The Kidney-Vascular-Bone Axis in the Chronic Kidney Disease-Mineral Bone Disorder

Abstract

The last 25 years have been characterized by dramatic improvements in short-term patient and allograft survival after kidney transplantation. Long-term patient and allograft survival remains limited by cardiovascular disease and chronic allograft injury, among other factors. Cardiovascular disease remains a significant contributor to mortality in native chronic kidney disease as well, as cardiovascular mortality in chronic kidney disease more than doubles that of the general population. The chronic kidney disease-mineral bone disorder (CKD-MBD) is a syndrome recently coined to embody the biochemical, skeletal, and cardiovascular pathophysiology that results from disrupting the complex systems biology between the kidney, skeleton, and cardiovascular system in native and transplant kidney disease. The CKD-MBD is a unique kidney disease-specific syndrome containing novel cardiovascular risk factors, with an impact reaching far beyond traditional notions of renal osteodystrophy and hyperparathyroidism. This Overview reviews current knowledge of the pathophysiology of the CKD-MBD, including emerging concepts surrounding the importance of circulating pathogenic factors released from the injured kidney that directly cause cardiovascular disease in native and transplant chronic kidney disease, with potential application to mechanisms of chronic allograft injury and vasculopathy.

Identifying early pathogenic events during vascular calcification in uremic rats

“…Only recently have we begun to understand this kind of systems pathology, exemplified by the relevance of the mineral and bone disorder in the nosology of VC. 1 Second, when calcification becomes visually apparent, the distorted artery wall is already a chaotic battlefield of molecules that have unclear roles in the calcification process and that are extremely difficult to untangle. 15 Third, with the logical objective of simplifying this complexity, the scientific community has been using in vitro methods of calcification that, unfortunately, were unrelated to cell-mediated ectopic calcification.…”

“…The ectopic calcification of large arteries is a common complication in chronic kidney disease (CKD), and in combination with abnormalities in circulating biomarkers and bone histomorphometry, it forms a part of CKD-mineral bone disorder (CKD-MBD). 1 Cardiovascular complications are the main cause of mortality in CKD patients, and medial vascular calcification (VC) is a contributing factor through arterial stiffening, left ventricle overload and hypertrophy, increased pulsatility, inappropriate blood supply to the organs, insufficient force for venous return, etc. 2 Calcium phosphate deposition in large arteries ends in the form of hydroxyapatite deposits, which cause structural changes to the wall layers, accompanied by gene expression and phenotype modifications of the vascular smooth muscle cells (VSMC) towards a pro-calcific, osteochondrogenic phenotype.…”

Vitamin D Levels in Chronic Kidney Disease Stage 3, 4, and 5

“…5 Calcification and stiffness of blood vessels may cause increased systolic blood pressure and left ventricular hypertrophy. 13 The results of this study indicate that there was hypovitaminosis D starting from CKD stage 3 (Table 2). This study did not measure vitamin D levels in CKD stage 1 and 2 because at those stages, there are no signs and symptoms of CKD yet.…”

“…12 High bone turnover due to secondary hyperparathyroidism leads to high bone resorption (higher than bone formation) that induces hypercalcaemia, hyperphosphatemia, osteopenia and osteoporosis. 12,13 Cardiovascular disease in form of vascular wall calcifications may occur due to hyperphosphatemia and hypercalcaemia. 5 Calcification and stiffness of blood vessels may cause increased systolic blood pressure and left ventricular hypertrophy.…”

“…6,11 Hypovitaminosis D may also cause mineral and bone disorder which leads to osteopenia and osteoporosis that may increase the risk of fracture. 12,13 Therefore, mineral and bone disorder may cause disability and reduce the quality of life of patients with CKD. Kidney disease itself is a disease with the second largest funding from Healthcare and Social Security Agency (Badan Penyelenggara Jaminan Sosial Kesehatan, BPJS Kesehatan) after heart disease.…”