Phosphate – The Silent Stealthy Cardiorenal Culprit in All Stages of Chronic Kidney Disease

Abstract

Background and Aim: Due to increasing evidence suggesting a link between hyperphosphatemia and cardiovascular disease (CVD), mediated through vascular calcification in patients on dialysis, the following question arises: At what stage of chronic kidney disease (CKD) does the relationship between elevated phosphate levels, vascular calcification and increased cardiovascular mortality begin? Therefore, the purpose of the current study was to critically review the current literature regarding this issue. Methods: We performed a systematic search of the National Library of Medicine and the Cochrane Library databases from January 1985 to February 2008 to identify clinical studies examining the effects of plasma phosphate on cardiovascular outcome, mortality and progression of kidney disease in subjects with and without CKD who have not yet received dialysis. The primary outcome measure was the development of CVD, mortality and progression of kidney disease. Results: Twelve clinical trials investigated the role of serum phosphate levels and adverse outcome (9 studies examining CVD outcome and 3 examining progression of kidney disease). After adjustment for risk factors for mortality, adverse cardiovascular outcome and progression of kidney disease, all studies found a graded independent significant association between phosphate levels and mortality, development of CVD and progression of kidney disease. There was no such association with plasma calcium levels. Conclusions: There is a graded independent association between serum phosphate levels and mortality, mainly cardiovascular events, and the progression of renal disease in subjects with and without definable (loss of glomerular filtration rate) CKD.

The Mechanism of Decreased Serum Phosphorus Levels in Rats with Chronic Kidney Disease after Oral Administration of <i>Bifidobacterium longum</i>

“…Hyperphosphatemia is a widely recognized risk factor for mortality and cardiovascular disease in all stages of CKD [20]. In the present study, oral administration of B-HD capsule halted the onset and progression of hyperphosphatemia in CKD rats, as previously observed in our study on HD patients [13].…”

Conjoint Effects of Serum Calcium and Phosphate on Risk of Total, Cardiovascular, and Noncardiovascular Mortality in the Community

“…19 Similarly, it was recently shown in predialysis CKD patients that higher serum Pi, within the normal range, were associated with the degree of vascular calcification, arterial stiffness, 7,20 and increased mortality risk. 21 Our long-term, prospective study provides additional support that higher serum Pi is associated with higher risk of cardiovascular mortality.…”

Elevated serum retinol-binding protein 4 concentrations are associated with chronic kidney disease but not with the higher carotid intima-media thickness in type 2 diabetic subjects

“…Additionally, CKD is associated with many risk factors for atherosclerosis. Except for the traditional factors, the altered bone mineral metabolism leading to hyperphosphatemia and increased vascular calcification [27], the increased oxidative stress, cytokines, and endothelial dysfunction [28][29][30] are also accountable for the increase of atheroclerosis. In view of such complexity of the CVD risk factors on subjects of type 2 DM with CKD; the lack of association between RBP4 concentrations with levels of CIMT is not unreasonable.…”