Chronic kidney disease (CKD) is commonly associated with disorders of mineral and bone metabolism, manifested by either one or a combination of extra-skeletal calcification; abnormalities in bone turnover, mineralization or strength; or abnormalities of calcium, phosphorus, PTH and vitamin D metabolism.
Chronic kidney disease mineral and bone disorder (CKD-MBD) has a very early onset, commonly occurring during early CKD when kidney disease causes a decrease in bone formation. It is unfortunately associated with high mortality rates, primarily from cardiovascular complications. Several treatment modalities for CKD-MBD have presented themselves over the years.
One is the modulation of the Klotho gene. Klotho is a gene which regulates aging in mammals and has been implicated directly in the pathogenesis of CKD. Klotho levels decrease early in CKD and klotho deficiency could in turn cause vascular calcification culminating in atherosclerosis, osteoporosis, ectopic calcification, premature aging, apoptosis and CKD progression.
It has been determined that the FGF23 gene decreases calcitriol levels and inhibits transcription if the klotho gene. Elevated FGF23 genes are associated with inflammatory markers in CKD. The importance of FGF23 and klotho to the pathogenesis of CKD-MBD underscores how silly it is to focus solely on vitamin D and calcium.
Bone mineral disorder can be prevented by paying attention to phosphate levels. For every 1mg/dL increase in phosphate, a person’s risk of mortality from CKD increases 10-62%. Higher phosphate levels lead to a faster decline in renal function. Dietary management is the primary way of managing this risk. Phosphorus binders should also be taken.
It is also prudent to screen patients for vitamin D deficiency. The PRIMO and OPERA studies failed to demonstrate improvements in clinically relevant outcomes but did demonstrate increased risk of hypercalcaemia. Accordingly, routine use of calcitriol and its analogues in CKD 3a-5 is no longer recommended.