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Abstract Chronic kidney disease (CKD) is a major worldwide health problem, affecting a large proportion of the world’s population and leading to higher morbidity and death rates. The early stages of CKD sometimes present without visible symptoms, causing patients to be unaware. Early detection and treatments are critical in reducing complications and improving the overall quality of life for people afflicted. In this work, we investigate the use of an explainable artificial intelligence (XAI)-based strategy, leveraging clinical characteristics, to predict CKD. This study collected clinical data from 491 patients, comprising 56 with CKD and 435 without CKD, encompassing clinical, laboratory, and demographic variables. To develop the predictive model, five machine learning (ML) methods, namely logistic regression (LR), random forest (RF), decision tree (DT), Naïve Bayes (NB), and extreme gradient boosting (XGBoost), were employed. The optimal model was selected based on accuracy and area under the curve (AUC). Additionally, the SHAP (SHapley Additive exPlanations) and LIME (Local Interpretable Model-agnostic Explanations) algorithms were utilized to demonstrate the influence of the features on the optimal model. Among the five models developed, the XGBoost model achieved the best performance with an AUC of 0.9689 and an accuracy of 93.29%. The analysis of feature importance revealed that creatinine, glycosylated hemoglobin type A1C (HgbA1C), and age were the three most influential features in the XGBoost model. The SHAP force analysis further illustrated the model’s visualization of individualized CKD predictions. For further insights into individual predictions, we also utilized the LIME algorithm. This study presents an interpretable ML-based approach for the early prediction of CKD. The SHAP and LIME methods enhance the interpretability of ML models and help clinicians better understand the rationale behind the predicted outcomes more effectively.

Abstract Previous studies had reported the mutual relation between depression and chronic kidney diseases (CKD). This study aimed to investigate potential bidirectional relationships between depression and CKD. Participants more than 45 years from the China Health and Retirement Longitudinal Study (CHARLS) were included in present study. In study I, we tended to assess the association between baseline depression with the risk of subsequent CKD. In study II, we aimed to examine whether the onset of CKD could predict the development of depression. Multivariate logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs) in study I and study II, respectively. In study I, 301 (6.16%) respondents experienced CKD in participants without depression, and 233 (8.48%) respondents experienced CKD in participants with depression. Participants with depression had higher risk of developing CKD with the corresponding ORs (95% CIs) was 1.38(1.08–1.76). In study II, 1333 (22.29%) subjects in the non-CKD group and 97 (27.17%) in CKD group developed depressive symptoms. Individuals with CKD had higher risk of developing depression than those without CKD, with the multivariate ORs (95% CIs) was 1.48(1.23–1.78). Significant bidirectional relationships remained in both sensitivity and subgroup analyses. Findings demonstrate bidirectional relationships between depression and CKD. Individuals with depression were associated with increasing risk of CKD; in addition, CKD patients had higher risk of developing depression.

Abstract Purpose We aimed to determine predictors of chronic kidney disease (CKD) prevention among patients with diabetes. Method A cross-sectional study was conducted on 1000 selected respondents based on socio-demographic, socio-economic, general CKD perception knowledge, self-monitoring advocacy, preventive behavior, treatment compliance, and psychosocial factors. Using multiple logistic regression, variables and their association with impaired perception of CKD prevention were analyzed. Results Overall, 74% had poor perception regarding CKD prevention (68.7% of men and 31.3% of women). In multivariable analysis, those with weak illness identity fear were two times more likely to have poor perceptions (95% CI 1.563–3.196, p

Abstract Chronic kidney disease is a major public health concern that affects millions of people globally. Alterations in gut microbiota composition have been observed in patients with chronic kidney disease. Nevertheless, the correlation between the gut microbiota and disease severity has not been investigated. In this study, we performed shot-gun metagenomics sequencing and identified several taxonomic and functional signatures associated with disease severity in patients with chronic kidney disease. We noted that 19 microbial genera were significantly associated with the severity of chronic kidney disease. The butyrate-producing bacteria were reduced in patients with advanced stages of chronic kidney diseases. In addition, functional metagenomics showed that two-component systems, metabolic activity and regulation of co-factor were significantly associated with the disease severity. Our study provides valuable information for the development of microbiota-oriented therapeutic strategies for chronic kidney disease.

Abstract In this study we conducted a cross sectional study to comprehensively evaluated the risk factors of chronic kidney disease (CKD) in a large sample of Chinese adults under primary care for type 2 diabetes mellitus (T2DM). We investigated the risk factors associated with the prevalence of CKD in adults with T2DM, who were enrolled in the Risk Factor Assessment and Management Programme for Patients with Diabetes Mellitus (RAMP-DM) of Hong Kong from July 2014 to June 2017. We collected the individual data of 31,574 subjects, with mean age of 63.0 (±10.8) years and mean DM duration of 7.4 (±6.4) years. Of them 9,386 (29.7%) had CKD and 7,452 (23.6%) had micro- or macro-albuminuria. After adjustment for multiple demographic and lifestyle confounders, we identified several modifiable risk factors associated with higher rate of CKD: obesity (OR = 1.54), current smoking (OR = 1.33), higher systolic blood pressure (OR = 1.01), dyslipidemia (OR = 1.32 and 0.61 for triglycerides (TG) and high-density lipoprotein cholesterol (HDL-C)), hyperglycemia (OR = 1.11 for HbA1c), diabetic retinopathy (OR = 1.36 and 2.60 for non-sight and sight threatening retinopathy), and stroke (OR = 1.43). The risk factors of lower dialytic blood pressure and coronary heart disease were identified only in men, whereas peripheral arterial disease only in women. In conclusion, several modifiable and gender specific risk factors were significantly associated with higher prevalence of CKD in Chinese adults with T2DM. The high-risk populations identified in this study shall receive regular screening for renal functions to achieve better patient management in primary care settings.

Abstract Cisplatin is the most commonly used platinum-based treatment for nasopharyngeal carcinoma (NPC). However, its clinical application is limited owing to its nephrotoxicity and gastrointestinal reactions. Proton pump inhibitors (PPIs) have been reported to increase nephrotoxicity risk in previous studies. We aimed to evaluate whether PPIs increase cisplatin-induced nephrotoxicity in patients with NPC. In total, 295 patients were included in this prospective cohort study: 145 in the PPIs group and 150 in the non-PPIs group. All patients underwent cisplatin-based induction chemotherapy, followed by cisplatin-based concurrent chemoradiotherapy. The PPIs group received 40 mg of intravenous esomeprazole sodium for 7 days in each chemotherapy cycle. Chi-squared test and logistic regression analyses with odds ratios and 95% confidence intervals were applied to assess the association between PPIs and the risk of acute kidney injury (AKI). AKI incidence in the PPIs group was significantly higher than that in the non-PPIs group (P = 0.005). After adjusting for various confounders including demographic features, clinical features, and renal function indices, PPIs use was significantly associated with a higher AKI risk (odds ratio: 2.775; 95% confidence interval 1.280–6.020; P = 0.010). The incidences of acute and chronic kidney diseases were similar between both groups (P > 0.05), whereas the incidence of nausea was lower in the PPIs group than in the non-PPIs group (P = 0.029). This study has shown that PPIs use may increase the risk of cisplatin-induced acute nephrotoxicity in patients with NPC.

Abstract This study aimed to investigate the estimated burden attributed to lead exposure (LE), at the national and subnational levels from 1990 to 2019 in Iran. The burden attributed to LE was determined through the estimation of deaths, disability-adjusted life years (DALYs), years of life lost (YLLs) and years lived with disability (YLDs) using the comparative risk assessment method of Global Burden of Disease (GBD) study presenting as age-standardized per 100,000 person year (PY) with 95% uncertainty intervals (95% UI). Furthermore, the burden of each disease were recorded independently. Eventually, the age-standardized YLLs, DALYs, deaths and YLDs rates attributed to LE demonstrated a decrease of 50.7%, 48.9%, 38.0%, and 36.4%, respectively, from 1990 to 2019. The most important causes of LE burden are divided into two acute and chronic categories: acute, mainly causes mental disorders (DALYs rate of 36.0 in 2019), and chronic, results in cardiovascular diseases (CVDs) (DALYs rate of 391.8) and chronic kidney diseases (CKDs) (DALYs rate of 26.6), with CVDs bearing the most significant burden. At the sub-national level, a decrease in burden was evident in most provinces; moreover, low and low-middle SDI provinces born the highest burden. The burden increased mainly by ageing and was higher in males than females. It was concluded that although the overall decrease in the burden; still it is high, especially in low and low-middle SDI provinces, in advanced ages and in males. Among IDID, CKDs and CVDs that are the most important causes of LE-attributed burden in Iran; CVDs bear the highest burden.

Abstract Renal fibrosis (RF) is the common pathway for a variety of chronic kidney diseases that progress to end-stage renal disease. Chitosan oligosaccharide (COS) has been identified as possessing many health functions. However, it is not clear whether COS can prevent RF. The purpose of this paper was to explore the action and mechanism of COS in alleviating RF. First, an acute unilateral ureteral obstruction operation (UUO) in male BALB/c mice was performed to induce RF, and COS or fosinopril (positive control drug) were administered for 7 consecutive days. Data from our experiments indicated that COS treatment can significantly alleviate kidney injury and decrease the levels of blood urea nitrogen (BUN) and serum creatinine (SCr) in the UUO mouse model. More importantly, our results show that COS can reduce collagen deposition and decrease the expression of fibrosis proteins, such as collagen IV, fibronectin, collagen I, α-smooth muscle actin (α-SMA) and E-cadherin, ameliorating experimental renal fibrosis in vivo. In addition, we also found that COS suppressed oxidative stress and inflammation in RF model mice. Further studies indicated that the mechanism by which COS alleviates renal fibrosis is closely related to the regulation of the TGF-β1/Smad pathway. COS has a therapeutic effect on ameliorating renal fibrosis similar to that of the positive control drug fosinopril. Taken together, COS can alleviate renal fibrosis induced by UUO by reducing oxidative stress damage and regulating the TGF-β1/Smad pathway.

Abstract Podocyte abnormalities are common mechanism driving the progression of glomerular diseases, which account for most chronic kidney diseases (CKDs). However, the role of podocyte in the mechanism of high-risk long-term CKD caused by prematurity has not been well clarified. In present study, urine samples of 86 preterm infants and 32 full-term infants were collected, and podocyte-specific podocin mRNA levels in urine pellet were applied to indicate urinary podocyte mRNA excretion. In addition, in a preterm animal rat model, preterm rats were identified by delivery 2 days early. From the age of 3 weeks–12 months, urine samples were collected to examine podocyte mRNA excretion by measuring podocyte-specific podocin mRNA levels. Kidney samples at the age of 3 weeks, 2 months, and 12 months were collected from 8, 5 and 6 preterm rats and 9, 6 and 8 full-term rats, respectively, to examine podocyte density and podocyte area by measuring the podocyte specific nuclear marker WT-1 and the podocyte specific marker synaptopodin. As results, a more than threefold increase of urinary podocyte-specific podocin mRNA excretion rate was found in preterm infants compared with full-term infants. In addition, there was negative correlation between gestational age at birth and urinary podocin mRNA excretion. In preterm rats, a reduction in the total number of differentiated podocytes in glomeruli and an increased podocyte podocin mRNA excretion rate in urine were detected at the end of kidney differentiation. Moreover, long-term follow-up data in preterm rats showed there was an increased the risk of renal disease indicated by persistent podocyte mRNA loss, proteinuria, and enlarged glomeruli. In conclusion, increasing podocyte mRNA excretion in urine and podocyte loss in kidney led by prematurity drive the progression of long-term abnormal kidney function and could potentially explain the high risk of long-term CKD in preterm infants.

Abstract Patients with chronic kidney diseases (CKD) are often treated with antiplatelets due to aberrant haemostasis. This study aimed to evaluate the bleeding risk with CKD patients undergoing pentoxifylline (PTX) treatment with/without aspirin. In this retrospective study, we used Taiwan’s National Health Insurance Research Database to identify PTX treated CKD patients. Patients undergoing PTX treatment after CKD diagnosis were PTX group. A 1:4 age, sex and aspirin used condition matched CKD patients non-using PTX were identified as controls. The outcome was major bleeding event (MBE: intracranial haemorrhage (ICH) and gastrointestinal tract bleeding) during 2-year follow-up period. Risk factors were estimated using Cox regression for overall and stratified analysis. The PTX group had higher MBE risk than controls (hazard ratio (HR) 1.19; 95% confidence interval (CI) 0.94–1.50). In stratified analysis, hyperlipidaemia was a significant risk factor (HR: 1.42; 95% CI 1.01–2.01) of MBE. A daily PTX dose larger than 800 mg, females, non-regular aspirin usage, and ischaemic stroke were risk factors for MBE in PTX group. When prescribing PTX in CKD patients, bleeding should be closely monitored, especially in those with daily dose more than 800 mg, aspirin users, and with a history of ischaemic stroke.

Abstract Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) may be linked to development of chronic kidney diseases (CKD). The FIB4 index, a noninvasive liver fibrosis score, has been reported to predict CKD in non-diabetic patients, but there are no reports yet in diabetic cases. Therefore, we evaluated the prognostic impact of FIB4 index on the risk of developing diabetic kidney disease (DKD) in Japanese patients with type 2 diabetes in a retrospective cohort study. We assessed patients with type 2 diabetes with an eGFR ≥ 60 mL/min/1.73 m2 and without dipstick positive proteinuria (≥ 1 +) at their first visit to our department. Participants were divided into two groups based on the FIB4 index at their first visit: FIB4 index > 1.3 and FIB4 index ≤ 1.3. The primary endpoint was defined as a decrease in eGFR 1.3 (32.0%) and the median observation period was 6.0 (3.8–11.0) years. Kaplan–Meier survival analysis indicated that the risks of developing DKD, eGFR 1.3 patients than in FIB4 ≤ 1.3 patients. In the Cox regression analysis, an FIB4 index > 1.3 was a significant predictor for onset of DKD (HR 1.54, 95% CI 1.15–2.08) and proteinuria (HR 1.55, 95% CI 1.08–2.23), but not for an eGFR 1.3 has a prognostic impact on the development of CKD and proteinuria in type 2 diabetic patients. This warrants further investigation of the prognostic impact of the development of DKD or proteinuria.

Abstract Although both angiotensin receptor blockers (ARBs) and dihydropyridine calcium channel blockers (CCBs) are all suitable for the initiation of antihypertensive treatment, studies investigating efficacy and safety between ARBs and CCBs are limited, and there is no previous study comparing their clinical outcomes during long-term follow-up periods in real world setting. We compared cardiovascular (CV) events between ARBs and CCBs in 464,948 hypertensive adults using the Korean National Health Insurance Service database during a 3-year follow-up. The patients with hypertension without heart failure, ischemic heart disease, cerebrovascular disease, or peripheral artery disease were enrolled. The CV events between only single prescription of CCBs and ARBs were finally compared. The primary endpoint for this study was the first occurrence of a major adverse CV events, defined as the composite of all-cause death, cardiac death, nonfatal myocardial infarction, or nonfatal stroke. ARB was significantly more administered in male and patients with higher income, diabetes mellitus, chronic kidney diseases, and higher Charlson comorbidity index. The primary endpoints occurred in 10,526 patients (5.2%) in the ARB group and in 19,363 patients (7.3%) in the CCB group (p

Abstract Glomerular endothelial cells (GEC) are a crucial component of the glomerular physiology and their damage contributes to the progression of chronic kidney diseases. How GEC affect the pathology of Alport syndrome (AS) however, is unclear. We characterized GEC from wild type (WT) and col4α5 knockout AS mice, a hereditary disorder characterized by progressive renal failure. We used endothelial-specific Tek-tdTomato reporter mice to isolate GEC by FACS and performed transcriptome analysis on them from WT and AS mice, followed by in vitro functional assays and confocal and intravital imaging studies. Biopsies from patients with chronic kidney disease, including AS were compared with our findings in mice. We identified two subpopulations of GEC (dimtdT and brighttdT) based on the fluorescence intensity of the TektdT signal. In AS mice, the brighttdT cell number increased and presented differential expression of endothelial markers compared to WT. RNA-seq analysis revealed differences in the immune and metabolic signaling pathways. In AS mice, dimtdT and brighttdT cells had different expression profiles of matrix-associated genes (Svep1, Itgβ6), metabolic activity (Apom, Pgc1α) and immune modulation (Apelin, Icam1) compared to WT mice. We confirmed a new pro-inflammatory role of Apelin in AS mice and in cultured human GEC. Gene modulations were identified comparable to the biopsies from patients with AS and focal segmental glomerulosclerosis, possibly indicating that the same mechanisms apply to humans. We report the presence of two GEC subpopulations that differ between AS and healthy mice or humans. This finding paves the way to a better understanding of the pathogenic role of GEC in AS progression and could lead to novel therapeutic targets.

Abstract We investigated the association between dietary patterns and prevalent chronic kidney diseases (CKD), in participants of the 2005–2012 US National Health and Nutrition Examination Survey (NHANES) conducted between 2005 and 2012, who had measured data on dietary intake and kidney function. Analyse of covariance (ANCOVA) and logistic regression models were employed to account for the survey design and sample weights. A total of 21,649 eligible participants (634 with and 20,015 without prevalent CKD) were included in the final analysis. Three food patterns together explained 50.8% of the variance of the dietary nutrients consumption. The first food pattern was representative of a diet containing high levels of saturated and mono-unsaturated fatty acids; the second food pattern comprised vitamins and trace elements; and the third food pattern was mainly representative of polyunsaturated fatty acids. The odd of prevalent CKD decreased across increasing quarters of vitamins and trace elements, so that the top quarter was associated with a 53% (95%CI: 42–62%) lower odds of CKD in age, sex and race adjusted logistic regression models. These results suggest that vitamins and trace elements intake are associated with lower risk of prevalent CKD.

Abstract Accumulating evidence suggests that dysregulation of hypoxia-regulated transcriptional mechanisms is involved in development of chronic kidney diseases (CKD). However, it remains unclear how hypoxia-induced transcription factors (HIFs) and subsequent biological processes contribute to CKD development and progression. In our study, genome-wide expression profiles of more than 200 renal biopsies from patients with different CKD stages revealed significant correlation of HIF-target genes with eGFR in glomeruli and tubulointerstitium. These correlations were positive and negative and in part compartment-specific. Microarrays of proximal tubular cells and podocytes with stable HIF1α and/or HIF2α suppression displayed cell type-specific HIF1/HIF2-dependencies as well as dysregulation of several pathways. WGCNA analysis identified gene sets that were highly coregulated within modules. Characterization of the modules revealed common as well as cell group- and condition-specific pathways, GO-Terms and transcription factors. Gene expression analysis of the hypoxia-interconnected pathways in patients with different CKD stages revealed an increased dysregulation with loss of renal function. In conclusion, our data clearly point to a compartment- and cell type-specific dysregulation of hypoxia-associated gene transcripts and might help to improve the understanding of hypoxia, HIF dysregulation, and transcriptional program response in CKD.

Abstract We aimed to assess the prevalence of chronic kidney diseases (CKD) markers among the married residents with fertility desire in rural China. Demographic and clinical data were collected from the National Free Pre-Conception Health Examination Project. Estimated glomerular filtration rate (eGFR)