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.

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.

Chronic kidney disease (CKD) is a heterogeneous disorder that affects the kidney structure and function. This study investigated the effect of the interaction between genetic factors and dietary pattern on kidney dysfunction in Korean adults.
Baseline data were obtained from the Ansan and Ansung Study of the Korean Genome and Epidemiology Study involving 8230 participants aged 40-69 years. Kidney dysfunction was defined as an estimated glomerular filtration rate < 90 mL/minute/1.73 m2. Genomic DNAs genotyped on the Affymetrix® Genome-Wide Human SNP array 5.0 were isolated from peripheral blood. A genome-wide association study using a generalized linear model was performed on 1,590,162 single-nucleotide polymorphisms (SNPs). To select significant SNPs, the threshold criterion was set at P-value < 5 × 10-8. Linkage disequilibrium clumping was performed based on the R2 value, and 94 SNPs had a significant effect. Participants were divided into two groups based on their generic risk score (GRS): the low-GR group had GRS > 0, while the high-GR group had GRS ≤ 0.
Three distinct dietary patterns were extracted, namely, the \"prudent pattern,\" \"flour-based and animal food pattern,\" and \"white rice pattern,\" to analyze the effect of dietary pattern on kidney function. In the \"flour-based and animal food pattern,\" higher pattern scores were associated with a higher prevalence of kidney dysfunction in both the low and high GR groups (P for trend < 0.0001 in the low-, high-GR groups of model 1; 0.0050 and 0.0065 in the low-, high-GR groups of model 2, respectively).
The results highlight a significant association between the \'flour-based and animal food pattern\' and higher kidney dysfunction prevalence in individuals with both low and high GR. These findings suggest that personalized nutritional interventions based on GR profiles may become the basis for presenting GR-based individual dietary patterns for kidney dysfunction.

UNASSIGNED: Identifying the biomarkers associated with new-onset glomerular filtration rate (GFR) decrease in an initially healthy population could offer a better understanding of kidney function decline and help improving patient management.
UNASSIGNED: Here we described the proteomic and transcriptomic footprints associated with new-onset kidney function decline in an initially healthy and well-characterized population with a 20-year follow-up. This study was based on 1087 individuals from the familial longitudinal Suivi Temporaire Annuel Non-Invasif de la Santé des Lorrains Assurés Sociaux (STANISLAS) cohort who attended both visit 1 (from 1993 to 1995) and visit 4 (from 2011 to 2016). New-onset kidney function decline was approached both in quantitative (GFR slope for each individual) and qualitative (defined as a decrease in GFR of >15 ml/min/1.7 m2) ways. We analysed associations of 445 proteins measured both at visit 1 and visit 4 using Olink Proseek® panels and 119 765 genes expressions measured at visit 4 with GFR decline. Associations were assessed using multivariable models. The Bonferroni correction was applied.
UNASSIGNED: We found several proteins (including PLC, placental growth factor (PGF), members of the tumour necrosis factor receptor superfamily), genes (including CCL18, SESN3), and a newly discovered miRNA-mRNA pair (MIR1205-DNAJC6) to be independently associated with new-onset kidney function decline. Complex network analysis highlighted both extracellular matrix and cardiovascular remodelling (since visit 1) as well as inflammation (at visit 4) as key features of early GFR decrease.
UNASSIGNED: These findings lay the foundation to further assess whether the proteins and genes herein identified may represent potential biomarkers or therapeutic targets to prevent renal function impairment.

Autosomal dominant polycystic kidney disease (ADPKD) is characterized by epithelial proliferation and progressive cyst enlargement. Using a non-targeted high-resolution metabolomics approach, we analyzed biofluids from 36 ADPKD and 18 healthy controls with estimated glomerular filtration rate (eGFR) > 60 ml/min to identify features specific to ADPKD or that associate with disease severity [eGFR or height-corrected total kidney volume (htTKV)]. Multiple pathways differed between ADPKD subjects and controls, with the histidine pathway being the most highly represented. Plasma histidine, urinary N-methylhistamine, methylimidazole-acetaldehyde, and imidazole-acetaldehyde, as well as 3-methylhistidine and anserine were increased, while plasma N-acetylhistamine and urinary imidazole-acetic acid were decreased in ADPKD compared to controls. In ADPKD, urinary histidine and a histidine derivative, urocanate (a precursor of glutamate), were significantly associated. HtTKV and eGFR were inversely associated with urinary glutamine and plasma 4-imidazolone-5-propionic acid, respectively. Supernatant from cultured human ADPKD renal cystic epithelia demonstrated increased aspartate and glutamate levels at 8 and 24 hours compared to primary tubular epithelia (p < 0.001). Following exposure over 48 hours to α-fluromethylhistidine, an inhibitor of histamine production, primary human PKD1 cyst epithelia proliferation increased significantly from baseline (p < 0.01) and greater than non-cystic epithelia (p < 0.05). The histidine ammonia lyase inhibitor nitromethane reversed α-fluromethylhistidine-induced cyst epithelia proliferation indicating a role for glutamate in cyst growth. In conclusion, histidine metabolism is altered preferentially leading to glutamate production and epithelial proliferation in ADPKD and associates with disease severity.

BACKGROUND: Currently, kidney disease is an increasing major health problem worldwide. It is expected to be the 5th ranked cause of death by 2040. If it is early detected, further complication caused by kidney disease will be minimized. An assessment of impaired glomerular filtration rate (eGFR) has potential aids in early identification and treatment of kidney disease. However, in hospital practice instead of using eGFR, direct measurement of serum creatinine level is used for assessing renal function. Hence, this study is aimed to assess the magnitude and associated factors of impaired glomerular filtration rate among admitted patients in Wolkite University Specialized Teaching Hospital (WKUSTH).
OBJECTIVE: To assess the magnitude and associated factors of impaired glomerular filtration rate in WKUSTH, Ethiopia 2023.
METHODS: Institutional based cross-sectional study with secondary data was conducted. 338 participants were selected by a convenient sampling technique. Epidata 3.1 version for data entry and SPSS version 20 for data analysis was used. Bivariate analysis was used to screen candidate variables for multivariate analysis. In the multivariate analysis a P-value < 0.05 were considered statistically significant.
RESULTS: The study enrolled 338 patients admitted to WUSTH. Seventy (20.7%) (95% CI: 16.6-25.4%) of them had impaired eGFR according to Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation and Modification of Diet in Renal Disease (MDRD-4). older age (AOR 3.38, 95% CI; 1.31, 8.71), hypertension (AOR 17.8, 95% CI; 7.75, 41.22), anemia (AOR 2.51, 95% CI; 1.11, 5.83) DM (AOR 11.2, 95% CI; 4.11, 30.73), and high BMI (AOR 7.56, 95% CI; 3.16, 18.08), were independently associated with impaired eGFR.
CONCLUSIONS: The magnitude of impaired eGFR was prevalent among adult patients admitted to WKUSTH medical ward with different medical conditions. Old age, Hypertension, Diabetes, high body mass index, and Anemia were significantly associated with impaired eGFR both in CKD-EPI and MDRD-4 equation. Estimation of GFR for all hospitalized adults with known CKD risk factors might help in early detection of CKD and prevent complications.

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: Metabolic and bariatric surgery (MBS) reduces glomerular hyperfiltration. The renoprotective effects of GLP-1 analogs were derived from clinical studies in type 2 diabetes (T2D). The objective of this study was to evaluate the changes in glomerular filtration rate (GFR) over time associated with weight loss in patients with a BMI ≥ 35 kg/m2 treated with liraglutide compared with patients treated with MBS.
UNASSIGNED: A longitudinal study derived from a retrospective cohort of patients with BMI ≥ 35 kg/m2 treated with either MBS or liraglutide 3 mg/day, with follow-up ≥1 year. Clinical variables, baseline GFR, and 1-year GFR were analyzed. A generalized estimating equation (GEE) model was used to compare changes in GFR between both groups while controlling for confounding variables.
UNASSIGNED: A total of 159 patients were included in the analysis. Of these, 129 patients underwent MBS (median age 60.5 years [IQR 51.8-66.6], body mass index (BMI) 40.9 kg/m2 [IQR 0.68-0.89]), and 30 patients were treated with liraglutide (median age 56 years [IQR 46-62], BMI 37.4 kg/m2 [IQR 0.69-0.93]). No difference in baseline GFR or at 12 months of follow-up was found between the two interventions. GEE analysis revealed an increase of 0.32 mL/min/1.73 m2 per month of follow-up. Factors associated with a greater increase in GFR were the percentage total weight loss (%TWL) (0.12 mL/min/1.73 m2, p = 0.023) and baseline GFR (0.69 mL/min/1.73 m2, p > 0.001) for both interventions, independent of a history of T2D.
UNASSIGNED: In patients with BMI ≥ 35 kg/m2, changes in GFR are related to %TWL and baseline GFR, regardless of the presence of diabetes or the type of intervention used.

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.

Chronic kidney disease (CKD) is a microvascular complication that frequently affects numerous patients diagnosed with diabetes. For the diagnosis of CKD, the guidelines recommend the identification of the urinary albumin/creatinine ratio and the determination of serum creatinine, based on which the estimated rate of glomerular filtration (eGFR) is calculated. Serum creatinine is routinely measured in clinical practice and reported as creatinine-based estimated glomerular filtration rate (eGFRcr). It has enormous importance in numerous clinical decisions, including the detection and management of CKD, the interpretation of symptoms potentially related to this pathology and the determination of drug dosage. The equations based on cystatin C involve smaller differences between race groups compared to GFR estimates based solely on creatinine. The cystatin C-based estimated glomerular filtration rate (eGFRcys) or its combination with creatinine (eGFRcr-cys) are suggested as confirmatory tests in cases where creatinine is known to be less precise or where a more valid GFR estimate is necessary for medical decisions. Serum creatinine is influenced by numerous factors: age, gender, race, muscle mass, high-protein diet, including protein supplements, and the use of medications that decrease tubular creatinine excretion (H2 blockers, trimethoprim, fenofibrate, ritonavir, and other HIV drugs). The low levels of creatinine stemming from a vegetarian diet, limb amputation, and conditions associated with sarcopenia such as cirrhosis, malnutrition, and malignancies may lead to inaccurately lower eGFRcr values. Therefore, determining the GFR based on serum creatinine is not very precise. This review aims to identify a new perspective in monitoring renal function, considering the disadvantages of determining the GFR based exclusively on serum creatinine.