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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., (© 2024. The Author(s).)

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., (© 2022. The Author(s).)

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 < 0.001). Respondents with weak medical practice (AOR = 2.33, 95% CI 1.609-2.381, p < 0.001) and weak cooperation (AOR = 1.563; 95% CI 1.099-2.224, p < 0.001) were more likely to have poor perceptions on CKD prevention. Concerning poor perception, significant predictors were self-employment, housewives, working in private jobs, weak knowledge on clear glycosuria, sleep problems, print media, digital media, illness identity fear, weak medical practice, and weak co-operation factors. Conclusion Media support is crucial for supporting and improving positive views regarding CKD knowledge. Interventions to reach people with limited awareness on CKD prevention, lower socioeconomic status, and poor social support may improve identification of patients with early-stage CKD. Particular care should be taken to recognize and provide necessary services regarding the early detection of CKD., (© 2022. The Author(s).)

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., (© 2021. The Author(s).)

Saliva can be used as an alternative diagnostic fluid enabling easy and non-invasive disease monitoring. Urea and creatinine can be measured in saliva and both were shown to be increased in renal failure. However, the dynamics of these markers during the development of kidney diseases is unknown. We aimed to describe the dynamics of salivary urea and creatinine in various animal models of acute kidney injury (AKI) and chronic kidney disease (CKD) and in patients with different stages AKI or CKD. Ninety Wistar rats underwent bilateral nephrectomy (BNX), ischemia-reperfusion injury (IRI) or glycerol-induced kidney injury to model AKI. CKD was modelled using 5/6 nephrectomy. In the clinical part 57 children aged 12.6 ± 4.9 years with AKI (n = 11) or CKD (n = 46) and 29 healthy controls (aged 10.2 ± 3.7 years) were enrolled. Saliva and blood samples were collected in both, animal experiments and the human study. In animal models of AKI, plasma urea and creatinine were higher than in controls. An increase of salivary urea and creatinine (twofold) was observed in BNX and IRI, but only after 12 h and 24 h, respectively. In glycerol nephropathy and 5/6 nephrectomy, salivary urea increased (by 100% and by 50%), while salivary creatinine did not change during the observation period. Salivary urea and creatinine were significantly higher in all patients compared to controls (threefold) and in both, AKI and CKD they were associated with the severity of renal failure. Plasma and salivary concentrations correlated only in children with renal failure (R = 0.72 for urea; R = 0.93 for creatinine), but not in controls (R = -0.007 for urea; R = 0.02 for creatinine). Our study indicates that during the development of renal impairment saliva could be used for non-invasive monitoring in higher stages of AKI or CKD, rather than for screening of early stages of kidney diseases.

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 HbA 1c ), 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.

In the clinic, the pathological types of chronic kidney diseases (CKD) are considered references for choosing treatment protocols. From a statistical viewpoint, a non-invasive method to predict pathological types of CKD is a focus of our work. In the current study, following a frequency analysis of the clinical indices of 588 CKD patients in the department of nephrology, a third-grade class-A hospital, a novel theory is proposed: "bi-directional cumulative probability dichotomy". Further, two models for the prediction and differential diagnosis of CKD pathological type are established. The former indicates an occurrence probability of the pathological types, and the latter indicates an occurrence of CKD pathological type according to logistic binary regression. To verify the models, data were collected from 135 patients, and the results showed that the highest accuracy rate on membranous nephropathy (MN-100%), followed by IgA nephropathy (IgAN-83.33%) and mild lesion type (MLN-73.53%), whereas lower prediction accuracy was observed for mesangial proliferative glomerulonephritis (0%) and focal segmental sclerosis type (21.74%). The models of bi-directional probability prediction and differential diagnosis indicate a good prediction value in MN, IgAN and MLN and may be considered alternative methods for the pathological discrimination of CKD patients who are unable to undergo renal biopsy.

Epidemiological evidence on the relationship between lead exposure and mortality in specific chronic kidney disease (CKD) populations is limited. We aimed to examine the relationship between urinary lead and blood lead concentrations and all-cause mortality in US patients with CKD. This cohort study included 2320 participants with CKD from the National Health and Nutrition Examination Survey (2005-2018), with follow-up until December 31, 2019. All-cause mortality was ascertained by matching US National Death Index records. Hazard ratios (HRs) and 95% confidence intervals (CI) for urinary lead and blood lead concentrations in relation to all-cause mortality were estimated using a weighted Cox regression model. During a median follow-up period of 79 months, a total of 625 participants with CKD succumbed to mortality. Compared to the lowest quartile, the highest quartile of urine and blood lead concentrations was associated with an increased risk of all-cause mortality, with HRs and corresponding 95% CIs of 1.77 (1.05-2.99) and 2.65 (1.38-5.10), respectively. Furthermore, each additional unit increase in urinary and blood lead concentrations was associated with HRs for all-cause mortality of 1.21 (95% CI 1.06-1.38) and 1.09 (95% CI 1.01-1.19), respectively. Kaplan-Meier survival curve analysis and restricted cubic regression spline curve analysis demonstrated significant positive associations between elevated blood lead levels, elevated urinary lead levels, and all-cause mortality risk (P < 0.05). A nonlinear concentration-response relationship was observed between blood lead level and all-cause mortality risk (P Nonlinear  < 0.05), with an inflection point at a concentration of 1.613 µg/dL. Subgroup analysis as well as sensitivity analysis yielded consistent findings. Our findings demonstrate that elevated levels of lead in urine and blood are associated with a significantly increased mortality risk among patients with CKD, underscoring the importance of reducing lead exposure to mitigate mortality risk in individuals at high risk for CKD., (© 2024. The Author(s).)

Kidney diseases pose a significant global health challenge, requiring precise diagnostic tools to improve patient outcomes. This study addresses this need by investigating three main categories of renal diseases: kidney stones, cysts, and tumors. Utilizing a comprehensive dataset of 12,446 CT whole abdomen and urogram images, this study developed an advanced AI-driven diagnostic system specifically tailored for kidney disease classification. The innovative approach of this study combines the strengths of traditional convolutional neural network architecture (AlexNet) with modern advancements in ConvNeXt architectures. By integrating AlexNet's robust feature extraction capabilities with ConvNeXt's advanced attention mechanisms, the paper achieved an exceptional classification accuracy of 99.85%. A key advancement in this study's methodology lies in the strategic amalgamation of features from both networks. This paper concatenated hierarchical spatial information and incorporated self-attention mechanisms to enhance classification performance. Furthermore, the study introduced a custom optimization technique inspired by the Adam optimizer, which dynamically adjusts the step size based on gradient norms. This tailored optimizer facilitated faster convergence and more effective weight updates, imporving model performance. The model of this study demonstrated outstanding performance across various metrics, with an average precision of 99.89%, recall of 99.95%, and specificity of 99.83%. These results highlight the efficacy of the hybrid architecture and optimization strategy in accurately diagnosing kidney diseases. Additionally, the methodology of this paper emphasizes interpretability and explainability, which are crucial for the clinical deployment of deep learning models., (© 2024. The Author(s).)

Renal fibrosis is a failed regenerative process that facilitates chronic kidney disease progression. The current study was designed to study the effect of erlotinib, a receptor tyrosine kinase inhibitor, on the progression of renal fibrosis. The study included four groups of mice: control group; adenine group: received adenine (0.2% w/w) daily with food for 4 weeks; erlotinib group: received 80 mg/kg/day erlotinib orally (6 ml/kg/day, 1.3% w/v suspension in normal saline 0.9%) for 4 weeks; adenine + erlotinib group: received adenine and erlotinib concurrently. Kidney function and antioxidant biomarkers were measured. Renal expression of Bcl2 and p53 and histopathological changes (tubular injury and renal fibrosis) were scored. Renal tissue levels of transforming growth factor-β 1 , p-ERK1/2 and p-STAT3 were measured. Results obtained showed significant decrease (P < 0.001) in serum creatinine, urea and uric acid in erlotinib + adenine group. Level of malondialdehyde was decreased significantly (P < 0.001) while reduced glutathione and catalase levels were increased (P < 0.01) by erlotinib concurrent administration. Erlotinib markedly reduced fibrosis and tubular injury and decreased TGF-β1, p-ERK1/2 and p-STAT3 (P < 0.5). In addition, expression level of Bcl-2 was elevated (P < 0.001) while that of p53-was reduced compared to adenine alone. Erlotinib can attenuate renal fibrosis development and progression through anti-fibrotic, antioxidant and anti-apoptotic pathways.

The Japan Chronic Kidney Disease (CKD) Database (J-CKD-DB) is a large-scale, nation-wide registry based on electronic health record (EHR) data from participating university hospitals. Using a standardized exchangeable information storage, the J-CKD-DB succeeded to efficiently collect clinical data of CKD patients across hospitals despite their different EHR systems. CKD was defined as dipstick proteinuria ≥1+ and/or estimated glomerular filtration rate <60 mL/min/1.73 m 2 base on both out- and inpatient laboratory data. As an initial analysis, we analyzed 39,121 CKD outpatients (median age was 71 years, 54.7% were men, median eGFR was 51.3 mL/min/1.73 m 2 ) and observed that the number of patients with a CKD stage G1, G2, G3a, G3b, G4 and G5 were 1,001 (2.6%), 2,612 (6.7%), 23,333 (59.6%), 8,357 (21.4%), 2,710 (6.9%) and 1,108 (2.8%), respectively. According to the KDIGO risk classification, there were 30.1% and 25.5% of male and female patients with CKD at very high-risk, respectively. As the information from every clinical encounter from those participating hospitals will be continuously updated with an anonymized patient ID, the J-CKD-DB will be a dynamic registry of Japanese CKD patients by expanding and linking with other existing databases and a platform for a number of cross-sectional and prospective analyses to answer important clinical questions in CKD care.

Electrocardiographic left ventricular hypertrophy (LVH) could predict adverse renal outcomes in patients with hypertension. This study aimed to investigate the association between electrocardiographic LVH and future decline in renal function in the general population using a dataset of population-based health checkups from 2010 to 2019 including 19,825 participants. Electrocardiographic LVH was defined according to the Minnesota code. Renal function decline was defined as a decrease of ≥ 25% in the estimated glomerular filtration rate from baseline to < 60 mL/min/1.73 m 2 . Electrocardiographic LVH was found in 1263 participants at the baseline visit. The mean follow-up period was 3.4 ± 1.9 years. The incidence rates of renal function decline were 0.30 and 0.78 per 100 person-years in the non-LVH group and LVH groups, respectively. Electrocardiographic LVH was associated with the risk for renal function decline in the adjusted analysis (hazard ratio 1.69, 95% confidence interval 1.14-2.50, P = 0.009). This association was comparable across subgroups stratified by age, sex, body mass index, diagnosed hypertension, systolic blood pressure, hemoglobin A1c, and urinary protein. This study underscores the usefulness of electrocardiographic LVH to detect high-risk individuals for renal function decline in the setting of health checkups in the general population., (© 2024. The Author(s).)

Diabetic nephropathy (DN) is associated with kidney fibrosis. A previous study revealed that periostin (POSTN) contributes to kidney fibrosis. This study examined the role of POSTN in DN. The urinary concentrations of POSTN and TNC increased according to the severity of DN in human samples. Streptozotocin (STZ) was administered after unilateral nephrectomy (UNXSTZ) to induce DN in wild-type and Postn-null mice. Four experimental groups were generated: wild-typeham (WT Sham), wild-type UNXSTZ (WT STZ), Postn-null Sham (KO Sham), and Postn-null UNXSTZ (KO STZ). After 20 weeks, the KO STZ group had lower levels of urine albumin excretion, glomerular sclerosis, and interstitial fibrosis than those of the WT STZ group. Additionally, the KO STZ group had lower expression of fibrosis markers, including TNC. The KO STZ group showed better glucose regulation than the WT STZ model. Furthermore, the KO STZ group exhibited significantly preserved pancreatic islet integrity and insulin expression. HK-2 cells were used to observe the aggravation of fibrosis caused by POSTN under TGF-β conditions. We stimulated INS-1 cells with streptozotocin and evaluated the viability of these cells. The anti-POSTN antibody treatment of INS-1 cells with streptozotocin resulted in higher cell viability than that with treatment with streptozotocin alone. The absence of POSTN in DN contributes to renal fibrosis alleviation by improving pancreatic β-cell function. Additionally, there is an association between POSTN and TNC., (© 2023. Springer Nature Limited.)

The consequence of chronic kidney disease is the accumulation of metabolic products called uremic toxins in the body. Indoxyl sulfate (IS) is a toxin with a high affinity for proteins. This study focuses on the deleterious effect of IS, especially apoptosis induction, in mononuclear blood cells (MNCs). Thus, in MNCs treated with IS at three different concentrations for 24 h, the survival, mitochondrial potential, caspases activity and expression, Bcl-2 and Bax protein expression, DNA damage, and PARP degradation were estimated. The study showed a decrease in survival and mitochondrial potential of MNCs treated with IS compared to the control. IS increased the activity of caspase 2-, 3-, 9-, and the expression of caspase 3-, and 9- in MNCs but does not affect the activity of caspase 6- and 8. The treatment of MNCs with IS also increased DNA damage and degradation of PARP. Indoxyl sulfate significantly influences the expression of Bcl-2 and Bax proteins. Indoxyl sulfate induces the programmed death of MNCs through the intrinsic mitochondrial apoptotic pathway. The observed cellular changes are mostly dose-dependent., (© 2023. Springer Nature Limited.)

Renal failure, a public health concern, and the scarcity of nephrologists around the globe have necessitated the development of an AI-based system to auto-diagnose kidney diseases. This research deals with the three major renal diseases categories: kidney stones, cysts, and tumors, and gathered and annotated a total of 12,446 CT whole abdomen and urogram images in order to construct an AI-based kidney diseases diagnostic system and contribute to the AI community's research scope e.g., modeling digital-twin of renal functions. The collected images were exposed to exploratory data analysis, which revealed that the images from all of the classes had the same type of mean color distribution. Furthermore, six machine learning models were built, three of which are based on the state-of-the-art variants of the Vision transformers EANet, CCT, and Swin transformers, while the other three are based on well-known deep learning models Resnet, VGG16, and Inception v3, which were adjusted in the last layers. While the VGG16 and CCT models performed admirably, the swin transformer outperformed all of them in terms of accuracy, with an accuracy of 99.30 percent. The F1 score and precision and recall comparison reveal that the Swin transformer outperforms all other models and that it is the quickest to train. The study also revealed the blackbox of the VGG16, Resnet50, and Inception models, demonstrating that VGG16 is superior than Resnet50 and Inceptionv3 in terms of monitoring the necessary anatomy abnormalities. We believe that the superior accuracy of our Swin transformer-based model and the VGG16-based model can both be useful in diagnosing kidney tumors, cysts, and stones., (© 2022. The Author(s).)

The C-type lectin-related protein, Clr-f, encoded by Clec2h in the mouse NK gene complex (NKC), is a member of a family of immune regulatory lectins that guide immune responses at distinct tissues of the body. Clr-f is highly expressed in the kidney; however, its activity in this organ is unknown. To assess the requirement for Clr-f in kidney health and function, we generated a Clr-f-deficient mouse (Clr-f -/- ) by targeted deletions in the Clec2h gene. Mice lacking Clr-f exhibited glomerular and tubular lesions, immunoglobulin and C3 complement protein renal deposits, and significant abdominal and ectopic lipid accumulation. Whole kidney transcriptional profile analysis of Clr-f -/- mice at 7, 13, and 24 weeks of age revealed a dynamic dysregulation in lipid metabolic processes, stress responses, and inflammatory mediators. Examination of the immune contribution to the pathologies of Clr-f -/- mouse kidneys identified elevated IL-12 and IFNγ in cells of the tubulointerstitium, and an infiltrating population of neutrophils and T and B lymphocytes. The presence of these insults in a Rag1 -/- Clr-f -/- background reveals that Clr-f -/- mice are susceptible to a T and B lymphocyte-independent renal pathogenesis. Our data reveal a role for Clr-f in the maintenance of kidney immune and metabolic homeostasis., (© 2022. The Author(s).)

Transient receptor potential channel subfamily C, member 6 (TRPC6), a non-selective cation channel that controls influx of Ca 2+ and other monovalent cations into cells, is widely expressed in the kidney. TRPC6 gene variations have been linked to chronic kidney disease but its role in acute kidney injury (AKI) is unknown. Here we aimed to investigate the putative role of TRPC6 channels in AKI. We used Trpc6 -/- mice and pharmacological blockade (SH045 and BI-749327), to evaluate short-term AKI outcomes. Here, we demonstrate that neither Trpc6 deficiency nor pharmacological inhibition of TRPC6 influences the short-term outcomes of AKI. Serum markers, renal expression of epithelial damage markers, tubular injury, and renal inflammatory response assessed by the histological analysis were similar in wild-type mice compared to Trpc6 -/- mice as well as in vehicle-treated versus SH045- or BI-749327-treated mice. In addition, we also found no effect of TRPC6 modulation on renal arterial myogenic tone by using blockers to perfuse isolated kidneys. Therefore, we conclude that TRPC6 does not play a role in the acute phase of AKI. Our results may have clinical implications for safety and health of humans with TRPC6 gene variations, with respect to mutated TRPC6 channels in the response of the kidney to acute ischemic stimuli., (© 2022. The Author(s).)

The cardiorenal syndrome (CRS) is defined as the confluence of heart-kidney dysfunction. This study investigates the molecular differences at the level of the urinary peptidome between CRS patients and controls and their association to disease pathophysiology. The urinary peptidome of CRS patients (n = 353) was matched for age and sex with controls (n = 356) at a 1:1 ratio. Changes in the CRS peptidome versus controls were identified after applying the Mann-Whitney test, followed by correction for multiple testing. Proteasix tool was applied to investigate predicted proteases involved in CRS-associated peptide generation. Overall, 559 differentially excreted urinary peptides were associated with CRS patients. Of these, 193 peptides were specifically found in CRS when comparing with heart failure and chronic kidney disease urinary peptide profiles. Proteasix predicted 18 proteases involved in > 1% of proteolytic cleavage events including multiple forms of MMPs, proprotein convertases, cathepsins and kallikrein 4. Forty-four percent of the cleavage events were produced by 3 proteases including MMP13, MMP9 and MMP2. Pathway enrichment analysis supported that ECM-related pathways, fibrosis and inflammation were represented. Collectively, our study describes the changes in urinary peptides of CRS patients and potential proteases involved in their generation, laying the basis for further validation., (© 2021. The Author(s).)

There is limited information available regarding the association of plasma free fatty acids (FFA) and inflammation mediators with ischemic stroke. At the same time, new treatment strategies are being pursued. The aim of this study was to carry out a thorough analysis of inflammation with multiple FFA-derivative mediators after and ischemic stroke and standard treatment. HPLC separations of 17 eicosanoids were performed using an Agilent Technologies 1,260 liquid chromatograph. The profiles of the esters of fatty acids were labelled by means of gas chromatography. FFA, and eicosanoid profiles in the group of patients after ischemic stroke significantly differed from the profile of the control group. Studies confirmed the involvement of derivative synthesis pathways responsible for the inflammation, especially palmitic acid (9 and 13 HODE), arachidonic acid, EPA and DHA. Arachidonic acid derivatives were synthesised on 5LOX, 15 LOX and COX pathways with the participation of prostaglandins while omega 3 derivatives strengthened the synthesis of resolvins, RevD1 in particular. The ability to accelerate the quenching of inflammation after ischemic stroke seems to be a promising strategy of stroke treatment in its early stage. In this context, our study points to lipoxins, RevD1, and 9, 13 HODE as the most important derivatives.

Blood metabolites of the tryptophan pathway were found to be associated with kidney function and disease in observational studies. In order to evaluate causal relationship and direction, we designed a study using a bidirectional Mendelian randomization approach. The analyses were based on published summary statistics with study sizes ranging from 1,960 to 133,413. After correction for multiple testing, results provided no evidence of an effect of metabolites of the tryptophan pathway on estimated glomerular filtration rate (eGFR). Conversely, lower eGFR was related to higher levels of four metabolites: C-glycosyltryptophan (effect estimate = - 0.16, 95% confidence interval [CI] (- 0.22; - 0.1); p = 9.2e-08), kynurenine (effect estimate = - 0.18, 95% CI (- 0.25; - 0.11); p = 1.1e-06), 3-indoxyl sulfate (effect estimate = - 0.25, 95% CI (- 0.4; - 0.11); p = 6.3e-04) and indole-3-lactate (effect estimate = - 0.26, 95% CI (- 0.38; - 0.13); p = 5.4e-05). Our study supports that lower eGFR causes higher blood metabolite levels of the tryptophan pathway including kynurenine, C-glycosyltryptophan, 3-indoxyl sulfate, and indole-3-lactate. These findings aid the notion that metabolites of the tryptophan pathway are a consequence rather than a cause of reduced eGFR. Further research is needed to specifically examine relationships with respect to chronic kidney disease (CKD) progression among patients with existing CKD.

We reported a large Chinese family diagnosed with autosomal dominant tubulointerstitial kidney disease caused by MUC1 mutation (ADTKD-MUC1). Cytosine duplication within a string of 7 cytosines in the variable-number tandem repeats (VNTR) region of the MUC1 gene was detected by long-read single-molecule real-time (SMRT) sequencing. MUC1 frameshift protein (MUC1fs) was found to be expressed in renal tubules and urinary exfoliated cells by pathological examination. The family, which consisted of 5 generations including 137 individuals, was followed for 5 years. Genetic testing was performed in thirty-four individuals, 17 of whom carried MUC1 mutations. The ADTKD-MUC1-affected individuals had an elevated incidence of hyperuricaemia without gout attack. Within five years, higher baseline levels of urinary α1-microglobulin were detected in affected individuals with rapidly progressing renal failure than in affected individuals with stable renal function, and the increases manifested even before increases in serum creatinine. This study demonstrates that SMRT sequencing is an effective method for the identification of MUC1 mutations. The pathological examination of MUC1fs expression in renal tissue and urinary exfoliated cells can contribute to early screening of family members suspected to be affected. It is suggested that affected individuals with elevated urinary α1-microglobulin levels should be closely monitored for renal function.

This cross-sectional study aimed to investigate the prevalence and risk factors of chronic kidney disease (CKD) among 1,096 primary care type 2 diabetes (T2DM) patients in northern Thailand between October 2016 and September 2017. CKD was defined as estimated glomerular rate filtration values of <60 mL/min/1.73 m 2 . Prevalence with confidence intervals across CKD advanced stages 3-5 were estimated. Factors associated with CKD were evaluated by multivariate logistic regression. The overall prevalence of CKD was 24.4% (21.9-27.0), with severities of 11.4% (9.7-13.4), 6.8% (5.5-8.5), 4.6% (3.5-6.0), and 1.6% (1.0-2.5) for stages 3 A, 3B, 4, and 5, respectively. Regarding age and glycaemic control, individuals older than 75 years and those with a haemoglobin A1c ≥ 8% had the highest prevalence of 61.3% (51.7-70.1) and 38.6% (34.3-43.2), respectively. The multivariable logistic regression model explained 87.3% of the probability of CKD. The six independent significant risk factors of CKD were older age, retinopathy, albuminuria, haemoglobin A1c ≥ 7%, anaemia, and uric acid>7.5 mg/dL. A relatively high prevalence of CKD, especially in older patients and those with diabetic complications-related to poor glycaemic control, was encountered in this primary care practice. Early identification may help to target optimise care and prevention programs for CKD among T2DM patients.

Chronic kidney disease (CKD) and chronic obstructive pulmonary disease (COPD) are known risk factors for mortality. In this study, we examined the overlap of CKD and airflow limitation (AFL) that characterises COPD and its effect on 10-year mortality in a community-based population. This study included 1,233 health check-up participants (mean age, 63.7 years; 46.7% men). We defined serum creatinine-based CKD (CKDcr) and serum cystatin C-based CKD (CKDcys) as glomerular filtration rate <60 mL/min/1.73 m 2 , estimated using serum creatinine or cystatin C, and/or dipstick proteinuria ≥1+. AFL was defined as forced expiratory volume in 1 s to forced vital capacity ratio <70% on spirometry. Compared with subjects without AFL, those with AFL showed a significantly higher prevalence of CKDcys but not of CKDcr. Cox proportional hazard analysis adjusted for confounders showed that the hazard ratio (95% confidence interval) for all-cause mortality was 1.45 (0.77-2.63) in subjects with CKDcys alone, 1.29 (0.60-2.54) in those with AFL alone, and 2.94 (1.33-6.12) in those with both CKDcys and AFL, with subjects without both AFL and CKD as the reference. This study showed that AFL and CKDcys are strongly associated and that their overlap is a significant risk factor for mortality in community-based populations.

Altered circulatory asymmetric and symmetric dimethylarginines have been independently reported in patients with end-stage renal failure suggesting their potential role as mediators and early biomarkers of nephropathy. These alterations can also be reflected in urine. Herein, we aimed to evaluate urinary asymmetric to symmetric dimethylarginine ratio (ASR) for early prediction of diabetic nephropathy (DN). In this cross-sectional study, individuals with impaired glucose tolerance (IGT), newly diagnosed diabetes (NDD), diabetic microalbuminuria (MIC), macroalbuminuria (MAC), and normal glucose tolerance (NGT) were recruited from Dr. Mohans' Diabetes Specialties centre, India. Urinary ASR was measured using a validated high-throughput MALDI-MS/MS method. Significantly lower ASR was observed in MIC (0.909) and MAC (0.741) in comparison to the NGT and NDD groups. On regression models, ASR was associated with MIC [OR: 0.256; 95% CI: 0.158-0.491] and MAC [OR 0.146; 95% CI: 0.071-0.292] controlled for all the available confounding factors. ROC analysis revealed ASR cut-point of 0.95 had C-statistic of 0.691 (95% CI: 0.627-0.755) to discriminate MIC from NDD with 72% sensitivity. Whereas, an ASR cut-point of 0.82 had C-statistic of 0.846 (95% CI: 0.800 - 0.893) had 91% sensitivity for identifying MAC. Our results suggest ASR as a potential early diagnostic biomarker for DN among the Asian Indians.

Arterial medial calcification (AMC) involves an increased small extracellular vesicle (sEV) secretion and apatite calcium precipitation in the arterial wall. The mechanisms mediating AMC remain poorly understood. In the present study, smooth muscle-specific acid ceramidase (Ac) gene knockout mice (Asah1 fl/fl /SM Cre ) were used to demonstrate the role of lysosomal ceramide signaling pathway in AMC. Asah1 fl/fl /SM Cre mice were found to have more severe AMC in both aorta and coronary arteries compared to their littermates (Asah1 fl/fl /SM wt and WT/WT mice) after receiving a high dose vitamin D. These mice also had pronounced upregulation of osteopontin and RUNX2 (osteogenic markers), CD63, AnX2 (sEV markers) and ALP expression (mineralization marker) in the arterial media. In cultured coronary arterial smooth muscle cells (CASMCs) from Asah1 fl/fl /SM Cre mice, high dose of P i led to a significantly increased calcium deposition, phenotypic change and sEV secretion compared to WT CASMCs, which was associated with reduced lysosome-multivesicular body (MVB) interaction. Also, GW4869, sEV release inhibitor decreased sEV secretion and calcification in these cells. Lysosomal transient receptor potential mucolipin 1 (TRPML1) channels regulating lysosome interaction with MVBs were found remarkably inhibited in Asah1 fl/fl /SM Cre CASMCs as shown by GCaMP3 Ca 2+ imaging and Port-a-Patch patch clamping of lysosomes. Lysosomal Ac in SMCs controls sEV release by regulating lysosomal TRPML1 channel activity and lysosome-MVB interaction, which importantly contributes to phenotypic transition and AMC.

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., (© 2024. The Author(s).)

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., (© 2024. The Author(s).)

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., (© 2022. The Author(s).)

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., (© 2021. The Author(s).)

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.

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 m 2 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 < 60 mL/min/1.73 m 2 or the onset of proteinuria during the course of treatment. The average age of all 584 type 2 diabetic participants (360 [61.6%] men) was 55 ± 11 years. There were 187 patients in the FIB4 index group > 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 < 60 and proteinuria were all higher in FIB4 index > 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 < 60 (HR 1.14, 95% CI 0.79-1.99). To the best of our knowledge, this is the first study to demonstrate that an FIB4 index > 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.

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 < 0.001) during a 3-year follow-up (HR 0.96, 95% CI 0.93-0.98). All the components of CV events including all-cause death, cardiac death, nonfatal myocardial infarction, and nonfatal stroke occurred more frequently in the CCB group. With multivariable models adjusting age, sex, income, diabetes, chronic kidney disease, and Charlson comorbidity index, the primary endpoints less frequently developed in the ARB group than in the CCB group (HR 0.957, 95% CI 0.933-0.983, p < 0.001). After the propensity-score matching, baseline characteristics were similar and still showed significantly better primary endpoints in ARB group than CCB group (5.3% vs. 5.8%, p < 0.001). In this nationwide population-based simple hypertension study, administration of ARBs showed superior protection against CV events than CCBs during a 3-year follow-up. Our results suggest that ARBs could be preferred over CCBs as the initial choice of antihypertensive treatment regardless of age in real-world practice.

Chronic inflammation and proteinuria is a risk factor for cardiovascular disease (CVD) in patients with chronic kidney diseases and rheumatologic disorders. Our aim was to investigate the CVD events (CVDEs) and survival between the patients with FMF-related AA amyloidosis and glomerulonephropathies (GN) to define possible predictors for CVDEs. A prospective follow-up study with FMF-amyloidosis and glomerulonephropathy (GN) was performed and patients were followed for CVDEs. Flow-mediated dilatation (FMD), FGF-23, serum lipid, hsCRP levels, BMI and HOMA were assessed. A Cox regression analysis was performed to evaluate the risk factors for CVDEs. There were 107 patients in the FMF-amyloidosis group and 126 patients with GN group. Forty-seven CVDEs were observed during the 4.2-years follow up; all 28 patients in the FMF-amyloidosis group and 14/19 patients with GN developed CVDEs before the age of 40 (p = 0.002). CVD mortality was 2.8 times higher (95% CI 1.02-7.76) in patients with FMF-amyloidosis. Across both groups, FMD and FGF23 (p < 0.001) levels were independently associated with the risk of CVDEs. Patients with FMF-amyloidosis are at increased risk of early CVDEs with premature mortality age. FGF 23, FMD and hsCRP can stratify the risk of early CVD in patients with FMF-related AA amyloidosis.

Midkine (MDK), a heparin-binding growth factor cytokine, is involved in the pathogenesis of kidney diseases by augmenting leukocyte trafficking and activation. Animal models and small case control studies have implicated MDK as a pathological biomarker in chronic kidney diseases (CKD), however this is yet to be confirmed in prospective human studies. In a prospective study of 499 elderly, predominantly Caucasian women aged over 70 years the association between serum MDK collected in 1998, and renal function change and the risk of CKD-related hospitalisations and deaths at 5 and 14.5 years, respectively, was examined. Baseline serum MDK was not associated with 5-year change in estimated glomerular filtration rate using the CKD Epidemiology Collaboration creatinine and cystatin C equation (Standardised β = - 0.09, 95% confidence interval - 3.76-0.48, p = 0.129), 5-year rapid decline in renal function (odds ratio = 0.97, 95% confidence interval 0.46-2.02, p = 0.927) or the risk of 14.5-year CKD-related hospitalisations and deaths (hazard ratio = 1.27, 95% confidence interval .66-2.46, p = 0.470) before or after adjusting for major risk factors. In conclusion, in this cohort of elderly women with normal or mildly impaired renal function, serum MDK was not associated with renal function change or future CKD-related hospitalisations and deaths, suggesting that MDK may not be an early biomarker for progression of CKD.

Although microbiome-host interactions are usual at steady state, gut microbiota dysbiosis can unbalance the physiological and behavioral parameters of the host, mostly via yet not understood mechanisms. Using the Drosophila model, we investigated the consequences of a gut chronic dysbiosis on the host physiology. Our results show that adult flies chronically infected with the non-pathogenic Erwinia carotorova caotovora bacteria displayed organ degeneration resembling wasting-like phenotypes reminiscent of Metabolic Syndrome associated pathologies. Genetic manipulations demonstrate that a local reduction of insulin signaling consecutive to a peptidoglycan-dependent NF-κB activation in the excretory system of the flies is responsible for several of the observed phenotypes. This work establishes a functional crosstalk between bacteria-derived peptidoglycan and the immune NF-κB cascade that contributes to the onset of metabolic disorders by reducing insulin signal transduction. Giving the high degree of evolutionary conservation of the mechanisms and pathways involved, this study is likely to provide a helpful model to elucidate the contribution of altered intestinal microbiota in triggering human chronic kidney diseases.

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 (dim tdT and bright tdT ) based on the fluorescence intensity of the Tek tdT signal. In AS mice, the bright tdT 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, dim tdT and bright tdT 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.

Chronic kidney diseases have become a major issue worldwide. The spectrum of biopsy proven renal diseases differs between locations and changes over time. It is therefore essential to describe the local epidemiological trends and the prevalence of renal biopsy in various regions to shine new light on the pathogenesis of various renal diseases and provide a basis for further hypothesis-driven research. We retrospectively analyzed 34,630 hospitalized patients undergoing native renal biopsy between January 1, 2009 and December 31, 2018. Indications for renal biopsy and histological diagnosis were analyzed to describe the prevalence of renal biopsy, and changing prevalence between period 1 (2009-2013) and period 2 (2014-2018) were further analyzed. Nephrotic syndrome (NS) was the most common indication for biopsy. Membranous nephropathy (MN, 24.96%) and IgA nephropathy (IgAN, 24.09%) were the most common primary glomerulonephritis (PGN). MN was most common in adults, with IgAN more prevalent in children. Lupus nephritis (LN) was the most common secondary glomerulonephritis (SGN) in adults, while Henöch-Schönlein purpura nephritis (HSPN) in children. The prevalence of MN increased significantly and nearly doubled from period 1 (15.98%) to period 2 (30.81%) (P = 0.0004). The same trend appeared with membranoproliferative glomerulonephritis (MPGN), diabetic nephropathy (DN) and obesity-related glomerulopathy (ORG), while the frequencies of minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), LN and hepatitis B associated glomerulonephritis (HBV-GN) significantly decreased between the two intervals. NS was the most common indication for biopsy across all age groups and genders. MN has overtaken IgAN to become the most common PGN in adults, while IgAN was the most common PGN in children. LN was the most common SGN in adults, and HSPN the most common in children.

Connexins (Cxs) are membrane-spanning proteins which enable flow of information important for kidney homeostasis. Changes in their spatiotemporal patterning characterize blood vessel abnormalities and chronic kidney diseases (CKD). We analysed spatiotemporal expression of Cx37, Cx40, Cx43 and Cx45 in nephron and glomerular cells of developing, postnatal kidneys, and nephrotic syndrome of the Finnish type (CNF) by using immunohistochemistry, statistical methods and electron microscopy. During kidney development, strong Cx45 expression in proximal tubules and decreasing expression in glomeruli was observed. In developing distal nephron, Cx37 and Cx40 showed moderate-to-strong expression, while weak Cx43 expression gradually increased. Cx45/Cx40 co-localized in mesangial and granular cells. Cx43 /Cx45 co-localized in podocytes, mesangial and parietal epithelial cells, and with podocyte markers (synaptopodin, nephrin). Different Cxs co-expressed with endothelial (CD31) and VSMC (α -SMA) markers in vascular walls. Peak signalling of Cx37, Cx43 and Cx40 accompanied kidney nephrogenesis, while strongest Cx45 signalling paralleled nephron maturation. Spatiotemporal Cxs patterning indicate participation of Cx45 in differentiation of proximal tubules, and Cx43, Cx37 and Cx40 in distal tubules differentiation. CNF characterized disorganized Cx45 expression in proximal tubules, increased Cx43 expression in distal tubules and overall elevation of Cx40 and Cx37, while Cx40 co-localized with increased number of interstitial myofibroblasts.

Hepatocyte growth factor (HGF) and its receptor, cMet, activate biological pathways necessary for repair and regeneration following kidney injury. Because HGF is a highly unstable molecule in its biologically active form, we asked whether a monoclonal antibody (Ab) that displays full agonist activity at the receptor could protect the kidney from fibrosis. We attempted to determine whether the cMet agonistic Ab might reduce fibrosis, the final common pathway for chronic kidney diseases (CKD). A mouse model of kidney fibrosis disease induced by unilateral ureteral obstruction was introduced and subsequently validated with primary cultured human proximal tubular epithelial cells (PTECs). In kidney biopsy specimens from patients with CKD, cMet immunohistochemistry staining showed a remarkable increase compared with patients with normal renal functions. cMet Ab treatment significantly increased the levels of phospho-cMet and abrogated the protein expression of fibrosis markers such as fibronectin, collagen 1, and αSMA as well as Bax2, which is a marker of apoptosis triggered by recombinant TGF-β1 in PTECs. Remarkably, injections of cMet Ab significantly prevented kidney fibrosis in obstructed kidneys as quantified by Masson trichrome staining. Consistent with these data, cMet Ab treatment decreased the expression of fibrosis markers, such as collagen1 and αSMA, whereas the expression of E-cadherin, which is a cell-cell adhesion molecule, was restored. In conclusion, cMet-mediated signaling may play a considerable role in kidney fibrosis. Additionally, the cMet agonistic Ab may be a valuable substitute for HGF because it is more easily available in a biologically active, stable, and purified form.

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.

Sleep apnoea is associated with chronic kidney diseases. A high obstructive sleep apnoea (OSA) prevalence is shown in patients with hypertrophic cardiomyopathy (HCM). Whether the presence of OSA would affect the renal function of patients with HCM is unknown. Forty-five consecutive patients with HCM were divided into the HCM OSA- and OSA+ groups. Forty-three patients with OSA without HCM were recruited as controls. Clinical indices, including estimated glomerular filtration rate (eGFR) and urine 8-hydroxy-2-deoxyguanosine (8-OHdG), were measured. The eGFR was significantly lower in the HCM OSA+ group than in the HCM OSA- (P < 0.05) and OSA (P < 0.001) groups. Multivariate linear regression analysis identified that the apnoea-hypopnoea index was independently associated with eGFR in all patients with HCM (β = -1.329, 95% confidence interval: -1.942, -0.717, P < 0.001). The urine 8-OHdG level, an oxidative stress marker, was significantly higher in the HCM OSA+ group than in the HCM OSA- (P < 0.001) and OSA (P < 0.001) groups and significantly correlated with the AHI (r = 0.467, P = 0.003) and eGFR (r = -0.457, P = 0.004) in all patients with HCM. Our study suggests a risk of eGFR decline in patients with HCM and OSA.

Proteinuria is closely associated with the progression of chronic kidney diseases (CKD) by producing renal tubulointerstitial fibrosis. Over-activation of hypoxia inducible factor (HIF)-1α has been implicated in the progression of CKD. The present study tested the hypothesis that HIF-1α mediates albumin-induced profibrotic effect in cultured renal proximal tubular cells. Incubation of the cells with albumin (40 μg/ml) for 72 hrs significantly increased the protein levels of HIF-1α, tissue inhibitor of metalloproteinase (TIMP)-1 and collagen-I, which were blocked by HIF-1α shRNA. Albumin also stimulated an epithelial-mesenchymal transition (EMT) as indicated by the decrease in epithelial marker E-cadherin, and the increase in mesenchymal markers α-smooth muscle actin and fibroblast-specific protein 1. HIF-1α shRNA blocked albumin-induced changes in these EMT markers as well. Furthermore, albumin reduced the level of hydroxylated HIF-1α, indicating an inhibition of the activity of prolyl-hydroxylases, enzymes promoting the degradation of HIF-1α. An anti-oxidant ascorbate reversed albumin-induced inhibition of prolyl-hydroxylase activity. Overexpression of prolyl-hydroxylase 2 (PHD2) transgene, a predominant isoform of PHDs in renal tubules, to reduce HIF-1α level significantly attenuated albumin-induced increases in TIMP-1 and collagen-I levels. These results suggest that albumin-induced oxidative stress inhibits PHD activity to accumulate HIF-1α, which mediates albumin-induced profibrotic effects in renal tubular cells.