Renal Fibrosis In Patients Research Articles

The role of strain wave elastography in the evaluation of renal fibrosis in patients with kidney diseases

BackgroundA renal biopsy represents the gold standard in the diagnosis, prognosis and management of patients with chronic kidney disease and glomerulonephritis. Strain wave elastography (SE) is a developing technique to assess tissue elasticity. The aim of this study was to correlate between the strain index value of renal parenchyma and degree of renal fibrosis detected with renal biopsy. MethodFor 68 patients who were referred for a kidney biopsy, SE test was performed. The Banff scoring system was utilized to classify the IFTA grading of kidney fibrosis that assigns a severity level of mild, moderate, or severe. Receiver operating characteristic curve (ROC) was utilized to correlate between the severity of renal fibrosis and the grade of renal elasticity determined by SE. ResultsIn total, 38 males and 30 females, the echogenicity, qualitative and semiquantitative elastography showed significant positive correlation with serum creatinine, percentage of fibrosis, G score and tubular atrophy and significant negative correlation with eGFR. ROC curve of SE for diagnosis of interstitial fibrosis shown that echogenicity has sensitivity 100.0%, specificity 62.5%, positive predictive value (PPV) 75.0%, negative predictive value (NPV) 100.0% with area under curve (AUC) 0.906, while qualitative elastography has sensitivity 77.8%, specificity 75.0%, PPV 77.8%, NPV 75.0%, AUC 0.833, semi quantitative elastography has sensitivity 83.3%, specificity 93.8%, PPV 93.8%, NPV 83.3% with AUC 0.915. ConclusionSE approach is simple to use, and can differentiate between varying stages of renal fibrosis. However, further research is required before it can be frequently used in clinical practice.

The efficacy and safety of tonifying-kidney and invigorating-blood circulation (Bushen-Huoxue) formula on renal fibrosis in patients with chronic kidney disease: A protocol for systematic review and meta-analysis

Background: The incidence of chronic kidney disease (CKD) is increasing and the progression of renal interstitial fibrosis (RIF) in end-stage renal disease is attributed to the development of various CKD. One of the treatments for RIF is an oral treatment known as Bushen-Huoxue (BSHX), which stimulates blood circulation and tonifies the kidney. Randomized controlled trials of BSHX treatment of RIF have been reported, but their efficacy and safety have not been comprehensively examined. Therefore, our study aims to describe the efficacy and safety of oral application of the traditional Chinese medicine (TCM) formula of BSHX on treating RIF in CKD by systematic analysis and meta-analysis. Methods: A total of 13 databases, including PubMed, EMBASE, MEDLINE, Web of Science, Cochrane Library, SpringerLink, WHO International Clinical Trials Registry Platform, Wanfang China database, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, Chinese Scientific Journal Database, and China’s Conference Papers Database and China Dissertation database will be searched from inception to July 2023. In addition, other suitable search strategies will be used as well to complete this review. All randomized controlled trials that use the BSHX formula for RIF to apply TCM treatments externally for CKD will be included. The eligible studies will be selected to enroll by 2 independent researchers following a predetermined protocol. The review manager software (Rev-Man 5.3) will be used to assess the risk of bias, reporting bias, and data synthesis. Result: We will compile and discuss the recent examples of the TCM BSHX formula treatment for RIF in CKD. Conclusion: We will provide strong evidences for evaluating the efficacy and safety of the TCM BSHX formula treatment for RIF in CKD.

Interaction of estradiol and renin-angiotensin system with microRNAs-21 and -29 in renal fibrosis: focus on TGF-β/smad signaling pathway.

Kidney fibrosis is one of the complications of chronic kidney disease (CKD (and contributes to end-stage renal disease which requires dialysis and kidney transplantation. Several signaling pathways such as renin-angiotensin system (RAS), microRNAs (miRNAs) and transforming growth factor-β1 (TGF-β1)/Smad have a prominent role in pathophysiology and progression of renal fibrosis. Activation of classical RAS, the elevation of angiotensin II (Ang II) production and overexpression of AT1R, develop renal fibrosis via TGF-β/Smad pathway. While the non-classical RAS arm, Ang 1-7/AT2R, MasR reveals an anti-fibrotic effect via antagonizing Ang II. This review focused on studies illustrating the interaction of RAS with sexual female hormone estradiol and miRNAs in the progression of renal fibrosis with more emphasis on the TGF-β signaling pathway. MiRNAs, especially miRNA-21 and miRNA-29 showed regulatory effects in renal fibrosis. Also, 17β-estradiol (E2) is a renoprotective hormone that improved renal fibrosis. Beneficial effects of ACE inhibitors and ARBs are reported in the prevention of renal fibrosis in patients. Future studies are also merited to delineate the new therapy strategies such as miRNAs targeting, combination therapy of E2 or HRT, ACEis, and ARBs with miRNAs mimics and antagomirs in CKD to provide a new therapeutic approach for kidney patients.

Association of renal elasticity evaluated by real-time shear wave elastography with renal fibrosis in patients with chronic kidney disease.

Renal fibrosis is a final common pathological hallmark in the progression of chronic kidney disease (CKD). Non-invasive evaluation of renal fibrosis by mapping renal stiffness obtained by shear wave elastography (SWE) may facilitate the clinical therapeutic regimen for CKD patients. A cohort of 162 patients diagnosed with CKD, who underwent renal biopsy, was prospectively and consecutively recruited between April 2019 and December 2021. The assessment of renal cortex stiffness was performed using SWE imaging. The patients were classified into different groups based on pathological renal fibrosis (mild group: n = 74; moderate-to-severe group: n = 88). Binary logistic regression model and generalized additive model were conducted to investigate the association of renal elasticity with renal fibrosis. Compared with the mildly impaired group, the moderate-to-severe group showed a significant decline in renal elasticity (P < .001). In the fully adjusted model, each 10 kPa drop in renal elasticity was associated with a 3.5-fold increment in the risk of moderate-to-severe renal fibrosis (fully adjusted odds ratio, 4.54; 95% CI, 2.41-8.57). Particularly, participants in the lowest elasticity group (≤29.92 kPa) had a 20-fold increased chance of moderate-to-severe renal fibrosis than those in the group with highest elasticity (≥37.93 kPa). An inverse linear association was observed between renal elasticity increment and moderate-to-severe renal fibrosis risk. There is a negative linear association between increased renal elasticity and moderate-to-severe renal fibrosis risk among CKD patients. Patients with diminished renal stiffness have a higher risk of moderate-to-severe renal fibrosis. CKD patients with reduced renal stiffness have a higher likelihood of moderate-to-severe renal fibrosis.

Butyrate alleviates renal fibrosis in CKD by regulating NLRP3-mediated pyroptosis via the STING/NF-κB/p65 pathway

Chronic kidney disease (CKD) is a serious and irreversible disease primarily characterized by chronic inflammation and renal fibrosis. Recent studies have suggested that gut microbiota-related metabolites, particularly short-chain fatty acids (SCFAs) are significantly associated with kidney diseases. Notably, butyrate, a type of SCFAs, plays a crucial role in this correlation. However, the effect of butyrate on renal fibrosis in patients with CKD and its potential mechanisms remain unclear. In this study, we demonstrated that butyrate levels are reduced as CKD progresses using a CKD C57BL/6 mouse model established by a 0.2% adenine diet. Exogenous supplementation of butyrate effectively alleviated renal fibrosis and repressed the levels of proteins associated with NLRP3-mediated pyroptosis (NLRP3, IL-1β, caspase-1, and GSDMD). Additionally, we conducted an in vitro experiment using HK-2 cells, which also confirmed that the elevated levels of NLRP3-mediated pyroptosis proteins in TGF-β1-stimulated HK-2 cells are reversed by butyrate intervention. Further, butyrate mitigated the activity of the STING/NF-κB/p65 pathway, and STING overexpression impaired the protective function of butyrate in CKD. Hence, we suggest that butyrate may have a renoprotective role in CKD, alleviating renal fibrosis possibly by regulating NLRP3-mediated pyroptosis via the STING/NF-κB/p65 pathway.

YAP/ACSL4 Pathway-Mediated Ferroptosis Promotes Renal Fibrosis in the Presence of Kidney Stones.

The potential association between calcium oxalate stones and renal fibrosis has been extensively investigated; however, the underlying mechanisms remain unclear. Ferroptosis is a novel form of cell death characterized by iron-dependent lipid peroxidation and regulated by acyl coenzyme A synthase long-chain family member 4 (ACSL4). Yes-associated protein (YAP), a transcriptional co-activator in the Hippo pathway, promotes ferroptosis by modulating ACSL4 expression. Nevertheless, the involvement of YAP-ACSL4 axis-mediated ferroptosis in calcium oxalate crystal deposition-induced renal fibrosis and its molecular mechanisms have not been elucidated. In this study, we investigated ACSL4 expression and ferroptosis activation in the kidney tissues of patients with calcium oxalate stones and in mice using single-cell sequencing, transcriptome RNA sequencing, immunohistochemical analysis, and Western blot analysis. In vivo and in vitro experiments demonstrated that inhibiting ferroptosis or ACSL4 mitigated calcium oxalate crystal-induced renal fibrosis. Furthermore, YAP expression was elevated in the kidney tissues of patients with calcium oxalate stones and in calcium oxalate crystal-stimulated human renal tubular epithelial cell lines. Mechanistically, in calcium oxalate crystal-stimulated human renal tubular epithelial cell lines, activated YAP translocated to the nucleus and enhanced ACSL4 expression, consequently inducing cellular ferroptosis. Moreover, YAP silencing suppressed ferroptosis by downregulating ACSL4 expression, thereby attenuating calcium oxalate crystal-induced renal fibrosis. Conclusively, our findings suggest that YAP-ACSL4-mediated ferroptosis represents an important mechanism underlying the induction of renal fibrosis by calcium oxalate crystal deposition. Targeting the YAP-ACSL4 axis and ferroptosis may therefore hold promise as a potential therapeutic approach for preventing renal fibrosis in patients with kidney stones.

Development of renal fibrosis in patients with chronic kidney disease: Mechanisms, biomarkers, and clinical implications

CKD is a global health concern with significant implications for patients' well-being, morbidity, and mortality. The underlying mechanism of CKD development often involves progressive interstitial fibrosis. Understanding the processes and factors influencing fibrogenesis is crucial. This review aims to analyze recent literature on the pathophysiological mechanisms, early diagnosis, prevention, and treatment of renal fibrosis in CKD patients. It explores various aspects of kidney fibrogenesis, highlighting key pathogenic factors and signaling pathways that warrant further investigation.&#x0D; The review emphasizes the potential of urinary uromodulin (uUmod) as a biomarker for early renal fibrosis diagnosis and delves into the role of anemia, kidney hypoxia, vitamin D, and unique aspects of fibrosis development in diabetic kidney disease patients. Furthermore, it underscores the importance of inhibiting the renin-angiotensin-aldosterone system (RAAS) as a strategy for fibrosis prevention and attenuation.

Native T1 mapping for non-invasive quantitative evaluation of renal function and renal fibrosis in patients with chronic kidney disease.

To investigate the role of native T1 mapping in the non-invasive quantitative assessment of renal function and renal fibrosis (RF) in chronic kidney disease (CKD) patients. A prospective analysis of 71 consecutive patients [no RF (0%): 9 cases; mild RF (<25%): 36 cases; moderate RF (25-50%): 17 cases; severe RF (>50%): 9 cases] who were clinically diagnosed with CKD that was pathologically confirmed and who underwent magnetic resonance imaging (MRI) examination between October 2021 and September 2022 was performed. T1-C (mean cortical T1 value), T1-M (mean medullary T1 value), ΔT1 (mean corticomedullary difference) and T1% (mean corticomedullary ratio) values were compared. Correlations between T1 parameters and clinical and histopathological values were analyzed. Regression analysis was performed to determine independent predictors of RF. The areas under the receiver operating characteristic curve (AUC) were calculated to assess the diagnostic value of RF. The T1-C, ΔT1 and T1% values (P<0.05) were significantly different in the CKD group, but T1-M was not (P>0.05). The ΔT1 and T1% values showed significant differences in pairwise comparisons among CKD subgroups (P<0.05) except for CKD 2 and 3. ΔT1 and T1% were moderately correlated with the estimated glomerular filtration rate (ΔT1: rs=-0.561; T1%: r=-0.602), serum creatinine (ΔT1: rs=0.591; T1%: rs=0.563), blood urea nitrogen (ΔT1: rs=0.433; T1%: rs=0.435) and histopathological score (ΔT1: rs=0.630; T1%: rs=0.658). ΔT1 and T1%, but not T1-C, were independent predictors of RF (P<0.05). ΔT1 and T1% were set as -410.07 ms and 0.8222 with great specificity [ΔT1: 91.7% (77.5-98.2%); T1%: 97.2% (85.5-99.9%)] to identify mild RF and moderate-severe RF. The optimal cutoff values for differentiating severe RF from mild-moderate RF were -343.81 ms (ΔT1) and 0.8359 (T1%) with high sensitivity [both 100% (66.4-100%)] and specificity [ΔT1: 90.6% (79.3-96.9%); T1%: 94.3% (84.3-98.8%)]. ΔT1 and T1% overwhelm T1-C for assessment of renal function and RF in CKD patients. ΔT1 and T1% identify patients with <25% and >50% fibrosis, which can guide clinical decision-making and help to avoid biopsy-related bleeding.

Assessment of Renal Fibrosis in Patients With Chronic Kidney Disease Using Shear Wave Elastography and Clinical Features: A Random Forest Approach.

Renal fibrosis is the common pathological hallmark of chronic kidney disease (CKD) progression. In this study, a random forest (RF) classifier based on 2-D shear wave elastography (SWE) and clinical features for the differential severity of renal fibrosis in patients with CKD is proposed. A total of 162 patients diagnosed with CKD who underwent 2-D SWE and renal biopsy were prospectively enrolled from April 2019 to December 2021 and then randomized into training (n=114) and validation (n=48) cohorts at a ratio of 7:3. The least absolute shrinkage and selection operator (LASSO) regression and recursive feature elimination for support vector machines (SVM-RFE) algorithm were employed to select renal fibrosis-related features from clinical information and elastosonographic findings. An RF model was subsequently constructed using the aforementioned informative parameters in the training cohort and evaluated in terms of discrimination, calibration and clinical utility in both cohorts. The LASSO and SVM-RFE analyses revealed that age, sex, blood urea nitrogen, renal resistive index, hypertension and the 2D-SWE value were independent risk variables associated with renal fibrosis severity. The established RF model incorporating these six variables exhibited fine discrimination in both the derivation (area under the curve [AUC]: 0.84, 95% confidence interval [CI]: 0.76-0.91) and validation (AUC: 0.88, 95% CI: 0.77-0.98) cohorts. Moreover, the calibration curve revealed satisfactory predictive accuracy, and the decision curve analysis revealed a significant clinical net benefit. The developed RF model, via a combination of the 2-D SWE value and clinical information, indicated satisfactory diagnostic performance and clinical practicality toward differentiating moderate-severe from mild renal fibrosis, which may provide critical insight into risk stratification for patients with CKD.

Efficacy and safety of activating blood circulation and removing blood stasis of Traditional Chinese Medicine for managing renal fibrosis in patients with chronic kidney disease: a systematic review and Meta-analysis.

To evaluate the efficacy and safety of activating blood circulation and removing blood stasis in terms of Traditional Chinese Medicine (TCM) for managing renal fibrosis (RF) in patients with chronic kidney disease (CKD). We searched randomized controlled trials (RCTs) from eight databases. Sixteen eligible studies with 1,356 participants were included in this study. Compared to treatment with Western Medicine (WM) alone, the combined treatment with activating blood circulation and removing blood stasis in terms of TCM (ARTCM) and WM to manage RF in patients with CKD significantly ameliorated type Ⅳ collagen (CⅣ) (: 2.17, 95% : 3.01 to 1.34), type Ⅲ procollagen (PCⅢ) (: 1.08, 95% : 1.64 to 0.53), laminin (LN) (: 1.28, 95% : 1.65 to 0.90), transforming growth factor β 1 (TGFβ1) (: 0.65, 95% : 1.18 to 0.12), serum creatinine (Scr) (: 1.36, 95% : 1.85 to 0.87), blood urea nitrogen (BUN) (: 1.51, 95% : 2.59 to 0.43), and 24 h urine protein (24hUpro) (: 1.23; 95% : 1.96 to 0.50). The level of hyaluronic acid (HA) was similar in both types of treatment (: 0.74, 95% : 1.91 to 0.44). The subgroup analysis showed that the duration of 8 weeks might affect the concentration of C-Ⅳ, PC-Ⅲ, and LN (<0.05). The effectiveness of the longer duration to C-Ⅳ, PC-Ⅲ, and LN was not certain. However, the result should be interpreted in care. The safety of the treatment using ARTCM and WM could not be evaluated because a few studies had reported adverse effects. The results of the Metaanalysis were not stable enough. There was publication bias for the reports on Scr ( 0.001), C-Ⅳ ( 0.001), PC-Ⅲ ( 0.026), and LN ( 0.030) and no publication bias for the reports on BUN ( 0.293). The quality of evidence varied from low to very low. The combined treatment using ARTCM and WM to manage RF in patients with CKD has some advantages over treatment with WM alone. Highquality RCTs need to be conducted for the strong support.

Ultrasound-based radiomics analysis in the assessment of renal fibrosis in patients with chronic kidney disease.

Assessment of renal fibrosis non-invasively in chronic kidney disease (CKD) patients is still a clinical challenge. In this study, we aimed to establish a radiomics model integrating radiomics features derived from ultrasound (US) images with clinical characteristics for the assessment of renal fibrosis severity in CKD patients. A total of 160 patients with CKD who underwent kidney biopsy and renal US examination were prospectively enrolled. Patients were classified into the mild or moderate-severe fibrosis group based on pathology results. Radiomics features were extracted from the US images, and a radiomics signature was constructed using the maximum relevance minimum redundancy (mRMR) and least absolute shrinkage and selection operator (LASSO) regression algorithms. Multivariable logistic regression was employed to construct the radiomics model, which incorporated the radiomics signature and the selected clinical variables. The established model was evaluated for discrimination, calibration, and clinical utility in the derivation cohort and internal cross-validation (CV) analysis, respectively. The radiomics signature, consisting of nine identified fibrosis-related features, achieved moderate discriminatory ability with an area under the receiver operating characteristic curve (AUC) of 0.72 (95% confidence interval (CI) 0.64-0.79). By combining the radiomics signature with significant clinical risk factors, the radiomics model showed satisfactory discrimination performance, yielding an AUC of 0.85 (95% CI 0.79-0.91) in the derivation cohort and a mean AUC of 0.84 (95% CI 0.77-0.92) in the internal CV analysis. It also demonstrated fine accuracy via the calibration curve. Furthermore, the decision curve analysis indicated that the model was clinically useful. The proposed radiomics model showed favorable performance in determining the individualized risk of moderate-severe renal fibrosis in patients with CKD, which may facilitate more effective clinical decision-making.

P53 deacetylation alleviates calcium oxalate deposition-induced renal fibrosis by inhibiting ferroptosis

Calcium oxalate (CaOx) stones are among the most common types of kidney stones and are associated with renal tubular damage, interstitial fibrosis, and chronic kidney disease. The mechanism of CaOx crystal-induced renal fibrosis remains unknown. Ferroptosis, a type of regulated cell death, is characterised by iron-dependent lipid peroxidation, and the tumour suppressor p53 is a key regulator of ferroptosis. In the present study, our results demonstrated that ferroptosis was significantly activated in patients with nephrolithiasis and hyperoxaluric mice as well as verified the protective effects of ferroptosis inhibition on CaOx crystal-induced renal fibrosis. Moreover, the single-cell sequencing database, RNA-sequencing, and western blot analysis revealed that the expression of p53 was increased in patients with chronic kidney disease and the oxalate-stimulated human renal tubular epithelial cell line, HK-2. Additionally, the acetylation of p53 was enhanced by oxalate stimulation in HK-2 cells. Mechanistically, we found that the induction of p53 deacetylation, owing to either the SRT1720-induced activation of deacetylase sirtuin 1 or the triple mutation of p53, inhibited ferroptosis and alleviated renal fibrosis caused by CaOx crystals. We conclude that ferroptosis is one of the critical mechanisms contributing to CaOx crystal-induced renal fibrosis, and the pharmacological induction of ferroptosis via sirtuin 1-mediated p53 deacetylation may be a potential target for preventing renal fibrosis in patients with nephrolithiasis.

Shear Wave Elastography for Assessment of Biopsy-Proven Renal Fibrosis: A Systematic Review and Meta-analysis.

The purpose of this meta-analysis was to evaluate the diagnostic performance of shear wave elastography (SWE) for the staging of renal fibrosis in patients with chronic kidney disease (CKD). Classification of CKD into mild, moderate and severe fibrosis was based on renal biopsy pathology (glomerulosclerosis, tubulointerstitial injury and vascular sclerosis). The Cochrane Library, Medline, PubMed, Web of Science, EMBASE and CNKI databases were searched from January 1, 2009, to April 20, 2022. Pooled sensitivity, specificity, diagnostic odds ratio and area under the receiver operating characteristic curve (AUROC) were calculated using random effects models. A total of 1394 patients from 14 studies were included in the final analysis. For mild, moderate and severe renal fibrosis, SWE had a sensitivity of 0.79 (95% confidence interval [CI]: 0.67-0.88), 0.73 (95% CI: 0.65-0.80) and 0.87 (95% CI: 0.71-0.95); a specificity of 0.82 (95% CI: 0.75-0.87), 72% (95% CI: 0.67-0.77) and 0.83 (95% CI: 0.80-0.86); an AUROC of 0.87 (95% CI: 0.84-0.90), 0.78 (95% CI: 0.75-0.82) and 0.86 (95% CI: 0.82-0.88); and a diagnostic odds ratio of 17 (95% CI: 7-43), 7 (95% CI: 4-12) and 34 (95% CI: 13-88), respectively. Meta-regressions revealed that the publication date, system used and number of valid measurements of SWE were the main causes of heterogeneity. SWE is a good technique for diagnosing mild and severe renal fibrosis, as well as a fair technique for diagnosing moderate fibrosis.

Using elastography-based multilayer perceptron model to evaluate renal fibrosis in chronic kidney disease

Background Given its progressive deterioration in the clinical course, noninvasive assessment and risk stratification for the severity of renal fibrosis in chronic kidney disease (CKD) are required. We aimed to develop and validate an end-to-end multilayer perceptron (MLP) model for assessing renal fibrosis in CKD patients based on real-time two-dimensional shear wave elastography (2D-SWE) and clinical variables. Methods From April 2019 to December 2021, a total of 162 patients with CKD who underwent a kidney biopsy and 2D-SWE examination were included in this single-center, cross-sectional, and prospective clinical study. 2D-SWE was performed to measure the right renal cortex stiffness, and the corresponding elastic values were recorded. Patients were categorized into two groups according to their histopathological results: mild and moderate-severe renal fibrosis. The patients were randomly divided into a training cohort (n = 114) or a test cohort (n = 48). The MLP classifier using a machine learning algorithm was used to construct a diagnostic model incorporating elastic values with clinical features. Discrimination, calibration, and clinical utility were used to appraise the performance of the established MLP model in the training and test sets, respectively. Results The developed MLP model demonstrated good calibration and discrimination in both the training [area under the receiver operating characteristic curve (AUC) = 0.93; 95% confidence interval (CI) = 0.88 to 0.98] and test cohorts [AUC = 0.86; 95% CI = 0.75 to 0.97]. A decision curve analysis and a clinical impact curve also showed that the MLP model had a positive clinical impact and relatively few negative effects. Conclusions The proposed MLP model exhibited the satisfactory performance in identifying the individualized risk of moderate-severe renal fibrosis in patients with CKD, which is potentially helpful for clinical management and treatment decision-making.

Development and Deployment of a Novel Diagnostic Tool Based on Conventional Ultrasound for Fibrosis Assessment in Chronic Kidney Disease

Accurate identification of risk information about fibrosis severity is crucial for clinical decision-making and clinical management of patients with chronic kidney disease (CKD). This study aimed to develop an ultrasound (US)-derived computer-aided diagnosis tool for identifying CKD patients at high risk of developing moderate-severe renal fibrosis, in order to optimize treatment regimens and follow-up strategies. A total of 162 CKD patients undergoing renal biopsies and US examinations were prospectively enrolled and randomly divided into training (n=114) and validation (n=48) cohorts. A multivariate logistic regression approach was employed to develop the diagnostic tool named S-CKD for differentiating moderate-severe renal fibrosis from mild one in the training cohort by integrating the significant variables, which were screened out from demographic characteristics and conventional US features via the least absolute shrinkage and selection operator regression algorithm. The S-CKD was then deployed as both an online web-based and an offline document-based, easy-to-use auxiliary device. In both the training and validation cohorts, the S-CKD's diagnostic performance was evaluated through discrimination and calibration.The clinical benefit of using S-CKD was revealed by decision curve analysis (DCA) and clinical impact curves. The proposed S-CKD achieved an area under the receiver operating characteristic curve of 0.84 (95% confidence interval (CI): 0.77-0.91) and 0.81 (95% CI: 0.68-0.94) in the training and validation cohorts, respectively, indicating satisfactory diagnosis performance. Results of the calibration curves showed that S-CKD has excellent predictive accuracy (Hosmer-Lemeshow test: training cohort, p=0.497; validation cohort, p=0.205). The DCA and clinical impact curves exhibited a high clinical application value of the S-CKD at a wide range of risk probabilities. The S-CKD tool developed in this study is capable of discriminating between mild and moderate-severe renal fibrosis in patients with CKD and achieving promising clinical benefits, which may aid clinicians in personalizing medical decision-making and follow-up arrangement.

WCN23-0357 Quercetin potentially suppresses renal fibrosis in patients with COVID-19 under hypoxic state

WCN23-0357 Quercetin potentially suppresses renal fibrosis in patients with COVID-19 under hypoxic state

Urinary Markers of Tubular Injury and Renal Fibrosis in Patients with Type 2 Diabetes and Different Phenotypes of Chronic Kidney Disease

This study assessed the urinary excretion of markers and mediators of tubular injury and renal fibrosis in patients with type 2 diabetes (T2D) and non-albuminuric and albuminuric patterns of chronic kidney disease (CKD). One hundred and forty patients with long-term T2D and different patterns of CKD and twenty non-diabetic individuals were included. Urinary retinol-binding protein 4 (RBP-4), glutathione-S-transferase α1 and π (GST-α1 and GST-π), transforming growth factor β (TGF-β), type I and type IV collagen (Col1 and Col4), bone morphogenic protein 7 (BMP-7), and hepatocyte growth factor (HGF) were assessed by ELISA. Patients with T2D demonstrated increased urinary excretion of RBP-4, GST-π, Col4, BMP-7, and HGF (all p < 0.05 vs. control). The excretion of RBP-4, GST-π, Col1, and Col4 was increased in patients with elevated albumin-to-creatinine ratio (UACR; all p < 0.05 vs. control), while BMP-7 and HGF were increased innormoalbuminuric patients also (p < 0.05). Urinary RBP-4, GST-α1, Col1, Col4, and HGF correlated positively with UACR; meanwhile, no correlations with glomerular filtration rate were found. The results demonstrate that elevated urinary excretions of the markers of tubular injury (RBP-4, GST-π) and renal fibrosis (Col1, Col4), as well as HGF, an antifibrotic regulator, are associated with the albuminuric pattern of CKD in subjects with T2D.

A methodological study of 2D shear wave elastography for noninvasive quantitative assessment of renal fibrosis in patients with chronic kidney disease.

To determine the optimal measurement method of 2D shear wave elastography (2D-SWE) for noninvasive quantitative assessment of renal fibrosis in chronic kidney disease (CKD) patients. A total of 190 CKD patients were enrolled for 2D-SWE of right kidney. The success rates, coefficients of variation (CV), and pathological correlation of different measurement sites, body positions, and depths were compared. (1) Measurement sites: Success rate in the middle part (100%) was higher than that in the lower pole (97.3%, P > 0.05). CV in the middle part (10.2%) was lower than that in the lower pole (16.4%, P < 0.05). Pathological correlation of the middle part (r = - 0.452, P < 0.05) was higher than that of the lower pole (r = 0.097, P > 0.05). (2) Body positions: Success rate in left lateral decubitus position (100%) was higher than that in supine (99.4%, P > 0.05) and prone position (99.4%, P > 0.05). CV was lowest (11.9%) and pathological correlation was highest (r = -0.256, P < 0.05) in prone position. (3) Measurement depths: Success rate at depth < 4cm (100%) was higher than that at depth ≥ 4cm (98.8%, P > 0.05). CV at depth < 4cm (11.1%) was lower than that at depth ≥ 4cm (14.4%, P < 0.05). Pathological correlation at depth < 4cm (r = - 0.303, P < 0.05) was higher than that at depth ≥ 4cm (r = - 0.156, P > 0.05). The optimal measurement method of 2D-SWE for renal fibrosis assessment was prone position, renal middle part, and measurement depth < 4cm.

Associations between local acidosis induced by renal LDHA and renal fibrosis and mitochondrial abnormalities in patients with diabetic kidney disease

During the progression of diabetic kidney disease (DKD), renal lactate metabolism is rewired. The relationship between alterations in renal lactate metabolism and renal fibrosis in patients with diabetes has only been partially established due to a lack of biopsy tissues from patients with DKD and the intricate mechanism of lactate homeostasis. The role of lactate dehydrogenase A (LDHA)-mediated lactate generation in renal fibrosis and dysfunction in human and animal models of DKD was explored in this study. Measures of lactate metabolism (urinary lactate levels and LDHA expression) and measures of DKD progression (estimated glomerular filtration rate and Wilms' tumor-1 expression) were strongly negatively correlated in patients with DKD. Experiments with streptozotocin-induced DKD rat models and the rat renal mesangial cell model confirmed our findings. We found that the pathogenesis of DKD is linked to hypoxia-mediated lactic acidosis, which leads to fibrosis and mitochondrial abnormalities. The pathogenic characteristics of DKD were significantly reduced when aerobic glycolysis or LDHA expression was inhibited. Further studies will aim to investigate whether local acidosis caused by renal LDHA might be exploited as a therapeutic target in patients with DKD.

CXCR4 inhibition attenuates calcium oxalate crystal deposition-induced renal fibrosis

Nephrolithiasis is a highly prevalent urological disease and results in a correspondingly heavy socioeconomic and healthcare burden. Calcium oxalate (CaOx) stones are among the most common types of kidney stones. They are associated with renal tubular damage, interstitial fibrosis and chronic kidney disease (CKD). However, the molecular mechanisms in CaOx crystal deposition-induced renal fibrosis remain unclear. Chemokines and their receptors act a crucial role in the progression of renal fibrosis through inflammatory cell infiltration, autophagy activation, and epithelial-mesenchymal transition (EMT). The current work aims to study the action and mechanism of the C-X-C motif chemokine receptor 4 (CXCR4) in CaOx crystal deposition-induced renal fibrosis. Transcriptome RNA sequencing, qPCR, and immunohistochemistry revealed that the expression of CXCR4 was significantly upregulated in patients with nephrolithiasis and hyperoxaluric mice. Renal injury and fibrosis were significantly suppressed by inhibiting CXCR4 with AMD3100 or siRNA in hyperoxaluric mice and oxalate-stimulated HK-2 cells; EMT, reactive oxygen species (ROS) levels, and autophagy were also suppressed. Bioinformatic analysis revealed that the NF-κB pathway was activated in hyperoxaluric mice. Mechanistically, activation of the NF-κB pathway was suppressed by CXCR4 inhibition in CaOx crystal-induced renal fibrosis; this suppression was significantly aggravated by the NF-κB inhibitor BAY-11-7085. Moreover, inhibition of autophagy attenuated EMT progression in vitro. Our results suggest that CXCR4 inhibition attenuates CaOx crystal deposition-induced renal fibrosis by suppressing autophagy and EMT through the NF-κB pathway. Therefore, CXCR4 is a potential target for preventing renal fibrosis in patients with nephrolithiasis.