Changes of gut microbiota in diabetic nephropathy and its effect on the progression of kidney injury.

PURPOSE: We aimed to illustrate gut microbiota and short chain fatty acid (SCFA) levels in diabetic nephropathy (DN) patients, and investigate the mechanism of sodium butyrate in diabetic mellitus (DM) rats. METHODS: Gut microbiota and serum SCFA levels were measured by 16S rDNA and GC-MS. After being built by streptozotocin (DM rats), the DM rats were administered 300 mg/kg sodium butyrate for 12 weeks (DM + BU rats). Gut microbiota, serum and fecal butyrate level were measured. RT-PCR, WB and transmission electron microscopy were performed to explore LC3mRNA or LC3B protein expression, and autophagosomes in kidney tissues. AMPK/mTOR protein expression in renal tissue were also measured. RESULTS: The gut microbial dysbiosis was found in DM and DN groups, and some SCFAs-producing bacteria were decreased in DN group. The serum butyrate concentrations were lower in SCFA-DN group compared with SCFA-HC group and SCFA-DM group in the other cohort. Serum butyrate level was positively correlated with eGFR. Sodium butyrate increased serum and fecal butyrate levels, and improved the enlargement of glomerular area and fibronectin and collagen IV expressions in renal tissues in DM + BU rats. The LC3 mRNA, LC3BII/I ratio and number of autophagosomes were increased in renal tissue of DM + BU rats. Higher p-AMPK/AMPK ratio and lower p-mTOR/ mTOR ratio were shown in renal tissue of DM + BU rats compared with DM rats. CONCLUSIONS: We found the decrease in SCFAs-producing bacteria and low SCFAs concentrations in DN patients. Oral butyrate supplementation may improve kidney injury in DM rats, possibly by increasing autophagy via activating AMPK/mTOR pathway.

Neutrophil-lymphocyte ratio is associated with arterial stiffness in patients with peritoneal dialysis.

BACKGROUND: Patients with peritoneal dialysis are in the persistent inflammation state and have elevated arterial stiffness. Neutrophil-lymphocyte ratio(NLR) is a new inflammatory marker in renal and cardiac disorders. Brachial-ankle pulse wave velocity (baPWV) is a non-invasive measurement, which is widely used as a surrogate marker of arterial stiffness. However, there is little evidence to show an association between NLR and baPWV in patients with peritoneal dialysis. The aim of this cross-section study was to investigate the relationship between NLR and arterial stiffness measured by baPWV in patients with peritoneal dialysis. METHODS: In this cross-section study, 101 patients with peritoneal dialysis were enrolled from January 2014 to June 2015. According to average baPWV level (1847.54 cm/s), the patients were categorized into two groups, low group and high group. baPWV, which reflects arterial stiffness, was calculated using the single-point method. Clinical data were collected in details. NLR was calculated using complete blood count. Associations between NLR and baPWV were assessed using Pearson's correlation and linear regression analysis. RESULTS: The NLR was significantly lower in the low baPWV group than in the high baPWV group (p = 0.03). There were positive correlations between baPWV and neutrophil count (r = 0.24, p = 0.01) and NRL(r = 0.43, P < 0.01), and there was a negative correlation between baPWV and lymphocyte count (r = -0.23, p = 0.01). In addition, albumin, phosphorous and intact parathyroid hormone showed negative correlations with baPWV (r = -0.32, p < 0.01; r = -0.28, p < 0.01; r = -0.25, p = 0.01, respectively). Age and hsCRP showed positive correlations with baPWV (r = 0.47, p < 0.01; r = 0.25, p = 0.01). In multivariate analysis, NLR independently correlated with baPWV in patients with peritoneal dialysis (ß = 0.33, p < 0.01), even after adjustment for various confounders. CONCLUSION: Our study suggests that NLR was an independently associated with arterial stiffness in patients with peritoneal dialysis. However, further prospective studies are needed to confirm cause-and-effect relationship between NLR and baPWV, and to investigate whether anti-inflammatory treatment could improve arterial stiffness in patients with peritoneal dialysis.