Causal relationship between basal metabolic rate and kidney function: a bidirectional two-sample mendelian randomization study.

Background: The relationship between basal metabolic rate (BMR) and Chronic kidney disease (CKD) remains unclear and controversial. In this study, we investigated the causal role of BMR in renal injury, and inversely, whether altered renal function causes changes in BMR. Methods: In this two-sample mendelian randomization (MR) study, Genetic data were accessed from published genome-wide association studies (GWAS) for BMR ((n = 454,874) and indices of renal function, i.e. estimated glomerular filtration rate (eGFR) based on creatinine (n =1, 004, 040), CKD (n=480, 698), and blood urea nitrogen (BUN) (n =852, 678) in European. The inverse variance weighted (IVW) random-effects MR method serves as the main analysis, accompanied by several sensitivity MR analyses. We also performed a reverse MR to explore the causal effects of the above indices of renal function on the BMR. Results: We found that genetically predicted BMR was negatively related to eGFR, (ß= -0.032, P = 4.95*10-12). Similar results were obtained using the MR-Egger (ß= -0.040, P = 0.002), weighted median (ß= -0.04, P= 5.35×10-11) and weighted mode method (ß= -0.05, P=9.92×10-7). Higher BMR had a causal effect on an increased risk of CKD (OR =1.36, 95% CI = 1.11-1.66, P =0.003). In reverse MR, lower eGFR was related to higher BMR (ß= -0.64, P = 2.32×10-6, IVW analysis). Bidirectional MR supports no causal association was observed between BMR and BUN. Sensitivity analyses confirmed these findings, indicating the robustness of the results. Conclusion: Genetically predicted high BMR is associated with impaired kidney function. Conversely, genetically predicted decreased eGFR is associated with higher BMR.

Dipeptidyl peptidase 4 inhibitors vs. metformin for new-onset dementia: a propensity score-matched cohort study.

BACKGROUND: Hypoglycemic pharmacotherapy interventions for alleviating the risk of dementia remains controversial, particularly about dipeptidyl peptidase 4 (DPP4) inhibitors versus metformin. Our objective was to investigate whether the initiation of DPP4 inhibitors, as opposed to metformin, was linked to a reduced risk of dementia. METHODS: We included individuals with type 2 diabetes over 40 years old who were new users of DPP4 inhibitors or metformin in the Chinese Renal Disease Data System (CRDS) database between 2009 and 2020. The study employed Kaplan-Meier and Cox regression for survival analysis and the Fine and Gray model for the competing risk of death. RESULTS: Following a 1:1 propensity score matching, the analysis included 3626 DPP4 inhibitor new users and an equal number of metformin new users. After adjusting for potential confounders, the utilization of DPP4 inhibitors was associated with a decreased risk of all-cause dementia compared to metformin (hazard ratio (HR) 0.63, 95% confidence interval (CI) 0.45-0.89). Subgroup analysis revealed that the utilization of DPP4 inhibitors was associated with a reduced incidence of dementia in individuals who initiated drug therapy at the age of 60 years or older (HR 0.69, 95% CI 0.48-0.98), those without baseline macrovascular complications (HR 0.62, 95% CI 0.41-0.96), and those without baseline microvascular complications (HR 0.67, 95% CI 0.47-0.98). CONCLUSION: In this real-world study, we found that DPP4 inhibitors presented an association with a lower risk of dementia in individuals with type 2 diabetes than metformin, particularly in older people and those without diabetes-related comorbidities.

Polysaccharides from Dendrobium officinale delay diabetic kidney disease interstitial fibrosis through LncRNA XIST/TGF-ß1.

PURPOSE: Renal interstitial fibrosis is a pathological manifestation of the progression of diabetic kidney disease (DKD). Dendrobium officinale polysaccharides (DOP), one of the major active components of Dendrobium officinale, have hypoglycemic and hypolipidemic effects and are used clinically to treat diabetes. However, the role of DOP in delaying DKD progression remains unclear. This study aimed to explore the potential mechanisms by which DOP delays DKD renal interstitial fibrosis. METHODS: Using db/db mice as a model of DKD, we administered DOP by gavage and observed its therapeutic effectiveness. Employing ASO technology, we knocked down lncRNA XIST expression in kidney tissues and detected the expression of lncRNA XIST, TGF-ß1, and renal interstitial fibrosis-related molecules. RESULTS: DOP was primarily composed of monosaccharides, with 91.57% glucose and 1.41% mannose, forming a spheroid-like structure. It has a high polydispersity index with an Mw/Mn of 6.146, and the polysaccharides are mainly connected by 4-Man(p) and 4-Glc(p) linkages. In the kidneys of db/db mice, lncRNA XIST and TGF-ß1 are highly expressed; however, their expression is significantly reduced after gastric infusion with DOP, and upon knockdown of lncRNA XIST, it might delay the progression of renal interstitial fibrosis in DKD. CONCLUSION: DOP may delay the progression of DKD renal interstitial fibrosis through the regulation of the LncRNA XIST/TGF-ß1 related fibrotic pathway. This provides a new perspective for clinical strategies to delay the progression of DKD renal interstitial fibrosis.

Development and validation of a model for predicting the risk of cardiovascular events in maintenance hemodialysis patients.

The mortality rates for patients undergoing hemodialysis (HD) remain unacceptably high compared to the general population, and more specific information about the causes of death is not known. The study aimed to develop and validate a risk prediction model that uses common clinical factors to predict the probability of cardiovascular events in maintenance hemodialysis (MHD) patients. The study involved 3488 adult patients who received regular scheduled hemodialysis treatment at 20 hemodialysis centers in southwest China between June 2015 and August 2020, with follow-up until August 2021. The optimal parameter set was identified by multivariable Cox regression analyses and Cross-LASSO regression analyses and was used to establish a nomogram for predicting the risk of cardiovascular events in maintenance hemodialysis patients at 3 and 5 years. The performance of the model was evaluated using the consistency index (Harrell's C-index), the area under the receiver operating characteristic (ROC) curve, and calibration plots. The model was validated by tenfold cross-validation and bootstrapping with 1000 resamples. In the derivation cohort, the model yields an AUC of 0.764 [95% confidence interval (CI), 0.737-0.790] and 0.793 [CI, 0.757-0.829] for predicting the risk of cardiovascular events of MHD patients at 3 and 5 years. In the internal validation cohort AUC of 0.803 [95% CI, 0.756-0.849], AUC of 0.766 [95% CI, 0.686-0.846], and the external validation cohort AUC of 0.826 [95% CI, 0.765-0.888], AUC of 0.817 [95% CI, 0.745-0.889] at 3 and 5 years. The model's calibration curve is close to the ideal diagonal. By tenfold cross-validation analyses, the 3- and 5-year risk of cardiovascular events (AUC 0.732 and 0.771, respectively). By the bootstrap resampling method, the derivation cohort and validation cohort (Harrell's C-index 0.695 and 0.667, respectively) showed good uniformity with the model. The constructed model accurately predicted cardiovascular events of MHD patients in the 3rd and 5th years after dialysis. And the further research is needed to determine whether use of the risk prediction tool improves clinical outcomes.

Human pluripotent stem cell-derived kidney organoids: Current progress and challenges.

Human pluripotent stem cell (hPSC)-derived kidney organoids share similarities with the fetal kidney. However, the current hPSC-derived kidney organoids have some limitations, including the inability to perform nephrogenesis and lack of a corticomedullary definition, uniform vascular system, and coordinated exit pathway for urinary filtrate. Therefore, further studies are required to produce hPSC-derived kidney organoids that accurately mimic human kidneys to facilitate research on kidney development, regeneration, disease modeling, and drug screening. In this review, we discussed recent advances in the generation of hPSC-derived kidney organoids, how these organoids contribute to the understanding of human kidney development and research in disease modeling. Additionally, the limitations, future research focus, and applications of hPSC-derived kidney organoids were highlighted.

Diffusion Tensor and Kurtosis MRI-Based Radiomics Analysis of Kidney Injury in Type 2 Diabetes.

BACKGROUND: Diffusion tensor imaging (DTI) and diffusion kurtosis imaging (DKI) can provide quantitative parameters that show promise for evaluation of diabetic kidney disease (DKD). The combination of radiomics with DTI and DKI may hold potential clinical value in detecting DKD. PURPOSE: To investigate radiomics models of DKI and DTI for predicting DKD in type 2 diabetes mellitus (T2DM) and evaluate their performance in automated renal parenchyma segmentation. STUDY TYPE: Prospective. POPULATION: One hundred and sixty-three T2DM patients (87 DKD; 63 females; 27-80 years), randomly divided into training cohort (N = 114) and validation cohort (N = 49). FIELD STRENGTH/SEQUENCE: 1.5-T, diffusion spectrum imaging (DSI) with 9 different b-values. ASSESSMENT: The images of DSI were processed to generate DKI and DTI parameter maps, including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD). The Swin UNETR model was trained with 5-fold cross-validation using 100 samples for renal parenchyma segmentation. Subsequently, radiomics features were automatically extracted from each parameter map. The performance of the radiomics models on the validation cohort was evaluated by utilizing the receiver operating characteristic (ROC) curve. STATISTICAL TESTS: Mann-Whitney U test, Chi-squared test, Pearson correlation coefficient, least absolute shrinkage and selection operator (LASSO), dice similarity coefficient (DSC), decision curve analysis (DCA), area under the curve (AUC), and DeLong's test. The threshold for statistical significance was set at P < 0.05. RESULTS: The DKI_MD achieved the best segmentation performance (DSC, 0.925 ± 0.011). A combined radiomics model (DTI_FA, DTI_MD, DKI_FA, DKI_MD, and DKI_RD) showed the best performance (AUC, 0.918; 95% confidence interval [CI]: 0.820-0.991). When the threshold probability was greater than 20%, the combined model provided the greatest net benefit. Among the single parameter maps, the DTI_FA exhibited superior diagnostic performance (AUC, 887; 95% CI: 0.779-0.972). DATA CONCLUSION: The radiomics signature constructed based on DKI and DTI may be used as an accurate and non-invasive tool to identify T2DM and DKD. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 2.

Facilitating Growth of Maize (Zea mays L.) by Biostimulants: A Perspective from the Interaction between Root Transcriptome and Rhizosphere Microbiome.

The plant growth-promoting effects of biostimulants have been widely documented, while little is known about the intrinsic mechanism. In our study, a pot experiment was conducted to investigate the effects of biostimulants on maize, and the maize root transcriptome and rhizosphere microbiome were assessed. The physicochemical properties of the soil were significantly altered with various trends, and the growth and yield of maize were promoted by biostimulants. Sampling time and maize strain were the strongest factors that altered the rhizosphere microorganisms. Rhizosphere microbiota with biostimulant application exhibited high community robustness. Root transcriptome analysis suggested an altered expression profile induced by biostimulants and maize strains. An integrated correlation analysis demonstrated that phosphate and nitrate metabolism genes are tightly associated with some rhizosphere microbiota. These results implied the plant growth-promoting effects of biostimulants might act in a rhizosphere microorganism-dependent manner and help to expand the use of biostimulants in sustainable agriculture.

Causal effects of gut microbiota on sepsis and sepsis-related death: insights from genome-wide Mendelian randomization, single-cell RNA, bulk RNA sequencing, and network pharmacology.

BACKGROUND: Gut microbiota alterations have been implicated in sepsis and related infectious diseases, but the causal relationship and underlying mechanisms remain unclear. METHODS: We evaluated the association between gut microbiota composition and sepsis using two-sample Mendelian randomization (MR) analysis based on published genome-wide association study (GWAS) summary statistics. Sensitivity analyses were conducted to validate the robustness of the results. Reverse MR analysis and integration of GWAS and expression quantitative trait loci (eQTL) data were performed to identify potential genes and therapeutic targets. RESULTS: Our analysis identified 11 causal bacterial taxa associated with sepsis, with increased abundance of six taxa showing positive causal relationships. Ten taxa had causal effects on the 28-day survival outcome of septic patients, with increased abundance of six taxa showing positive associations. Sensitivity analyses confirmed the robustness of these associations. Reverse MR analysis did not provide evidence of reverse causality. Integration of GWAS and eQTL data revealed 76 genes passing the summary data-based Mendelian randomization (SMR) test. Differential expression of these genes was observed between sepsis patients and healthy individuals. These genes represent potential therapeutic targets for sepsis. Molecular docking analysis predicted potential drug-target interactions, further supporting their therapeutic potential. CONCLUSION: Our study provides insights for the development of personalized treatment strategies for sepsis and offers preliminary candidate targets and drugs for future drug development.

Incidence, Risk Factors and Outcome of Postoperative Acute Kidney Injury in China.

BACKGROUND AND HYPOTHESIS: Postoperative acute kidney injury (AKI) is a common condition after surgery, however, the available data about nationwide epidemiology of postoperative AKI in China from the large and high-quality studies is limited. This study was aimed to determine the incidence, risk factors, and outcomes of postoperative AKI among patients undergoing surgery in China. METHODS: This was a large, multicenter, retrospective study performed in 16 tertiary medical centers in China. Adult (at least 18 years old) patients who undergoing surgical procedures from January 1, 2013 to December 31, 2019 were included. Postoperative AKI was defined by the Kidney Disease: Improving Global Outcomes creatinine criteria. The associations of AKI and in-hospital outcomes were investigated using logistic regression models adjusted for potential confounders. RESULTS: Among 520 707 patients included in our study, 25 830 (5.0%) patients developed postoperative AKI. The incidence of postoperative AKI varied by surgery type, which was highest in cardiac (34.6%) surgery, followed by urologic (8.7%), and general (4.2%) surgeries. 89.2% postoperative AKI cases were detected in the first 2 postoperative days. However, only 584 (2.3%) patients with postoperative AKI were diagnosed with AKI on discharge. Risk factors for postoperative AKI included advanced age, male sex, lower baseline kidney function, pre-surgery hospital stay ≤ 3 days or > 7 days, hypertension, diabetes mellitus, and use of PPIs or diuretics. The risk of in-hospital death increased with the stage of AKI. In addition, patients with postoperative AKI had longer length of hospital stay (12 vs 19 days), were more likely to require intensive unit care (13.1% vs 45.0%) and renal replacement therapy (0.4% vs 7.7%). CONCLUSIONS: Postoperative AKI was common across surgery type in China, particularly for patients undergoing cardiac surgery. Implementation and evaluation of an alarm system is important for the battle against postoperative AKI.

[High mobility group nucleosome binding protein 1 (HMGN1) induces activation of mouse BV2 microglia and upregulates their pro-inflammatory mediator expression by activating TLR4/MyD88/NF-κB p65/IKK-ß signal pathway].

Objective To explore the effects and mechanism of high-mobility group nucleosome-binding protein 1 (HMGN1) on the inflammatory response of mouse BV2 microglia. Methods BV2 cells were incubated with recombinant HMGN1 at different concentrations (0, 100, 200, 500, 1000, 2000 ng/mL) for 6 hours, and the morphological changes were observed under a microscope. The mRNA levels of tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), interleukin-1ß (IL-1ß) and monocyte chemotactic protein 1 (MCP-1) were detected by real time quantitative PCR. Microglial cells were then randomly divided into a control group, model group, inhibitor group and antagonist group. The cells in the model group were treated with 500 ng/mL HMGN1, while the antagonist group was treated with 500 ng/mL TAK-242 (resatorvid), a Toll-like receptor 4 (TLR4) antagonist, in addition to HMGN1. Real time quantitative PCR and immunofluorescence were used to detect the expression of M1/M2 markers in the four groups, and Western blot analysis was used to measure the protein expression levels of inducible nitric-oxide synthase (iNOS), TLR4, myeloid differentiation factor88 (MyD88), nuclear factor κB p65 (NF-κB p65) and inhibitor of NF-κB(IκB)kinase ß(IKK-ß). Results After the treatment of HMGN1, the morphology of BV2 cells changed significantly, showing an amoeba-like appearance. The mRNA levels of TNF-α, IL-6, IL-1ß and MCP-1 increased with the HMGN1 concentration, with a statistically significant difference compared to the 0 ng/mL HMGN1 group. At the same time, the mRNA level of iNOS, a M1 phenotype marker, increased with the HMGN1 concentration, while the level of CD206, a M2 phenotype marker, decreased with HMGN1 concentration, showing a statistically significant difference compared to the 0 ng/mL HMGN1 group. Compared with the model group, the mRNA level of M1 phenotypic marker iNOS in the antagonist group was significantly lower, and the level of M2 phenotypic marker CD206 was significantly higher. The results of immunofluorescence cytochemistry also showed that the expression of M1 phenotypic marker iNOS in the antagonist group was lower. The results of Western blot suggested that the protein expression levels of iNOS, TLR4, MyD88, NF-κB p65 and IKK-ß decreased significantly in the antagonist group. Conclusion HMGN1 may induce the activation of BV2 microglial cells by upregulating pro-inflammatory mediators through activating the TLR4/MyD88/NF-κB p65/IKK-ß signaling pathway.

Monocyte-to-lymphocyte ratio and gastrointestinal disorder-related hospitalization in patients on maintenance hemodialysis.

INTRODUCTION: To explore the association between monocyte-to-lymphocyte ratio (MLR) and the risk of hospitalization due to gastrointestinal (GI) disorder in hemodialysis (HD) patients. METHODS: In this multicenter, observational cohort study, 1626 patients were enrolled in 2019 and followed up to 2 years. Cox regression models were performed to estimate the association of MLR with GI disorder-related hospitalization risk. Receiver-operating characteristic (ROC) analyses were conducted to evaluate the cutoff value of MLR in identifying GI disorder-related hospitalization. RESULTS: During a median follow-up of 24 months, GI disorder-related hospitalization occurred in 107 patients. Higher MLR was independently associated with greater risks of GI disorder-related hospitalization. Furthermore, a cut-off value of 0.42 differentiated patients with GI disorder-related hospitalization from those without GI involvement. CONCLUSION: MLR was associated with the occurrence of GI disorder-related hospitalization in HD patients. The blood MLR could be monitored as a useful marker to predict GI disorder-related hospitalization.

Management of nocturnal hypertension: An expert consensus document from Chinese Hypertension League.

Nocturnal hypertension is highly prevalent among Chinese and Asian populations, which is mainly attributed to high salt intake and high salt sensitivity. Nocturnal hypertension increases the risk of cardiovascular and all-cause mortality, independent of daytime blood pressure (BP). However, it can usually be detected by 24-h ambulatory BP monitoring, rather than routine office or home BP measurement, thus is often underdiagnosed in clinical practice. Currently, no specific guidance is available for the management of nocturnal hypertension in China or worldwide. Experts from the Chinese Hypertension League summarized the epidemiologic and pathophysiologic characteristics and clinical phenotype of nocturnal hypertension and provided consensus recommendations on optimal management of nocturnal hypertension, with the goal of maximally reducing the cardiovascular disease risks. In this consensus document, 24-h ABPM is recommended for screening and diagnosis of nocturnal hypertension, especially in the elderly, patients with diabetes, chronic kidney diseases, obstructive sleep apnea and other conditions prone to high nocturnal BP. Lifestyle modifications including salt intake restriction, exercise, weight loss, sleep improvement, and mental stress relief are recommended. Long-acting antihypertensive medications are preferred for nocturnal and 24-h BP control. Some newly developed agents, renal denervation, and other device-based therapy on nocturnal BP reduction are evaluated.

Risk of Hospital-Acquired Acute Kidney Injury among Adult Opioid Analgesic Users: A Multicenter Real-World Data Analysis.

Introduction: Comprehensive data on the risk of hospital-acquired (HA) acute kidney injury (AKI) among adult users of opioid analgesics are lacking. This study aimed to systematically compare the risk of HA-AKI among the users of various opioid analgesics. Methods: This multicenter, retrospective real-world study analyzed 255,265 adult hospitalized patients who received at least one prescription of opioid analgesic during the first 30 days of hospitalization. The primary outcome was the time from the first opioid analgesic prescription to HA-AKI occurrence. 12 subtypes of opioid analgesics were analyzed, including 9 for treating moderate-to-severe pain and 3 for mild-to-moderate pain. We examined the association between the exposure to each subtype of opioid analgesic and the risk of HA-AKI using Cox proportional hazards models, using the most commonly used opioid analgesic as the reference group. Results: As compared to dezocine, the most commonly used opioid analgesic for treating moderate-to-severe pain, exposure to morphine, but not the other 7 types of opioid analgesics, was associated with a significantly increased risk of HA-AKI (adjusted hazard ratio: 1.56, 95% confidence interval: 1.40-1.78). The association was consistent in stratified analyses and in a propensity-matched cohort. There were no significant differences in the risk of HA-AKI among the opioid analgesic users with mild-to-moderate pain after adjusting for confounders. Conclusion: The use of morphine was associated with an increased risk of HA-AKI in adult patients with moderate-to-severe pain. Opioid analgesics other than morphine should be chosen preferentially in adult patients with high risk of HA-AKI when treating moderate-to-severe pain.

Central administration of Dapagliflozin alleviates a hypothalamic neuroinflammatory signature and changing tubular lipid metabolism in type 2 diabetic nephropathy by upregulating MCPIP1.

BACKGROUND: Hypothalamic neuroinflammation is associated with disorders of lipid metabolism. Considering the anti-neuroinflammation effects of sodium-glucose cotransporter 2(SGLT2) inhibitors, a central administration of Dapagliflozin is postulated to provide hypothalamic protection and change lipid metabolism in kidney against diabetic kidney disease (DKD). METHODS: Blood samples of DKD patients were collected. Male Sprague-Dawley (SD) rats with 30 mg/kg streptozotocin and a high-fat diet, db/db mice and palmitic acid (PA)-stimulated BV2 microglia were used for study models. 0.28 mg/3ul dapagliflozin was injected into the lateral ventricle in db/db mice. Genes and protein expression levels were determined by qPCR, western blotting, immunofluorescence, and immunohistochemistry staining. Secreted IL-1ß and IL-6 were quantified by ELISA. Oil red O staining, lipidomic, and non-targeted metabolomics were performed to evaluate abnormal lipid metabolism in kidney. RESULTS: The decrease of serum MCPIP1 was an independent risk factor for renal progression in DKD patients (OR=1.22, 95 %CI: 1.02-1.45, P = 0.033). Higher microglia marker IBA1 and lower MCPIP1 in the hypothalamus, as well as lipid droplet deposition increasing in the kidney were observed in DKD rats. Central dapagliflozin could reduce the blood sugar, hypothalamic inflammatory cytokines, lipid droplet deposition in renal tubular. Lipidomics and metabolomics results showed that dapagliflozin changed 37 lipids and 19 metabolites considered on promoting lipolysis. These lipid metabolism changes were attributed to dapagliflozin by upregulating MCPIP1, and inhibiting cytokines in the microglia induced by PA. CONCLUSIONS: Central administrated Dapagliflozin elicits an anti-inflammatory effect by upregulating MCPIP1 levels in microglia and changes lipid metabolism in kidney of DKD.

A radiomics based approach using adrenal gland and periadrenal fat CT images to allocate COVID-19 health care resources fairly.

BACKGROUND: The value of radiomics features from the adrenal gland and periadrenal fat CT images for predicting disease progression in patients with COVID-19 has not been studied extensively. We assess the value of radiomics features from the adrenal gland and periadrenal fat CT images in predicting COVID-19 disease exacerbation. METHODS: A total of 1,245 patients (685 moderate and 560 severe patients) were enrolled in a retrospective study. We proposed a 3D V-net to segment adrenal glands in onset CT images automatically, and periadrenal fat was obtained using inflation operation around the adrenal gland. Next, we built a clinical model (CM), three radiomics models (adrenal gland model [AM], periadrenal fat model [PM], and fusion of adrenal gland and periadrenal fat model [FM]), and radiomics nomogram (RN) after radiomics features extracted. RESULTS: The auto-segmentation framework yielded a dice value 0.79 in the training set. CM, AM, PM, FM, and RN obtained AUCs of 0.717, 0.716, 0.736, 0.760, and 0.833 in the validation set. FM and RN had better predictive efficacy than CM (P < 0.0001) in the training set. RN showed that there was no significant difference in the validation set (mean absolute error [MAE] = 0.04) and test set (MAE = 0.075) between predictive and actual results. Decision curve analysis showed that if the threshold probability was between 0.4 and 0.8 in the validation set or between 0.3 and 0.7 in the test set, it could gain more net benefits using RN than FM and CM. CONCLUSIONS: Radiomics features extracted from the adrenal gland and periadrenal fat CT images are related to disease exacerbation in patients with COVID-19.

Decreased Intracellular to Total Body Water Ratio and Depressive Symptoms in Patients with Maintenance Hemodialysis.

Objective: Depression is a common psychiatric disorder and related to poor outcomes in patients undergoing maintenance hemodialysis (MHD). Previous studies have reported some associations between sarcopenia and depressive symptoms. Recently, intracellular water (ICW) and total body water (TBW) have been found to reflect muscle function and muscle mass. ICW/TBW ratio is a marker of sarcopenia that is simple to assess. However, the relationship between ICW/TBW ratio and depression has not been explored in MHD patients. Methods: In our cross-sectional and multi-center study, 3300 adult MHD patients were included from June 1, 2021, to August 30, 2021. Depressive symptoms were evaluated using the Beck Depression Inventory-II (BDI-II). TBW and ICW were measured by Body Composition Monitor (BCM). Multivariable logistic regression, stratified analyses, and interactive analyses were conducted to assess the relationship between ICW/TBW ratio and depression. Results: About 16.5% of the 3300 MHD patients were found to have depressive symptoms. The prevalence of depression increased with decreasing quartiles of ICW/TBW ratios, and decreased ICW/TBW ratio was independently associated with depression after adjusting for potential confounders. Patients in Quartile 1 of ICW/TBW ratios were more likely to have depressive symptoms (odds ratio 1.55, 95% confidence interval 1.07-2.22; p=0.002) than those in Quartile 4. History of diabetes and education status had interactive roles in the relationship between depression and ICW/TBW ratios (p < 0.05). The association of ICW/TBW ratios and depression existed in patients of both genders and different education levels, but only in non-diabetic patients. Conclusion: In MHD patients, the decreased ratio of ICW/TBW was independently related to high depression rates.

Epidemiology and outcomes of post-AKI proteinuria.

Background: Acute kidney injury (AKI) has been associated with increased risks of new-onset and worsening proteinuria. However, epidemiologic data for post-AKI proteinuria was still lacking. This study aimed to determine the incidence, risk factors and clinical correlations of post-AKI proteinuria among hospitalized patients. Methods: This study was conducted in a multicenter cohort including patients aged 18-100 years with hospital-acquired AKI (HA-AKI) hospitalized at 19 medical centers throughout China. The primary outcome was the incidence of post-AKI proteinuria. Secondary outcomes included AKI recovery and kidney disease progression. The results of both quantitative and qualitative urinary protein tests were used to define post-AKI proteinuria. Cox proportional hazard model with stepwise regression was used to determine the risk factors for post-AKI proteinuria. Results: Of 6206 HA-AKI patients without proteinuria at baseline, 2102 (33.9%) had new-onset proteinuria, whereas of 5137 HA-AKI with baseline proteinuria, 894 (17.4%) had worsening proteinuria after AKI. Higher AKI stage and preexisting CKD diagnosis were risk factors for new-onset proteinuria and worsening proteinuria, whereas treatment with renin-angiotensin system inhibitors was associated with an 11% lower risk of incident proteinuria. About 60% and 75% of patients with post-AKI new-onset and worsening proteinuria, respectively, recovered within 3 months. Worsening proteinuria was associated with a lower incidence of AKI recovery and a higher risk of kidney disease progression. Conclusions: Post-AKI proteinuria is common and usually transient among hospitalized patients. The risk profiles for new-onset and worsening post-AKI proteinuria differed markedly. Worsening proteinuria after AKI was associated with adverse kidney outcomes, which emphasized the need for close monitoring of proteinuria after AKI.

Low Lean Tissue Index and Muscle Strength Combined with High Fat Tissue Index Are Associated with Cardiovascular Disease-Related Hospitalisation in Patients on Haemodialysis.

INTRODUCTION: The combined clinical impact of muscle mass, muscle function, and adipose mass on hospitalisation events, especially those that have exact causes, such as cardiovascular diseases (CVDs), had been rarely studied in patients on haemodialysis (HD). This study aimed to determine the influence of lean tissue index (LTI), fat tissue index (FTI), and hand grip strength (HGS) on the risk of CVD-related hospitalisation in patients undergoing chronic HD. METHODS: This multi-centre observational study enrolled a total of 2,041 clinically stable patients aged >18 years and who had undergone HD for at least 3 months at 17 HD units in 2019. The follow-up period was up to 2 years. LTI and FTI were assessed using a body composition monitoring machine, and HGS was measured by a CAMRY® dynamometer. Cox regression models were fit to estimate the associations of body composition and HGS with CVD-related hospitalisation risk. RESULTS: During a mean follow-up of 22.6 months, CVD-related hospitalisation occurred in 492 patients. Compared with the non-CVD group, patients with CVD-related hospitalisation were older; had lower diastolic blood pressure; were more likely to have a history of diabetes; had worse activity status scores and lower levels of LTI, HGS, serum uric acid, and serum creatinine; and had higher FTI levels, body mass index, and extracellular water/intracellular water ratio. In the Cox regression models, low LTI and high FTI were independently associated with CVD-related hospitalisation in both men and women. In men, low HGS was an independent risk factor for CVD-related hospitalisation. When patients were further stratified into four distinct groups according to the sex-specific median values of LTI and FTI, the combination of low LTI and high FTI was an independent risk factor for CVD-related hospitalization (hazard ratio [HR] = 1.79 in men, 95% confidence interval 1.26-2.55; HR = 2.48 in women, 95% confidence interval 1.66-3.71; reference: high LTI/low FTI group). CONCLUSIONS: Among patients on chronic HD, low LTI, and high FTI were associated with CVD-related hospitalisation in men and women, whereas HGS was an independent risk factor for CVD-related hospitalisation in men but not in women. Combining low LTI and high FTI increased the association with hospitalisation risk and was an independent predictor of CVD-related hospitalisation.

Decreased intracellular water is associated with sarcopenic obesity in chronic haemodialysis patients.

OBJECTIVE: To explore the association between intracellular water (ICW) and sarcopenic obesity in patients undergoing chronic haemodialysis (HD). METHODS: A multicentre, cross-sectional study of 3354 adult chronic HD patients was conducted in 20 haemodialysis centres from June 1, 2021, to August 30, 2021. The diagnosis of sarcopenic obesity was made according to the revised Asian Working Group's definition of sarcopenia combined with obesity per the body fat percentage definition. Body composition was evaluated by a body composition monitor using bioimpedance spectroscopy. Multiple logistic regression models, stratified analyses, interactive analyses, and receiver-operating characteristic analyses were conducted. RESULTS: A total of 752 patients were diagnosed with sarcopenic obesity among 3354 participants. The patients were grouped by sex-specific ICW median levels, and the prevalence of sarcopenic obesity was significantly higher in the low ICW group than in the high ICW group (41.3%vs 3.0%). Decreased ICW was significantly associated with sarcopenic obesity. The association remained statistically significant even after adjusting for dialysis vintage, age, body mass index, biochemical indicators, and various medical histories. The odds ratios of the low ICW group were much higher than those of the high ICW group in both males and females (P for trend < 0.001). The association was stable across subgroups, and the interaction analysis showed that age, body mass index and history of diabetes had interactive roles in the association between ICW and sarcopenic obesity (P for interaction < 0.05). Furthermore, the ICW cut-off values for identifying sarcopenic obesity were 19.1 kg and 14.5 kg for males and females, respectively. CONCLUSION: Decreased ICW was an independent risk factor for sarcopenic obesity in chronic HD patients. The measurement of ICW by bioimpedance spectroscopy might be a non-invasive and valid means for identifying the risk of future sarcopenic obesity in HD patients.

The association of left ventricular fraction shortening with cardiovascular events in peritoneal dialysis patients.

BACKGROUND: Peritoneal dialysis (PD) patients have a high incidence of cardiovascular events (CVEs). Left ventricular fraction shortening (LVFS), one of the echocardiographic parameters, is an independent risk factor for mortality in previous studies. The aim of this study was to evaluate associations between LVFS and CVEs in PD patients. METHODS: This was a single-center observational cohort study. Seven hundred and eighty-four PD patients were enrolled from 1 January 2012 to 1 June 2021 and followed until 1 June 2022. The primary outcome was the incidence of CVEs. PD patients were categorized into three groups according to the tertiles of LVFS levels (tertile 1-tertile 3). Kaplan-Meier method, Cox proportional hazard models and competing risk regression models were used for survival analysis. The areas under the curve (AUC) of receiver-operating characteristic analysis was used to determine the predictive values of LVFS for CVEs. A preplanned subgroup analysis was assessed according to age, gender, and the presence of hypertension and dyslipidemia, etc. RESULTS: During a median follow-up period of 42.3 months (interquartile range 24.0-79.0 months), 259 CVEs occurred. Compared to the other two groups respectively, patients in tertile 3 group had the lowest incidence of CVEs (24.5% vs 31.6% vs 43.0%, respectively, p < 0.05). After multiple adjustments, the tertile 3 group was associated with the 45.1% decrease in the CVEs hazard compared to that of the tertile1 group (SHR = 0.549, 95%CI: 0.395-0.762, p < 0.001). Subgroup analysis demonstrated that tertile 1 group as the reference, the association between LVFS and CVEs in tertile 3 group was robust among female patients (HR = 0.506, 95%CI: 0.309-0.829, p = 0.007), aged < 45 years (HR = 0.496, 95%CI: 0.331-0.744, p = 0.001), history of hypertension (HR = 0.586, 95%CI: 0.349-0.872, p = 0.008) and combined with dyslipidemia (HR = 0.464, 95%CI: 0.269-0.799, p = 0.006). CONCLUSIONS: This study suggests that LVFS is independently associated with the increased risk of CVEs in PD patients, especially those with aged < 45 years, female, with hypertension and dyslipidemia.