UNASSIGNED: Limited investigation is available on the correlation between environmental phenols\' exposure and estimated glomerular filtration rate (eGFR). Our target is established a robust and explainable machine learning (ML) model that associates environmental phenols\' exposure with eGFR.
UNASSIGNED: Our datasets for constructing the associations between environmental phenols\' and eGFR were collected from the National Health and Nutrition Examination Survey (NHANES, 2013-2016). Five ML models were contained and fine-tuned to eGFR regression by phenols\' exposure. Regression evaluation metrics were used to extract the limitation of the models. The most effective model was then utilized for regression, with interpretation of its features carried out using shapley additive explanations (SHAP) and the game theory python package to represent the model\'s regression capacity.
UNASSIGNED: The study identified the top-performing random forest (RF) regressor with a mean absolute error of 0.621 and a coefficient of determination of 0.998 among 3,371 participants. Six environmental phenols with eGFR in linear regression models revealed that the concentrations of triclosan (TCS) and bisphenol S (BPS) in urine were positively correlated with eGFR, and the correlation coefficients were β = 0.010 (p = 0.026) and β = 0.007 (p = 0.004) respectively. SHAP values indicate that BPS (1.38), bisphenol F (BPF) (0.97), 2,5-dichlorophenol (0.87), TCS (0.78), BP3 (0.60), bisphenol A (BPA) (0.59) and 2,4-dichlorophenol (0.47) in urinary contributed to the model.
UNASSIGNED: The RF model was efficient in identifying a correlation between phenols\' exposure and eGFR among United States NHANES 2013-2016 participants. The findings indicate that BPA, BPF, and BPS are inversely associated with eGFR.

BACKGROUND: Parkinson\'s disease (PD) is a neurodegenerative influenced by various clinical factors. The potential relationship between renal function and the risk of PD remains poorly understood. This study aims to explore the association between kidney function and the risk of developing PD.
METHODS: A population-based cohort study was conducted using data from 400,571 UK Biobank participants. Renal function was assessed using the estimated glomerular filtration rate (eGFR), calculated from serum creatinine and cystatin C levels. The association between eGFR levels and PD risk was evaluated using univariate and multivariate Cox regression analyses, Restricted Cubic Spline (RCS) analysis, and Kaplan-Meier analysis. Additionally, a clinical prediction model was developed and its diagnostic accuracy was evaluated using ROC analysis. A heatmap was also constructed to examine the relationship between clinical factors and gray matter volume in various brain regions.
RESULTS: Over a median observation period of 13.8 years, 2740 PD events were recorded. Cox regression and Kaplan-Meier analyses revealed a significant association between decreased eGFR and increased PD risk, particularly in participants with eGFR < 30 ml/min/1.73 m2. This association was confirmed across three adjusted models. RCS analysis demonstrated a nonlinear relationship between decreasing eGFR and increasing PD risk. Furthermore, changes in eGFR were correlated with alterations in subcortical gray matter volume in regions such as the frontal cortex, striatum, and cerebellum. The clinical prediction model showed high diagnostic accuracy with AUC values of 0.776, 0.780, and 0.824 for 4-, 8-, and 16-year predictions, respectively.
CONCLUSIONS: Renal insufficiency is significantly associated with an increased risk of PD, highlighting the importance of maintaining good kidney function as a potential preventive measure against PD.

UNASSIGNED: The oxidative balance score (OBS) is a comprehensive concept that includes 20 oxidative stressors and can be used to assess individual pro-oxidant versus antioxidant exposure, and the aim of the present study was to investigate the association between OBS and the risk of diabetic kidney disease (DKD), low estimated glomerular filtration rate (low-eGFR) and albuminuria in patients with diabetes mellitus (DM).
UNASSIGNED: This cross-sectional study included nationally representative consecutive National Health and Nutrition Examination Survey DM patients aged 18 years and older from 2003-2018. The continuous variable OBS was converted into categorical variables by quartiles, and weighted multiple logistic regression analyses and restricted triple spline models were used to explore the relationships. We also performed subgroup analyses and interaction tests to verify the stability of the results.
UNASSIGNED: A total of 5389 participants were included, representing 23.6 million non-institutionalized US residents. The results from both multivariate logistic regression analysis and restricted cubic spline models indicated that OBS and dietary OBS levels were negatively associated with the risk of DKD, low-eGFR, and albuminuria, without finding a significant correlation between lifestyle OBS and these clinical outcomes. Compared to the lowest OBS quartile group, the prevalence risk of DKD (OR = 0.61, 95% CI: 0.46-0.80), low-eGFR (OR = 0.46, 95% CI: 0.33-0.64) and albuminuria (OR = 0.68, 95% CI: 0.51-0.92) decreased by 39%, 54% and 32%, respectively, in the highest OBS quartile group. The results remained stable in subgroup analyses and no interaction between subgroups was found.
UNASSIGNED: Higher levels of OBS and dietary OBS were associated with a lower risk of DKD, low-eGFR, and albuminuria. These findings provided preliminary evidence for the importance of adhering to an antioxidant-rich diet and lifestyle among individuals with diabetes.

UNASSIGNED: High serum levels of B-cell activation factor (BAFF) and a proliferation-inducing ligand (APRIL) have been observed in patients with idiopathic membranous nephropathy (iMN); however, their relationships with disease severity and progression remain unclear.
UNASSIGNED: Patients with iMN diagnosed via renal biopsy were enrolled in this study. The concentrations of BAFF and APRIL were determined using ELISA kits. Proteinuria remission, including complete remission (CR) and partial remission (PR), and renal function deterioration were defined as clinical events. The Cox proportional hazards method was used to analyze the relationship between cytokine levels and disease progression.
UNASSIGNED: Seventy iMN patients were enrolled in this study, with a median follow-up time of 24 months (range 6-72 months). The serum levels of BAFF and APRIL were higher in iMN patients than in healthy controls but lower than those in minimal change disease (MCD) patients. The serum BAFF level was positively correlated with the serum APRIL level, serum anti-phospholipase A2 receptor (anti-PLA2R) antibody level, and 24-h proteinuria and negatively correlated with the serum albumin (ALB) level. However, no significant correlation was observed between the serum APRIL level and clinical parameters. According to the multivariate Cox proportional hazards regression model adjusted for sex, age, systolic blood pressure (SBP), estimated glomerular filtration rate (eGFR), immunosuppressive agent use, 24-h proteinuria, APRIL level, and anti-PLA2R antibody, only the serum BAFF level was identified as an independent predictor of PR (HR, 0.613; 95% CI, 0.405-0.927; p = 0.021) and CR of proteinuria (HR, 0.362; 95% CI, 0.202-0.648; p < 0.001).
UNASSIGNED: A high serum BAFF level is associated with severe clinical manifestations and poor disease progression in patients with iMN.

Glomerular hyperfiltration(GHF), as an early manifestation of prediabetes and diabetic kidney disease, occurs mainly by the mechanism of glomerular-tubular feedback and hemodynamic alterations, and the risk of hyperfiltration can be elevated in younger patients, shorter duration of the disease, poor glycemic control, and high-protein, low-salt diet. Currently, there is no recognized standard for the definition of GHF, GHF lacks typical clinical manifestations, imaging diagnostic criteria are unclear, and GHF-related laboratory markers need to be further studied. Hyperfiltration, if not diagnosed and intervened in time, can accelerate the damage of nephron and the rate of nephropathy progression, and increase the risk of complications and death. Sodium-glucose cotransporter 2 inhibitor(SGLT2i), glucagon-like peptide-1 receptor agonist(GLP-1RA)and so on can effectively reverse the hyperfiltration state. Clinical attention should be paid to the diagnosis of diabetic hyperfiltration and the prevention of its poor prognosis.
肾小球高滤过（GHF）作为糖尿病（DM）的早期表现，其发生机制主要是球管反馈（TGF）和血流动力学改变，年轻患者、病程较短、血糖控制不佳、高蛋白低盐饮食等可增加肾小球高滤过的风险。目前，GHF缺乏公认界定标准、典型的临床表现、影像学诊断标准，相关的实验室标志物也待进一步研究。肾小球高滤过若不及时诊断和干预，可加速肾单位的损害和肾病进展速度，增加糖尿病患者发生并发症和死亡风险。钠-葡萄糖共转运蛋白2抑制剂（SGLT2i）、胰高糖素样肽-1受体激动剂（GLP-1RA）等均可有效逆转糖尿病高滤过状态。临床上应重视糖尿病高滤过的诊断及其不良预后的预防。.

UNASSIGNED: Extensive researches highlight the detrimental impact of sleep disorders such as insomnia and insufficient sleep duration on kidney function. However, establishing a clear causal relationship between insomnia, sleep duration, and kidney function remains challenging. This study aims to estimate this relationship using Mendelian randomization (MR).
UNASSIGNED: Independent genetic variants strongly associated with insomnia (N = 462,341) and sleep duration (N = 460,099) were selected as instrumental variables from corresponding genome-wide association studies (GWAS). Kidney function parameters, including serum creatinine, estimated glomerular filtration rate by cystatin C (eGFRcys), acute renal failure (ARF), chronic renal failure (CRF), kidney injury molecule-1, neutrophil gelatinase associated lipocalin, microalbuminuria, cystatin C, and β2 microglobulin, were derived from GWAS databases. A two-sample MR study was conducted to assess the causal relationship between sleep disorders and kidney function, and multivariable MR was used to identify potential mediators. The inverse-variance weighted was used as the primary estimate.
UNASSIGNED: MR analysis found robust evidence indicating that insomnia and short sleep duration were associated with an increased risk of elevated serum creatinine, regardless of adjusting for obesity. Causal links between sleep duration and eGFRcys or cystatin C were also identified. While genetically predicted insomnia and sleep duration were found to potentially impact ARF, CRF, microalbuminuria, and β2 microglobulin, the p-values in multivariable MR analysis became nonsignificant. No pleiotropy was detected.
UNASSIGNED: This study demonstrates a causal impact of insomnia on the risk of elevated serum creatinine and a positive effect of sleep duration on serum creatinine, eGFRcys, and cystatin C. Our findings also suggest their potential indirect effects on ARF, CRF, microalbuminuria, and β2 microglobulin mediated by obesity.

UNASSIGNED: Despite the potential demonstrated by targeted plasma metabolite modulators in halting the progression of chronic kidney disease (CKD), a lingering uncertainty persists concerning the causal relationship between distinct plasma metabolites and the onset and progression of CKD.
UNASSIGNED: A genome-wide association study was conducted on 1,091 metabolites and 309 metabolite ratios derived from a cohort of 8,299 unrelated individuals of European descent. Employing a bidirectional two-sample Mendelian randomization (MR) analysis in conjunction with colocalization analysis, we systematically investigated the associations between these metabolites and three phenotypes: CKD, creatinine-estimated glomerular filtration rate (creatinine-eGFR), and urine albumin creatinine ratio (UACR). In the MR analysis, the primary analytical approach employed was inverse variance weighting (IVW), and sensitivity analysis was executed utilizing the MR-Egger method and MR-pleiotropy residual sum and outlier (MR-PRESSO). Heterogeneity was carefully evaluated through Cochrane\'s Q test. To ensure the robustness of our MR results, the leave-one-out method was implemented, and the strength of causal relationships was subjected to scrutiny via Bonferroni correction.
UNASSIGNED: Our thorough MR analysis involving 1,400 plasma metabolites and three clinical phenotypes yielded a discerning identification of 21 plasma metabolites significantly associated with diverse outcomes. Specifically, in the forward MR analysis, 6 plasma metabolites were determined to be causally associated with CKD, 16 with creatinine-eGFR, and 7 with UACR. Substantiated by robust evidence from colocalization analysis, 6 plasma metabolites shared causal variants with CKD, 16 with creatinine-eGFR, and 7 with UACR. In the reverse analysis, a diminished creatinine-eGFR was linked to elevated levels of nine plasma metabolites. Notably, no discernible associations were observed between other plasma metabolites and CKD, creatinine-eGFR, and UACR. Importantly, our analysis detected no evidence of horizontal pleiotropy.
UNASSIGNED: This study elucidates specific plasma metabolites causally associated with CKD and renal functions, providing potential targets for intervention. These findings contribute to an enriched understanding of the genetic underpinnings of CKD and renal functions, paving the way for precision medicine applications and therapeutic strategies aimed at impeding disease progression.

UNASSIGNED: Population aging is a pivotal trend observed globally, and the exposure to heavy metals can exacerbate the aging process and lead to kidney damage. However, the impact of combined heavy metal exposure on renal function among older individuals remains elusive. Our study employs machine learning techniques to delve into the effects and underlying mechanisms of mixed exposure to heavy metals on the renal function of the aging population.
UNASSIGNED: This study extracted comprehensive data from the National Health and Nutrition Examination Survey (NHANES) conducted between 2015 and 2020. A total of 3,175 participants aged 60 years and above, with complete information on six metals - lead, cadmium, manganese, cobalt, mercury, and selenium, along with relevant covariates, were included in the study. To assess the impact of single or mixed metal exposure on the renal function of older adult individuals, various statistical techniques were employed: multiple logistic regression, weighted quantitative sum (WQS) regression, Bayesian kernel machine regression (BKMR), and mediation effects analysis.
UNASSIGNED: Multiple logistic regression revealed that selenium and manganese were protective factors for chronic kidney disease (CKD). Cobalt was a risk factor for CKD. High concentrations of lead, cadmium, and cobalt were risk factors for urinary albumin creatinine ratio (ACR). WQS analyses revealed that mixed metal exposure was positively correlated with estimated glomerular filtration rate (eGFR) but negatively correlated with CKD. Selenium and manganese can neutralize the effects of other metals on eGFR. Mixed metal exposure was positively correlated with ACR, with lead and cadmium having a substantial effect. Mediation analysis showed that uric acid (UA) had a mediating effect of 9.7% and -19.7% in the association between mixed metals exposure and proteinuria and CKD, respectively.
UNASSIGNED: The impact of heavy metals on renal function in the older adult differs from that of adolescents and adults. This study suggests that elevated levels of mixed metals exposure are linked to proteinuria and CKD, with UA serving as a mediating factor.

BACKGROUND: The neutrophil-percentage-to-albumin ratio (NPAR), a novel inflammatory biomarker, has been used to predict the prognosis of patients with cancer and cardiovascular disease. However, the relationship between NPAR and chronic kidney disease (CKD) remains unknown. The purpose of this study was to investigate the possible association between NPAR and CKD.
METHODS: The cross-sectional study included participants with complete information on NPAR, serum creatinine (Scr), or urinary albumin-to-creatinine ratio (UACR) from the 2009-2018 National Health and Nutrition Examination Survey (NHANES). CKD was defined as the presence of either low estimated glomerular filtration rate (eGFR) or albuminuria. Univariate and multivariate logistic regression and restricted cubic spline regression were used to assess the linear and nonlinear associations between NPAR and renal function. Subgroup and interactive analyses were performed to explore potential interactive effects of covariates. Missing values were imputed using random forest.
RESULTS: A total of 25,236 participants were enrolled in the study, of whom 4518 (17.9%) were diagnosed with CKD. After adjustment for covariates, the odds ratios (ORs) for prevalent CKD were 1.19 (95% CI = 1.07-1.31, p <0.05) for the Q2 group, 1.53 (95% CI = 1.39-1.69, p < 0.001) for the Q3 group, and 2.78 (95% CI = 2.53-3.05, p < 0.001) for the Q4 group. There was a significant interaction between age and diabetes mellitus on the association between NPAR and CKD (both p for interaction < 0.05). And there was a non-linear association between NPAR levels and CKD in the whole population (p for non-linear < 0.001). All sensitivity analyses supported the positive association between NPAR and CKD.
CONCLUSIONS: NPAR was positively correlated with increased risk of CKD. The NPAR may serve as an available and cost-effective tool for identifying and intervening the individuals at risk of CKD.

UNASSIGNED: This study aimed to evaluate the efficacy and safety of polyethylene glycol loxenatide (PEG-Loxe) compared to those of dapagliflozin in patients with mild-to-moderate diabetic kidney disease (DKD), a prevalent microvascular complication of type 2 diabetes mellitus (T2DM). The study is set against the backdrop of increasing global diabetes incidence and the need for effective DKD management.
UNASSIGNED: This study constituted a single-center, randomized, open-label, clinical trial. The trial included patients with mild-to-moderate DKD and suboptimal glycemic control. Eligible participants were randomly allocated to one of the two groups for treatment with either PEG-Loxe or dapagliflozin. The primary endpoint was the change in UACR from baseline at 24 weeks.
UNASSIGNED: Overall, 106 patients were randomized and 80 patients completed the study. Following 24 weeks of treatment, the PEG-Loxe group exhibited a mean percent change in baseline UACR of -29.3% (95% confidence interval [CI]: -34.8, -23.7), compared to that of -31.8% in the dapagliflozin group (95% CI: -34.8, -23.7). Both PEG-Loxe and dapagliflozin showed similar efficacy in reducing UACR, with no significant difference between the groups (p = 0.336). The HbA1c levels decreased by -1.30% (95% CI: -1.43, -1.18) in the PEG-Loxe group and by -1.29% (95% CI: -1.42, -1.17) in the dapagliflozin group (p = 0.905). The TG levels decreased by -0.56 mmol/L (95% CI: -0.71, -0.42) in the PEG-Loxe group and -0.33 mmol/L (95% CI: -0.48, -0.19) in the dapagliflozin group (p = 0.023). Differences in TC, HDL-C, LDL-C, SBP, and DBP levels between the groups were not statistically significant (all p > 0.05). Safety profiles were consistent with previous findings, with gastrointestinal adverse events being more common in the PEG-Loxe group.
UNASSIGNED: PEG-Loxe is as effective as dapagliflozin in improving urine protein levels in patients with mild-to-moderate DKD and offers superior benefits in improving lipid profiles. These findings support the use of PEG-Loxe in DKD management, contributing to evidence-based treatment options.
UNASSIGNED: www.chictr.org.cn, identifier ChiCTR2300070919.