Gut microbiome in hemodialysis patients treated with calcium acetate or treated with sucroferric oxyhydroxide: a pilot study

Abstract

Purpose It has been proved that the gut microbiome is altered in patients with chronic kidney disease. This contributes to chronic inflammation and increases cardiovascular risk and mortality, especially in those undergoing hemodialysis. Phosphate binders may potentially induce changes in their microbiome. This trial aimed to compare the changes in the gut microbiome of hemodialysis patients treated with calcium acetate to those treated with sucroferric oxyhydroxide. Methods Twelve hemodialysis patients were distributed to receive calcium acetate or sucroferric oxyhydroxide for 5 months. Blood samples (for biochemical analysis) and stool samples (for microbiome analysis) were collected at baseline, 4, 12, and 20 weeks after treatment initiation. Fecal DNA was extracted and a 16S rRNA sequencing library was constructed targeting the V3 and V4 hypervariable regions. Results Regarding clinical variables and laboratory parameters, no statistically significant differences were observed between calcium acetate or sucroferric oxyhydroxide groups. When analyzing stool samples, we found that all patients were different (p = 0.001) among themselves and these differences were kept along the 20 weeks of treatment. The clustering analysis in microbial profiles grouped the samples of the same patient independently of the treatment followed and the stage of the treatment. Conclusion These results suggest that a 5-month treatment with either calcium acetate or sucroferric oxyhydroxide did not modify baseline diversity or baseline bacterial composition in hemodialysis patients, also about the high-variability profiles of the gut microbiome found among these patients.

Impact of sucroferric oxyhydroxide on the oral and intestinal microbiome in hemodialysis patients

“…All in all, it is plausible that out-competition of siderophore-non-producers is reduced under iron plethora conditions. Comparable to our study, overall, both Iguchi et al 6 and Merino-Ribas et al 7 found no significant changes in the gut microbiome after SFOH intake. However, Iguchi et al found a significant increase in the families Clostridiaceae (0.6%, 2.6%, p = 0.0264) and Oscillospiraceae (0.21%, 0.40%, p = 0.023) and the genus Oscillibacter (t0 0.20%, t12weeks 0.44%, p = 0.022).…”

“…Recently, Iguchi et al 6 found no significant change in bacterial diversity investigating all taxonomic levels, but potential uremic toxins such as serum indoxyl sulfate and p -cresyl sulfate were significantly elevated in the test group. Merino-Ribas et al 7 confirmed the long-term stability of the gut microbiome on SFOH in a pilot study based on seven patients and another five patients switching to calcium acetate as phosphate binder. Both studies were limited to the intestinal microbiome, whereas major effects would be expected to occur in the oral cavity given the rapid disintegration of SFOH in saliva.…”

“…After screening the literature and a reference genome ( O. valericigenes strain Sjm18-20) it can be concluded that this strictly anaerobic genus does not produce any metal binding chelators, again supporting our model. Merino-Ribas et al concluded that the individual was the most important qualifier and that the long-term treatment with both phosphate binders (calcium acetate and SFOH) did not further modify this diversity 7 . However, without given any details, they found statistically significant differences by ANOSIM (p = 0.002) and PERMANOVA (p = 0.001) between both groups, indicating that influencing factors—with siderophores as candidate—might have been overlooked.…”

Recent advances of gut microbiota in chronic kidney disease patients

“…Spearman's correlation analysis exhibited that relative abundance of Coprococcus_3 was positively correlated with the levels of trimethylamine N-oxide, indoxyl sulfate, cholic acid, deoxycholic acid and betaine, in serum [84]. Merino-Ribas and his colleague [85] demonstrated that a 5-month treatment with either calcium acetate or sucroferric oxyhydroxide did not affect baseline diversity and bacterial composition in patients with hemodialysis, also revealed high-variability profiles of gut microbiome among patients with hemodialysis. Moreover, a randomized controlled trial indicated that treatment with β-glucan prebiotics significantly changed intestinal-derived uremic toxin levels and favorably affected gut microbiome [86].…”

Evolving Concepts on Inflammatory Biomarkers and Malnutrition in Chronic Kidney Disease

“…Even though other sources of inflammation beyond CKD/uremic toxins (more than 25% of which are dietary o gut-derived) [ 24 , 25 , 26 ], such as infections or thrombotic events related to vascular access in HD patients, peritonitis in patients undergoing peritoneal dialysis, infections and immunosuppression in transplant patients, the intrinsic mechanisms associated with the development of a proinflammatory milieu is comparable in all CKD patients [ 2 ]. Further inflammatory factors are summarized in Figure 1 .…”