Effects of Uremic Clearance Granules on p38 MAPK/NF-κB Signaling Pathway, Microbial and Metabolic Profiles in End-Stage Renal DiseasRats Receiving Peritoneal Dialysis

Abstract

Background: End-stage renal disease (ESRD) is the final stage of chronic kidney disease (CKD). In the clinic, Uremic Clearance Granules (UCG) are mainly used in the treatment of early CKD and stabilized renal function. However, the benefits and mechanisms of UCG on ESRD remain unclear. Methods: Rats were randomly divided into four groups: sham group, model group, peritoneal dialysis (PD) group and UCG group. Except for the sham-operated group, ESRD was induced by 5/6 nephrectomy in the other three groups. The PD group and UCG group were then subjected to PD. In addition, the UCG group was given UCG by gavage when PD. Changes in body weight and final kidney weight of rats in each group were monitored. HE and Masson staining were performed to confirm the extent of renal fibrosis. Biochemical kits were used to detect blood urea nitrogen (BUN), serum and urine creatinine (Scr, Cre), and urine protein (UPr) levels. ELISA was used to detect the rats’ inflammatory responses. qRT-PCR, WB, and IHC were probed to determine the expression levels of NF-κB and MAPK. 16S rDNA sequencing was performed to analyze the composition of gut microbiota in rats. A liquid chromatograph-mass spectrometer was performed to reveal serum metabolomics changes. Results: UCG increased renal volume and body weight, improved renal fibrosis. It enhanced renal function and decreased the levels of BUN, Scr, Upr, Cre, inflammatory responses, as well as NF-κB and MAPK expressions in renal and colon tissues of ESRD rats. The relative abundances of Bacteroidetes and Firmicutes changed in ESRD rats in response to UCG. Serum metabolomics was utilized to identify 70 differentiated metabolites, which were associated with D-glutamine and D-glutamate metabolism, and Phenylalanine metabolism. Conclusion: Our study confirmed that UCG alleviated ESRD by regulating p38 MAPK/NF-κB signaling pathway, microbial and metabolic profiles.