in the general population, 24,25 the impact of magnesium disorders on the prognosis of patients with chronic kidney disease has received a great deal of interest.…”

The Relationship Between Osteoprotegerin/RANKL Axis and Arterial Stiffness in Osteopenic/Osteoporotic Renal Transplantation Recipients

“…Koçyiğit İ et al : OPG/RANKL Axis and Arterial Stiffness in Renal Transplantation the important factors in this process is OPG and RANK-RANKL system (26). Animal studies have shown that OPG-deficient mice develop both severe osteoporosis and vascular calcification (27).…”