Cardiovascular risk in chronic kidney disease (CKD): the CKD-mineral bone disorder (CKD-MBD).
Recent advances in our understanding of the excess mortality of chronic kidney disease (CKD) due to cardiovascular complications, obtained through observational studies, demonstrate 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 led 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 among pediatric patients, but they are present. However, CKD-induced vascular disease causes stiffness of the arterial tree causing, in turn, 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, which focuses on the pediatric patient population, 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.
Hruska
Keith A
KA
Division of Pediatric Nephrology, Washington University, St. Louis, MO, USA. hruska_k@kids.wustl.edu
Choi
Eric T
ET
Memon
Imran
I
Davis
T Keefe
TK
Mathew
Suresh
S
D050197:Atherosclerosis / Q000150:complications / Q000378:metabolism / Q000473:pathology; D002114:Calcinosis / Q000150:complications / Q000378:metabolism / Q000473:pathology; D002318:Cardiovascular Diseases / Q000150:complications* / Q000378:metabolism / Q000503:physiopathology; D012080:Chronic Kidney Disease-Mineral and Bone Disorder / Q000150:complications* / Q000378:metabolism / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology; D006801:Humans; D006962:Hyperparathyroidism, Secondary; D054559:Hyperphosphatemia / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D007676:Kidney Failure, Chronic / Q000150:complications* / Q000378:metabolism / Q000503:physiopathology; D012307:Risk Factors