Cardiorenal syndrome and vitamin D receptor activation in chronic kidney disease

Cardiorenal syndrome (CRS) refers to a constellation of conditions whereby heart and kidney diseases are pathophysiologically connected. For clinical purposes, it would be more appropriate to emphasize the pathophysiological pathways to classify CRS into: (1) hemodynamic, (2) atherosclerotic, (3) uremic, (4) neurohumoral, (5) anemic??hematologic, (6) inflammatory-oxidative, (7) vitamin D receptor (VDR) and/or FGF23-, and (8) multifactorial CRS. In recent years, there have been a preponderance data indicating that vitamin D and VDR play an important role in the combination of renal and cardiac diseases. This review focuses on some important findings about VDR activation and its role in CRS, which exists frequently in chronic kidney disease patients and is a main cause of morbidity and mortality. Pathophysiological pathways related to suboptimal or defective VDR activation may play a role in causing or aggravating CRS. VDR activation using newer agents including vitamin D mimetics (such as paricalcitol and maxacalcitol) are promising agents, which may be related to their selectivity in activating VDR by means of attracting different post-D-complex cofactors. Some, but not all, studies have confirmed the survival advantages of D-mimetics as compared to non-selective VDR activators. Higher doses of D-mimetic per unit of parathyroid hormone (paricalcitol to parathyroid hormone ratio) is associated with greater survival, and the survival advantages of African American dialysis patients could be explained by higher doses of paricalcitol (>10 microg/week). More studies are needed to verify these data and to explore additional avenues for CRS management via modulating VDR pathway.

Organic and inorganic dietary phosphorus and its management in chronic kidney disease

Dietary phosphorus control is often a main strategy in the management of patients with chronic kidney disease. Dietary protein is a major source of phosphorus intake. Recent data indicate that imposed dietary phosphorus restriction may compromise the need for adequate protein intake, leading to protein-energy wasting and possibly to increased mortality. The two main sources of dietary phosphorus are organic, including animal and vegetarian proteins, and inorganic, mostly food preservatives. Animal-based foods and plant are abundant in organic phosphorus. Usually 40% to 60% of animal-based phosphorus is absorbed; this varies by degree of gastrointestinal vitamin-D-receptor activation, whereas plant phosphorus, mostly associated with phytates, is less absorbable by human gastrointestinal tract. Up to 100% of inorganic phosphorus in processed foods may be absorbed; ie, phosphorus in processed cheese and some soda [cola] drinks. A recent study suggests that a higher dietary phosphorus-protein intake ratio is associated with incremental death risk in patients on long-term hemodialysis. Hence, for phosphorus management in chronic kidney disease, in addition to absolute dietary phosphorus content, the chemical structure [inorganic versus organic], type [animal versus plant], and phosphorus-protein ratio should be considered. We recommend foods and supplements with no or lowest quantity of inorganic phosphorus additives, more plant-based proteins, and a dietary phosphorus-protein ratio of less than 10 mg/g. Fresh [nonprocessed] egg white [phosphorus-protein ratio less than 2 mg/g] is a good example of desirable food, which contains a high proportion of essential amino acids with low amounts of fat, cholesterol, and phosphorus