The pathogenic mechanism of monosodium urate crystal-induced kidney injury in a rat model.

Objective: (MSU) crystals usually in the kidney tubules especially collecting ducts in the medulla. Previous animal models have not fully reproduced the impact of MSU on kidneys under non-hyperuricemic conditions. Methods: In the group treated with MSU, the upper pole of the rat kidney was injected intrarenally with 50 mg/kg of MSU, while the lower pole was injected with an equivalent volume of PBS solution. The body weight and kidney mass of the rats were observed and counted. H&E staining was used to observe the pathological damage of the kidney and to count the number of inflammatory cells. Masoon staining was used to observe the interstitial fibrosis in the kidneys of the rat model. Flow cytometric analysis was used for counting inflammatory cells in rats. ElISA was used to measure the concentration of serum and urine uric acid, creatinine and urea nitrogen in rats. Results: At the MSU injection site, a significantly higher infiltration of inflammatory cells and a substantial increase in the area of interstitial fibrosis compared to the control group and the site of PBS injection were observed. The serum creatinine level was significantly increased in the MSU group. However, there were no significant differences in the rats' general conditions or blood inflammatory cell counts when compared to the control group. Conclusion: The injection of urate crystals into the kidney compromised renal function, caused local pathological damage, and increased inflammatory cell infiltration and interstitial fibrosis. Intrarenal injection of MSU crystals may result in urate nephropathy. The method of intrarenal injection did not induce surgical infection or systemic inflammatory response.

Analysis of the chemical constituents and their metabolites in Orthosiphon stamineus Benth. via UHPLC-Q exactive orbitrap-HRMS and AFADESI-MSI techniques.

BACKGROUND: Known for its strong diuretic properties, the perennial herbaceous plant Orthosiphon stamineus Benth. is believed to preserve the kidney disease. This study compared the boiling water extract with powdered Orthosiphon stamineus Benth. and used a highly sensitive and high resolution UHPLC-Q-Exactive-Orbitrap-HRMS technology to evaluate its chemical composition. RESULTS: Furthermore, by monitoring the absorption of prototype components in rat plasma following oral treatment, the beneficial ingredients of the Orthosiphon stamineus Benth. decoction was discovered. Approximately 92 substances underwent a preliminary identification utilizing relevant databases, relevant literature, and reference standards. As the compound differences between the powdered Orthosiphon stamineus Benth. and its water decoction were analyzed, it was found that boiling produced additional compounds, 48 of which were new. 45 blood absorption prototype components and 49 OS metabolites were discovered from rat serum, and a kidney tissue homogenate revealed an additional 28 prototype components. Early differences in the distribution of ferulic acid, cis 4 coumaric acid, and rosmarinic acid were shown using spatial metabolomics. It was elucidated that the renal cortex region is where rosmarinic acid largely acts, offering a theoretical foundation for further studies on the application of OS in the prevention and treatment of illness as well as the preservation of kidney function. SIGNIFICANCE: In this study, UHPLC-Q Exactive Orbitrap-HRMS was employed to discern OS's chemical composition, and a rapid, sensitive, and broad-coverage AFADESI-MSI method was developed to visualize the spatial distribution of compounds in tissues.

Secretory leukocyte protease inhibitor as a novel predictive biomarker in patients with diabetic kidney disease.

Background: Secretory leukocyte protease inhibitor (SLPI) is a multifunctional protein involved in the chronic inflammatory process, implicated in the pathogenesis of diabetic kidney disease (DKD). However, its potential as a diagnostic and prognostic biomarker of DKD has yet to be evaluated. This study explored the clinical utility of SLPI in the diagnosis and prognosis of renal endpoint events in patients with DKD. Methods: A multi-center cross-sectional study comprised of 266 patients with DKD and a predictive cohort study comprised of 120 patients with stage IV DKD conducted between December 2016 and January 2022. The clinical parameters were collected for statistical analysis, a multivariate Cox proportional hazards model was used to evaluate the independent risk factors for renal endpoints. Results: Serum SLPI levels gradually increased with DKD progression (p<0.01). A significant correlation was observed between serum SLPI levels and renal function in patients with DKD. The mean follow-up duration in this cohort study was 2.32 ± 1.30 years. Multivariate Cox regression analysis showed SLPI levels≥51.61ng/mL (HR=2.95, 95% CI[1.55, 5.60], p<0.01), 24h urinary protein levels≥3500 mg/24h (HR=3.02, 95% CI[1.66, 5.52], p<0.01), Alb levels<30g/l (HR=2.19, 95% CI[1.12, 4.28], p<0.05), HGB levels<13g/dl (HR=3.18, 95% CI[1.49, 6.80], p<0.01), and urea levels≥7.1 mmol/L (HR=8.27, 95% CI[1.96, 34.93], p<0.01) were the independent risk factors for renal endpoint events in DKD patients. Conclusions: Serum SLPI levels increased with DKD progression and were associated with clinical parameters of DKD. Moreover, elevated SLPI levels showed potential prognostic value for renal endpoint events in individuals with DKD. These findings validate the results of previous studies on SLPI in patients with DKD and provide new insights into the role of SLPI as a biomarker for the diagnosis and prognosis of DKD that require validation.

Qing-Re-Xiao-Zheng-Yi-Qi formula relieves kidney damage and activates mitophagy in diabetic kidney disease.

Introduction: Qing-Re-Xiao-Zheng-Yi-Qi Formula is an effective prescription in diabetic kidney disease treatment, we have confirmed the efficacy of Qing-Re-Xiao-Zheng therapy in diabetic kidney disease through clinical trials. In this study, we investigated the mechanisms of Qing-Re-Xiao-Zheng-Yi-Qi Formula in the treatment of diabetic kidney disease. Methods: We used Vanquish UHPLCTM to analyze the chemical profiling of Qing-Re-Xiao-Zheng-Yi-Qi Formula freeze-dried powder. We constructed diabetic kidney disease rat models induced by unilateral nephrectomy and high-dose streptozocin injection. We examined blood urea nitrogen, serum creatinine, serum glucose, total cholesterol, triglyceride, serum total protein, albumin, alanine aminotransferase, aspartate aminotransferase and 24 h urinary total protein in diabetic kidney disease rats. The renal pathological changes were observed by HE, Masson, PAS stanning and transmission electron microscopy. The levels of fibrosis-related proteins and mitophagy-related proteins were detected by western blot analysis. We also conducted an immunofluorescence co-localization analysis on podocytes to further investigate the effect of Qing-Re-Xiao-Zheng-Yi-Qi Formula treatment on mitophagy. Results: A total of 27 constituents in Qing-Re-Xiao-Zheng-Yi-Qi Formula were tentatively identified. We found PINK1/Parkin-mediated mitophagy was inhibited in diabetic kidney disease. Qing-Re-Xiao-Zheng-Yi-Qi Formula treatment could raise body weight and reduce renal index, reduce proteinuria, improve glycolipid metabolic disorders, ameliorate renal fibrosis, and reduce the expression of Col Ⅳ and TGF-ß1 in diabetic kidney disease rats. Qing-Re-Xiao-Zheng-Yi-Qi Formula treatment could also increase the expression of nephrin, activate mitophagy and protect podocytes in diabetic kidney disease rats and high glucose cultured podocytes. Conclusion: PINK1/Parkin-mediated mitophagy was inhibited in diabetic kidney disease, and Qing-Re-Xiao-Zheng-Yi-Qi Formula treatment could not only ameliorate pathological damage, but also promote mitophagy to protect podocytes in diabetic kidney disease.

Prevalence, risk factors and clinical characteristics of renal dysfunction in Chinese outpatients with growth simple renal cysts.

BACKGROUND: Researchers have proved that simple renal cysts (SRCs) might be correlated with renal dysfunction, but it is still controversial. Thus, we conducted clinical research study with large sample size and long-term follow-up to clarify the relationship between SRCs and renal dysfunction. METHODS: A total of 571 SRCs patients in outpatients of nephrology department were included, we investigated the clinical characteristics of growth SRCs compared with non-growth SRCs, evaluated the incidence of renal dysfunction in SRCs and explored the risk factors of renal dysfunction in growth SRCs. RESULTS: The mean baseline age was 51.31 ± 14.37 years in the whole cohort, ranging from 19 to 79 years, and 57.6% of them were male. The median follow-up duration was 3 years, ranging from 1 to 10 years. In addition, the final maximum diameter increased 1 mm (2.74%) per year. Patients in growth SRCs group tented to have higher percentage of hypertension, hematuria, large cyst and multiple cysts compared with non-growth SRCs group. The prevalence of renal dysfunction was 15.6% after the follow-up, and the prevalence of renal dysfunction was about 10 times higher in growth SRCs group than non-growth SRCs group (23.3% vs. 2.4%). Renal dysfunction was significantly associated with age, female, total cholesterol, diastolic blood pressure, final maximum diameter and yearly change in maximum diameter in growth SRCs. CONCLUSIONS: SRCs were closely related to the decline of renal function, we recommend close follow-up for growth SRCs.

The Profile and Function of Gut Microbiota in Diabetic Nephropathy.

INTRODUCTION: Dysbiosis of gut microbiota impairs the homeostasis of immune and metabolic systems. Although previous studies have revealed the correlation between gut microbiota and various diseases, the function between gut microbiota and diabetic nephropathy (DN) has not been discovered distinctly. In this study, we tried to investigate the profile and function of gut microbiota in DN. METHODS: A total of 100 people were enrolled in this study. Twenty were healthy people, 20 were diabetes patients, and 60 were DN patients. The DN patients were divided into three stages including stage III, IV, and V. We conducted taxonomic analyses in different groups. The distributions of phyla, classes, orders, families, and genera in different groups and samples were investigated. We also evaluated the correlations between clinical parameters and gut microbiota in 60 DN patients. RESULTS: The gut microbiota in the healthy group, diabetes group, and DN group had 1764 operational taxonomic units (OTUs) in total. The healthy group had 1034 OTUs, the diabetes group had 899 OTUs, and the DN group had 1602 OTUs. The diversity of gut microbiota in the stage III DN group was smaller than that in the other groups. 24-h urinary protein was positively correlated with Alistipes and Subdoligranulum, cholesterol was positively correlated with Bacteroides and Lachnoclostridium, and estimated glomerular filtration rate was negatively correlated with Ruminococcus torques group. DISCUSSION: The gut microbiota might play an important role in the development and pathogenesis of DN. A change in gut microbiota diversity is correlated with disease progression. Some kinds of gut microbiota including Alistipes, Bacteroides, Subdoligranulum, Lachnoclostridium, and Ruminococcus torques group might be detrimental factors in DN.