Emodin inhibits M1 macrophage activation that related to acute and chronic kidney injury through EGFR/MAPK pathway.

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-1ß, 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-1ß 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. CONCLUSION: 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.

Genetic Characterization of Kidney Failure of Unknown Etiology in Spain: Findings From the GENSEN Study.

RATIONALE & OBJECTIVE: Chronic kidney disease of unknown etiology (CKDUE) is one of the main global causes of kidney failure. Genetic studies may identify an etiology in these patients, but few studies have implemented genetic testing of CKDUE in a population-based series of patients, which was the focus of the GENSEN Study. STUDY DESIGN: Case series. SETTINGS & PARTICIPANTS: 818 patients aged≤45 years at 51 Spanish centers with CKDUE, and either an estimated glomerular filtration rate of<15mL/min/1.73m2 or treatment with maintenance dialysis or transplantation. OBSERVATIONS: Genetic testing for 529 genes associated with inherited nephropathies using high-throughput sequencing (HTS). Pathogenic and/or likely pathogenic (P/LP) gene variants concordant with the inheritance pattern were detected in 203 patients (24.8%). Variants in type IV collagen genes were the most frequent (COL4A5, COL4A4, COL4A3; 35% of total gene variants), followed by NPHP1, PAX2, UMOD, MUC1, and INF2 (7.3%, 5.9%, 2.5%, 2.5%, and 2.5%, respectively). Overall, 87 novel variants classified as P/LP were identified. The top 5 most common previously undiagnosed diseases were Alport syndrome spectrum (35% of total positive reports), genetic podocytopathies (19%), nephronophthisis (11%), autosomal dominant tubulointerstitial kidney disease (7%), and congenital anomalies of the kidney and urinary tract (CAKUT, 5%). A family history of kidney disease was reported by 191 participants (23.3%) and by 65 of 203 patients (32.0%) with P/LP variants. LIMITATIONS: Missing data, and selection bias resulting from voluntary enrollment. CONCLUSIONS: Genomic testing with HTS identified a genetic cause of kidney disease in approximately one quarter of young patients with CKDUE and advanced kidney disease. These findings suggest that genetic studies are a potentially useful tool for the evaluation of people with CKDUE. PLAIN-LANGUAGE SUMMARY: The cause of kidney disease is unknown for 1 in 5 patients requiring kidney replacement therapy, reflecting possible prior missed treatment opportunities. We assessed the diagnostic utility of genetic testing in children and adults aged≤45 years with either an estimated glomerular filtration rate of<15mL/min/1.73m2 or treatment with maintenance dialysis or transplantation. Genetic testing identified the cause of kidney disease in approximately 1 in 4 patients without a previously known cause of kidney disease, suggesting that genetic studies are a potentially useful tool for the evaluation of these patients.

Evaluation of a proteomic signature coupled with the kidney failure risk equation in predicting end stage kidney disease in a chronic kidney disease cohort.

BACKGROUND: The early identification of patients at high-risk for end-stage renal disease (ESRD) is essential for providing optimal care and implementing targeted prevention strategies. While the Kidney Failure Risk Equation (KFRE) offers a more accurate prediction of ESRD risk compared to static eGFR-based thresholds, it does not provide insights into the patient-specific biological mechanisms that drive ESRD. This study focused on evaluating the effectiveness of KFRE in a UK-based advanced chronic kidney disease (CKD) cohort and investigating whether the integration of a proteomic signature could enhance 5-year ESRD prediction. METHODS: Using the Salford Kidney Study biobank, a UK-based prospective cohort of over 3000 non-dialysis CKD patients, 433 patients met our inclusion criteria: a minimum of four eGFR measurements over a two-year period and a linear eGFR trajectory. Plasma samples were obtained and analysed for novel proteomic signals using SWATH-Mass-Spectrometry. The 4-variable UK-calibrated KFRE was calculated for each patient based on their baseline clinical characteristics. Boruta machine learning algorithm was used for the selection of proteins most contributing to differentiation between patient groups. Logistic regression was employed for estimation of ESRD prediction by (1) proteomic features; (2) KFRE; and (3) proteomic features alongside KFRE. RESULTS: SWATH maps with 943 quantified proteins were generated and investigated in tandem with available clinical data to identify potential progression biomarkers. We identified a set of proteins (SPTA1, MYL6 and C6) that, when used alongside the 4-variable UK-KFRE, improved the prediction of 5-year risk of ESRD (AUC = 0.75 vs AUC = 0.70). Functional enrichment analysis revealed Rho GTPases and regulation of the actin cytoskeleton pathways to be statistically significant, inferring their role in kidney function and the pathogenesis of renal disease. CONCLUSIONS: Proteins SPTA1, MYL6 and C6, when used alongside the 4-variable UK-KFRE achieve an improved performance when predicting a 5-year risk of ESRD. Specific pathways implicated in the pathogenesis of podocyte dysfunction were also identified, which could serve as potential therapeutic targets. The findings of our study carry implications for comprehending the involvement of the Rho family GTPases in the pathophysiology of kidney disease, advancing our understanding of the proteomic factors influencing susceptibility to renal damage.

Role of ferroptosis in chronic kidney disease.

Chronic kidney disease (CKD) has historically been a significant global health concern, profoundly impacting both life and well-being. In the process of CKD, with the gradual loss of renal function, the incidence of various life-threatening complications, such as cardiovascular diseases, cerebrovascular accident, infection and stroke, is also increasing rapidly. Unfortunately, existing treatments exhibit limited ability to halt the progression of kidney injury in CKD, emphasizing the urgent need to delve into the precise molecular mechanisms governing the occurrence and development of CKD while identifying novel therapeutic targets. Renal fibrosis, a typical pathological feature of CKD, plays a pivotal role in disrupting normal renal structures and the loss of renal function. Ferroptosis is a recently discovered iron-dependent form of cell death characterized by lipid peroxide accumulation. Ferroptosis has emerged as a potential key player in various diseases and the initiation of organ fibrosis. Substantial evidence suggests that ferroptosis may significantly contribute to the intricate interplay between CKD and its progression. This review comprehensively outlines the intricate relationship between CKD and ferroptosis in terms of iron metabolism and lipid peroxidation, and discusses the current landscape of pharmacological research on ferroptosis, shedding light on promising avenues for intervention. It further illustrates recent breakthroughs in ferroptosis-related regulatory mechanisms implicated in the progression of CKD, thereby providing new insights for CKD treatment. Video Abstract.

Integrin-linked kinase mRNA expression in circulating mononuclear cells as a biomarker of kidney and vascular damage in experimental chronic kidney disease.

BACKGROUND: Traditional biomarkers of chronic kidney disease (CKD) detect the disease in its late stages and hardly predict associated vascular damage. Integrin-linked kinase (ILK) is a scaffolding protein and a serine/threonine protein kinase that plays multiple roles in several pathophysiological processes during renal damage. However, the involvement of ILK as a biomarker of CKD and its associated vascular problems remains to be fully elucidated. METHODS: CKD was induced by an adenine-rich diet for 6 weeks in mice. We used an inducible ILK knockdown mice (cKD-ILK) model to decrease ILK expression. ILK content in mice's peripheral blood mononuclear cells (PBMCs) was determined and correlated with renal function parameters and with the expression of ILK and fibrosis and inflammation markers in renal and aortic tissues. Also, the expression of five miRNAs that target ILK was analyzed in whole blood of mice. RESULTS: The adenine diet increased ILK expression in PBMCs, renal cortex, and aortas, and creatinine and urea nitrogen concentrations in the plasma of WT mice, while these increases were not observed in cKD-ILK mice. Furthermore, ILK content in PBMCs directly correlated with renal function parameters and with the expression of renal and vascular ILK and fibrosis and inflammation markers. Finally, the expression of the five miRNAs increased in the whole blood of adenine-fed mice, although only four correlated with plasma urea nitrogen, and of those, three were downregulated in cKD-ILK mice. CONCLUSIONS: ILK, in circulating mononuclear cells, could be a potential biomarker of CKD and CKD-associated renal and vascular damage.

Metabolic dysfunction-associated steatotic liver disease (SLD) and alcohol-associated liver disease, but not SLD without metabolic dysfunction, are independently associated with new onset of chronic kidney disease during a 10-year follow-up period.

AIMS: 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.

Is mild dehydration a risk for progression of childhood chronic kidney disease?

Children with chronic kidney disease (CKD) can have an inherent vulnerability to dehydration. Younger children are unable to freely access water, and CKD aetiology and stage can associate with reduced kidney concentrating capacity, which can also impact risk. This article aims to review the risk factors and consequences of mild dehydration and underhydration in CKD, with a particular focus on evidence for risk of CKD progression. We discuss that assessment of dehydration in the CKD population is more challenging than in the healthy population, thus complicating the definition of adequate hydration and clinical research in this field. We review pathophysiologic studies that suggest mild dehydration and underhydration may cause hyperfiltration injury and impact renal function, with arginine vasopressin as a key mediator. Randomised controlled trials in adults have not shown an impact of improved hydration in CKD outcomes, but more vulnerable populations with baseline low fluid intake or poor kidney concentrating capacity need to be studied. There is little published data on the frequency of dehydration, and risk of complications, acute or chronic, in children with CKD. Despite conflicting evidence and the need for more research, we propose that paediatric CKD management should routinely include an assessment of individual dehydration risk along with a treatment plan, and we provide a framework that could be used in outpatient settings.

Associations of dietary inflammatory index with low estimated glomerular filtration rate, albuminuria and chronic kidney disease in U.S adults: Results from the NHANES 2011-2018.

BACKGROUND AND AIMS: Chronic Kidney Disease (CKD) is characterized by a high inflammation status with ever-increasing prevalence, and defined as low estimated glomerular filtration rate (eGFR) or albuminuria. Both low eGFR and albuminuria can have independent effects on the body. The dietary inflammatory index (DII) is a validated tool used to assess the inflammatory potential of the diet. We aim to explore not only the association between DII and CKD, but also the associations of DII with low eGFR and albuminuria, respectively. In addition, their associations in different subgroups remain to be explored. METHODS AND RESULTS: 18,070 participants from the 2011-2018 NHANES with complete data of dietary intake and laboratory data were involved in our study. The data of 24-hour dietary recall interview was used to calculate DII, CKD could be reflected by laboratory data of creatinine and albumin. Then weighted multivariate logistic regression models and subgroup analyses were performed. The prevalence of low eGFR, albuminuria and CKD were 6.8%, 9.8% and 14.5%, respectively. A positive association between DII and low eGFR was observed (OR=1.12, 95%CI: 1.05-1.21), Q2, Q3 and Q4 are positively associated with a significant 39%, 65% and 71% increased risk of low eGFR compared with Q1 (P for trend<0.05). DII was also associated with CKD (OR=1.06, 95%CI: 1.01-1.11). CONCLUSION: Significant positive associations of DII with CKD and low eGFR were observed. But we didn't find such association between DII and albuminuria.

Association of serum uric acid with all-cause and cardiovascular mortality in chronic kidney disease stages 3-5.

BACKGROUND AND AIMS: The role of serum uric acid (SUA) in the prognosis of chronic kidney disease (CKD) is inconclusive. To explore the association of SUA level with all-cause and cardiovascular disease (CVD) mortality in patients with CKD. METHODS AND RESULTS: Leveraging data from the National Health and Nutritional Examination Survey (NHANES) and linked national death records up to December 31 2019, we explored the association of SUA with all-cause and CVD mortality using weighted cox proportional hazards regression models and restricted cubic spline (RCS) models in patients with CKD stages 3-5. The study finally included 2644 patients with CKD stages 3-5, with a median SUA level of 6.5 mg/dL. After a median follow-up of 55 months, a total of 763 deaths were recorded, with 279 of them attributed to CVD. In the fully adjusted model, per 1 mg/dL increment in SUA concentration was found to be associated with increased HRs (95% CIs) of 1.07 (1.00, 1.14) for all-cause mortality and 1.11 (1.00, 1.24) for CVD mortality. Compared to Q2 (reference), those in Q4 had adjusted HRs of 1.72 (1.36, 2.17) for all-cause mortality and 2.17 (1.38, 3.41) for CVD mortality, while those in Q1 had adjusted HRs of 1.49 (1.19, 1.85) for all-cause mortality and 1.93 (1.26, 2.98) for CVD mortality. CONCLUSIONS: Both higher and lower SUA levels were associated with increased risks of all-cause and CVD mortality in patients with CKD stages 3-5.

Multicenter randomized controlled trial of intensive uric acid lowering therapy for CKD patients with hyperuricemia: TARGET-UA.

BACKGROUND: We investigate whether Intensive uric acid (UA)-lowering therapy (ULT) provides increased renal protection compared with standard therapy in chronic kidney disease (CKD) patients. METHODS: This was a multicenter randomized controlled trial. Only CKD patients with hyperuricemia were included in this study. The participants were randomly assigned to either the Intensive therapy group (target serum UA level ≥ 4.0 mg/dL and < 5.0 mg/dL) or the standard therapy group (serum UA level ≥ 6.0 mg/dL and < 7.0 mg/dL). ULT was performed using topiroxostat, a non-purine-type selective xanthine oxidase inhibitor. The primary endpoint was change in the logarithmic value of urine albumin to the creatinine ratio (ACR) between baseline and week 52 of the treatment. RESULTS: Three hundred fifty-two patients were included in the full analysis set. In the Standard therapy group, mean serum UA was 8.23 mg/dL at baseline and 6.13 mg/dL at 52 weeks. In the Intensive therapy group, mean serum UA was 8.15 mg/dL at baseline and 5.25 mg/dL at 52 weeks. There was no significant difference in changes in log ACR at 52 weeks between the Intensive therapy and the Standard therapy groups. CONCLUSION: This study did not reveal the benefit of Intensive ULT to improve albuminuria levels. (UMIN000026741 and jRCTs051180146).

Effect of ferric citrate hydrate on fibroblast growth factor 23 and platelets in non-dialysis-dependent chronic kidney disease and non-chronic kidney disease patients with iron deficiency anemia.

BACKGROUND: Iron deficiency anemia (IDA) increases levels of C-terminal fibroblast growth factor 23 (cFGF23) and platelet count (PLT), each of which is associated with cardiovascular events. Therefore, we hypothesized that iron replacement with ferric citrate hydrate (FC) would decrease cFGF23 levels and PLT in patients with IDA. METHODS: In a randomized, open-label, multicenter, 24-week clinical trial, patients with non-dialysis-dependent chronic kidney disease (CKD) and non-CKD complicated by IDA (8.0 ≤ hemoglobin < 11.0 g/dL; and serum ferritin < 50 ng/mL [CKD]; < 12 ng/mL [non-CKD]) were randomized 1:1 to FC-low (500 mg: approximately 120 mg elemental iron/day) or FC-high (1000 mg: approximately 240 mg elemental iron/day). If sufficient iron replacement had been achieved after week 8, further treatment was discontinued. RESULTS: Seventy-three patients were allocated to FC-low (CKD n = 21, non-CKD n = 15) and FC-high (CKD n = 21, non-CKD n = 16). Regardless of CKD status, FC increased serum ferritin and transferrin saturation, did not change intact FGF23 or serum phosphorus, but decreased cFGF23. In FC-low group, median changes in cFGF23 from baseline to week 8 were -58.00 RU/mL in CKD and -725.00 RU/mL in non-CKD; in FC-high group, the median changes were -66.00 RU/mL in CKD and -649.50 RU/mL in non-CKD. By week 8, FC treatment normalized PLT in all patients with high PLT at baseline (>35.2 × 104/µL; FC-low: 1 CKD, 8 non-CKD; FC-high: 3 CKD, 8 non-CKD). CONCLUSION: Regardless of CKD status, iron replacement with FC decreased elevated cFGF23 levels and normalized elevated PLT in patients with IDA. CLINICAL TRIAL REGISTRATION NUMBER: jRCT2080223943.

Use of kidney failure risk equation as a tool to evaluate referrals from primary care to specialist nephrology care.

BACKGROUND: With rising costs and burden of chronic kidney disease (CKD), timely referral of patients to a kidney specialist is crucial. Currently, Kidney Health Australia (KHA) uses a 'heat map' based on severity and not future risk of kidney failure, whereas the kidney failure risk equation (KFRE) score predicts future risk of progression. AIMS: Evaluate whether a KFRE score assists with timing of CKD referrals. METHODS: Retrospective cohort of 2137 adult patients, referred to tertiary hospital outpatient nephrologist between 2012 and 2020, were analysed. Referrals were analysed for concordance with the KHA referral guidelines and, with the KFRE score, a recommended practice. RESULTS: Of 2137 patients, 626 (29%) did not have urine albumin-to-creatinine ratio (UACR) measurement at referral. For those who had a UACR, the number who met KFRE preferred referral criteria was 36% less than KHA criteria. If the recommended KFRE score was used, then fewer older patients (≥40 years) needed referral. Positively, many diabetes patients were referred, even if their risk of kidney failure was low, and 29% had a KFRE over 3%. For patients evaluated meeting KFRE criteria, a larger proportion (76%) remained in follow-up, with only 8% being discharged. CONCLUSIONS: KFRE could reduce referrals and be a useful tool to assist timely referrals. Using KFRE for triage may allow those patients with very low risk of future kidney failure not be referred, remaining longer in primary care, saving health resources and reducing patients' stress and wait times. Using KFRE encourages albuminuria measurement.

Gender, age and nationality differences in chronic kidney disease prevalence in the emirate of Abu Dhabi, UAE.

AIM: We aimed to better understand the prevalence of chronic kidney disease in Abu Dhabi, UAE, where a very diverse ethnic population lives, each with their own risk profile. METHODS: Data were analysed on all patients who were tested for serum creatinine in December 2019 for 4 years within our healthcare network. We analysed data for kidney disease by age, gender and nationality to study differences in prevalence and risk. RESULTS: The entire cohort (EC) consisted 1 925 672 samples from 703 122 patients. 24% of patients had GFR < 90 mL/min/1.73 m2 (CKD2-5), 4% had more severe kidney dysfunction (CKD3-5) and 2% had UACR >3 mg/mmol and with GFR > 90 (CKD1). The long follow-up (LFU) group comprised 45.6% of patients who had eGFR on at least two occasions more than 90 days apart, and of these 19.5% had sustained eGFR <90, and 5.2% had CKD3-5. Males had lower eGFR than females in the EC (RR 1.68) and the LFU group (RR 1.76). Emirati Females had the lowest prevalence in the EC (2.9%) and expatriate females in the LFU (3.5%) groups. The relative risks of CKD in expatriate males were highest in the EC (2.14) and the LFU (2.39) groups. When we looked at the age distribution by nationality there were highly significant differences in some populations being highly represented at younger ages. CONCLUSION: The prevalence of kidney disease in Abu Dhabi has a male predominance, with younger expatriates highly represented. A targeted strategy to identify those at high risk may identify early CKD to prevent progression to end-stage kidney disease.

How renal toxins respond to renal function deterioration and oral toxic adsorbent in pH-controlled releasing capsule.

The number of patients with chronic kidney disease (CKD) is increasing. Oral toxin adsorbents may provide some value. Several uremic toxins, including indoxyl sulfate (IS), p-cresol (PCS), acrolein, per- and poly-fluoroalkyl substances (PFAS), and inflammation markers (interleukin 6 [IL-6] and tumor necrosis factor [TNF]-alpha) have been shown to be related to CKD progression. A total of 81 patients taking oral activated charcoal toxin adsorbents (AC-134), which were embedded in capsules that dissolved in the terminal ileum, three times a day for 1 month, were recruited. The renal function, hemoglobulin (Hb), inflammation markers, three PFAS (PFOA, PFOS, and PFNA), and acrolein were quantified. Compared with the baseline, an improved glomerular filtration rate (GFR) and significantly lower acrolein were noted. Furthermore, the CKD stage 4 and 5 group had significantly higher concentrations of IS, PCS, IL-6, and TNF but lower levels of Hb and PFAS compared with the CKD Stage 3 group at baseline and after the intervention. Hb was increased only in the CKD Stage 3 group after the trial (p = .032). Acrolein did not differ between the different CKD stage groups. Patients with improved GFR (responders) (about 77%) and nonresponders had similar baseline GFR. Responders had higher acrolein and PFOA levels throughout the study and a more significant reduction in acrolein, indicating a better digestion function. Both the higher PFOA and lower acrolein may be related to improved eGFR (and possibly to improvements in proteinuria, which we did not measure. Proteinuria is associated with PFAS loss in the urine), AC-134 showed the potential to improve the GFR and decrease acrolein, which might better indicate renal function change. Future studies are needed with longer follow-ups.

An extra honey polyphenols-rich diet ameliorates the high-fat diet induced chronic kidney disease via modulating gut microbiota in C57BL/6 mice.

Honey is not equivalent to sugar and possess a worldwide health promoting effects such as antioxidant, antibacterial, anti-inflammatory, and hepatoprotective activities. Nevertheless, the potential impacts of honey on high-fat diet induced chronic kidney disease (CKD) and gut microbiota remain to be explored. Herein a high-fat diet was used to induce a mouse CKD model, and analysis was conducted on liver, kidney, spleen indices, tissue morphology, biochemical parameters, CKD related genes, and gut microbial diversity. The results indicated that significant inhibitory effects on renal damage caused by a high-fat diet in mice and improvement in disease symptoms were observed upon honey treatment. Significant changes were also found in serum TC, TG, UA, and BUN as well as the inflammation-related protein TNF-α and IL-6 levels in renal tissues. Gene expression analysis revealed that honey intake closely relates to gut microbiota diversity, which can regulate the composition of gut microbiota, increase microbial diversity, especially Bifidobacteriales and S24_7 and promote the synthesis of short chain fatty acids (SCFAs). In summary, this study suggests that honey has both preventive and therapeutic effects on CKD, which may be associated with its ability to improve microbial composition, increase microbial diversity, and regulate SCFAs levels.

Current status and development trends in CKD with frailty research from 2000 to 2021: a bibliometric analysis.

INTRODUCTION: The prevalence of chronic kidney disease (CKD) is gradually increasing in the elderly population. At the same time, frailty has become one of the research hotspots in the field of geriatrics. Bibliometric analyses help to understand the direction of a field. Therefore, this study aimed to analyze the status and emerging trends of frailty in CKD patients. DATA AND METHODS: The Web of Science Core Collection (WoSCC) database was screened for relevant literature published between 1 January 2000 and 31 December 2021. Next, publications were analyzed for information including authors, journals, cited references, citing journals, institutions, countries and regions, high-frequency keywords and co-citations using VOSviewer, Microsoft Excel, and R software. RESULTS: A total of 2223 articles were obtained, from which 613 relevant articles were selected based on title and abstract screening. There was an upward trend in the number of annual publications and Johansen KL was considered the most contributing author in the field. The Clinical Journal of the American Society of Nephrology was the most productive research journal. Johns Hopkins University is the most published organization. The United States is the global leader in the field and contributes the most to research. Research hotspots focus on epidemiological studies of frailty and frailty intervention. CONCLUSIONS: This study presents a comprehensive bibliometric analysis of CKD and frailty research. Key findings highlight the current focus on early screening and assessment of frailty in CKD patients, as well as physical function interventions in frail patients.

Noninvasive diagnosis of interstitial fibrosis in chronic kidney disease: a systematic review and meta-analysis.

RATIONALE AND OBJECTIVES: Researchers have delved into noninvasive diagnostic methods of renal fibrosis (RF) in chronic kidney disease, including ultrasound (US), magnetic resonance imaging (MRI), and radiomics. However, the value of these diagnostic methods in the noninvasive diagnosis of RF remains contentious. Consequently, the present study aimed to systematically delineate the accuracy of the noninvasive diagnosis of RF. MATERIALS AND METHODS: A systematic search covering PubMed, Embase, Cochrane Library, and Web of Science databases for all data available up to 28 July 2023 was conducted for eligible studies. RESULTS: We included 21 studies covering 4885 participants. Among them, nine studies utilized US as a noninvasive diagnostic method, eight studies used MRI, and four articles employed radiomics. The sensitivity and specificity of US for detecting RF were 0.81 (95% CI: 0.76-0.86) and 0.79 (95% CI: 0.72-0.84). The sensitivity and specificity of MRI were 0.77 (95% CI: 0.70-0.83) and 0.92 (95% CI: 0.85-0.96). The sensitivity and specificity of radiomics were 0.69 (95% CI: 0.59-0.77) and 0.78 (95% CI: 0.68-0.85). CONCLUSIONS: The current early noninvasive diagnostic methods for RF include US, MRI, and radiomics. However, this study demonstrates that US has a higher sensitivity for the detection of RF compared to MRI. Compared to US, radiomics studies based on US did not show superior advantages. Therefore, challenges still exist in the current radiomics approaches for diagnosing RF, and further exploration of optimized artificial intelligence (AI) algorithms and technologies is needed.

Risk factors for cardio-cerebrovascular events among patients undergoing continuous ambulatory peritoneal dialysis and their association with serum magnesium.

Serum magnesium levels exceeding 0.9 mmol/L are associated with increased survival rates in patients with CKD. This retrospective study aimed to identify risk factors for cardio-cerebrovascular events among patients receiving continuous ambulatory peritoneal dialysis (CAPD) and to examine their correlations with serum magnesium levels. Sociodemographic data, clinical physiological and biochemical indexes, and cardio-cerebrovascular event data were collected from 189 patients undergoing CAPD. Risk factors associated with cardio-cerebrovascular events were identified by univariate binary logistic regression analysis. Correlations between the risk factors and serum magnesium levels were determined by correlation analysis. Univariate regression analysis identified age, C-reactive protein (CRP), red cell volume distribution width standard deviation, red cell volume distribution width corpuscular volume, serum albumin, serum potassium, serum sodium, serum chlorine, serum magnesium, and serum uric acid as risk factors for cardio-cerebrovascular events. Among them, serum magnesium ≤0.8 mmol/L had the highest odds ratio (3.996). Multivariate regression analysis revealed that serum magnesium was an independent risk factor, while serum UA (<440 µmol/L) was an independent protective factor for cardio-cerebrovascular events. The incidence of cardio-cerebrovascular events differed significantly among patients with different grades of serum magnesium (χ2 = 12.023, p = 0.002), with the highest incidence observed in patients with a serum magnesium concentration <0.8 mmol/L. High serum magnesium levels were correlated with high levels of serum albumin (r = 0.399, p < 0.001), serum potassium (r = 0.423, p < 0.001), and serum uric acid (r = 0.411, p < 0.001), and low levels of CRP (r = -0.279, p < 0.001). In conclusion, low serum magnesium may predict cardio-cerebrovascular events in patients receiving CAPD.

Nonlinear association between proteinuria levels and the risk of cardiovascular disease events and all-cause mortality among chronic kidney disease patients.

BACKGROUND: The association between proteinuria levels and cardiovascular disease (CVD) development and all-cause mortality in chronic kidney disease (CKD) patients remains controversial. METHODS: In this investigation, we conducted a retrospective analysis involving 1138 patients who were registered in the CKD-Research of Outcomes in Treatment and Epidemiology (ROUTE) study. The primary outcome of this study was the composite of cardiovascular events or all-cause death. Cox proportional hazards regression, smooth curve fitting, piecewise linear regression, and subgroup analyses were used. RESULTS: The mean age of the included individuals was 67.3 ± 13.6 years old. Adjusted hazard ratios (HRs) for UPCR in middle and high groups, compared to the low group, were 1.93 (95% CI: 1.28-2.91) and 4.12 (95% CI: 2.87-5.92), respectively, after multivariable adjustment. Further adjustments maintained significant associations; HRs for middle and high groups were 1.71 (95% CI: 1.12-2.61) and 3.07 (95% CI: 2.08-4.54). A nonlinear UPCR-primary outcome relationship was observed, with an inflection point at 3.93 g/gCr. CONCLUSION: Among non-dialyzed patients with stage G2-G5 CKD, a nonlinear association between UPCR and the primary outcome was observed. A higher UPCR (when UPCR < 3.93 g/gCr) was an independent predictor of the primary outcome. Importantly, our study predates SGLT2 inhibitor use, showcasing outcomes achievable without these medications. Future research considerations will involve factors like SGLT-2 inhibitor utilization.

Heat-treated and/or lysozyme-treated Enterococcus faecalis (FK-23) improves the progression of renal disease in a unilateral ischemia-reperfusion injury rat model.

The prevalence of chronic kidney disease (CKD) is increasing owing to the elderly population. Here, we investigated the effects of heat-treated Enterococcus faecalis (FK-23) and lysozyme-treated FK-23 (LFK) on the progression of CKD in rats. A CKD model was established using male Wistar rats by subjecting them to right nephrectomy (1K), followed by ischemia and reperfusion (IR). FK-23 or LFK was fed ad libitum as a mixed diet after right nephrectomy. Animals subjected to renal ischemia-reperfusion injury (IRI) showed increased plasma creatinine and blood urea nitrogen levels. Furthermore, in the kidneys, collagen accumulation and α-smooth muscle actin, indicative of fibroblast activation and fibrosis-related gene and protein expression, increased 3 weeks after IRI. FK-23 and LFK suppressed the increase in the mRNA levels of some of these genes. The increase in oxidative stress markers, 4-hydroxy-2-nonenal, endothelial nitric oxide synthase, and nitrotyrosine in the kidney, as well as increased plasma uremic toxins after IRI, were also ameliorated by FK-23 and LFK. Metagenomic analysis of fecal samples revealed that gut microbial alteration caused by IRI was also ameliorated by LFK treatment. These results suggest that Enterococcus faecalis ingredients may improve CKD progression by suppressing oxidative stress and correcting the balance of the intestinal microflora.