The uremic toxin indoxyl sulfate (IS) has been related to the development of various medical conditions notably chronic kidney disease (CKD). Hence, quantification of this biomarker in biological fluids may be a diagnostic tool to evaluate renal system functionality. Numerous analytical methods including liquid chromatography, gas chromatography, spectroscopy, and electrochemical techniques have since been used to analyze IS in different biological fluids. The current review highlights the relevant studies that assessed IS with a special focus on sample preparation, which is essential to reduce or eliminate the effect of endogenous components from the matrix in bioanalysis.

UNASSIGNED: Chronic kidney disease (CKD) is a major public health burden and is often undiagnosed in the primary care setting. Untested and untreated, this often leads to renal failure and dialysis.
UNASSIGNED: This was a cross-sectional study of adults aged 20 years and over, diagnosed with type 2 diabetes mellitus and/or hypertension, with no previous history or record of CKD, and attending three chronic disease clinics in the Eastern Regional Health Authority (ERHA). Patients were screened for risk of CKD by using the albumin creatinine ratio. The eGFR was calculated based on serum creatinine by using the CKD Epidemiology Collaboration (EPI) 2009 equation.
UNASSIGNED: In total, 430 patients agreed to participate with 61.2% of response rate. Of the 385 with complete data, 357 (92%) were detected as having a high risk for CKD; older patients (>66 years) and those with both diabetes and hypertension had high proportions of risk for CKD. There were significant associations between age, systolic hypertension, and the severity of risk for CKD.
UNASSIGNED: CKD is common at the primary care level among adults with NCDs in Trinidad, with many patients having been left out without being tested for CKD. Primary care physicians must take this into consideration in caring for NCD patients.

Introduction: Vascular calcification is accelerated in patients with chronic kidney disease (CKD) and increases the risk of cardiovascular events. CKD is frequently associated with anemia. Daprodustat (DPD) is a prolyl hydroxylase inhibitor for the treatment of CKD-associated anemia that enhances erythropoiesis through the activation of the hypoxia-inducible factor 1 (HIF-1) pathway. Studies showed that DPD promotes osteogenic differentiation of human aortic smooth muscle cells (HAoSMCs) and increases aorta calcification in mice with CKD. HIF-1 activation has been linked with endoplasmic reticulum (ER) stress; therefore, here we investigated the potential contribution of ER stress, particularly activating transcription factor 4 (ATF4), to the pro-calcification effect of DPD. Methods: Here, we used an adenine-induced CKD mouse model and HAoSMCs as an in vitro vascular calcification model to study the effect of DPD. Results: DPD treatment (15 mg/kg/day) corrects anemia but increases the expression of hypoxia (Glut1, VEGFA), ER stress (ATF4, CHOP, and GRP78), and osteo-/chondrogenic (Runx2, Sox9, BMP2, and Msx2) markers and accelerates aorta and kidney calcification in CKD mice. DPD activates the PERK/eIF2α/ATF4/CHOP pathway and promotes high phosphate-induced osteo-/chondrogenic differentiation of HAoSMCs. Inhibition of ER stress with 4-PBA or silencing of ATF4 attenuates HAoSMC calcification. DPD-induced ATF4 expression is abolished in the absence of HIF-1α; however, knockdown of ATF4 does not affect HIF-1α expression. Conclusion: We concluded that DPD induces ER stress in vitro and in vivo, in which ATF4 serves as a downstream effector of HIF-1 activation. Targeting ATF4 could be a potential therapeutic approach to attenuate the pro-calcific effect of DPD.

One of the hallmarks of chronic kidney disease (CKD) is the development of vascular calcification. Inorganic pyrophosphate is a potent inhibitor of calcification, and previous studies have reported low plasma pyrophosphate levels in hemodialysis patients. A long-term mouse model of CKD-accelerated vascular calcification was developed to study pyrophosphate metabolism and to test whether oral pyrophosphate supplementation attenuates the propensity for arterial calcification. CKD was induced by repeated injections of aristolochic acid in wild-type and Abcc6-/- mice, which tend to develop vascular calcifications. CKD accelerated the development of vascular calcifications in Abcc6-/- mice, in the aorta and small renal arteries, and decreased circulating pyrophosphate levels. Oral pyrophosphate supplementation for 6 months attenuated CKD-induced vascular calcification in this model. These results show that oral pyrophosphate may be of interest in preventing vascular calcification in patients with CKD. KEY MESSAGES: Chronic kidney disease accelerates the development of vascular calcification in pyrophosphate-deficient mice. Oral pyrophosphate supplementation for 6 months attenuates chronic kidney disease-induced vascular calcification in a mouse model. Oral pyrophosphate may be of interest in preventing vascular calcification in patients with chronic kidney disease.

UNASSIGNED: Matrix metalloproteinase 2 (MMP-2) plays an important role in the development of fibrosis, the final common pathway of chronic kidney disease (CKD). This study aimed to assess the relationship between repeated measures of MMP-2 and CKD progression in a large, diverse prospective cohort.
UNASSIGNED: In a prospective cohort of Chronic Renal Insufficiency Cohort (CRIC) participants (N = 3,827), MMP-2 was measured at baseline. In a case-cohort design, MMP-2 was additionally measured at year 2 in a randomly selected subcohort and cases of estimated glomerular filtration rate (eGFR) halving or kidney replacement therapy (KRT) (N = 1,439).
UNASSIGNED: CRIC is a multicenter prospective cohort of adults with CKD.
UNASSIGNED: MMP-2 measured in plasma at baseline and at year 2.
UNASSIGNED: A composite kidney endpoint (KRT/eGFR halving).
UNASSIGNED: Weighted Cox proportional hazards models for case-cohort participants.
UNASSIGNED: Participants were followed for a median of 4.6 years from year 2 and 6.9 years from the baseline. Persistently elevated MMP-2 (≥300 ng/mL at both baseline and year 2) increased the hazard of the composite kidney endpoint (HR, 1.61; 95% CI, 1.07-2.42; P = 0.09) after adjusting for covariates. The relationship of persistently elevated MMP-2 was modified by levels of inflammation, with a 2.6 times higher rate of the composite kidney endpoint in those with high-sensitivity C-reactive protein < 2.5 g/dL at study entry. Heterogeneity of effect was found with proteinuria, with a baseline MMP-2 level of ≥300 ng/mL associated with an increased risk of the composite kidney endpoint (HR, 1.30; 95% CI, 1.09-1.54) only with proteinuria ≥ 442 mg/g.
UNASSIGNED: The observational study design limits causal interpretation.
UNASSIGNED: Elevated MMP-2 is associated with CKD progression, particularly among those with low inflammation and those with proteinuria. Future investigations are warranted to confirm the reduction in risk of CKD progression among these subgroups of patients with CKD.
Matrix metalloproteinase 2 (MMP-2) is a matrix-degrading protease involved in fibrosis and elevated in chronic kidney disease (CKD). Longitudinal patterns of MMP-2 have not previously been assessed as a predictor of CKD progression in a large prospective cohort. Here, we found that a higher baseline level and an increasing or persistently elevated 2-year pattern of MMP-2 were associated with CKD progression, independent of all covariates except proteinuria. The association of baseline MMP-2 with CKD progression differed by level of proteinuria, whereas levels of inflammation modified the associations of 2-year MMP-2 patterns with CKD progression.

OBJECTIVE: The new nomenclature of steatotic liver disease (SLD) including metabolic dysfunction-associated SLD (MASLD), MASLD and increased alcohol intake (MetALD), and alcohol-associated liver disease (ALD) has recently been proposed. We aimed to elucidate the relationship between each category of SLD and chronic kidney disease (CKD).
METHODS: We investigated the effects of various SLDs on the development of CKD, defined as estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 or positive for urinary protein, during a 10-year period in 12 138 Japanese subjects (men / women, 7984/4154; mean age, 48 years) who received annual health examinations including abdominal ultrasonography.
RESULTS: The prevalences of SLD without metabolic dysfunction (SLD-MD[-]), MASLD, MetALD, and ALD were 1.7%, 26.3%, 4.9%, and 1.9%, respectively. During the follow-up period, 1963 subjects (16.2%) (men / women, 1374 [17.2%]/589 [14.2%]) had new onset of CKD. Multivariable Cox proportional hazard model analyses after adjustment of age, sex, eGFR, current smoking habit, diabetes mellitus, hypertension, and dyslipidemia showed that the hazard ratios (HR [95% confidence interval]) for the development of CKD in subjects with MASLD (1.20 [1.08-1.33], p = 0.001) and those with ALD (1.41 [1.05-1.88], p = 0.022), but not those with MetALD (1.11 [0.90-1.36], p = 0.332), were significantly higher than the HR in subjects with non-SLD. Interestingly, subjects with SLD-MD[-] had a significantly lower HR (0.61 [0.39-0.96], p = 0.034) than that in subjects with non-SLD. The addition of the novel classification of SLDs into traditional risk factors for the development of CKD significantly improved the discriminatory capacity.
CONCLUSIONS: MASLD and ALD, but not SLD-MD[-], are independently associated with the development of CKD.

OBJECTIVE: Calciprotein particles (CPPs) are circulating calcium and phosphate nanoparticles associated with development of vascular calcification (VC) in chronic kidney disease (CKD). Although recent studies have been focusing on associations of CPPs with presence of VC in CKD, insights in the underlying processes and mechanisms by which CPPs might aggravate VC and vascular dysfunction in vivo are currently lacking. Here, we assessed overall burden of abdominal VC in healthy kidney donors and CKD patients, and subsequently performed transcriptome profiling in vascular tissue obtained from these subjects, linking outcome to CPP counts and calcification propensity.
RESULTS: Calcification scores were quantified in renal arteries, iliac arteries and abdominal aorta, using computed tomography (CT) scans of kidney donors and CKD patients. Vascular tissue was collected from kidney donors (renal artery) and CKD patients (iliac artery), after which bulk RNA sequencing and gene set enrichment analysis (GSEA) was performed on a subset of patients. Calcification propensity (crystallization time, T50) was measured using nephelometry, and CPP counts with microparticle flow cytometric analysis. Increased calcification scores (based on CT) were found in CKD patients compared to kidney donors. Transcriptome profiling revealed enrichment for processes related to endothelial activation, inflammation, extracellular matrix (ECM) remodelling and ossification in CKD vascular biopsies compared to kidney donors. Calcification propensity was increased in CKD, as well as CPP counts, of which the latter significantly associated with markers of vascular remodelling.
CONCLUSIONS: Our findings reveal that CKD is characterized by systemic VC with increased calcification propensity and CPP counts. Transcriptome profiling showed altered vascular gene expression with enrichment for endothelial activation, inflammation, ECM remodelling and ossification. Moreover, we demonstrate for the first time that vascular remodelling processes are associated with increased circulating CPP counts. Interventions targeting CPPs are promising avenues for alleviating vascular remodelling and VC in CKD.

UNASSIGNED: Kidney diseases are considered silent killers due to the lack of well-defined symptoms. Public knowledge about chronic kidney disease (CKD) management has been shown to decrease the risk of CKD onset and progression to end-stage renal disease and renal failure. The main objective of this study was to assess the knowledge of kidney function, CKD symptoms, etiology, prevention and treatment in the general population.
UNASSIGNED: A cross-sectional study using a validated questionnaire was conducted in Jordan to assess public knowledge of CKD. Public knowledge of CKD was assessed using a questionnaire consisting of 32 knowledge questions, including risk factors, symptoms, treatment, protective measures and kidney function. The knowledge level was classified according to the total score: poor (0-50%), intermediate (51-70%) and good/high (71-100%). Multiple regression analysis was performed to compare knowledge scores (KS) and predict associations with the participants\' baseline characteristics.
UNASSIGNED: The level of knowledge about CKD among the 2181 participants was intermediate. The KS was significantly higher among participants with health issues such as hypertension, diabetes and heart problems, first-degree relatives working in the medical field, majors relevant to health, married, employed, highly educated, high-income and smokers. The main sources of knowledge about CKD were health professionals, TV shows, books and magazines. Multiple regression analysis showed an association between KS and age, sex, functional status, educational level and field, income, smoking status, having a family member/spouse work in the medical field, and knowledge source.
UNASSIGNED: The public level of knowledge about CKD management is greatly influenced by participants\' health and social factors. Thus, improving public knowledge and perception through education and the media will significantly reduce CKD prevalence and incidence.
Public awareness and educating the public about chronic kidney diseases (CKDs) is essential because of the high prevalence, and increased awareness can contribute to early detection, management and potentially slow down the progression of CKD.Creating awareness of the risk factors for CKD enables health policy developers to adopt preventive measures.CKD can significantly affect quality of life, and public awareness campaigns can emphasize the impact of CKD on overall well-being, motivating individuals to prioritize kidney health.

UNASSIGNED: Renal artery pseudoaneurysm (RAP) is one of the most stressful and life-threatening complications of partial nephrectomy, the standard treatment for small renal cell carcinoma. The use of a monopolar soft coagulation system for hemostasis during robot-assisted partial nephrectomy (RAPN) is expected to prevent post-surgical RAP development. In this study, we aimed to investigate how the use of a soft coagulation system in RAPN reduces postoperative pseudoaneurysms and changes renal function over time.
UNASSIGNED: The incidence of pseudoaneurysms and postoperative renal function were compared in 208 partial nephrectomies performed between May 2016 and March 2023 at a single institution, with propensity score matching to balance patient backgrounds. Outcomes were analyzed using multivariate logistic or linear regression analyses.
UNASSIGNED: In total, 80 matched pairs were analyzed. One (1.2%) and eighteen (22.5%) pseudoaneurysms were found in the soft coagulation users and non-users, respectively (P<0.001). Compared to the non-user group, postoperative estimated glomerular filtration rates (eGFRs) in the user group were 89% vs. 96% (P<0.001), 87% vs. 93% (P=0.009), and 88% vs. 92% (P=0.15) at 1, 3, and 12 months, respectively. Subsequent multivariate analyses showed a lower incidence of pseudoaneurysms in the user group with an odds ratio of 0.05 [95% confidence interval (CI): 0.01 to 0.44; P=0.007], and no significant difference in the rate of change in renal function at 12 months postoperatively (-1.1%, 95% CI: -5.5% to 3.3%; P=0.61).
UNASSIGNED: The use of a soft coagulation system reduces pseudoaneurysm occurrence after partial nephrectomy. Although renal function decreased in the short-term for the use group, no long-term differences were observed.

BACKGROUND: Macrophages are the main inflammatory cells involved in kidney injury and play a significant role in the development of acute kidney injury (AKI) and progression of chronic kidney disease (CKD). Emodin is believed to stabilize macrophage homeostasis under pathological conditions. The objective of this study aimed to explore the underlying mechanisms and effects of Emodin on M1 macrophages.
METHODS: Network pharmacology methods were used to predict target proteins associated with renal injury and identify the pathways affected by emodin. RAW264.7 macrophages were induced into M1 polarization using LPS and then treated with emodin at 20, 40, and 80 µM. The effects of emodin on cell viability, cytokines (IL-1β, IL-6, TNF-α), M1 macrophage markers (F4/80 + CD86+), and the EGFR/MAPK pathway were evaluated. Additionally, we transfected RAW264.7 cells with an EGFR shRNA interference lentivirus to assess its effects on RAW264.7 cells function and MAPK pathway. After RAW264.7 cells were passaged to expanded culture and transfected with EGFR-interfering plasmid, macrophages were induced to polarize towards M1 with LPS and then treated with 80 µM emodin. CKD modeling was performed to test how emodin is regulated during CKD.
RESULTS: There are 15 common targets between emodin and kidney injury, of which the EGFR/MAPK pathway is the pathway through which emodin affects macrophage function. Emodin significantly reduced the levels of IL-6, IL-1β and TNF-α (p < 0.05) and the ratio of M1 macrophage surface markers F4/80 + CD86+ (p < 0.01) in the supernatant of RAW264.7 cells in a dose-dependent manner. Furthermore, the inhibitory effect of emodin on RAW264.7 cells was achieved by interfering with the EGFR/MAPK pathway. Moreover, emodin also affected the mRNA and protein expression of EGFR and Ras, leading to a decrease in the rate of M1 macrophages, thus inhibiting the pro-inflammatory effect of M1 macrophages. The addition of emodin reduced the rate of M1 macrophages in CKD and inhibited the further polarization of M1 macrophages, thus maintaining the pro-inflammatory and anti-inflammatory homeostasis in CKD, and these effects were achieved by emodin through the control of the EGRF/ERK pathway.
CONCLUSIONS: Emodin attenuates M1 macrophage polarization and pro-inflammatory responses via the EGFR/MAPK signalling pathway. And the addition of emodin maintains pro- and anti-inflammatory homeostasis, which is important for maintaining organ function and tissue repair.