Phosphate, Microbiota and CKD.

Phosphate is a key uremic toxin associated with adverse outcomes. As chronic kidney disease (CKD) progresses, the kidney capacity to excrete excess dietary phosphate decreases, triggering compensatory endocrine responses that drive CKD-mineral and bone disorder (CKD-MBD). Eventually, hyperphosphatemia develops, and low phosphate diet and phosphate binders are prescribed. Recent data have identified a potential role of the gut microbiota in mineral bone disorders. Thus, parathyroid hormone (PTH) only caused bone loss in mice whose microbiota was enriched in the Th17 cell-inducing taxa segmented filamentous bacteria. Furthermore, the microbiota was required for PTH to stimulate bone formation and increase bone mass, and this was dependent on bacterial production of the short-chain fatty acid butyrate. We review current knowledge on the relationship between phosphate, microbiota and CKD-MBD. Topics include microbial bioactive compounds of special interest in CKD, the impact of dietary phosphate and phosphate binders on the gut microbiota, the modulation of CKD-MBD by the microbiota and the potential therapeutic use of microbiota to treat CKD-MBD through the clinical translation of concepts from other fields of science such as the optimization of phosphorus utilization and the use of phosphate-accumulating organisms.

Effects of high dialysate calcium concentration on bone remodelling, serum biochemistry, and parathyroid hormone in patients with renal osteodystrophy.

The influence of a dialysate calcium concentration of 8.0 mg/100 ml (treatment period 2) vs. 7.0 mg/100 ml (treatment period 1) on plasma calcium, phosphorus, serum immunoreactive parathyroid hormone (iPTH), bone histology, intestinal calcium absorption, and calcium transfer across the dialysis membrane was investigated in six patients with renal osteodystrophy undergoing intermittent hemodialysis. During the periods 1 and 2, the plasma calcium changes before and after dialysis were not significantly different. A significant increase in mean postdialysis plasma calcium level was observed during both periods when compared to mean predialysis level. A significant, inverse relation was found between predialysis plasma calcium and the increase in plasma calcium during hemodialysis runs. Calcium transfer across the dialysis membrane and fractional intestinal absorption of calcium in the postdialysis state were determined in four out of the six patients. During period 2, calcium transfer was higher in all four patients but intestinal calcium absorption was moderately higher only in one and strikingly lower in the remaining three patients when compared to period 1. Although brought up to 8.0 mg/100 ml, this higher dialysate calcium significantly decreased the level of serum iPTH only in one out of the six patients; in this patient, osteoclast count, active resorption surface, and periosteocytic osteolysis decreased. In a second patient, although the level of serum iPTH seemed to decrease markedly osteoclastic and osteocytic resorption did not change. In the remaining four patients, the level of serum iPTH was unchanged and bone resorption parameters were found unchanged or aggravated. It is concluded that providing additional calcium (using a dialysate calcium concentration of 8.0 mg/100 ml), the goal of which was to decrease secondary hyperparathyroidism, proved to be successful only in one patient and failed to do so in the five others. Secondary hyperparathyroidism was even found aggravated in three of them. Thus, the use of a dialysate calcium concentration of 8.0 mg/100 ml did not result in any advantage over that of 7.0 mg/100 ml in five out of six patients studied.