Contribution of Gut Microbiota-Derived Uremic Toxins to the Cardiovascular System Mineralization.

Chronic kidney disease (CKD) affects more than 10% of the world population and leads to excess morbidity and mortality (with cardiovascular disease as a leading cause of death). Vascular calcification (VC) is a phenomenon of disseminated deposition of mineral content within the media layer of arteries preceded by phenotypic changes in vascular smooth muscle cells (VSMC) and/or accumulation of mineral content within the atherosclerotic lesions. Medial VC results in vascular stiffness and significantly contributes to increased cardio-vascular (CV) morbidity, whereas VC of plaques may rather increase their stability. Mineral and bone disorders of CKD (CKD-MBD) contribute to VC, which is further aggravated by accumulation of uremic toxins. Both CKD-MBD and uremic toxin accumulation affect not only patients with advanced CKD (glomerular filtration rate (GFR) less than 15 mL/min./1.72 m2, end-stage kidney disease) but also those on earlier stages of a disease. The key uremic toxins that contribute to VC, i.e., p-cresyl sulphate (PCS), indoxyl sulphate (IS) and trimethylamine-N-oxide (TMAO) originate from bacterial metabolism of gut microbiota. All mentioned toxins promote VC by several mechanisms, including: Transdifferentiation and apoptosis of VSMC, dysfunction of endothelial cells, oxidative stress, interaction with local renin-angiotensin-aldosterone system or miRNA profile modification. Several attractive methods of gut microbiota manipulations have been proposed in order to modify their metabolism and to limit vascular damage (and VC) triggered by uremic toxins. Unfortunately, to date no such method was demonstrated to be effective at the level of "hard" patient-oriented or even clinically relevant surrogate endpoints.

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.

Chlamydia trachomatis infection in chronically hemodialyzed patients.

PURPOSE: In the general population there is association between Chlamydia trachomatis (Ch. trachomatis) infection and reactive arthritis (RA). RA is a systemic illness characterized by inflammatory synovitis. Arthritis tends to be oligoarticular and involves mainly the lower limbs. The aim of this study is to assess the age and sex specific prevalence of Ch. trachomatis infection in dialysis population and to find possible relationship between manifestation of infection and renal osteodystrophy. MATERIAL AND METHODS: The study was conducted in 53 patients: 22 women (W) and 31 men (M), with a mean age of 58.1 +/- 15 years, treated with HD for 28.5 +/- 28.2 months. The Ch. trachomatis infection was assessed by the detection IgG antibodies for Ch. trachomatis. Also some other biochemical parameters of osteodystrophy, inflammation and malnutrition were measured. RESULTS: The presence of a high titre of anti-Ch. trachomatis antibodies was found in 22 patients--41% [G IgG (+)]. Mean level of anti-Ch. trachomatis antibodies was significantly higher in G IgG (+) than in seronegative patients [G IgG (-)]: 19.0 +/- 8.6 vs 4.0 +/- 2.1 U/ml, p<0.001. There was no difference in mean age of seropositive and seronegative patients for Ch. trachomatis (62.4 +/- 13.1 vs 56.2 +/- 15.9 years). We did not observe in both groups of patients any differences in mean level of C-reactive protein (CRP): 12106.2 +/- 10791.0 vs 14015.3 +/- 11194.3 ng/ml. The mean ferritin level was significantly higher in G IgG (+): 624.3 +/- 375.7 vs 418.3 +/- 341.4 ng/ml, p<0.05. Significant negative correlations were found in G IgG (+) between IgG antibodies and transferrin saturation (r=-0.645719, p<0.001) and between CRP and calcium (r=-0.4526, p<0.05). IgG antibodies were detected frequently in W (60%) than in M (29%). Mean level of IgG was significantly higher in seropositive W than in seropositive M (23.3 +/- 7.8 vs 12.1 +/- 4.2 U/ml, p<0.0001). The seropositive W were older (67.9 +/- 11.8 vs. 53.8 +/- 11.0 years, p<0.02) and seropositive W were shorter treated with HD (18.1 +/- 16.6 vs 43.7 +/- 30.6 months, p<0.02). The mean serum calcium conc. and phosphorus were significantly lower in seropositive W (2.1 +/- 0.1 vs 2.3 +/- 0.2 mmol/l, p<0.05 and respectively 1.3 +/- 0.3 vs 1.8 +/- 0.2 mmol/l, p<0.005). Likewise the mean transferrin saturation (TS) was significantly lower in that group (25.7 +/- 7.3 vs 38.0 +/- 11.3%, p<0.01). There were no differences between seropositive men and women in mean serum concentrations of CRP, iPTH, albumin and hemoglobin. We found in seropositive W significant negative correlation between IgG antibodies and age (r=-0.633, p<0.02). CONCLUSIONS: The patients treated with HD were quite frequently shown significantly elevated level of IgG antibodies for Ch. trachomatis. It could have be connected with past infection. The antibodies were more commonly detected in women, particularly in younger patients. No relationship between osteodystrophy and Ch. trachomatis infection was found.