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Chronic kidney disease (CKD) is a multifactorial condition with diverse etiologies, such as diabetes mellitus, hypertension, and genetic disorders, often culminating in end-stage renal disease (ESRD). A hallmark of CKD progression is kidney fibrosis, characterized by the excessive accumulation of extracellular matrix components, for which there is currently no effective anti-fibrotic therapy. Recent literature highlights the critical role of sphingosine 1-phosphate (S1P) signaling in CKD pathogenesis and renal fibrosis. This review provides an in-depth analysis of the latest findings on S1P metabolism and signaling in renal fibrosis and in specific CKDs, including diabetic nephropathy (DN), lupus nephritis (LN), focal segmental glomerulosclerosis (FSGS), Fabry disease (FD), and IgA nephropathy (IgAN). Emerging studies underscore the therapeutic potential of modulating S1P signaling with receptor modulators and inhibitors, such as fingolimod (FTY720) and more selective agents like ozanimod and cenerimod. Additionally, the current knowledge about the effects of established kidney protective therapies such as glucocorticoids and SGLT2 and ACE inhibitors on S1P signaling will be summarized. Furthermore, the review highlights the potential role of S1P as a biomarker for disease progression in CKD models, particularly in Fabry disease and diabetic nephropathy. Advanced technologies, including spatial transcriptomics, are further refining our understanding of S1P's role within specific kidney compartments. Collectively, these insights emphasize the need for continued research into S1P signaling pathways as promising targets for CKD treatment strategies., (© 2024. The Author(s).)

Chronic kidney disease (CKD) represents a significant global health challenge, characterized by kidney damage and decreased function. Its prevalence has steadily increased, necessitating a comprehensive understanding of its epidemiology, risk factors, and management strategies. While traditional prognostic markers such as estimated glomerular filtration rate (eGFR) and albuminuria provide valuable insights, they may not fully capture the complexity of CKD progression and associated cardiovascular (CV) risks.This paper reviews the current state of renal and CV risk prediction in CKD, highlighting the limitations of traditional models and the potential for integrating artificial intelligence (AI) techniques. AI, particularly machine learning (ML) and deep learning (DL), offers a promising avenue for enhancing risk prediction by analyzing vast and diverse patient data, including genetic markers, biomarkers, and imaging. By identifying intricate patterns and relationships within datasets, AI algorithms can generate more comprehensive risk profiles, enabling personalized and nuanced risk assessments.Despite its potential, the integration of AI into clinical practice faces challenges such as the opacity of some algorithms and concerns regarding data quality, privacy, and bias. Efforts towards explainable AI (XAI) and rigorous data governance are essential to ensure transparency, interpretability, and trustworthiness in AI-driven predictions., (© 2024. The Author(s).)

A critical degree of podocyte depletion causes glomerulosclerosis, and persistent podocyte loss in glomerular diseases drives the progression to end-stage kidney disease. The extent of podocyte injury at a point in time can be histologically assessed by measuring podocyte number, size, and density ("Biopsy podometrics"). However, repeated invasive renal biopsies are associated with increased risk and cost. A noninvasive method for assessing podocyte injury and depletion is required. Albuminuria and proteinuria do not always correlate with disease activity. Podocytes are located on the urinary space side of the glomerular basement membrane, and as they undergo stress or detach, their products can be identified in urine. This raises the possibility that urinary podocyte products can serve as clinically useful markers for monitoring glomerular disease activity and progression ("Urinary podometrics"). We previously reported that urinary sediment podocyte mRNA reflects disease activity in both animal models and human glomerular diseases. This includes diabetes and hypertension which together account for 60% of new-onset dialysis induction patients. Improving approaches to preventing progression is an urgent priority for the renal community. Sufficient evidence now exists to indicate that monitoring urinary podocyte markers could serve as a useful adjunctive strategy for determining the level of current disease activity and response to therapy in progressive glomerular diseases., (© 2024. The Author(s).)

Background Children living with HIV frequently show high plasma levels of fibroblast growth factor-2 (FGF-2/bFGF). FGF-2 accelerates the progression of several experimental kidney diseases; however, the role of circulating FGF-2 in childhood HIV-chronic kidney diseases (HIV-CKDs) is unknown. We carried out this study to determine whether high plasma FGF-2 levels were associated with the development of HIV-CKDs in children. Methods The plasma and urine FGF-2 levels were measured in 84 children (< 12 years of age) living with HIV during the pre-modern antiretroviral era, and followed for at least 3 years to determine the prevalence of proteinuria and HIV-CKDs. We also assessed the distribution of the kidney FGF-2 binding sites by autoradiography and Alcian blue staining, and explored potential mechanisms by which circulating FGF-2 may precipitate HIV-CKDs in cultured kidney epithelial and mononuclear cells derived from children with HIV-CKDs. Results High plasma FGF-2 levels were associated with a high viral load. Thirteen children (~ 15%) developed HIV-CKDs and showed a large reservoir of FGF-2 low-affinity binding sites in the kidney, which can facilitate the recruitment of circulating FGF-2. Children with high plasma and urine FGF-2 levels had 73-fold increased odds (95% CI 9-791) of having HIV-CKDs relative to those with normal FGF-2 values. FGF-2 induced the proliferation and decreased the expression of APOL-1 mRNA in podocytes, and increased the attachment and survival of infected mononuclear cells cultured from children with HIV-CKDs. Conclusions High plasma FGF-2 levels appear to be an additional risk factor for developing progressive childhood HIV-CKDs. Graphical abstract, Author(s): Patricio E. Ray [sup.1] , Jinliang Li [sup.2] [sup.3] , Jharna R. Das [sup.2] [sup.3] , Jing Yu [sup.1] Author Affiliations: (1) grid.27755.32, 0000 0000 9136 933X, Child Health [...]

Background: Magnesium deficiency is common in patients with chronic kidney diseases (CKD) due to restricted magnesium intake and impaired magnesium reabsorption. Based on pathophysiological risk factors influencing kidney magnesium reabsorption, a magnesium depletion score (MDS) was developed. Using MDS as a novel indicator for assessing body magnesium status, we hypothesized that it was associated with clinical prognosis., Methods: We conducted a prospective population-based cohort study using data from the National Health and Nutrition Examination Survey 1999-2014 to explore the impact of MDS on the clinical outcomes of CKD patients. Propensity score-matched analyses were conducted to increase comparability. The primary outcome was all-cause mortality, and the secondary outcomes were cardiovascular-cause and cancer-cause mortality., Results: After propensity score matching, 3294 CKD patients were divided into 2 groups: MDS ≤ 2 (N = 1647), and MDS > 2 (N = 1647). During a median follow-up of 75 months, Kaplan-Meier analyses showed that MDS > 2 was associated with worse 5- and 10-year overall survival (78.5% vs 73.4%; 53.1% vs 43.1%, P < 0.001). After adjusting for confounding variables, MDS was found to be an independent risk factor for all-cause mortality (HR:1.34, 95% CI 1.20-1.50, P < 0.001). MDS > 2 was also associated with higher cardiovascular-cause mortality (16.2% VS 11.6%, P = 0.005). Multivariate competing risk analysis revealed that MDS > 2 was an independent risk factor (HR: 1.33, 95% CI 1.06-1.66, P = 0.012). Subgroup analyses reported that MDS > 2 increased all-cause mortality and cardiovascular-cause mortality only in patients with inadequate magnesium intake (P < 0.001, P < 0.001) but not in those with adequate intake (P = 0.068, P = 0.920)., Conclusions: A magnesium depletion score > 2 was independently associated with higher long-term cardiovascular-cause and all-cause mortality in CKD patients., (© 2022. The Author(s) under exclusive licence to Italian Society of Nephrology.)

Background: Cardiovascular disease (CVD) is the most common cause of death in patients with renal diseases. Cardiac arrhythmia and sudden cardiac death are particularly important, and the burden is higher in patients on hemodialysis. The aim of this study is to compare specific ECG changes as markers of arrhythmias in patients with CKD and patients with end-stage renal disease (ESRD); all without clinically manifest heart disease, with normal control subjects., Results: Seventy-five ESRD patients on regular hemodialysis, 75 patients with stage 3-5 CKD and 40 healthy control subjects were included. All candidates were subjected to thorough clinical evaluation and laboratory tests including serum creatinine, glomerular filtration rate calculation, serum potassium, magnesium, calcium, phosphorus, iron, parathyroid hormone, and total iron binding capacity (TIBC). Resting twelve-lead ECG was done to calculate P wave dispersion (P-WD), corrected QT interval, QTc dispersion, Tpeak-Tend interval (Tp-e), and Tp-e/QT. Patients with ESRD had a significantly higher QTc dispersion (p < 0.001) and P-WD (p = 0.001) when compared to the other 2 groups. In the ESRD group, males had a significantly higher P-WD (p = 0.045), insignificantly higher QTc dispersion (p = 0.445), and insignificantly lower Tp-e/QT ratio (p = 0.252) as compared to females. Multivariate linear regression analysis for ESRD patients showed that serum creatinine (β = 0.279, p = 0.012) and transferrin saturation (β =  - 0.333, p = 0.003) were independent predictors of increased QTc dispersion while ejection fraction (β = 0.320, p = 0.002), hypertension (β =  - 0.319, p = 0.002), hemoglobin level (β =  - 0.345, p = 0.001), male gender (β =  - 0.274, p = 0.009) and TIBC (β =  - 0.220, p = 0.030) were independent predictors of increased P wave dispersion. In the CKD group, TIBC (β =  - 0.285, p = 0.013) was an independent predictor of QTc dispersion while serum calcium (β = 0.320, p = 0.002) and male gender (β =  - 0.274, p = 0.009) were independent predictors of Tp-e/QT ratio., Conclusions: Patients with stage 3-5 CKD and those with ESRD on regular hemodialysis exhibit significant ECG changes that are considered substrates for ventricular as well as supraventricular arrhythmias. Those changes were more evident in patients on hemodialysis., (© 2023. The Author(s).)

p53 is a major regulator of cell cycle arrest, apoptosis, and senescence. While involvement of p53 in tumorigenesis is well established, recent studies implicate p53 in the initiation and progression of several renal diseases, which is the focus of this review. Ischemic-, aristolochic acid (AA) -, diabetic-, HIV-associated-, obstructive- and podocyte-induced nephropathies are accompanied by activation and/or elevated expression of p53. Studies utilizing chemical or renal-specific inhibition of p53 in mice confirm the pathogenic role of this transcription factor in acute kidney injury and chronic kidney disease. TGF-β1, NOX, ATM/ATR kinases, Cyclin G, HIPK, MDM2 and certain micro-RNAs are important determinants of renal p53 function in response to trauma. AA, cisplatin or TGF-β1-mediated ROS generation via NOXs promotes p53 phosphorylation and subsequent tubular dysfunction. p53-SMAD3 transcriptional cooperation downstream of TGF-β1 orchestrates induction of fibrotic factors, extracellular matrix accumulation and pathogenic renal cell communication. TGF-β1-induced micro-RNAs (such as mir-192) could facilitate p53 activation, leading to renal hypertrophy and matrix expansion in response to diabetic insults while AA-mediated mir-192 induction regulates p53 dependent epithelial G 2 /M arrest. The widespread involvement of p53 in tubular maladaptive repair, interstitial fibrosis, and podocyte injury indicate that p53 clinical targeting may hold promise as a novel therapeutic strategy for halting progression of certain acute and chronic renal diseases, which affect hundreds of million people worldwide., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Prolonged consumption of foods containing toxic metals can elevate the risk of noncommunicable diseases, including chronic kidney disease of uncertain etiology (CKDu). Despite the increasing number of CKDu cases in Maradankulama and Mahakanadrawa Grama Niladhari Divisions (GN) in Sri Lanka, no prior studies have examined the accumulation of heavy metal(loid)s and their potential association with CKDu prevalence. Furthermore, there is an absence of comprehensive analyses using chemometric techniques such as PCA and hierarchical studies regarding CKDu and heavy metal contamination in Sri Lanka. This study aims to provide initial insights into the accumulation and potential pathways of toxic metals in staple foods within local diets and their subsequent presence in the agricultural environment of examined GNs. Cr, Cd, As, and Ni concentrations in analyzed foods were within permissible limits (MPLs), whereas Pb levels exceeded MPLs in rice (Oryza sativa), gotukola (Centella asiatica), lime (Citrus crenatifolia), and inland fish (Etroplus suratensis). High target hazard quotient (THQt) values in polished rice suggest possible health risks with prolonged intake. Hierarchical analysis suggested a common source of Pb accumulation. PCA and hierarchical clustering revealed the intricate connection between As and Cd, with their concurrent clustering in samples suggesting a potential common origin. This indicates that while individual concentrations comply with acceptable standards, the potential synergistic effects of Cd and As accumulation might pose elevated health risks. Further, the gut tissues of inland fish exhibited pronounced metal concentrations and significant (p < 0.05) positive correlations with toxic metals in the tank sediments suggesting a diet-based bioaccumulation pathway through sediments., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Dietary exposure of selected Hofmeister ions-fluoride, chloride, sulfate, phosphate, sodium, potassium, magnesium, and calcium from black tea consumption in chronic kidney disease of unknown etiology (CKDu) prevalent areas in Sri Lanka-were assessed in order to understand exposure and risk. Black tea samples (n = 25) were collected from CKDu prevalent areas and control areas (n = 15). Total fluoride content in alkali fused digested black tea samples was determined. The available Hofmeister ions in tea infusions prepared using deionized water and the groundwater collected by CKDu endemic areas were compared. Dietary exposure was calculated by chronic daily intake data. Total fluoride concentrations ranged from 80 to 269 mg/kg in tea collected from the CKDu endemic regions and 62.5-123.5 mg/kg in non-endemic regions. The fluoride content in infusions ranged from 1.45 to 2.04 mg/L in CKDu endemic areas and 1.11-1.38 mg/L in control samples. The infusions prepared with local groundwater from the CKDu endemic areas showed an elevated level of fluoride 95% than that of the infusion prepared using same tea with deionized water. Aggregated chronic daily intake value from tea and groundwater exceeds the estimated adequate daily intake value of fluoride. The hazard quotient (HQ) values of fluoride in 5 min and 120 min tea infusions were 1.60 and 2.20, respectively, and indicate an adverse health risk. Potassium content in tea infusions collected from CKDu endemic areas is higher than in the control. Even though these values are less than the adequate intake, it may pose an impairment on a weak kidney. Chronic daily intake of Hofmeister ions, i.e., fluoride and potassium from black tea consumed in CKDu endemic areas may induce a risk for CKDu., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Communicating risk is a key component of shared decision-making and is vital for the management of advanced chronic kidney disease (CKD). Despite this, there is little evidence to suggest how best to communicate health risk information to people living with CKD. The aim of this review was to identify and understand the nature of evidence-based risk communication strategies for people living with CKD., Methods: We searched MEDLINE, CINAHL and Scopus databases for articles which described or evaluated the use of risk communication strategies within the renal population. Similar risk communication strategies were collated and summarised narratively., Results: A total of 3700 sources were retrieved from the search, of which 19 were included in the review. Eleven studies reported primary research, and eight reported either narrative or systematic reviews. Seven main risk communication strategies were identified: framing, absolute versus relative risk, natural frequencies versus percentages, personalised risk estimates, qualitative risk communication, best-case/worst-case framework and use of graphs and graphics. There was a paucity of risk communication strategies specific to the CKD population., Conclusion: Evidence-based strategies to improve health risk communication for patients living with CKD are lacking. There is a need to establish the informational and communication preferences for patients living with CKD to better understand how to best communicate health risk information to individuals in this population., (© 2024. The Author(s).)

Inflammation is a vital and normal physiological response; however, excessive inflammation can contribute to the development of various diseases. Artemisia sieversiana, a traditional Chinese medicinal plant, contains a variety of chemical compounds. One such compound, 3-oxo-11αH-germacra-1(10)E,4Z-dien-12,6α-olide, a germacranolide sesquiterpenoid (germacranolide, GMO), has not been thoroughly investigated regarding its potential anti-inflammatory properties. In this study, the anti-inflammatory and antioxidant properties of GMO were investigated for the lipopolysaccharide (LPS)-induced inflammation in RAW264.7 cells. It was demonstrated that GMO effectively suppressed the production of inflammatory mediators, decreased the phosphorylation of nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) in RAW264.7 cells. Additionally, GMO exhibited the capacity to mitigate oxidative damage induced by LPS, as indicated by assessments of reactive oxygen species and mitochondrial membrane potential. In summary, GMO possesses significant anti-inflammatory effects by modulating the NF-κB/MAPK pathway and antioxidant effects by regulating ROS production., (© 2024. The Author(s) under exclusive licence to The Japanese Society of Pharmacognosy.)

Chronic kidney disease has emerged as a major health issue both in China and worldwide. Renal anemia frequently occurs in patients with chronic kidney disease, and its severity and incidence rate increase as the disease progresses. Over the last 30 years, the administration of exogenous EPO and EPO stimulants has been employed to alleviate renal anemia, suggesting that a relative deficiency in EPO may be a primary cause. However, this approach has overshadowed other contributing factors, particularly eryptosis, which results from the reduced lifespan of red blood cells. Numerous studies reveal that there are nephrogenic and extrarenal EPO secretion indicating that an absolute deficiency of EPO is not always present in patients. Therefore, this paper speculates that renal anemia may arise when EPO-driven erythropoiesis fails to adequately compensate for aggravating eryptosis. Other factors including iron metabolism disorder, uremic toxin accumulation, inflammatory state, oxidative stress, and secondary hyperparathyroidism affect EPO reactivity bone marrow hematopoiesis and eryptosis, leading to an imbalance between red blood cell production and destruction, and cause anemia ultimately. More further studies on the pathogenesis and treatment of renal anemia would be expected to provide evidence to support our opinion., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Chronic kidney disease is a significant cause of morbidity and mortality worldwide. In recent years, Galectin-3 has been put forward as a potential biomarker of chronic kidney disease progression. This review aims to assess the clinical utility of Galectin-3 in various pathological processes leading up to chronic kidney disease such as diabetes and lupus nephritis. We conducted a systematic search on PubMed from inception to September 2023, using the search term ("Galectin-3" OR "gal-3") AND ("renal" OR "kidney"). Galectin-3 has been shown to be both pro-fibrotic and protective against renal fibrosis through various mechanisms such as apoptotic body clearance and modulation of the Wnt pathway. Studies have found associations between raised Galectin-3, incidence and progression of chronic kidney disease. In lupus nephritis, Galectin-3 may serve as a biomarker for lupus nephritis activity. Although Galectin-3 inhibits cystogenesis, there is no correlation between total kidney volume and Galectin-3 in polycystic kidney disease. The role of Galectin-3 in staging and prognostication of renal cell carcinoma is yet to be determined. Galectin-3 has potential in predicting chronic kidney disease progression, in combination with other biomarkers. However, more trials are required given that present studies demonstrate conflicting results on the relationship between Galectin-3 and clinical outcomes in chronic kidney disease patients of varying aetiologies., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Research into the potential therapeutic benefits of herbal remedies for treating chronic kidney disease (CKD), a condition marked by renal fibrosis and persistent inflammation, has become popular. Eucommiae cortex (EC) is a vital herb for strengthening bones and muscles and tonifying the kidneys and liver. In the study, C57 BL/6 mice were given a diet containing 0.2% adenine to create a CKD model. The findings demonstrated that exogenous EC supplementation successfully decreased the levels of creatinine and urea nitrogen, down-regulated the TGF-β1/Smad signaling pathway's expression levels of TGF-β1, α-SMA, Smad3, and phospho-Smad3, and prevented renal fibrosis. Consequently, it was determined that EC might have a nephroprotective impact., (© 2024. The Author(s) under exclusive licence to The Japanese Society of Pharmacognosy.)

This study investigated arsenic (As) concentrations in diverse environmental components and their potential impact on the health risks faced by residents of the arsenic (As)-contaminated Nadia district in West Bengal, India. A random selection of 182 cattle and 255 goats from 40 livestock farmers in the district revealed that both animals and humans were naturally exposed to elevated arsenic levels through contaminated drinking water, foods, grasses, concentrate feeds, various fodder tree leaves, and other food/feed resources. The mean As concentration in roughages (483.18 µg/kg DM) was significantly higher (p < 0.001) than in tree leaves (391.53 µg/kg DM), and concentrate feed/ingredients (186.66 µg/kg DM). Pond water exhibited higher arsenic levels (106.11 µg/L) compared to shallow tube well water (47.96 µg/L) and deep tube well water/tap water (10.64 µg/L and 10.04 µg/L, respectively). The mean arsenic concentration in soils DM of fodder fields, crop fields, and grassland was 10.25, 10.58, and 10.20 mg/kg, respectively. It was observed that protein-rich feeds had lower levels of arsenic accumulation (p < 0.048), while fiber-rich feeds containing more cellulose, hemicellulose, and lignin had higher arsenic levels (p < 0.017). Goats consumed 73.46% more arsenic per kg body weight compared to dairy cows. Although chronic and sub-chronic arsenic exposure in the district did not typically manifest symptoms or visible signs in ruminant animals, concentrations in the hair and feces of both cattle and goats exceeded normal values. Cattle feces had significantly higher arsenic (410.43 µg/kg DM) levels (p < 0.001) than goat feces (227.00 µg/kg DM), and arsenic concentration in cattle hair (1917.74 µg/kg DM) was also significantly greater (p < 0.001) than goat hair (1435.74 µg/kg DM). Arsenic levels in milk samples from both species were below 10 µg/kg. Liver (356.02 µg/kg DM) and kidney (317.22 µg/kg DM) contained significantly higher (p < 0.001) levels of arsenic compared to muscle (204.23 µg/kg DM), and bone (161.98 µg/kg DM) in local meat-type adult male goats. The skin accumulated the highest amount of arsenic (576.24 µg/kg DM) among the non-edible parts of the goat carcass. The cumulative cancer risk value for adults was 4.96 × 10 -3 , exceeding the threshold value (1 × 10 -6 ). This suggests a significant risk of cancer development for the population in arsenic-affected areas. Non-cancer risks (hazard indexes) were estimated at 11.01 for adults. Our observations revealed that the highest bioaccumulation of arsenic occurred in the hair of cows, and goats in the examined localities. The biotransformation factor (BTF) for hair was much higher compared to other excreted samples from both species. The calculated BTF followed the order: hair > feces > milk for cows and goats. Livestock farmers in Nadia district are advised to carefully select feed resources, prioritizing those high in crude protein and low in neutral detergent fiber, and they should provide drinking water from deep aquifers to ensure the safety of milk and meat for human consumption., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Chronic kidney disease is a progressive disorder often leading to End-stage renal disease, necessitating hemodialysis treatment. Mild depression is prevalent among hemodialysis patients, adversely affecting their quality of life. This study aimed to evaluate the effect of a smartphone-based recreational therapy intervention on mild depression in hemodialysis patients., Methods: This randomized controlled trial was conducted at Montaserieh Hospital, Mashhad, Iran, involving 72 patients undergoing hemodialysis. Participants were randomly assigned to either the intervention group, receiving a custom-designed recreational therapy mobile app (including music, comedy, exercise, and educational content), or the control group, receiving standard care. The trial was registered with the Iranian Registry of Clinical Trials (IRCT20220803055608N1). Outcome assessors and statisticians were blinded to minimize bias. Sample size was calculated for an expected effect size of 0.90 with 80% power, resulting in 36 participants per group, adjusted for a 6% attrition rate. Depression levels were assessed using the Beck Depression Inventory-II (BDI-II) at baseline and after a 30-day intervention., Results: A total of 72 patients (36 per group) completed the analysis. The intervention group showed a significant decrease in depression scores compared to the control group (mean BDI-II score reduction: intervention group = 10.3 ± 4.1, control group = 4.6 ± 3.8; p < 0.001). Post-intervention, 86.1% of patients in the intervention group exhibited minimal depression (BDI-II score ≤ 13), compared to 61.1% in the control group (p = 0.005)., Conclusion: The smartphone-based recreational therapy intervention significantly reduced mild depression in hemodialysis patients. This approach can serve as a valuable complementary strategy to manage mild depression in this population. Further research is warranted to explore the long-term sustainability of these benefits and the intervention's impact on other patient-reported outcomes., Trial Registration: This study was registered in the Iranian Registry of Clinical Trials (no. IRCT20220803055608N1) on 28/08/2022., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Introduction: The commonly used clinical indicators are not sensitive and comprehensive enough to evaluate the early staging of chronic kidney disease (CKD). This study aimed to evaluate the differences in arterial spin labeling (ASL) and blood oxygenation level-dependent functional magnetic resonance imaging (BOLD-MRI) parameter values among patients at various stages of chronic kidney disease and healthy individuals., Methods: Electronic databases PubMed, Web of Science, Cochrane, and Embase were searched from inception to March 29, 2024, to identify relevant studies on ASL and BOLD in CKD. The renal blood flow (RBF) and apparent relaxation rate (R2*) values were obtained from healthy individuals and patients with various stages of CKD. The meta-analysis was conducted using STATA version 12.0. The random-effects model was used to obtain estimates of the effects, and the results were expressed as 95% confidence intervals (CIs) and mean differences (MDs) of continuous variables., Results: A total of 18 published studies were included in this meta-analysis. The cortical RBF and R2 * values and medulla RBF values were considerably distinct between patients with various stages of CKD and healthy controls (MD, - 78.162; 95% CI, - 85.103 to - 71.221; MD, 2.440; 95% CI, 1.843 to 3.037; and MD, - 36.787; 95% CI, - 47.107 to - 26.468, respectively). No obvious difference in medulla R2 * values was noted between patients with various stages of CKD and healthy controls (MD, - 1.475; 95% CI, - 4.646 to 1.696)., Conclusion: ASL and BOLD may provide complementary and distinct information regarding renal function and could potentially be used together to gain a more comprehensive understanding of renal physiology., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Chronic kidney disease of unknown etiology [CKDu] is a condition characterized by decline in kidney function and is not associated with diabetic nephropathy or hypertensive nephropathy. In this review, we have done a detailed literature analysis on CKDu in India, and then had a comparison with that of Mesoamerica and Sri Lanka. In India, CKDu became the second most common type of CKD after diabetic nephropathy. Silica was seen in the groundwater of both India and Sri Lanka, whereas in Mesoamerica silica exposure through particulate matter was seen among CKDu communities. DDE is a common agrochemical seen in both India and Sri Lanka. The risk factors vary from region to region and it is important to categorize CKDu population based on the risk factors to avoid misinterpretation of the condition as non-CKDu category and to evade further complications. More studies have to be conducted to reveal the detailed pathophysiological mechanisms and its relation with irrational exploitation of environmental resources., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Cigarette smoking is one of the most important life-modifiable risk factors for CVD events. The effect on CKD progression caused by smoking remained uncertain, while the effect on CVD had been established., Method: The study population included participants from the specific health check and specific health guidance, an annual health check-up for all inhabitants of Japan who were aged between 40 and 74 years. 149,260 subjects (male, 37.1%; female, 62.9%) were included in this analysis., Results: The relationship between smoking status along with new-onset proteinuria and eGFR deterioration more than 15 mL/min/1.73 m2 was examined. Median observation periods were 1427 days [738, 1813] in males and 1437 days [729, 1816] in females. In male participants, the strongest factor upon kidney dysfunction was new-onset proteinuria (1.41 [1.31 1.51], P < 0.001). The second strongest factor on kidney deterioration was smoking (1.24 [1.16 1.31], P < 0.001). In female participants, strongest factor upon kidney dysfunction was smoking (1.27 [1.16-1.39], P < 0.001). The second strongest factor on kidney deterioration was new-onset proteinuria (1.26 [1.17 1.36], P < 0.001). To reveal the relationship of effects from new-onset proteinuria and smoking on the kidney function, the participants were divided into four groups with and without new-onset proteinuria and smoking. The group with both proteinuria and smoking had significantly worst renal prognosis (P for trend < 0.001)., Conclusion: Large longitudinal observation study revealed smoking has an evil effect on the progression of CKD. This evil effect could be observed in CKD patients with proteinuria as well as in general population without new-onset proteinuria., (© 2024. The Author(s), under exclusive licence to Japanese Society of Nephrology.)

Background: Chronic kidney disease (CKD) is associated with increased mortality. Individual mortality prediction could be of interest to improve individual clinical outcomes. Using an independent regional dataset, the aim of the present study was to externally validate the recently published 2-year all-cause mortality prediction tool developed using machine learning., Methods: A validation dataset of stage 4 or 5 CKD outpatients was used. External validation performance of the prediction tool at the optimal cutoff-point was assessed by the area under the receiver operating characteristic curve (AUC-ROC), accuracy, sensitivity, and specificity. A survival analysis was then performed using the Kaplan-Meier method., Results: Data of 527 outpatients with stage 4 or 5 CKD were analyzed. During the 2 years of follow-up, 91 patients died and 436 survived. Compared to the learning dataset, patients in the validation dataset were significantly younger, and the ratio of deceased patients in the validation dataset was significantly lower. The performance of the prediction tool at the optimal cutoff-point was: AUC-ROC = 0.72, accuracy = 63.6%, sensitivity = 72.5%, and specificity = 61.7%. The survival curves of the predicted survived and the predicted deceased groups were significantly different (p < 0.001)., Conclusion: The 2-year all-cause mortality prediction tool for patients with stage 4 or 5 CKD showed satisfactory discriminatory capacity with emphasis on sensitivity. The proposed prediction tool appears to be of clinical interest for further development., (© 2024. The Author(s) under exclusive licence to Italian Society of Nephrology.)

Diabetic kidney disease (DKD) affects 30-40% of all patients with diabetes and contributes significantly to the cardiovascular burden of chronic kidney disease (CKD). Despite the availability of evidence-based medications like finerenone and simple screening tests such as Urinary Albumin-to-Creatinine Ratio (UACR), more resources are still needed to care for DKD patients. Physician Associates (PAs) play a crucial role in the multidisciplinary team responsible for DKD diagnosis, monitoring, and management. A nonsteroidal mineralocorticoid receptor antagonist, namely finerenone, was approved by the FDA in adults with CKD associated with type 2 diabetes to reduce the risk of renal and cardiovascular outcomes. Finerenone is considered among the pillars of care for DKD, furthermore, the addition of finerenone in combination with renin-angiotensin system inhibitors and/or other renal protective medications may offer additional benefits. Primary care providers prescribe finerenone less frequently than specialized care providers, indicating a need to empower physician associates in medication prescription and other renal protection strategies. As part of a multidisciplinary team, physician associates can play an important role in evaluating risk factors that contribute to heart disease and metabolic health. They can also monitor not only kidney function by ordering tests, such as serum creatinine and urinary albumin-to-creatinine ratio every 3-12 months, but also serum potassium levels. Additionally, physician associates can encourage patients to take responsibility for their health by regularly monitoring their blood pressure, blood glucose levels, and body weight. With early detection and management, kidney failure and cardiovascular events may be preventable. Specialized physician associates also play a significant role in the comprehensive care of DKD patients, especially in the later stages. DKD care can be hindered by numerous factors such as lack of patient engagement during counseling, cost disparities, and a complex referral system that requires multidisciplinary guidelines to improve professional communication. It is necessary to re-envision the physician associates' role in primary care and empower them in goal-directed therapies., (© 2024. The Author(s).)

The Baihe River, a tributary of the Yellow River located in the Ngawa Tibetan and Qiang Autonomous Prefecture in Northern Sichuan, is surrounded by natural resources suitable for animal development. However, the impact of livestock activities water microbiome in this area remains unexplored. This study collected water samples from areas with captive yaks and sheep (NS and YS) and compared them with water samples from Hongyuan Baihe River. Through amplicon sequencing, we investigated the impact of livestock activities on aquatic microorganisms. Diversity analysis, significance analysis, and microbial phenotype prediction indicated a significant decrease in microbial community diversity and function in the NS and YS groups. Pathogenic microorganisms such as Bacteroidales and Thelebolaceae and antibiotic-resistant bacteria genes such as Flavobacteriales and Burkholderiaceae were significantly higher in livestock breeding areas. Additionally, bacteria adapted to acidification, hypoxia, and eutrophication (e.g., Acidobacteria, Flavobacteriales, Deltaproteobacteria, Rhodobacterales) were more abundant in these areas. Our results demonstrate that livestock activities significantly alter the structure and function of microbial communities in surrounding water bodies, deteriorating water quality., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: Calcium-sensing receptor (CASR) influences the expression pattern of multiple genes in renal tubular epithelial cells. The objective of this inquiry was to explore the molecular mechanisms of CASR in renal tubular epithelial cells and nephrolithiasis., Methods: HK-2 cells were transfected with lentiviruses carrying either CASR (named CASR) or an empty vector negative control (named NC), as well as shRNA intended to target CASR (named shCASR) or its corresponding negative control (named shNC). CCK-8 assay was used to detect the effect of CASR on the proliferation of HK-2 cells. RNA-Sequencing was applied to explore potential pathways regulated by CASR in HK-2 cells., Results: PCR and western blot results showed that CASR expression was significantly increased in CASR cells and was decreased in shCASR cells when compared to their corresponding negative control, respectively. CCK-8 assay revealed that CASR inhibited the proliferation of HK-2 cells. RNA-Sequencing results suggested that the shCASR HK-2 cells exhibited a significant up-regulation of 345 genes and a down-regulation of 366 genes. These differentially expressed genes (DEGs) were related to cell apoptosis and cell development. In CASR HK-2 cells, 1103 DEGs primarily functioned in mitochondrial energy metabolism, and amino acid metabolism. With the Venn diagram, 4 DEGs (Clorf116, ENPP3, IL20RB, and CLDN2) were selected as the hub genes regulated by CASR. Enrichment analysis revealed that these hub genes were involved in cell-cell junction, and epithelial cell development., Conclusions: In summary, our investigation has the potential to offer novel perspectives on CASR regulating cell-cell junction in HK-2 cells., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Acute kidney injury (AKI) diagnosis often lacks a baseline serum creatinine (Cr) value. Our study aimed to create a regression equation linking kidney morphology to function in kidney donors and chronic kidney disease patients. We also sought to estimate baseline Cr in minimal change disease (MCD) patients, a common AKI-predisposing condition., Methods: We analyzed 119 participants (mean age 60 years, 50% male, 40% donors) with CT scans, dividing them into derivation and validation groups. An equation based on kidney parenchymal volume (PV) was developed in the derivation group and validated in the validation group. We estimated baseline Cr in 43 MCD patients (mean age 45 years, 61% male) using the PV-based equation and compared with their 6 month post-MCD onset Cr values., Results: In the derivation group, the equation for the estimated glomerular filtration rate (eGFR) was: eGFR (mL/min/1.73m 2 ) = 0.375 × PV (cm 3 ) + (- 0.395) × age (years) + (- 2.93) × male sex + (- 13.3) × hypertension + (- 14.0) × diabetes + (- 0.210) × height (cm) + 82.0 (intercept). In the validation group, the eGFR and estimated Cr values correlated well with the measured values (r = 0.46, p = 0.01; r = 0.51, p = 0.004, respectively). In the MCD group, the baseline Cr values were significantly correlated with the estimated baseline Cr values (r = 0.52, p < 0.001), effectively diagnosing AKI (kappa = 0.76, p < 0.001)., Conclusions: The PV-based regression equation established in this study holds promise for estimating baseline Cr values and diagnosing AKI in patients with MCD. Further validation in diverse AKI populations is warranted., (© 2024. The Author(s), under exclusive licence to Japanese Society of Nephrology.)

Background: Although vaccination has been reported to reduce the morbidity and severity of COVID-19 infection in patients with kidney disease, gross hematuria is frequently reported following vaccination in patients with IgA nephropathy. We investigated the frequency of gross hematuria following COVID-19 vaccination and its effect on renal function in IgA nephropathy patients., Methods: Adverse reactions after two or more COVID-19 vaccine doses were investigated in 295 IgA nephropathy patients attending Osaka Cty general hospital from September 2021 to November 2022. We compared differences in background characteristics and other adverse reactions between groups with and without gross hematuria after vaccination, and examined changes in renal function and proteinuria., Results: Twenty-eight patients (9.5%) had gross hematuria. The median age of patients with and without gross hematuria was 44 (29-48) and 49 (42-61) years, respectively, indicating a significant difference. The percentage of patients with microscopic hematuria before vaccination differed significantly between those with (65.2%) and without (32%) gross hematuria. Adverse reactions, such as fever, chills, headache and arthralgia, were more frequent in patients with gross hematuria. There was no difference in renal functional decline after approximately 1 year between patients with and without gross hematuria. We also found no significant changes in estimated glomerular filtration rate or proteinuria before and after vaccination in the gross hematuria group. However, some patients clearly had worsening of renal function., Conclusions: While COVID-19 vaccination is beneficial, care is required since it might adversely affect renal function in some patients., (© 2024. The Author(s), under exclusive licence to Japanese Society of Nephrology.)

Abstract The coronavirus disease (COVID-19) infection is causing significant morbidity and mortality rates worldwide. A comprehensive investigation of the disease characteristics, especially among vulnerable disease groups, could help better manage the disease and reduce the pathogen's effect. This retrospective study examined the impact of COVID-19 infection on three groups of patients with chronic diseases. We investigated the clinical characteristics and outcomes of 535 COVID-19 patients with cardiovascular diseases (CVD), chronic kidney diseases (CKD), and Cancer that were admitted to the Intensive Care Unit (ICU). Of the total cases, 433 patients (80.93%) were discharged from the ICU, and 102 patients (19.06%) were declared dead. Patients’ symptoms, their clinical laboratory findings, number and type of medications, length of ICU stay, and outcome were collected and analyzed. Most COVID-19 patients included in our study were associated with other comorbidities such as diabetes mellitus, hypertension, and heart disease and failure. Upon ICU admission, the main COVID-19-related symptoms in CVD, CKD, and cancer patients were cough (55.73, 50.42, and 50.5%, respectively), Shortness of Breath (SOB) (59.38, 43.1, and 43.7%, respectively), and fever (41.15%, 48.75%, and 28.2%, respectively). In terms of lab findings, D-dimer, LDH, and inflammatory markers, in particular, were outside the normal range. Treatment options for patients with COVID-19 in ICU were mainly antibiotics, synthetic glucocorticoids, and Low Molecular Weight Heparin (LMWH). Furthermore, CKD patients had a longer ICU stay (13.93 ± 15.87 days) which illustrates the poorer outcome in this group of patients compared with the others. In conclusion, our results highlighted the significant risk factors among COVID-19 patients within the three groups. This can guide physicians in prioritizing ICU admission and help in the management of critically ill patients with COVID-19.

Chronic kidney disease (CKD) can progress to kidney failure and require dialysis or transplantation, while early diagnosis can alter the course of disease and lead to better outcomes in both pediatric and adult patients. Significant CKD comorbidities include the manifestation of cardiovascular disease, heart failure, coronary disease, and hypertension. The pathogenesis of chronic kidney diseases can present as subtle and especially difficult to distinguish between different glomerular pathologies. Early detection of adult and pediatric CKD and detailed mechanistic understanding of the kidney damage can be helpful in delaying or curtailing disease progression via precise intervention toward diagnosis and prognosis. Clinically, serum creatinine and albumin levels can be indicative of CKD, but often are a lagging indicator only significantly affected once kidney function has severely diminished. The evolution of proteomics and mass spectrometry technologies has begun to provide a powerful research tool in defining these mechanisms and identifying novel biomarkers of CKD. Many of the same challenges and advances in proteomics apply to adult and pediatric patient populations. Additionally, proteomic analysis of adult CKD patients can be transferred directly toward advancing our knowledge of pediatric CKD as well. In this review, we highlight applications of proteomics that have yielded such biomarkers as PLA2R, SEMA3B, and other markers of membranous nephropathy as well as KIM-1, MCP-1, and NGAL in lupus nephritis among other potential diagnostic and prognostic markers. The potential for improving the clinical toolkit toward better treatment of pediatric kidney diseases is significantly aided by current and future development of proteomic applications., Author(s): Timothy D. Cummins [sup.1] , Erik A. Korte [sup.2] , Sagar Bhayana [sup.3] , Michael L. Merchant [sup.1] , Michelle T. Barati [sup.1] , William E. Smoyer [sup.3] , [...]

Background: Five hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) have been approved for marketing in Japan. However, marked differences exist in terms of drug potency, dose requirement, and pharmacokinetics., Methods: The primary evaluation in this study was the changes in hemoglobin levels, dose escalation, drug potency, and cost among HIF-PHIs, 3 months after the initiation of treatment., Results: All patients treated with HIF-PHI between August 2020 and December 2023 were enrolled in this study. In total, 124 patients were administered daprodustat (N = 37), enarodustat (N = 44), molidustat (N = 13), or vadadustat (N = 30). The mean hemoglobin levels of daprodustat, enarodustat, molidustat, and vadadustat at 3 months were 11.7 g/dL, 11.8 g/dL, 12.2 g/dL, and 11.3 g/dL, respectively. At 3 months, the mean doses of daprodustat, enarodustat, molidustat, and vadadustat increased by 110%, 177%, 125%, and 152%, respectively, from the initial dose. The HIF-PHI potency indices (HPI) of daprodustat, enarodustat, molidustat, and vadadustat at 3 months were 0.168, 0.307, 0.184, and 0.254, respectively. At 3 months, the mean daily costs of daprodustat, enarodustat, molidustat, and vadadustat were JPY 345, JPY 434, JPY 206, and JPY 565, respectively., Conclusion: The difference in dose escalation for anemia treatment among HIF-PHIs is due to differences in drug potency, where the HPI significantly differs among HIF-PHIs. The disparity between the HPI and the cost of the initial dose accounts for the variance in the daily costs of renal anemia treatment among HIF-PHIs., (© 2024. The Author(s), under exclusive licence to Japanese Society of Nephrology.)

Purpose: There are few studies on the establishment of diagnostic models for diabetic nephropathy (DN) in in type 2 diabetes mellitus (T2DM) patients based on biomarkers. This study was to establish a model for diagnosing DN in T2DM., Methods: In this cross-sectional study, data were collected from the Second Hospital of Shijiazhuang between August 2018 to March 2021. Totally, 359 eligible participants were included. Clinical characteristics and laboratory data were collected. LASSO regression analysis was used to screen out diagnostic factors, and the selected factors were input into the decision tree for fivefold cross validation; then a diagnostic model was established. The performances of the diagnosis model were evaluated by the area under the receiver operator characteristic curve (AUC), sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy. The diagnostic performance of the model was also validated through risk stratifications., Results: Totally, 199 patients (55.43%) were diagnosed with DN. Age, diastolic blood pressure (DBP), fasting blood glucose, insulin treatment, mean corpuscular hemoglobin concentration (MCHC), platelet distribution width (PDW), uric acid (UA), serum creatinine (SCR), fibrinogen (FIB), international normalized ratio (INR), and low-density lipoprotein cholesterol (LDL-C) were the diagnostic factors for DN in T2DM. The diagnostic model presented good performances, with the sensitivity, specificity, PPV, NPV, AUC, and accuracy being 0.849, 0.969, 0.971, 0.838, 0.965, and 0.903, respectively. The diagnostic model based on the stratifications also showed excellent diagnostic performance for diagnosing DN in T2DM patients., Conclusion: Our diagnostic model with simple and accessible factors provides a noninvasive method for the diagnosis of DN., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Introduction: Accurate diagnosis and treatment of kidney tumors greatly benefit from automated solutions for detection and classification on MRI. In this study, we explore the application of a deep learning algorithm, YOLOv7, for detecting kidney tumors on contrast-enhanced MRI., Material and Methods: We assessed the performance of YOLOv7 tumor detection on excretory phase MRIs in a large institutional cohort of patients with RCC. Tumors were segmented on MRI using ITK-SNAP and converted to bounding boxes. The cohort was randomly divided into ten benchmarks for training and testing the YOLOv7 algorithm. The model was evaluated using both 2-dimensional and a novel in-house developed 2.5-dimensional approach. Performance measures included F1, Positive Predictive Value (PPV), Sensitivity, F1 curve, PPV-Sensitivity curve, Intersection over Union (IoU), and mean average PPV (mAP)., Results: A total of 326 patients with 1034 tumors with 7 different pathologies were analyzed across ten benchmarks. The average 2D evaluation results were as follows: Positive Predictive Value (PPV) of 0.69 ± 0.05, sensitivity of 0.39 ± 0.02, and F1 score of 0.43 ± 0.03. For the 2.5D evaluation, the average results included a PPV of 0.72 ± 0.06, sensitivity of 0.61 ± 0.06, and F1 score of 0.66 ± 0.04. The best model performance demonstrated a 2.5D PPV of 0.75, sensitivity of 0.69, and F1 score of 0.72., Conclusion: Using computer vision for tumor identification is a cutting-edge and rapidly expanding subject. In this work, we showed that YOLOv7 can be utilized in the detection of kidney cancers., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Purpose: The development of roxadustat is a standard treatment for renal anemia, and multiple clinical trials have proved its safety and efficacy. However, less information is available from trials of the population with diabetic nephropathy (DN). This study aimed to determine whether roxadustat is effective for treating DN., Methods: This was a single-center, retrospective, institutional review board-approved cohort study. The patients with DN were chosen and given roxadustat or erythropoietin (EPO) for 8 weeks. The mean hemoglobin (Hb) level after 8 weeks of treatment served as the primary outcome. Alterations in the iron index and lipid levels were considered secondary objectives. Sub-group analysis was performed to observe the impact of inflammation and glycemic status on Hb., Results: A total of 80 patients were enrolled, 40 in each group. After 8 weeks of treatment, the Hb levels in the roxadustat group were higher than those in the control group. The number of patients who achieved Hb response was higher in the roxadustat group than in the control group (77.5% versus 27.5%; P < 0.001). In addition to lowering total cholesterol and low-density lipoprotein cholesterol, roxadustat decreased ferritin and elevated total iron-binding capacity. Compared to the control group, roxadustat was more beneficial for patients with an inflammatory condition and poor glycemic control., Conclusions: Roxadustat treatment remarkably corrected anemia in patients with DN, and its effectiveness was unaffected by inflammation or glycemic control levels. In addition, roxadustat can also reduce a patient's blood lipid level and enhance the body's use of iron., Clinical Trial Registration: ChiCTR2200057232., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Purpose: Idiopathic membranous nephropathy (IMN) is the most frequent global cause of nephrotic syndrome in non-diabetic people. In clinical practice, An effective and mild treatment for IMN patients with subnephrotic proteinuria has been adopted. Colquhounia root tablet (CRT) is a traditional Chinese medicine that is widely used in China to treat glomerulopathies. In this study, the effectiveness and safety of CRT in the treatment of IMN with subnephrotic proteinuria have been determined by reviewing the clinical records of 44 patients with IMN., Methods: Retrospective analysis of IMN patients with subnephrotic proteinuria treated with CRT in combination with ACEI/ARB or ACEI/ARB alone. The remission rate (complete or partial remission) was the main outcome observed, and proteinuria, estimated glomerular filtration rate (eGFR), serum albumin levels, and adverse effects were the secondary outcomes., Results: This clinical trial included 44 patients, and the overall remission rates at months 6, 9, and 12 after treatment were 68.2% versus 27.3% (p = 0.016), 72.7% versus 36.4% (p = 0.015), and 77.3% versus 36.4% (p = 0.006) in the treatment and control groups, respectively. The application of CRT treatment was an independent predictor of proteinuria remission (p = 0.024). In addition, in patients who were positive for phospholipase A2 receptor (PLA2R) antibodies, the overall remission rate was higher in the treatment group than in the control group after 9 months of treatment (75% versus 23.08%, p = 0.017)., Conclusion: This retrospective study illustrates that, based on supportive therapy, CRT could be effective in the treatment of IMN with subnephrotic proteinuria with a good safety profile at the same time., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Chronic kidney disease (CKD) poses a significant health risk in contemporary society. Current CKD treatments primarily involve renin-angiotensin-aldosterone system inhibitors and mineralocorticoid receptor antagonists, albeit associated with hyperkalemia risks. A novel selective mineralocorticoid receptor antagonist, finerenone, offers a promising, safer alternative for CKD therapy. This review comprehensively assesses the role and efficacy of finerenone in CKD treatment by analyzing clinical and animal studies. Emerging evidence consistently supports finerenone's ability to effectively slow the progression of CKD. By targeting the mineralocorticoid receptor, finerenone not only mitigates renal damage but also exhibits a favorable safety profile, minimizing hyperkalemia concerns., Conclusion: Finerenone emerges as a valuable addition to CKD therapy, demonstrating potential benefits in delaying CKD progression while minimizing side effects. Nevertheless, further clinical trials are necessary to provide a comprehensive understanding of its safety and efficacy., (© 2023. The Author(s), under exclusive licence to Japanese Society of Nephrology.)

Diabetic kidney disease (DKD) is a significant healthcare burden worldwide that substantially increases the risk of kidney failure and cardiovascular events. To reduce the prevalence of DKD, extensive research is being conducted to determine the risk factors and consequently implement early interventions. Patients with type 2 diabetes mellitus (T2DM) are more likely to be obese. Abdominal adiposity is associated with a greater risk of kidney damage than general obesity. Abdominal adipose tissue can be divided into different fat depots according to the location and function, including visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), perirenal adipose tissue (PAT), and renal sinus adipose tissue (RSAT), which can be accurately measured by radiology techniques, such as computed tomography (CT) and magnetic resonance imaging (MRI). Abdominal fat depots may affect the development of DKD through different mechanisms, and radiologic abdominal adipose characteristics may serve as imaging indicators of DKD risk. This review will first describe the CT/MRI-based assessment of abdominal adipose depots and subsequently describe the current studies on abdominal adipose tissue and DKD development, as well as the underlying mechanisms in patients of T2DM with DKD., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Ischemic stroke (IS) remains a leading cause of death and long-term disability globally. Several mechanisms including glutamate excitotoxicity, calcium overload, neuroinflammation, oxidative stress, mitochondrial damage, and apoptosis are known to be involved in the pathogenesis of IS, but the underlying pathophysiology mechanisms of IS are not fully clarified. During the past decade, gut microbiota were recognized as a key regulator to affect the health of the host either directly or via their metabolites. Recent studies indicate that gut bacterial dysbiosis is closely related to hypertension, diabetes, obesity, dyslipidemia, and metabolic syndrome, which are the main risk factors for cardiovascular diseases. Increasing evidence indicates that IS can lead to perturbation in gut microbiota and increased permeability of the gut mucosa, known as "leaky gut," resulting in endotoxemia and bacterial translocation. In turn, gut dysbiosis and impaired intestinal permeability can alter gut bacterial metabolite signaling profile from the gut to the brain. Microbiota-derived products and metabolites, such as short-chain fatty acids (SCFAs), bile acids (BAs), trimethylamine N-oxide (TMAO), lipopolysaccharides (LPS), and phenylacetylglutamine (PAGln) can exert beneficial or detrimental effects on various extraintestinal organs, including the brain, liver, and heart. These metabolites have been increasingly acknowledged as biomarkers and mediators of IS. However, the specific role of the gut bacterial metabolites in the context of stroke remains incompletely understood. In-depth studies on these products and metabolites may provide new insight for the development of novel therapeutics for IS., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Alpha-1,6 fucosylation of N-glycans (core fucosylation, CF) represents a unique form of N-glycans and is widely involved in disease progression. In order to accurately identify CF glycoproteins, several approaches have been developed based on sequential cleavage with different glycosidases to truncate the N-glycans. Since multi-step sample treatments may introduce quantitation bias and affect the practicality of these approaches in large-scale applications. Here, we systematically evaluated the performance of the single-step treatment of intact glycopeptides by endoglycosidase F3 for CF glycoproteome. The single-step truncation (SST) strategy demonstrated higher quantitative stability and higher efficiency compared with previous approaches. The strategy was further practiced on both cell lines and serum samples. The dysregulation of CF glycopeptides between preoperative and postoperative serum from patients with pancreatic ductal adenocarcinoma was revealed, and the CF modifications of BCHE&#95;N369, CDH5&#95;N112 and SERPIND1&#95;N49 were found to be potential prognostic markers. This study thus provides an efficient solution for large-scale quantitative analysis of the CF glycoproteome., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: To investigate the association of free triiodothyronine to free thyroxine (FT3/FT4) ratio with 5-year mortality in patients with chronic kidney disease (CKD) using data from the National Health and Nutrition Examination Survey (NHANES) through 2001-2002 and 2007-2012., Methods: Two thousand four hundred twenty-four patients with CKD stage 1-5 were included. Patients' baseline characteristics were collected. Cox proportional hazards models were used to investigate the association of FT3/FT4 ratio with 5-year all-cause and cardiovascular mortality. Subgroup analysis was performed., Results: Within 5 years of follow-up duration, 425 (17.53%) deaths were recorded, and 154 patients died from cardiovascular disease. A J-shaped association between FT3/FT4 ratio and 5-year mortality was observed. After fully adjustment, the elevated FT3/FT4 ratio was significantly associated with a decreased 5-year all-cause mortality risk (HR: 0.79, 95% CI 0.63-0.99) among patients with CKD stage 1-5 when FT3/FT4 ratio < 4.71, and is significantly associated with an increased 5-year all-cause mortality risk in CKD patients with advanced CKD stages or low UACR when FT3/FT4 ratio ≥ 4.71 (HR: 2.74, 95% CI 1.20-6.29; HR: 3.09, 95% CI 1.12-8.57, respectively). The elevated FT3/FT4 ratio also showed a J-shaped association with the 5-year cardiovascular mortality which disappears after fully adjustment., Conclusion: The FT3/FT4 ratio is closely associated with 5-year mortality risk among patients with CKD, indicating a potential role of FT3/FT4 ratio as a biomarker for mortality prediction in CKD patients., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Chronic kidney disease (CKD) is has been rising over the past few years, and obstructive sleep apnea (OSA) is a prevalent comorbidity in this population., Aim: To determine the prevalence of OSA in patients with chronic kidney disease stages I-V and end-stage renal disease (ESRD)., Methods: Patients with CKD of varying grades and ESRD routinely visiting outpatient nephrology clinic or admitted in department of nephrology were included in the study. Stages I-III were categorized as early stages of CKD and stages IV-V and ESRD as late stages of CKD. Patients were categorized into a high risk group based on STOP-BANG and Berlin questionnaires. Patients who were high risk were subjected to in-hospital overnight level III polysomnography. Student's independent t-test and analysis of variance (ANOVA) were employed for the comparison of continuous variables. Chi-square test and Fisher's exact test, as appropriate, were used for the comparison of categorical variables., Results: Of 111 patients, 46 (41%) were found to have OSA. Of these patients, 15 (33%) had mild OSA (AHI 5-14/h), 13 (28%) had moderate OSA (15-29/h), and 18 (39%) had severe OSA (AHI ≥ 30/h). Overall, 31% of patients in the early stage of CKD and 45% in the late stage were found to have OSA., Conclusion: This study demonstrated a high prevalence of OSA in patients with CKD when compared to the general population affecting both genders equally. The risk of OSA was higher in the advanced stages of CKD compared to the early stages, and dialysis had no effect on prevalence. Since OSA increases the cardiovascular morbidity in CKD the leading cause of death in these patients, early diagnosis and treatment of OSA may have promise to affect the mortality., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: Our main objective was to present a multidisciplinary review on the epidemiology of sudden cardiac death (SCD) and the tools that could be used to identify malignant ventricular arrhythmias (VAs) and to perform risk stratification. In addition, indications and contraindications for the use of implantable cardioverter defibrillator (ICD) in general and in special populations including the elderly and patients with chronic kidney disease (CKD) are also given., Methods: An expert group from the Inter American Society of Cardiology (IASC), through their HF Council (CIFACAH) and Electrocardiology Council (ElectroSIAC), together with the Latin American Heart Rhythm Society (LAHRS), reviewed and discussed the literature regarding the appropriate use of an ICD in people with heart failure (HF) with reduced ejection fraction (HFpEF). Indications and contraindications for the use of ICD are presented in this multidisciplinary review., Results: Numerous clinical studies have demonstrated the usefulness of ICD in both primary and secondary prevention of SCD in HFpEF. There are currently precise indications and contraindications for the use of these devices., Conclusions: In some Latin American countries, a low rate of implantation is correlated with low incomes, but this is not the case for all Latin America. Determinants of the low rates of ICD implantation in many Latin American countries are still a matter of research. VA remains one of the most common causes of cardiovascular death associated with HFrEF and different tools are available for stratifying the risk of SCD in this population., (© 2022. The Author(s).)

Background: Obesity is associated with the development and progression of chronic kidney disease (CKD). In the general population, the amount of renal sinus fat was associated with hypertension and renal impairment. However, its impact upon those with CKD remains uncertain., Methods: We prospectively included CKD patients who underwent renal biopsy and simultaneously measured their renal sinus fat volume. The association between the percentage of renal sinus fat volume, which was adjusted by kidney volume, and renal outcomes was investigated., Results: A total of 56 patients (median 55 years old, 35 men) were included. Among baseline characteristics, age and visceral fat volume were positively correlated with the percentage of renal sinus fat volume (p < 0.05). The percentage of renal sinus fat volume was associated with hypertension (p < 0.01) and tended to be associated with max glomerular diameter (p = 0.078) and urine angiotensinogen creatinine ratio (p = 0.064) after adjustment with several clinical factors. The percentage of renal sinus fat volume was significantly associated with a future > 50% decline in estimated glomerular filtration rate (p < 0.05)., Conclusions: Among those with CKD who required renal biopsy, the amount of renal sinus fat was associated with poor renal outcomes accompanied by systemic hypertension., (© 2023. The Author(s), under exclusive licence to The Japanese Society of Nephrology.)

Colorimetric sensors have emerged as a powerful tool in the detection of water pollutants. Plasmonic nanoparticles use localized surface plasmon resonance (LSPR)-based colorimetric sensing. LSPR-based sensing can be accomplished through different strategies such as etching, growth, aggregation, and anti-aggregation. Based on these strategies, various sensors have been developed. This review focuses on the newly developed anti-aggregation-based strategy of plasmonic nanoparticles. Sensors based on this strategy have attracted increasing interest because of their exciting properties of high sensitivity, selectivity, and applicability. This review highlights LSPR-based anti-aggregation sensors, their classification, and role of plasmonic nanoparticles in these sensors for the detection of water pollutants. The anti-aggregation based sensing of major water pollutants such as heavy metal ions, anions, and small organic molecules has been summarized herein. This review also provides some personal insights into current challenges associated with anti-aggregation strategy of LSPR-based colorimetric sensors and proposes future research directions., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

IgA nephropathy (IgAN) is one of the most common glomerulonephritides. The disease is characterized by haematuria, proteinuria, deposition of galactose-deficient IgA1 in the glomerular mesangium and mesangial hypercellularity, further leading to extracellular matrix expansion. Kidney biopsy is the gold standard for IgAN diagnosis. Due to the invasiveness of renal biopsy, there is an unmet need for noninvasive biomarkers to diagnose and estimate the severity of IgAN. Understanding the role of RNA molecules as genetic markers to target diseases may allow developing therapeutic and diagnostic markers. In this review we have focused on intrarenal, extrarenal and extracellular noncoding RNAs involved in the progression of IgAN. This narrative review summarizes the pathogenesis of IgAN along with the correlation of noncoding RNA molecules such as microRNAs, small interfering RNAs, circular RNAs and long non-coding RNAs that play an important role in regulating gene expression, and that represent another type of regulation affecting the expression of specific glycosyltranferases, a key element contributing to the development of IgAN., (© 2022. The Author(s) under exclusive licence to Italian Society of Nephrology.)

Aluminum, one of the most abundant metallic elements, is known to be toxic to multiple organs including the kidneys. This study aimed to investigate the pleiotropic nephroprotective effects of Hesperidin in aluminum chloride (ALCL3)-induced renal injury, highlighting the potential molecular mechanisms underlying. Twenty-four male albino rats were divided into four groups: control, Hesperidin (80 mg/kg BW, orally), ALCL3 (10 mg/kg BW, IP), and ALCL3 + Hesperidin groups. By the end of the study, blood samples were collected, and tissue samples were harvested at sacrifice. ALCL3 rats showed dramatically declined renal function, enhanced intrarenal oxidative stress, inflammation, apoptosis, and extravagant renal histopathological damage with interstitial fibrosis as shown by a higher Endothelial, Glomerular, Tubular, and Interstitial (EGTI) score. Hesperidin significantly reversed all the aforementioned detrimental effects in ALCL3-treated rats. The study verified the nephroprotective effects of Hesperidin on ALCL3-induced renal damage and confirmed the critical role of extracellular matrix (ECM) remodeling and apoptosis inhibition., (© 2022. The Author(s).)

Background: The clinical significance of intrarenal vascular lesions has not been elucidated in primary IgA nephropathy (IgAN), especially in non-hypertensive subjects., Methods: From January 2003 to December 2020, data of 3435 patients with biopsy-proven IgAN were reviewed. Two hundred-forty non-hypertensive patients who met the criteria for IgAN and had intrarenal vascular lesions (IgAN-vas) were selected. The control cohort was constructed with 1:1 matched cases of non-hypertensive IgAN patients without vascular lesions according to age, gender, estimated glomerular filtration rate (eGFR) and follow-up time., Results: The IgAN-vas cohort had significantly higher serum uric acid levels than the control IgAN cohort (P < 0.05); glomerulosclerosis was more common in IgAN-vas patients. Moreover, cluster analysis indicated that the serum uric acid level was associated with serum creatinine (s-Cr) levels in IgAN-vas while it was associated with serum lactate dehydrogenase (LDH) levels in control cases with IgAN. Both Kaplan-Meier analysis and generalized linear mixed-effects models revealed that the prognosis of the IgAN-vas cohort was significantly worse than that of the IgAN cohort after > 5 years of follow-up. Intimal thickening was an independent risk factor associated with reaching the endpoint (eGFR decrease ≥ 30% from the baseline or reaching end-stage renal disease [ESRD] or death)., Conclusions: The prognosis of non-hypertensive patients with IgAN-vas was worse than that of matched individuals with IgAN. The clinicopathologic manifestation of IgAN-vas was more severe, and included a higher proportion of glomerulosclerosis, and a higher serum uric acid level correlated with renal function impairment., (© 2022. The Author(s) under exclusive licence to Italian Society of Nephrology.)

Background: Polypharmacy is common in patients with chronic kidney disease (CKD) and is associated with a decline in kidney function. However, its impact on patients without CKD has not been adequately elucidated. Therefore, we aimed to investigate the association between polypharmacy and the incidence of CKD., Methods: We conducted retrospective cohort study using 1221 participants who were enrolled in the Fukushima Cohort Study with one or more risk factors of CKD, an estimated glomerular filtration rate (eGFR) of ≥ 60 mL/min/1.73 m 2 , and without proteinuria. Participants were categorized into three groups based on the number of medications: non-polypharmacy, 0-4 medications; polypharmacy, 5-9 medications; and hyper-polypharmacy, ≥ 10 medications., Results: The median age was 62 years, 49% were men, the median eGFR was 75.4 ml/min/1.73 m 2 , and the median number of medications was 5. Polypharmacy and hyper-polypharmacy were noted in 506 (41%) and 250 (20%) participants, respectively. During follow-up, 288 participants developed CKD and 67 cardiovascular events were observed. Compared to the non-polypharmacy group, the hyper-polypharmacy group had a higher risk of CKD and cardiovascular events. The adjusted hazard ratios were 1.41 (95% CI1.01-1.99) and 2.24 (95% CI1.05-4.78) for the incidence of CKD and cardiovascular events, respectively. Sensitivity analyses yielded similar findings for the restricted cubic spline function models., Conclusions: Hyper-polypharmacy is associated with a higher risk of CKD and cardiovascular events., (© 2022. The Author(s), under exclusive licence to The Japanese Society of Nephrology.)

Ageing is a complex process characterized by deteriorated performance at multiple levels, starting from cellular dysfunction to organ degeneration. Stem cell-based therapies aim to administrate stem cells that eventually migrate to the injured site to replenish the damaged tissue and recover tissue functionality. Stem cells can be easily obtained and cultured in vitro, and display several qualities such as self-renewal, differentiation, and immunomodulation that make them suitable candidates for stem cell-based therapies. Current animal studies and clinical trials are being performed to assess the safety and beneficial effects of stem cell engraftments for regenerative medicine in ageing and age-related diseases.Since alterations in cell-cell communication have been associated with the development of pathophysiological processes, new research is focusing on the modulation of the microenvironment. Recent research has highlighted the important role of some microenvironment components that modulate cell-cell communication, thus spreading signals from damaged ageing cells to neighbor healthy cells, thereby promoting systemic ageing. Extracellular vesicles (EVs) are small-rounded vesicles released by almost every cell type. EVs cargo includes several bioactive molecules, such as lipids, proteins, and genetic material. Once internalized by target cells, their specific cargo can induce epigenetic modifications and alter the fate of the recipient cells. Also, EV's content is dependent on the releasing cells, thus, EVs can be used as biomarkers for several diseases. Moreover, EVs have been proposed to be used as cell-free therapies that focus on their administration to slow or even reverse some hallmarks of physiological ageing. It is not surprising that EVs are also under study as next-generation therapies for age-related diseases., (© 2023. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

Mesenchymal stem/stromal cells (MSCs) are multipotent cells with immunomodulatory effects that have been attempted as a possible treatment for neurologic disorders. Since currently available drugs for neurologic disorders are limited, special attention has been paid to MSCs. With the ability to differentiate into neural cells, it has been shown that MSCs exert their effects in a paracrine manner by producing extracellular vesicles (EVs). Extracellular vesicles are small vesicles with a size of 30-1000 nm that are released by cells, such as MSCs, T cells, B cells, etc. EVs contain various molecules, including proteins, lipids, mRNAs, and microRNAs (miRNAs). In recent years, the administration of EVs in models of neurological disorders has been shown to improve neurological dysfunctions. miRNAs from MSC-EVs as one of the important mediators which regulate various genes and reduce neuropathological change have been identified in different neurological disorders. Here, we review the effects of EVs miRNAs from MSCs on different neurological disorders and their potential applications., (© 2022. The Author(s) under exclusive licence to Japan Human Cell Society.)

Diabetes is a chronic metabolic disease characterized by an excess of glucose in the blood. If the constant sugar level is not managed correctly in diabetic patients, it may lead to microvascular complications such as diabetic retinopathy, neuropathy, and nephropathy. There are several synthetic drugs for the management of diabetes; however, these drugs produce immense adverse effects in long-term use. Flavonoids are naturally occurring substances categorized in various classes. They are known for their diverse pharmacological actions, and one of them is prominent antihyperglycemic action and their activities in diabetic complications. In the last few decades, many research studies emphasized the potential of flavonoids in diabetes management. Nevertheless, most flavonoids are insoluble in water and cannot produce desired therapeutic action when administered in conventional dosage forms. To overcome this issue, flavonoids were formulated into different nanoformulations to enhance solubility, absorption, and therapeutic efficacy. This review article focuses on flavonoid nanoformulations and in vitro and in vivo studies reported to overcome diabetes mellitus and its complications., (© 2022. Controlled Release Society.)