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Introduction: Uremic pruritus (UP) is a prevalent symptom in patients suffering from uremia, yet its underlying etiology and mechanisms remain incompletely elucidated. Given the significant incidence of UP, identifying specific alterations in proteins present in the blood of UP patients could offer insights into the potential biological pathways associated with UP and facilitate the exploration of biomarkers. Methods: In this study, we employed LC-MS/MS-based data-independent acquisition (DIA) mode to analyze serum samples obtained from 54 UP patients categorized as DKD-UP, HN-UP, and GN-UP (n = 18 for each subgroup), along with 18 uremic patients without pruritus (Negative) and 18 CKD patients without pruritus (CKD). Through DIA mode analysis, a total of 7075 peptides and 959 proteins were quantified. Within these, we identified four upregulated and 13 downregulated Differentially Expressed Proteins (DEPs) in DKD-UP versus Negative, five upregulated and 22 downregulated DEPs in HN-UP versus Negative, and three upregulated and 23 downregulated DEPs in GN-UP versus Negative. Furthermore, we conducted an intersection analysis of the DEPs across these three comparison groups to derive a set of common DEPs (COMP). Subsequently, a total of 67 common DEPs were identified in the three UP groups when compared to the CKD group, with 40 DEPs showing upregulation and 27 DEPs displaying downregulation. Results: Following Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Protein-Protein Interaction (PPI) analyses, we observed that the DEPs distinguishing UP from CKD were primarily associated with mitochondrial function (MT-CYB, PRDX2, TOMM22), inflammation (CD59, CSF1), renal injury (WFDC2), and neural function (CAP1, VGF). Discussion: Our findings contribute to a potential molecular comprehension of UP pathogenesis, shedding light on the identification of these DEPs as plausible biomarkers for UP.
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Objective The relationship between calcified nanoparticles (CNPs) and the formation of urinary stones is drawing increasing attention and the specific mechanisms involved. This study aims to investigate the mechanisms of the formation of kidney stone caused by CNPs. Methods A total of 48 rats were randomly and equally divided into a CNPs group (each rat was injected with 2 mL CNPs through the tail vein to establish a rat kidney stone model of CNPs), and a control group (injected the same amount of sterile isotonic saline instead of CNPs). We compared the expression levels of autophagy-related proteins, such as Beclin-1 and LC-3, the formation of autophagosomes and calcium salt crystals in renal tissues at time points of 3h, 6h, 12h, 24h, 1w, 2w, 4w and 8w in two groups. Results The relative expression levels and positive cells of Beclin-1 and LC-3 in CNPs group at 3h,6h,12h,24h, 1w, 2w, 4w, 8w were significantly higher than those in the control group (P< 0.05), and reached the highest value at 24 (P< 0.05). The number of autophagosomes at 24h, 1w, 2w, 4w, and 8w in the CNPs group ((2.83±0.32), (3.00±0.26), (3.70±0.44), (3.90±0.98), (4.70±0.51)/HP, respectively) were significantly higher than those in the control group (0.73±0.15)/HP (P <0.05). The scores of calcium salt crystals in the CNPs group at 2w, 4w, and 8w significantly increased compared to the control group (P <0.05). The calcium salt crystal formation score ((0.92 ± 0.98) points) was positively correlated with the expression intensities of Beclin-1 and LC-3 ((6.78 ± 4.25), (2.61 ± 2.57), respectively) (r = 0.843, 0.628, P <0.05), which was positively correlated with the number of autophagosomes (2.53 ± 1.41) (r = 0.923, P <0.001). Conclusion CNPs may damage renal tubular epithelial cells, and induce immediate autophagic activity, also increase expression of autophagy-related proteins and autophagosome formation, which will promote the formation and aggregation of calcium salt crystals in renal tubules to some extent.
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Objective At present, the traditional model of urinary tract infection is not only complex in operation process but also easy to be infected, and the model with simple transurethral bacterial injection is not stable enough. This study established a rat model of foreign body-associated urinary tract infection. A spiral polyethylene tube (PT) was placed transurethrally into the bladder by transurethral inoculation with extended-spectrum β-lactamases-producing Escherichia coli (ESBLs E.coli).Methods SD female rats were randomly divided into blank control group, no foreign body groups at 7d and 14d, foreign body groups at 7d and 14d. ESBLs E.coli was injected transurethrally by foreign body into the bladder in foreign body groups. The same volumes of ESBLs E.coli and sterile saline were injected respectively in no foreign body and blank groups. Examination was made on bilateral renal gravity index, the numbers of white blood cells and neutrophils, the bacteriological and pathological changes in urine and kidney.Results The bilateral renal gravity index, the percentage of neutrophils and and the positive rates of renal and urine bacteria culture in foreign body groups at 7d and 14d were significantly higher than those in blank control group and no foreign body groups(P＜0.05). The number of white blood cells in foreign body group at 7d was significantly higher than those of blank control and no foreign body group(P＜0.05). The positive rates of renal and urine bacteria culture were 100% in the foreign body groups at 7d and 14d. The positive rate of urine bacteria culture in no foreign body at 7d was 33.3%. Under the light microscope, there were inflammatory changes in the kidney and bladder tissues of the rats in foreign body groups, and a few fibrous tissues were formed around glomeruli in foreign body group at 14d.Conclusion The establishment of a highly successful and stable rat model of urinary tract infection can be successfully achieved by injection of ESBLS E.coli through transurethral foreign body placed in bladder.
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Objective To compare the subjective and objective outcomes of flexible ureterorenoscopy (F-URS) and extracorporeal shock wave lithotripsy (ESWL) for the treatment of inferior calyceal calculi between 10 to 20 mm. Method A retrospective analysis was performed for inferior calyceal calculi between 10 to 20 mm at our institution on a total of 112 patients treated with holmium laser lithotripsy or ESWL from September 2013 to September 2016. Retreatment rate, complications, stone clearance rate and subjective patient-reported outcomes were compared. Result Stone clearance rate was significantly higher in F-URS group compared with ESWL group (86.1% vs 61.8%, P < 0.05). Retreatment rate (44.7% vs 8.3%, P < 0.05) was higher in ESWL. There was no significant difference in complication (11.1% vs 7.9%, P > 0.05). Overall satisfaction score [(2.92 ± 1.24) vs (2.07 ± 1.35), P < 0.05] and voiding symptom score [(3.87 ± 0.64) vs (2.23 ± 0.73), P < 0.05)] were significantly higher in F-URS than ESWL. More patients in F-URS were willing to undergo the procedure again (83.3% vs 55.3%, P<0.05). Conclusion For the treatment of intermediate size inferior calyceal calculi,F-URS is superior to ESWL in terms of stone clearance rate, retreatment rate and subjective satisfaction.
