Chronic kidney disease (CKD) is a fast growing global public health concern, with lifestyle factors contributing significantly to its risk. The purpose of this study was to investigate the relationship between a healthy lifestyle and the risk of incident CKD. We examined healthy lifestyle and CKD risk in 502,621 China Kadoorie Biobank (CKB) participants. Six low-risk lifestyle factors were assessed: 1) non-smoking or quitting for at least 6 months, 2) drinking alcohol weekly, 3) engaging in moderate or greater physical activity, 4) following a healthy diet, 5) maintaining a body mass index (BMI) of 18.5–23.9 kg/m2, and 6) having a waist-to-hip ratio (WHR) of < 0.90 for men and < 0.85 for women. Adequate physical activity was defined as achieving at least the gender-specific median level of total metabolic equivalent task hours per day. A Simplified Healthy Eating Index score in the highest quartile indicated a healthy diet.The proportion of CKD cases that could have been prevented was estimated using the population attributable risk percent. In multivariable-adjusted analyses, all six low-risk lifestyle factors—never smoking or quitting not for illness, drinking alcohol weekly, maintaining a healthy diet, having a normal BMI, and possessing a normal WHR—were independently linked to a reduced risk of CKD. Participants with a minimum of five low-risk lifestyle factors demonstrated a 47

With population ageing, multimorbidity has become a major public health concern. Although healthy lifestyles are associated with reduced risks of single chronic diseases and mortality, their relationship with multimorbidity patterns among older Chinese remains insufficiently explored. Data from 16,820 participants aged 60 and older, from the 2008–2018 waves of the China Longitudinal Healthy Longevity Survey (CLHLS), were analyzed. Participants were categorized into three lifestyle groups (favorable, average, and unfavorable) based on five modifiable lifestyle factors: social engagement, physical activity, smoking, drinking, and diet. Disease progression was assessed using multimorbidity networks, and all-cause mortality was analyzed with Cox proportional hazards models. Compared to an unfavorable lifestyle, a favorable lifestyle was associated with a lower risk of all-cause mortality (HR = 1.63, 95

BackgroundImmunoglobulin A nephropathy (IgAN) is one of the most common types of primary glomerulonephritis and is an important cause of end-stage renal disease (ESRD) worldwide. Inflammation has been shown to be associated with its basic pathogenesis. The lactate dehydrogenase-to-albumin ratio (LAR), a novel marker of inflammation and nutritional status, has been studied in various diseases. However, whether the LAR also plays a critical role in Chinese patients with IgAN remains unknown. Thus, we conducted this retrospective study to evaluate the role of the LAR in predicting clinicopathologic changes and disease prognosis in IgAN patients.MethodsA total of 1,276 patients with biopsy-proven IgAN were enrolled in this study. The patients were grouped into a high LAR group (LAR ≥4.05, n = 738) and a low LAR group (LAR <4.05, n = 538) based on the cutoff value of the LAR with regard to the Youden index. The study endpoint was a composite endpoint that referred to ESRD and/or an estimated glomerular filtration rate (eGFR) that decreased by more than 50% compared with baseline. The predictive value was determined by the area under the receiver operating characteristic curve (AUROC). Kaplan–Meier and Cox proportional hazards analyses were performed to evaluate the value of the LAR in predicting renal progression and patient prognosis.ResultsIgAN patients with a high LAR had an increased incidence of anemia and increased levels of proteinuria, serum creatinine, and serum lipids. Multivariate Cox regression analysis indicated that a high LAR was an independent risk factor for IgAN even after adjustment for important clinicopathological parameters (HR = 1.844, 95% CI = 1.138–2.988, p = 0.013). Kaplan–Meier analysis revealed that a high LAR was significantly associated with a poor renal prognosis in patients with IgAN (p < 0.001). According to subgroup analysis stratified by sex, renal function, treatment, anemia status, or proteinuria level, a high LAR was consistently related to a worse renal outcome.ConclusionAn elevated LAR affects renal progression and prognosis in patients with IgAN and could be a novel marker for the management of IgAN patients in the future.

Background: Immunoglobulin A nephropathy (IgAN), a common primary glomerulonephritis worldwide, has been investigated, and complex factors are involved in disease progression. A group of evidence emerged that nutrition status plays a nonsubstitutable role in the management of chronic kidney disease. Meanwhile, a novel marker of nutrition and inflammation, the prognostic nutritional index (PNI), has been studied in various diseases. Whether PNI can predict the renal outcome of patients with IgAN remains unclear. Thus, we aimed to evaluate the relationships between PNI and clinicopathologic features, renal progression and renal prognosis in patients with IgAN. Methods: A total of 1,377 patients with biopsy-proven IgAN were recruited for this retrospective study. All patients were divided into two groups based on the cutoff value of PNI: the high group (PNI >= 47.1, n = 886) and the low group (PNI < 47.1, n = 491). Our study endpoint was end-stage renal disease [estimated glomerular filtration rate (eGFR) < 15 mL/min/1.73 m(2) or performance of renal replacement therapy]. A correlation test was conducted to explore the relationship between PNI and other important clinicopathologic parameters. The predictive value was determined by the area under the receiver operating characteristic curve (AUROC). Kaplan-Meier and Cox proportional hazards analyses were performed to assess the value of PNI in predicting renal progression and prognosis. Results: The correlation test revealed that PNI was positively associated with eGFR (r = 0.16, p < 0.001) and negatively related to 24-h proteinuria (r = -0.387, p < 0.001). Multivariate Cox regression analysis indicated that low PNI was an independent risk factor for IgAN patients even after adjusting for important clinical and pathological parameters (HR, 0.664; 95% CI, 0.443-0.994; p = 0.047). Kaplan-Meier analysis showed that low PNI was significantly correlated with severe renal outcome in patients with IgAN (p < 0.001). Moreover, the subgroup analyses of Kaplan-Meier survival demonstrated that low PNI predicted severe renal prognosis in different types of IgAN patients when considering the level of glomerular filtration rate, 24 h proteinuria and hemoglobin. Conclusion: PNI is associated with renal function and pathologic lesions in IgAN patients and could be a novel marker for the evaluation of renal progression and prognosis.

Diabetic kidney disease is one of the common complications in diabetic patients and has gradually become an important pathogenic factor in chronic kidney disease. Therefore, studying the mechanisms of its occurrence and development is of great significance for the prevention and treatment of diabetic kidney disease. Some researchers have pointed out that there is a phenomenon of hypoxia in diabetic kidney tissue and believe that hypoxia-inducible factor-1α is closely related to the occurrence and progression of diabetic kidney disease. Additionally, the homeostasis of zinc plays a key role in the body’s adaptation to hypoxic environments. However, the specific relationship among these three factors remains unclear. This article provides a detailed review of the multiple roles of hypoxia-inducible factor-1α in the pathogenesis of diabetic kidney disease, including: regulating angiogenesis, increasing the expression of erythropoietin, modulating oxidative stress through the PI3K/AKT and HIF-1α/HO-1 pathways, promoting inflammatory cell infiltration and the release of inflammatory factors to induce inflammatory responses, facilitating epithelial-mesenchymal transition, pathological angiogenesis, and promoting the release of fibrotic factors, ultimately leading to renal fibrosis. Furthermore, HIF-1α also participates in the occurrence and development of diabetic kidney disease through mechanisms such as regulating apoptosis, inducing mitochondrial autophagy, and vascular calcification. At the same time, this article clarifies the regulatory role of the trace element zinc on hypoxia-inducible factor-1α in diabetic kidney disease. This article provides references and insights for further research on the pathogenesis and progression of diabetic kidney disease.

The optimal blood pressure (BP) in patients with chronic kidney disease (CKD) remains uncertain. Therefore, this cohort study aimed to investigate the prognostic value of ambulatory blood pressure (ABP) in patients with CKD and to determine the optimal range for ABP. In total, 1051 hospitalized patients with CKD were enrolled. The prognosis of patients with CKD was evaluated in terms of all-cause death, cardiovascular death, cardiovascular events, and renal events. Our results showed that systolic blood pressure (SBP) had a higher predictive value than diastolic blood pressure in the multivariate-adjusted models. Additionally, nighttime SBP was found to be the best predictor of prognosis in patients with CKD. Furthermore, when dividing the nighttime SBP into quartiles (quartile 1: <110 mmHg, quartile 2: 110–124 mmHg, quartile 3:124–139 mmHg, and quartile 4: ≥139 mmHg). Nighttime SBP ≥ 124 mmHg had an impact on prognosis in patients with CKD, nighttime SBP 124–139 mmHg: total mortality (hazard ratio [HR], 3.017 [95

Long-term exposure to particulate matter has been increasingly implicated in the progression of chronic kidney disease (CKD). However, its impact on IgA nephropathy (IgAN), a leading cause of end-stage renal disease (ESRD), remains unclear. A total of 1768 IgAN patients, confirmed by renal biopsy were included in this cohort study. Long-term exposure to PM2.5 and PM10 was assessed using high-resolution satellite-based data from the China High Air Pollutants (CHAP) dataset. Cox proportional hazards models were used to estimate the associations between PM2.5 or PM10 and ESRD risk, adjusting for demographic, clinical, and biochemical covariates. Over a median follow-up of 3.63 years, 209 participants progressed to ESRD. Higher exposure to both PM2.5 and PM10 was significantly associated with an increased risk, with hazard ratios of 1.62 and 1.36 per 10 µg/m3 increase, respectively. A nonlinear dose-response relationship was observed, with risk increasing markedly beyond threshold levels. Trajectory modeling of prebaseline exposure identified a subgroup with persistently high and fluctuating particulate matter exposure that showed the highest risk. This study provides strong evidence that prolonged exposure to ambient particulate matter contributes to renal disease progression in individuals with IgAN.

Background IgA nephropathy (IgAN) is the most common primary glomerular disease in the world, and specific therapeutic methods for IgAN are limited. Telitacicept is a humanized fusion protein composed of a transmembrane activator and calcium-modulating cyclophilin ligand interactor receptor and human IgG.Aim To evaluate the efficacy and safety of telitacicept in adult patients with IgAN in a real-world study.Methods Biopsy-proven IgAN patients with 24-hour proteinuria greater than 0.5 g/d who received 240 mg telitacicept weekly were recruited for this study and 1:1:1 matched with patients who received supportive treatment only or immunosuppressive treatment by propensity score matching. The primary outcome was the change from baseline in 24-hour proteinuria over the 3-month follow-up.Results Twenty-one patients in each group were enrolled. Telitacicept reduced median proteinuria by 0.72 g/d (54.6%) from baseline, compared with a reduction of 0.18 g/d (20%) in the supportive treatment group and 1.12 g/d (72.1%) in the immunosuppressive treatment group. Preserved eGFR levels were observed in the telitacicept group, whereas eGFR levels decreased in the other two groups. No serious adverse events were observed in the telitacicept treatment group.Conclusion Telitacicept may be an effective treatment for IgAN patients by reducing proteinuria and preserving eGFR, and showed a favorable safety profile.

Several organic pollutants, including dioxins, furans, and coplanar polychlorinated biphenyls (PCBs), have become a growing concern due to their significant capacity for accumulation and migration across regions, as well as their extended half-lives and relatively high toxicity. Our study aimed to assess the impact of these pollutants on mortality, inflammatory states, and chronic diseases. Exposure was quantified in serum through high-resolution gas chromatography and isotope-dilution high-resolution mass spectrometry. Statistical analyses employed multivariate Cox regression, multivariate logistic regression, restricted cubic splines and subgroup analysis. The results indicated a significant increase in mortality (p < 0.05) associated with the seven substances classified as dioxins, furans, and PCBs. Moreover, these pollutants were linked to a higher incidence of chronic diseases, including hematological disorders, chronic kidney disease, hypertension, and diabetes (p < 0.05). Additionally, a robust correlation was observed between serum C-reactive protein (CRP) and neutrophil-tolymphocyte ratio (NLR) concentrations and these substances, revealing their proinflammatory effects at specific concentrations. Consequently, our research unmasked that exposure to dioxins, furans, and coplanar PCBs could be associated with an elevated mortality rate, increased inflammatory conditions, and a higher incidence of chronic diseases. We proposed that exposure to these pollutants may initiate various afflictions by activating the inflammatory system, ultimately resulting in increased mortality. However, this hypothesis requires further empirical investigation to validate its assertions.

BackgroundTraditional risk models for immunoglobulin A nephropathy (IgAN), which primarily rely on renal indicators, lack comprehensive assessment and therapeutic guidance, necessitating more refined and integrative approaches. ObjectiveThis study integrated network biomarkers with unsupervised learning clustering (k-means clustering based on network biomarkers [KMN]) to refine risk stratification in IgAN and explore its clinical value. MethodsInvolving a multicenter prospective cohort, we analyzed 1460 patients and validated the approach externally with 200 additional patients. Deeper metabolic and microbiomic insights were gained from 2 distinct cohorts: 63 patients underwent ultraperformance liquid chromatography–mass spectrometry, while another 45 underwent fecal 16S RNA sequencing. Our approach used hierarchical clustering and k-means methods, using 3 sets of indicators: demographic and renal indicators, renal and extrarenal indicators, and network biomarkers derived from all indicators. ResultsAmong 6 clustering methods tested, the KMN scheme was the most effective, accurately reflecting patient severity and prognosis with a prognostic accuracy area under the curve (AUC) of 0.77, achieved solely through cluster grouping without additional indicators. The KMN stratification significantly outperformed the existing International IgA Nephropathy Prediction Tool (AUC of 0.72) and renal function-renal histology grading schemes (AUC of 0.69). Clinically, this stratification facilitated personalized treatment, recommending angiotensin-converting enzyme inhibitors or angiotensin receptor blockers for lower-risk groups and considering immunosuppressive therapy for higher-risk groups. Preliminary findings also indicated a correlation between IgAN progression and alterations in serum metabolites and gut microbiota, although further research is needed to establish causality. ConclusionsThe effectiveness and applicability of the KMN scheme indicate its substantial potential for clinical application in IgAN management.

Background:This study aimed to evaluate the efficacy and safety of telitacicept versus mycophenolate mofetil (MMF) in high-risk progressive immunoglobulin A nephropathy (IgAN). Methods:This retrospective, multicentre cohort study included patients with high-risk progressive IgAN who received telitacicept or MMF therapy, both combined with low-dose steroids. Clinical data were collected from treatment initiation to 12 months. Results:A total of 104 patients were included, with 56 receiving MMF and 48 receiving telitacicept. The average age was 36.9 ± 11.8 years. Baseline characteristics were well balanced between groups, except for serum albumin, uric acid and tubular pathology based on the Oxford classification, which showed significant differences. At 12 months, telitacicept plus low-dose steroids demonstrated superior proteinuria reduction (-62.5% versus -52.9%, P = .041) and stabilized renal function (4.1% improvement in estimated glomerular filtration rate versus 5.3% decline with MMF, P = .085). Telitacicept plus low-dose steroids achieved higher complete remission rates (33.3% versus 16.1%; P = .04) and significantly lower non-response rates (29.2% versus 48.2%, P = .048) compared with MMF plus low-dose steroids. Cumulative remission rates (complete + partial) favoured telitacicept at all time points, with the largest difference at 12 months. Notably, telitacicept required substantially lower cumulative glucocorticoid doses (P < .001) and exhibited a superior safety profile, with significantly fewer adverse events (22.9% versus 42.9%, P = .032) and no serious complications reported. Multivariable analysis indicated telitacicept was associated with a higher likelihood of achieving 12-month complete remission [adjusted hazard ratio 6 (95% confidence interval 1.41-25.62). Conclusions:Telitacicept may offer better efficacy compared with MMF for proteinuria reduction in high-risk IgAN patients, while reducing combined glucocorticoid requirements and demonstrating a more favourable safety profile. These advantages position it as a promising therapeutic option, warranting further randomized validation.

Acute kidney injury (AKI) is a common critical illness in clinical settings. Fibroblast growth factor 23 (FGF23) levels increase rapidly after AKI; however, the role of FGF23 in AKI remains unclear. We investigated the function and underlying mechanisms of FGF23 in patients with AKI and in folic acid (FA)-induced AKI models. FGF23 expression was significantly elevated in AKI patients as well as in both in vivo and in vitro FA-AKI models. GSDME-mediated pyroptosis occurred in renal tubular epithelial cells, with upregulated autophagy marker LC3B-II. Recombinant human FGF23 pretreatment activated the AMPK/ULK1 pathway, increased LC3B-II levels, and inhibited caspase-3/GSDME-mediated pyroptosis in HK-2 cells. Conversely, inhibition of FGF receptors suppressed AMPK/ULK1 activation and autophagy, thereby enhancing pyroptosis. In summary, FGF23 promots autophagy via the AMPK/ULK1 pathway and consequently inhibits caspase-3/GSDME-mediated pyroptosis in FA-AKI. Our findings reveal a novel protective role of FGF23 in AKI, clarify its underlying mechanism, and provide a theoretical foundation for the development of new AKI diagnostic and therapeutic approaches based on FGF23.

Objective: To analyze the effect of Yishen Tongluo Formula combined with sulodexide in treating patients with diabetic nephropathy and renal failure. Methods: A hundred patients with diabetic nephropathy accompanied by renal failure who were admitted to the hospital for treatment from March 2021 to March 2024 were randomly divided into the control group and the observation group, and were treated with sulodexide therapy and Yishen Tongluo Formula + sulodexide therapy, respectively. The treatment efficacy of the two groups was evaluated. Results: After treatment, fasting blood glucose and other levels were lower in the observation group, P < 0.05; renal function indexes in the observation group improved, where levels of 24-hour urinary protein, blood urea nitrogen, and blood creatinine were significantly lower than those of the pre-treatment and control group; the effect of microinflammatory state relief was significant, as demonstrated by the significant decrease of interleukin-6 and other indexes, P < 0.05. Conclusion: In the treatment of diabetic nephropathy patients with renal failure, we should pay attention to the protection of renal function, applying sulodexide to improve patients’ blood glucose indexes, and at the same time, utilizing Yishen Tongluo Formula to alleviate patients’ microinflammatory state and enhance the recovery of renal function.

Introduction: The aim of this study was to evaluate the predictive value of the serum IgA/C3 ratio and glomerular C3 deposits in kidney biopsy in adult IgA nephropathy. Methods: The study included 718 adult IgAN patients diagnosed based on kidney biopsy. Patients without corticosteroids or immunosuppressive drugs >1 month were regularly followed up for at least 1 year or until the study endpoint. The optimum serum IgA/C3 ratio was calculated by the AUROC-based cutoff ratio. Proteinuria, creatinine, eGFR, serum IgA, and serum C3 were evaluated at baseline. Kidney biopsy was categorized using the Oxford classification, with a calculation of the MEST-C score. The degree of glomerular C3 staining was semiquantitatively determined (Grade 0, no or trace; Grade 1, mild; Grade 2, moderate; Grade 3, marked) by immunofluorescence microscopy. The patients were divided into four groups by the serum IgA/C3 ratio and glomerular C3 staining. Results: The baseline data suggested that when the serum IgA/C3 ratio was at the same level, patients with a high glomerular C3 staining score (≥2) always had mesangial proliferation, segmental glomerulosclerosis and tubular atrophy/interstitial fibrosis (Group 1 vs Group 2; Group 3 vs Group 4). When glomerular C3 staining was at the same level, proteinuria was significantly higher in patients with serum IgA/C3<2.806 (Group 1 vs Group 3; Group 2 vs Group 4), which was contrary to previous studies that have suggested that the serum level of IgA/C3 was associated with disease severity. Hence, this study set out to investigate the combined effects of the serum IgA/C3 ratio and glomerular C3 staining on the renal outcome in adult IgA nephropathy. Renal survival analysis indicated that serum IgA/C3 ≥2.806 and glomerular C3 staining ≥2 (Group 1) may be correlated with a poorer prognosis, especially in different clinicopathological characteristics of IgAN patients based on the subgroup analysis. Multivariate Cox analysis demonstrated that hypertension, serum creatinine, CKD stage, T1/2 and C3 staining were independent predictive factors of renal survival. Conclusions: The combination of serum IgA/C3 and C3 staining may contribute to improved optimization of the prognostic model in IgAN patients, especially patients with different sexes and degrees of disease. However, further study is required for validation in the future.

BACKGROUND:The ongoing debate surrounding the use of immunosuppressive treatments for IgA nephropathy (IgAN) underscores the demand for personalized and effective strategies. METHODS:Analyzed data from 807 IgAN patients over 5+ years using three methods: Random Forest with molecular biomarkers, network biomarkers with graph engineering, and an auto-encoder model. All models were trained using identical demographic, clinical, and pathological data, employing an 80-20 split for training and testing purposes. RESULTS:In the comprehensive assessment of IgAN prognosis, the Random Forest model, employing molecular biomarkers, demonstrated strong performance metrics (AUC = 0.83, sensitivity = 0.51, specificity = 0.96). However, traditional graph feature engineering on patient-specific networks outperformed these results with an AUC of 0.90, sensitivity of 0.64, and specificity of 0.94. The Auto-encoder model showed the best accuracy (AUC = 0.91, sensitivity = 0.46, specificity = 0.96). The findings highlighted the superior predictive capabilities of network biomarkers over molecular biomarkers for adverse renal outcome prediction in IgAN. Consequently, we integrated Auto-encoder-derived Network Biomarkers with Random Forest Models to enhance prognostic precision in diverse IgAN treatment scenarios. The prediction for the prognosis of patients receiving supportive care, glucocorticoid therapy, and immunosuppressant treatment yielded AUC values of 0.95, 0.96, and 1, respectively, indicating high specificity. Drawing from these insights, we pioneered the development of an innovative decision support model for IgAN treatment. This model demonstrated the ability to make medical decisions comparable to those by experienced nephrologists, enabling the customization of personalized disease management strategies. CONCLUSION:Our system accurately predicted IgAN prognosis and evaluated various treatment efficacies, aiding physicians in devising optimal therapeutic strategies for patients.

Background: Organochlorine pesticides, with their environmental persistence and bioaccumulation potential, have gained significant attention. This study explores the impact of organochlorine pesticides on mortality and chronic diseases, investigates their link to inflammatory states, and examines the role of anti-inflammatory diets in mitigating adverse reactions to these pesticides. Methods: This study, with 2,847 participants, used gas chromatography and mass spectrometry to measure organochlorine pesticide exposure in NHANES data. Conventional statistical methodologies, encompassing survival curves, Cox proportional hazards regression, regression analysis, and restricted quadratic spline analysis, were employed to investigate the association between pesticides and mortality, chronic ailments, and inflammation. Furthermore, machine learning techniques, comprising RF, AdaBoost, Extra-Trees, LightGBM, and BPNN, were leveraged to evaluate the impact of pesticides on chronic disease and mortality prognostication. Results: Organochlorine pesticides were significantly and positively correlated with increased mortality (p<0.05). Additionally, these pollutants were linked to the incidence of chronic diseases such as chronic kidney disease, diabetes, and hypertension (p< 0.05). Our study, utilizing various machine learning models, also showed a notable increase in the Area Under the Curve when incorporating organochlorine pesticide indicators into the model as opposed to excluding them. Furthermore, strong correlations were observed between serum c-reactive protein (CRP) and CRP to serum albumin ratio (CAR) concentrations with these substances, demonstrating their pro-inflammatory effects at specific concentrations. Interestingly, cutting down on dietary inflammation through changes in diet effectively reduced the risk of death at high organochlorine pesticide exposure levels, but the effect was less noticeable at low to moderate exposure levels. Conclusions: Exposure to organochlorine pesticides was linked to a higher risk of mortality, likely due to an increased prevalence of chronic diseases. In this context, inflammation played a crucial role, and adopting an anti-inflammatory diet significantly reduced the mortality risk associated with these pesticides.

The systemic inflammatory response index (SIRI), a straightforward and easily accessible measure of inflammation and prognosis, has drawn more attention lately. It is unknown, however, if SIRI is important for IgA nephropathy (IgAN) patients’ outcomes. To better clarify these concerns, we conducted this investigation. This retrospective study involved 981 patients with biopsy-confirmed IgAN from West China Hospital of Sichuan University between 2008 and 2019. The patients were divided into two groups based on the SIRI’s optimal cut-off value calculated by the X-tile: the low SIRI group (SIRI ≤ 0.63, n = 312) and the high SIRI group (SIRI > 0.63, n = 669). Basic clinical characteristics at the time of renal biopsy were evaluated, and the relationship between SIRI and the combined endpoint was analyzed. We also used the Cox proportional hazard model and Kaplan‒Meier curve to evaluate the renal prognosis of IgAN. A total of 981 IgAN patients were included. During a median follow-up period of 56.7 months (36.8–80.4 months), 122 patients progressed to the combined endpoint (12.4