Disparity of serum uric acid threshold for CKD among hypertensive and non-hypertensive individuals.

INTRODUCTION: Hypertension and rising serum uric acid (sUA) played a pivotal role in the development of Chronic Kidney Disease (CKD). This study investigates the interactive effect of sUA and hypertension on CKD and identifies the optimal threshold of sUA among individuals with and without hypertension in the Chinese community population. MATERIALS AND METHODS: The study included 4180 individuals aged 45-85 years, derived from the China Health and Retirement Longitudinal Study (CHARLS) between 2011 and 2015. Additionally, a hospital-based study enrolled subjects in the Department of Nephrology at Zhongshan Hospital, China from January 1, 2019, to December 31, 2021. The interaction effect analysis were used to assess the impact of sUA and hypertension on CKD. We also compared the distribution of sUA and the CKD risk in community populations, distinguishing between those with and without hypertension. For the hospital-based population, kidney injury was marked by a KIM-1 positive area. RESULTS: Our results indicate a higher prevalence of CKD in the community population with hypertension (10.2% vs. 3.9%, p < .001). A significant additive synergistic effects of the sUA and hypertension on the CKD risk were found. When the sUA level was < 4.55 mg/dL in the hypertensive population and < 5.58 mg/dL in the non-hypertensive population, the risk of CKD was comparable (p = .809). In the propensity score matched (PSM) population, the result remained roughly constant. CONCLUSION: Therefore, even moderate levels of sUA was associated with a higher risk of CKD in middle-aged hypertensive patients, who warrant stricter sUA control.

Associations between metabolic profiles and incident CKD in the Chinese population aged 45-85 years.

PURPOSE: The roles of metabolic indices in predicting chronic kidney disease (CKD) were lacking. This study aimed to examine the concomitant impact of metabolic and novel anthropometric indices on incident CKD in the Chinese populations. METHODS: This prospective cohort study included 1825 males and 2218 females aged between 45 and 85 years, derived from the ongoing prospectively cohort of China Health and Retirement Longitudinal Study (CHARLS), from 2011 to 2015. The outcome was defined as an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2. RESULTS: During the 5-years follow-up period, 3.0% (55/1825) of males and 4.1% (90/2218) of the females developed CKD. After multivariable adjustment, elevated triglyceride (TG), low high-density lipoprotein cholesterol (HDL-C), serum uric acid (sUA), elevated visceral fat index (VFI), elevated body shape index (BSI) and elevated body roundness index (BRI) in males, and sUA, and BRI in females were the independent predictors for CKD. Composite scores, composed of sUA, history of cardiovascular disease (CVD), waist circumstance (WC), HDL-C, and BRI in males and sUA, hypertension, and BRI in females were constructed that could accurately predict CKD. CONCLUSION: Our study found that elevated levels of TG, sUA, BSI, BRI, and diminished HDL in males and elevated levels of sUA, and BRI in females, are indicative of the incident CKD. The composite score, integrating a history of disease, metabolic indices, and noval anthropometric indices, could accurately differentiate individuals with and without incident CKD, proving useful for CKD care and management.

Syndecan-1 shedding destroys epithelial adherens junctions through STAT3 after renal ischemia/reperfusion injury.

Adherens junctions between tubular epithelial cells are disrupted in renal ischemia/reperfusion (I/R) injury. Syndecan-1 (SDC-1) is involved in maintaining cell morphology. We aimed to study the role of SDC-1 shedding induced by renal I/R in the destruction of intracellular adherens junctions. We found that SDC-1 shedding was increased while the expression of E-cadherin was decreased. This observation was accompanied by the activation of STAT3 in the kidneys. Inhibiting the shedding of SDC-1 induced by I/R could alleviate this effect. Mild renal I/R could induce more severe renal injury, lower E-cadherin expression, damaged cell junctions, and activated STAT3 in knockout mice with the tubule-specific deletion of SDC-1 mice. The results in vitro were consistent with those in vivo. Inhibiting the shedding of SDC-1 could alleviate the decreased expression of E-cadherin and damage of cell adherens junctions through inhibiting the activation of STAT3 during ischemic acute kidney injury.

Emodin Inhibits the Indoxyl Sulfate-Induced trans-Differentiation of Vascular Smooth Muscle Cells through Upregulating Thrombospondin-1.

BACKGROUND: Indoxyl sulfate (IS) is a protein-bound uremic toxin with vascular toxicity. The primary cause of death in uremic patients on maintenance hemodialysis is vascular disease, and it had been reported that vascular smooth muscle cells (VSMCs) trans-differentiation (VT) plays a vital role in the context of vascular diseases, but the underlying mechanisms remain obscure. Thrombospondin-1 (TSP-1) participates in vascular calcification by keeping the balance of extracellular matrix, but its role in IS-induced VT is unclear. METHODS: In this study, clinical specimens, animal models, and in vitro VSMCs were used to investigate the role of TSP-1 in IS induced VT and the potential therapeutic methods. RESULTS: We found that TSP-1 was significantly decreased in arterial samples from uremic patients, animal models, and in VSMCs after IS treatment. Downregulation of TSP-1 sufficiently induced the trans-differentiation genotypes of VSMCs. CONCLUSION: Emodin, the main monomer extracted from rhubarb, could alleviate IS-induced VT in vitro by upregulating TSP-1. Taken together, IS induces VT by downregulating TSP-1. Emodin might be a candidate drug to alleviate VT under IS treatment.

Serum Insulin-Like Growth Factor-Binding Protein 7 Deriving from Spleen and Lung Could Be Used for Early Recognition of Cardiac Surgery-Associated Acute Kidney Injury.

INTRODUCTION: The utility of arithmetic product of urinary tissue metalloproteinase inhibitor 2 (TIMP2) and insulin-like growth factor-binding protein 7 (IGFBP7) concentrations has been widely accepted on early diagnosis of acute kidney injury (AKI). However, which organ is the main source of those two factors and how the concentration of IGFBP7 and TIMP2 changed in serum during AKI still remain to be defined. METHODS: In mice, gene transcription and protein levels of IGFBP7/TIMP2 in the heart, liver, spleen, lung, and kidney were measured in both ischemia-reperfusion injury (IRI)- and cisplatin-induced AKI models. Serum IGFBP7 and TIMP2 levels were measured and compared in patients before cardiac surgery and at inclusion (0 h), 2 h, 6 h, and 12 h after intensive care unit (ICU) admission, and compared with serum creatinine (SCr), blood urea nitrogen (BUN), estimated glomerular filtration rate (eGFR), and serum uric acid (UA). RESULTS: In mouse IRI-AKI model, compared with the sham group, the expression levels of IGFBP7 and TIMP2 did not change in the kidney, but significantly upregulated in the spleen and lung. Compared with patients who did not develop AKI, the concentration of serum IGFBP7 at as early as 2 h after ICU admission (sIGFBP7-2 h) was significantly higher in patients who developed AKI. The relationships between sIGFBP7-2 h in AKI patients and log2 (SCr), log2 (BUN), log2 (eGFR), and log2 (UA) were statistically significant. The diagnostic performance of sIGFBP7-2 h measured by the macro-averaged area under the receiver operating characteristic curve was 0.948 (95% CI, 0.853-1.000; p < 0.001). CONCLUSION: The spleen and lung might be the main source of serum IGFBP7 and TIMP2 during AKI. The serum IGFBP7 value demonstrated good predictive accuracy for AKI following cardiac surgery within 2 h after ICU admission.

A NOVEL RAT MODEL OF CONTRAST-INDUCED ACUTE KIDNEY INJURY BASED ON RENAL CONGESTION AND THE RENO-PROTECTION OF MITOCHONDRIAL FISSION INHIBITION.

ABSTRACT: Contrast-induced acute kidney injury (CI-AKI) is a serious and common complication in patients receiving intravenous iodinated contrast medium (CM). Clinically, congestive heart failure is the most critical risk factor for CI-AKI and always leads to renal congestion for increased central venous pressure and fluid overload. Here, we aimed to investigate a novel CI-AKI rat model based on renal congestion. After the exploratory testing phase, we successfully constructed a CI-AKI rat model by inducing renal congestion by clamping the unilateral renal vein, removing the contralateral kidney, and a single tail vein injection of iohexol. This novel CI-AKI rat model showed elevated serum creatinine, urea nitrogen, and released tubular injury biomarkers (KIM-1 and NGAL), reduced glomerular filtration rate, and typical pathologic features of CM-induced tubular injury with extensive foamy degeneration, tubular edema, and necrosis. Electron microscopy and confocal laser scanning revealed excessive mitochondrial fission and increased translocation of Drp1 from the cytoplasm to the mitochondrial surface in tubular epithelial cells. As a Drp1 inhibitor, Mdivi-1 attenuated excessive mitochondrial fission and exerted reno-protection against CM injury. Simultaneously, Mdivi-1 alleviated oxidative stress, apoptosis, and inflammatory responses induced by CM toxicity. We concluded that renal congestion exacerbated CM toxicity and presented a novel CI-AKI rat model. Excessive mitochondrial fission plays a crucial role in CM reno-toxicity and is a promising target for preventing and treating CI-AKI.

Downregulation of KLF10 contributes to the regeneration of survived renal tubular cells in cisplatin-induced acute kidney injury via ZBTB7A-KLF10-PTEN axis.

Acute kidney injury (AKI) is a common clinical dysfunction with complicated pathophysiology and limited therapeutic methods. Renal tubular injury and the following regeneration process play a vital role in the course of AKI, but the underlining molecular mechanism remains unclear. In this study, network-based analysis of online transcriptional data of human kidney found that KLF10 was closely related to renal function, tubular injury and regeneration in various renal diseases. Three classical mouse models confirmed the downregulation of KLF10 in AKI and its correlation with tubular regeneration and AKI outcome. The 3D renal tubular model in vitro and fluorescent visualization system of cellular proliferation were constructed to show that KLF10 declined in survived cells but increased during tubular formation or conquering proliferative impediment. Furthermore, overexpression of KLF10 significantly inhibited, whereas knockdown of KLF10 extremely promoted the capacity of proliferation, injury repairing and lumen-formation of renal tubular cells. In mechanism, PTEN/AKT pathway were validated as the downstream of KLF10 and participated in its regulation of tubular regeneration. By adopting proteomic mass spectrum and dual-luciferase reporter assay, ZBTB7A were found to be the upstream transcription factor of KLF10. Our findings suggest that downregulation of KLF10 positively contributed to tubular regeneration in cisplatin induced acute kidney injury via ZBTB7A-KLF10-PTEN axis, which gives insight into the novel therapeutic and diagnostical target of AKI.

DNA binding protein YB-1 is a part of the neutrophil extracellular trap mediation of kidney damage and cross-organ effects.

Open-heart surgery is associated with high morbidity, with acute kidney injury (AKI) being one of the most commonly observed postoperative complications. Following open-heart surgery, in an observational study we found significantly higher numbers of blood neutrophils in a group of 13 patients with AKI compared to 25 patients without AKI (AKI: 12.9±5.4 ×109 cells/L; non-AKI: 10.1±2. 9 ×109 cells/L). Elevated serum levels of neutrophil extracellular trap (NETs) components, such as dsDNA, histone 3, and DNA binding protein Y-box protein (YB)-1, were found within the first 24 hours in patients who later developed AKI. We could demonstrate that NET formation and hypoxia triggered the release of YB-1, which was subsequently shown to act as a mediator of kidney tubular damage. Experimentally, in two models of AKI mimicking kidney hypoperfusion during cardiac surgery (bilateral ischemia/reperfusion (I/R) and systemic lipopolysaccharide (LPS) administration), a neutralizing YB-1 antibody was administered to mice. In both models, prophylactic YB-1 antibody administration significantly reduced the tubular damage (damage score range 1-4, the LPS model: non-specific IgG control, 0.92±0.23; anti-YB-1 0.65±0.18; and in the I/R model: non-specific IgG control 2.42±0.23; anti-YB-1 1.86±0.44). Even in a therapeutic, delayed treatment model, antagonism of YB-1 ameliorated AKI (damage score, non-specific IgG control 3.03±0.31; anti-YB-1 2.58±0.18). Thus, blocking extracellular YB-1 reduced the effects induced by hypoxia and NET formation in the kidney and significantly limited AKI, suggesting that YB-1 is part of the NET formation process and an integral mediator of cross-organ effects.

Proteinuria is a risk factor for acute kidney injury after cardiac surgery in patients with stages 3-4 chronic kidney disease: a case control study.

BACKGROUND: Acute kidney injury (AKI) is a common complication after cardiac surgery, and preoperative renal dysfunction is an important risk factor. Proteinuria indicates renal structural damage, but there are few studies on proteinuria and the risk of AKI after cardiac surgery in patients with renal dysfunction. This study aimed to elucidate whether proteinuria can predict AKI after cardiac surgery in patients with renal dysfunction. METHODS: Patients with stages 3-4 chronic kidney disease (CKD) who underwent cardiac surgery were included in this retrospective study. AKI was defined according to the KDIGO criteria. The association between proteinuria and AKI in patients with CKD stages 3-4 was investigated. RESULTS: The incidence of AKI in the entire cohort (n = 1546) was 53.55%. The in-hospital mortality of patients with was higher than patients without AKI (AKI vs. no AKI, 4.7 vs. 0.8%, P < 0.001). Multivariate logistic regression analysis showed that proteinuria was an independent risk factor for AKI (trace to 1+ OR 2.37; 2+ -3+ OR 5.16) and AKI requiring renal replacement therapy (AKI-RRT) (trace to 1+ OR 3.64; 2+-3+ OR 5.71). Mild proteinuria (trace to 1+ OR 2.59) was also an independent risk factor for in-hospital death. In patients with diabetes mellitus, mild proteinuria (OR 1.925), instead of severe proteinuria (2-3+), was a risk factor of AKI in patients with kidney dysfunction and diabetes. CONCLUSIONS: In the population of patients with renal dysfunction, the incidence of AKI was high, which significantly compromised renal and overall prognosis. As a simple and inexpensive routine test, preoperative proteinuria still has value in predicting AKI in patients with impaired renal function.

Identification of resident progenitors labeled with Top2a responsible for proximal tubular regeneration in ischemia reperfusion-induced acute kidney injury.

BACKGROUND: Acute kidney injury is a common fatal disease with complex etiology and limited treatment methods. Proximal tubules (PTs) are the most vulnerable segment. Not only in injured kidneys but also in normal kidneys, shedding of PTs often happens. However, the source cells and mechanism of their regeneration remain unclear. METHODS: ScRNA and snRNA sequencing data of acute injured or normal kidney were downloaded from GEO database to identify the candidate biomarker of progenitor of proximal tubules. SLICE algorithm and CytoTRACE analyses were employed to evaluate the stemness of progenitors. Then the repairing trajectory was constructed through pseudotime analyses. SCENIC algorithm was used to detect cell-type-specific regulon. With spatial transcriptome data, the location of progenitors was simulated. Neonatal/ adult/ aged mice and preconditioning AKI mice model and deconvolution of 2 RNA-seq data were employed for validation. RESULTS: Through cluster identification, PT cluster expressed Top2a specifically was identified to increase significantly during AKI. With relatively strong stemness, the Top2a-labeled PT cluster tended to be the origin of the repairing trajectory. Moreover, the cluster was regulated by Pbx3-based regulon and possessed great segmental heterogeneity. Changes of Top2a between neonatal and aged mice and among AKI models validated the progenitor role of Top2a-labeled cluster. CONCLUSIONS: Our study provided transcriptomic evidence that resident proximal tubular progenitors labeled with Top2a participated in regeneration. Considering the segmental heterogeneity, we find that there is a group of reserve progenitor cells in each tubular segment. When AKI occurs, the reserve progenitors of each tubular segment proliferate and replenish first, and PT-progenitors, a cluster with no obvious PT markers replenish each subpopulation of the reserve cells.

TWIK-related acid-sensitive K+ channel 2 promotes renal fibrosis by inducing cell-cycle arrest.

TWIK-related acid-sensitive K+ channel-2 (TASK-2, encoded by Kcnk5) is essential in cell biological processes, by regulating transmembrane K+ balance. In the present study, we aimed to clarify the role of TASK-2 in renal fibrosis and explore the underlying mechanism. We found that TASK-2 level was elevated in the renal tubular UUO- and UIR-induced renal fibrosis as well as in patients with renal tubulointerstitial fibrosis. Knockout of Kcnk5 or inhibition of TASK-2 in renal tubules attenuated G2/M cell-cycle arrest and alleviated renal fibrosis. Mechanistically, demethylase fat mass and obesity-associated protein (FTO) reduced N6-adenosine methylation (m6A) of Kcnk5 mRNA following renal fibrosis. FTO deficiency attenuated the upregulation of TASK-2 and renal fibrosis. The results demonstrated the crucial role of TASK-2 in renal fibrosis, which is conducive to a better understanding of the pathogenesis of renal fibrosis. TASK-2 may be a potential treatment strategy to alleviate the development of renal fibrosis.

Comprehensive Network-Based Analyses Reveal Novel Renal Function-Related Targets in Acute Kidney Injury.

Background: Acute kidney injury (AKI) is a common clinical syndrome with limited methods of treatment and diagnosis. Although several molecules associated with AKI have been discovered, molecular mechanisms underlying AKI still remain unclear. Weighted gene co-expression network analysis (WGCNA) is a novel method to uncover the relationship between co-expression genes and clinical traits at the system level. Methods: First, by employing WGCNA in transcriptional data on 30 patients with well/poor functioning kidney graft, we identified two co-expression modules that were significantly related to serum creatinine (SCr). Second, based on the modules, potential small molecular compound candidates for developing targeted therapeutics were obtained by connectivity map analysis. Furthermore, multiple validations of expression in space/time were carried out with two classical AKI models in vivo and other five databases of over 152 samples. Results: Two of the 14 modules were found to be closely correlated with SCr. Function enrichment analysis illustrated that one module was enriched in the immune system, while the other was in the metabolic process. Six key renal function-related genes (RFRGs) were finally obtained. Such genes performed well in cisplatin-induced or cecal ligation and puncture-induced AKI mouse models. Conclusion: The analysis suggests that WGCNA is a proper method to connect clinical traits with genome data to find novel targets in AKI. The kidney tissue with worse renal function tended to develop a "high immune but low metabolic activity" expression pattern. Also, ACSM2A, GLYAT, CORO1A, DPEP1, ALDH7A1, and EPHX2 are potential targets of molecular diagnosis and treatment in AKI.

Suppressing Syndecan-1 Shedding to Protect Against Renal Ischemia/Reperfusion Injury by Maintaining Polarity of Tubular Epithelial Cells.

ABSTRACT: Syndecan-1 (SDC-1), a type of heparan sulfate proteoglycan on the surface of epithelial cells, is involved in maintaining cell morphology. Loss of cell polarity constitutes the early stage of ischemic acute kidney injury (AKI). This study investigated the role of SDC-1 shedding in I/R-induced AKI and the underlying mechanisms. Levels of the shed SDC-1 in the serum were measured with ELISA 12 and 24 h after reperfusion in renal I/R model mice. Na+/K+-ATPase-α1 expression was evaluated using western blotting in vivo and immunofluorescence in hypoxia/reoxygenation (H/R) cysts. Renal tubular epithelial cell apoptosis was measured using TUNEL in vivo and flow cytometry in vitro. Furthermore, plasma syndecan-1 (pSDC-1) levels were measured in patients at the time of anesthesia resuscitation after cardiac surgery. We found that shed SDC-1 levels increased and Na+/K+-ATPase-α1 expression decreased after H/R in the three-dimensional (3D) tubular model, and this state was exacerbated with extended period of hypoxia. After the inhibition of SDC-1 shedding by GM6001, SDC-1 and Na+/K+-ATPase-α1 expression was restored, while H/R-induced apoptosis was decreased. In vivo, SDC-1 shedding was induced by renal I/R and was accompanied with a loss of renal tubular epithelial cell polarity and increased apoptosis. GM6001 pretreatment protected against I/R injury by alleviating the disruption of cell polarity and apoptosis. pSDC-1 levels were significantly higher in AKI patients than in non-AKI patients. ROC curve showed that the accuracy of pSDC-1 for AKI prediction was 0.769. In conclusion, inhibition of I/R-induced SDC-1 shedding could contribute to renal protection by restoring the loss of cell polarity and alleviating apoptosis in tubular epithelial cells.

Social Isolation Is Associated With Rapid Kidney Function Decline and the Development of Chronic Kidney Diseases in Middle-Aged and Elderly Adults: Findings From the China Health and Retirement Longitudinal Study (CHARLS).

Background: There is limited evidence on the relationship between social isolation and renal outcomes. To address this gap, this study estimated the prospective relationship of social isolation with rapid kidney function decline and the development of chronic kidney disease (CKD) in middle-aged and elderly Chinese with normal kidney function. Methods: We analyzed data from 3,031 participants aged ≥ 45 years with baseline estimated glomerular filtration rates (eGFR) ≥ 60 ml/min/1.73 m2. All data were obtained from the 2011 and 2015 waves of the Chinese Longitudinal Study of Health and Retirement (CHARLS). eGFR was estimated based on a combination of serum creatinine and cystatin C. The primary outcome was rapid decline in renal function, as defined by an eGFR decrease of > 5 ml/min/1.73 m2 per year, while the secondary outcome was the development of CKD, as defined by an eGFR decrease to a level < 60 ml/min/1.73 m2. Results: During the follow-up of 4 years, 258 (8.5%) participants experienced a rapid decline in renal function, while 87 (2.9%) developed CKD. In the fully adjusted model, high social isolation was significantly related to an increased risk of experiencing a rapid decline in renal function (OR 1.805, 95% CI 1.310-2.487) and CKD onset (OR 1.842, 95% CI 1.084-3.129). Among the five components of social isolation, being unmarried, not participating in social activities, and living alone independently predicted declined renal function. Conclusions: Social isolation is significantly associated with the risk of rapid eGFR decline and CKD onset in middle-aged and older adults with normal kidney function in China.

Rationale and validation of predicting high sodium intake by spot urinary chloride in patients with chronic kidney disease.

OBJECTIVE: To analyze the rationale and evaluate the validity of spot urinary chloride or derived formulas to predict high sodium intake in patients with chronic kidney disease (CKD). METHODS: We collected consecutive CKD patients at stages 1-4 who were admitted to our Nephrology department in a single center from January 01, 2014, to December 31, 2017, and tested spot and 24-hour urinary analysis on the same day. The feasibility of urinary chloride to predict urinary sodium was firstly analyzed by calculating their correlations. The validity of predicting excessive sodium intake by spot urinary sodium and chloride, two derived formulas based on spot urinary sodium or chloride, and our previous "CKDSALT" equation were accessed. We finally conducted Receiver operating characteristic (ROC) curves to compare their performance in detecting high sodium intake. RESULTS: All 5204 patients were eventually analyzed. In the derivation cohort (n = 2447), a strong positive linear correlation existed between urinary sodium and chloride in both spot urine (R2 = 0.804) and 24-hour urine samples (R2 = 0.905), and two predictive equations based on spot urinary sodium or chloride were derived. In the validation cohort (n = 2757), spot urinary sodium and chloride only showed "fair" performance. However, both urinary sodium and chloride equations had a "good" performance in ICC, Pearson's correlation, Bland-Altman plots, and ROC curves, while and CKDSALT equation showed the best performance. CONCLUSIONS: Spot urinary chloride is a feasible method to predict and monitor high sodium intake in CKD patients, while a novel derived formula could elevate its diagnostic accuracy.

Variations of tongue coating microbiota in children with Henoch-Schönlein purpura nephritis.

BACKGROUND: Variations in the oral microbiota have been significantly correlated with the progress of autoimmune diseases, such as immunoglobulin A nephropathy and Henoch-Schönlein purpura (HSP). However, there is no report outlining the character of tongue coating microbiota variations in children with Henoch-Schönlein purpura nephritis (HSPN). METHOD: A total of 20 children with HSPN and 14 healthy controls were recruited for this research. Tongue coating samples of two groups were collected for 16S rRNA gene sequencing. The diversity, principal component analysis (PCA), nonmetric multidimensional scaling (NMDS), partial least squares discriminant analysis (PLS-DA), and linear discriminant analysis (LDA) effect size (LEfSe) were performed. Microbial function was assessed using the PICRUST. RESULTS: The ACE and Chao indices were greatly lower in the HSPN group than in the HG (P = 0.001). The Shannon and Simpson indices were dramatically reduced in children with HSPN compared with those in the healthy controls (P = 0.005). Bacteroidales, Selenomonadales, Lactobacillales, Fusobacteriales, Neisseriales, and Actinomycetales composed more than 80% of all sequences, while Bacteroidales was the most generous order in both groups. PCA, NMDS and PLS-DA showed a marked difference between the control and HSPN groups. LEfSe analysis showed alteration of tongue coating microbiota in the HSPN group. There were 30 metabolic functions significantly differed between the two groups. CONCLUSIONS: Children with HSPN have substantially various tongue coating microbiota compared to healthy controls. Even though this research does not indicate causality, it is beneficial to enhance the possibility for coming microbial-based treatments to enhance the clinical effects of HSPN in children.

Association Between Muscle Strength and Cystatin C-Based Estimated Glomerular Filtration Rate Among Middle-Aged and Elderly Population: Findings Based on the China Health and Retirement Longitudinal Study (CHARLS), 2015.

BACKGROUND: Patients with chronic kidney disease (CKD) are prone to muscle strength degeneration. However, the relationship between mild-to-moderate renal insufficiency and low muscle strength remains unclear. As cystatin C is not subject to muscular conditions and is a sensitive serum marker in preclinical renal disease, we aimed to investigate the association between estimated glomerular filtration rate (eGFR) based on cystatin C and muscle strength in the Chinese population. METHODS: This was a cross-sectional study enrolling 12,398 Chinese participants aged above 45 years (5762 men and 6636 women) from the 2015 China Health and Retirement Longitudinal Study. Handgrip strength (HGS) was used to assess muscle strength. Locally weighted scatterplot smoothing (LOWESS) curves were employed to visualize the relationships between eGFR and HGS. Multivariable logistic regression was conducted to analyze the correlation between kidney function and low muscle strength. RESULTS: Significant differences in HGS by CKD stage were observed in both sexes after adjusting for age and body mass index. LOWESS curves demonstrated concomitant decreases in HGS and kidney function at eGFR levels below 120 mL/min/1.73 m2 in both sexes. According to multivariate logistic regression, participants with CKD stages 2 (odds ratio [OR]: 1.256, 95% confidence interval [CI]: 1.120-1.409), 3 (OR: 2.725, 95% CI: 2.2585-3.288), and 4-5 (OR: 3.069, 95% CI 1.747-5.392) had higher risk of low muscle strength than those who were normal or had CKD stage 1 after adjusting for demographic and clinical variables. CONCLUSION: Our study illustrated that CKD stage was independently associated with low muscle strength in Chinese middle-aged and elderly populations.

Novel predictive biomarkers for acute injury superimposed on chronic kidney disease / Novedosos biomarcadores predictivos para lesiones agudas superpuestas a una enfermedad renal crónica

INTRODUCTION AND OBJECTIVES: Chronic kidney disease (CKD) is a risk factor for the development of acute kidney injury (AKI). Recent studies have revealed numerous biomarkers eligible for AKI prediction. However, the expression and performance of AKI biomarkers in acute injury superimposed on preexisting CKD (AonC) remain elusive. The aim of this study was to evaluate whether biomarkers which robustly expressed in acute kidney injury could predict acute injury based on CKD. MATERIALS AND METHODS: Mice were classified into cohorts: AKI, CKD, AonC and sham. The AonC model mice were subjected to renal bilateral ischemia/reperfusion (I/R) injury fourteen days after intraperitoneally administrated with 20 mg/kg aristolochic acid. Severity of acute ischemic injury was stratified by clamping the dissected bilateral renal arteries with non-traumatic microvascular clips for 20 or 35 min. The AKI mice were induced with renal bilateral I/R injury and CKD mice were crafted with 20mg/kg aristolochic acid administrated intraperitoneally. Histology, genetic and protein expression of biomarkers were measured in three cohorts. RESULTS: We found that serum creatinine dramatically increased in severe (sAonC) but not in moderate (mAonC) injury mice. Upregulation of Kidney injury molecule-1 (KIM-1) mRNA, tissue inhibitor of metalloproteinase-2 (TIMP-2), Syndecan-1 (SDC-1) mRNA and insulin-like growth factor binding protein-7 (IGFBP7) protein indicated the onset of mAonC. An increase in neutrophil gelatinase-associated lipocalin (NGAL), rhomboid-like protein 2 (RHBDL2), Syndecan-1 (SDC-1) mRNA and protein, and a decrease in IGFBP7 protein were associated with sAonC. CONCLUSIONS: Our study revealed the variational expression of AKI biomarkers in AonC kidneys, and uncovered IGFBP7 protein can be used as a sensitive biomarker to predict and differentiate AonC severity. The performance of RHBDL2 and SDC-1 in predicting severe AonC was promising, providing new biomarkers for predicting AonC

INTRODUCCIÓN Y OBJETIVOS: La enfermedad renal crónica (ERC) es un factor de riesgo para el desarrollo de una lesión renal aguda (LRA). Estudios recientes han revelado numerosos biomarcadores para la predicción de LRA. No obstante, la expresión y el rendimiento de los biomarcadores de LRA en lesiones agudas superpuestas a una ERC preexistente (AonC, en inglés) siguen siendo imprecisos. El objetivo de este estudio fue evaluar si los biomarcadores que se encuentran muy expresados en la lesión renal aguda podrían predecir una lesión aguda superpuesta a una ERC. MATERIALES Y MÉTODOS: Se dividieron ratones en cohortes (LRA, ERC, AonC y grupo de referencia). A los ratones del modelo de AonC se les indujo una lesión renal bilateral por isquemia/reperfusión (I/R) 14 días después de la administración intraperitoneal de 20 mg/kg de ácido artistolóquico. La gravedad de la lesión isquémica aguda se estratificó pinzando las arterias renales bilaterales diseccionadas con horquillas microvasculares no traumáticas durante 20 o 35 min. A los ratones de LRA se les indujo una lesión renal bilateral por I/R y a los ratones de ERC se les administraron 20mg/kg de ácido artistolóquico por vía intraperitoneal. Se determinaron la histología, la genética y la expresión de proteínas en las tres cohortes. RESULTADOS: Observamos que la creatinina sérica aumentaba drásticamente en los ratones con lesiones graves (AonCg) pero no en aquellos con lesiones moderadas (AonCm) El aumento del ARNm de la molécula1 de lesión renal (KIM-1), del inhibidor tisular de metaloproteinasas 2 (TIMP-2), del ARNm de sindecán 1 (SDC-1) y de la proteína de unión al factor de crecimiento insulinoide 7 (IGFBP7) fue indicativo de aparición de AonCm. El incremento de la lipocalina asociada a la gelatinasa de neutrófilos (NGAL), la proteína romboidal 2 (RHBDL2) y el ARNm y la proteína de sindecán 1 (SDC-1), así como la reducción de la proteína IGFBP7, se asociaron a una AonCg. CONCLUSIONES: Nuestro estudio mostró la variación de la expresión de los biomarcadores de LRA en riñones con AonC y descubrió que la proteína IGFBP7 puede emplearse como biomarcador sensible para la predicción y la diferenciación de la gravedad de la AonC. El rendimiento de RHBDL2 y SDC-1 en la predicción de AonC graves resultó prometedor, lo que ofrece nuevos biomarcadores para la predicción de AonC

Novel predictive biomarkers for acute injury superimposed on chronic kidney disease.

INTRODUCTION AND OBJECTIVES: Chronic kidney disease (CKD) is a risk factor for the development of acute kidney injury (AKI). Recent studies have revealed numerous biomarkers eligible for AKI prediction. However, the expression and performance of AKI biomarkers in acute injury superimposed on preexisting CKD (AonC) remain elusive. The aim of this study was to evaluate whether biomarkers which robustly expressed in acute kidney injury could predict acute injury based on CKD. MATERIALS AND METHODS: Mice were classified into cohorts: AKI, CKD, AonC and sham. The AonC model mice were subjected to renal bilateral ischemia/reperfusion (I/R) injury fourteen days after intraperitoneally administrated with 20mg/kg aristolochic acid. Severity of acute ischemic injury was stratified by clamping the dissected bilateral renal arteries with non-traumatic microvascular clips for 20 or 35min. The AKI mice were induced with renal bilateral I/R injury and CKD mice were crafted with 20mg/kg aristolochic acid administrated intraperitoneally. Histology, genetic and protein expression of biomarkers were measured in three cohorts. RESULTS: We found that serum creatinine dramatically increased in severe (sAonC) but not in moderate (mAonC) injury mice. Upregulation of Kidney injury molecule-1 (KIM-1) mRNA, tissue inhibitor of metalloproteinase-2 (TIMP-2), Syndecan-1 (SDC-1) mRNA and insulin-like growth factor binding protein-7 (IGFBP7) protein indicated the onset of mAonC. An increase in neutrophil gelatinase-associated lipocalin (NGAL), rhomboid-like protein 2 (RHBDL2), Syndecan-1 (SDC-1) mRNA and protein, and a decrease in IGFBP7 protein were associated with sAonC. CONCLUSIONS: Our study revealed the variational expression of AKI biomarkers in AonC kidneys, and uncovered IGFBP7 protein can be used as a sensitive biomarker to predict and differentiate AonC severity. The performance of RHBDL2 and SDC-1 in predicting severe AonC was promising, providing new biomarkers for predicting AonC.

Erythrocyte transfusion limits the role of elevated red cell distribution width on predicting cardiac surgery associated acute kidney injury.

BACKGROUND: Acute kidney injury (AKI) is one of the more serious complications after cardiac surgery. Elevated red cell distribution width (RDW) was reported as a predictor for cardiac surgery associated acute kidney injury (CSAKI). However, the increment of RDW by erythrocyte transfusion makes its prognostic role doubtful. The aim of this study is to elucidate the impact of erythrocyte transfusion on the prognostic role of elevated RDW for predicting CSAKI. METHODS: A total of 3207 eligible patients who underwent cardiac surgery during 2016-2017 were enrolled. Changes of RDW was defined as the difference between preoperative RDW and RDW measured 24 h after cardiac surgery. The primary outcome was CSAKI which was defined by the Kidney Disease: Improving Global Outcomes Definition and Staging (KDIGO) criteria. Univariate and multivariate analysis were performed to identify predictors for CSAKI. RESULTS: The incidence of CSAKI was 38.07% and the mortality was 1.18%. CSAKI patients had higher elevated RDW than those without CSAKI (0.65% vs. 0.39%, p < 0.001). Multivariate regression showed that male, age, New York Heat Association classification 3-4, elevated RDW, estimated glomerular filtration rate < 60 mL/min/1.73 m2, cardiopulmonary bypass time > 120 min and erythrocyte transfusion were associated with CSAKI. Subgroup analysis showed elevated RDW was an independent predictor for CSAKI in the non-transfused subset (adjusted odds ratio: 1.616, p < 0.001) whereas no significant association between elevated RDW and CSAKI was found in the transfused patients (odds ratio: 1.040, p = 0.497). CONCLUSIONS: Elevated RDW is one of the independent predictors of CSAKI in the absence of erythrocyte transfusion, which limits the prognostic role of the former on predicting CSAKI.