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.

Women and renal replacement therapy in Europe: lower incidence, equal access to transplantation, longer survival than men.

In 2018, World Kidney Day (WKD) and International Women's Day coincide. The WKD editorial focuses on women's kidney health. The European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) Registry Annual Report 2015 summary provides an excellent snapshot of renal replacement therapy (RRT) epidemiology and women in Europe. The WKD editorial reports a lower incidence of RRT in women in major registries and potential limitations to women's access to transplantation. What is the situation in Europe? In Europe, the incidence of RRT is also lower in women: 38% of incident RRT patients are women. Does it represent milder chronic kidney disease (CKD) in women or barriers to RRT access? The question arises from the higher prevalence of CKD Stages G3-G5 in women than in men. However, in some European countries, such as Spain, non-dialysis CKD Stages G4-G5 is less frequent in women than in men, recapitulating the difference in RRT incidence. In the ERA-EDTA Registry, the incidence of transplantation as a first modality on Day 1 was slightly higher for women and survival on RRT was similar for women and men in the first 3 months, but an intergender gap favouring women increased as RRT vintage increased. However, women on RRT are worse off regarding survival when compared with women in the general population than men on RRT compared with men in the general population. In conclusion, the ERA-EDTA Registry Annual Report 2015 and European epidemiology data suggest a lower incidence of end-stage kidney disease in women, no gender differences in access to transplantation and better RRT survival in women.

Next-generation phosphate binders: focus on iron-based binders.

Phosphate excess is associated with increased mortality in patients with chronic kidney disease (CKD) and has recently been linked to accelerated aging. Oral phosphate binders are prescribed to patients with CKD to prevent absorption of dietary phosphate. Currently available binders have been associated with impaired outcomes (calcium-based binders) or are expensive (non-calcium-based binders). Iron-based phosphate binders represent a new class of phosphate binders. Four iron-based phosphate binders have undergone testing in clinical trials. The development of fermagate and SBR759 is currently on hold due to suboptimal and adverse effect profiles in at least some clinical trials. Ferric citrate and sucroferric oxyhydroxide (PA21) are at different stages of application for regulatory approval after being found safe and efficacious in decreasing serum phosphate. Iron from ferric citrate is more readily absorbed than that from sucroferric oxyhydroxide. Sucroferric oxyhydroxide was launched in the USA in 2014 for the treatment of hyperphosphatemia in adult dialysis patients. Ferric citrate may be more suited for chronic treatment of hyperphosphatemia in CKD patients requiring iron supplements but its use may have to be limited in time because of potential for iron overload in patients not needing iron or not receiving erythropoiesis-stimulating agents. In contrast, sucroferric oxyhydroxide may be more suited for hyperphosphatemic CKD patients not requiring iron supplements.