Cross-species single-cell analysis uncovers the immunopathological mechanisms associated with IgA nephropathy progression.

IgA nephropathy (IgAN) represents the main cause of renal failure, while the precise pathogenetic mechanisms have not been fully determined. Herein, we conducted a cross-species single-cell survey on human IgAN and mouse and rat IgAN models to explore the pathogenic programs. Cross-species single-cell RNA sequencing (scRNA-Seq) revealed that the IgAN mesangial cells (MCs) expressed high levels of inflammatory signatures CXCL12, CCL2, CSF1, and IL-34 and specifically interacted with IgAN macrophages via the CXCL12/CXCR4, CSF1/IL-34/CSF1 receptor, and integrin subunit alpha X/integrin subunit alpha M/complement C3 (C3) axes. IgAN macrophages expressed high levels of CXCR4, PDGFB, triggering receptor expressed on myeloid cells 2, TNF, and C3, and the trajectory analysis suggested that these cells derived from the differentiation of infiltrating blood monocytes. Additionally, protein profiling of 21 progression and 28 nonprogression IgAN samples revealed that proteins CXCL12, C3, mannose receptor C-type 1, and CD163 were negatively correlated with estimated glomerular filtration rate (eGFR) value and poor prognosis (30% eGFR as composite end point). Last, a functional experiment revealed that specific blockade of the Cxcl12/Cxcr4 pathway substantially attenuated the glomerulus and tubule inflammatory injury, fibrosis, and renal function decline in the mouse IgAN model. This study provides insights into IgAN progression and may aid in the refinement of IgAN diagnosis and the optimization of treatment strategies.

Acute kidney injury in hospitalized patients with nonmalignant pleural effusions: a retrospective cohort study.

BACKGROUND: Nonmalignant pleural effusion (NMPE) is common and remains a definite health care problem. Pleural effusion was supposed to be a risk factor for acute kidney injury (AKI). Incidence of AKI in NMPE patients and whether there is correlation between the size of effusions and AKI is unknown. OBJECTIVE: To assess the incidence of AKI in NMPE inpatients and its association with effusion size. STUDY DESIGN AND METHOD: We conducted a retrospective cohort study of inpatients admitted to the Chinese PLA General Hospital with pleural effusion from 2018-2021. All patients with pleural effusions confirmed by chest radiography (CT or X-ray) were included, excluding patients with diagnosis of malignancy, chronic dialysis, end-stage renal disease (ESRD), community-acquired AKI, hospital-acquired AKI before chest radiography, and fewer than two serum creatinine tests during hospitalization. Multivariate logistic regression and LASSO logistic regression models were used to identify risk factors associated with AKI. Subgroup analyses and interaction tests for effusion volume were performed adjusted for the variables selected by LASSO. Causal mediation analysis was used to estimate the mediating effect of heart failure, pneumonia, and eGFR < 60 ml/min/1.73m2 on AKI through effusion volume. RESULTS: NMPE was present in 7.8% of internal medicine inpatients. Of the 3047 patients included, 360 (11.8%) developed AKI during hospitalization. After adjustment by covariates selected by LASSO, moderate and large effusions increased the risk of AKI compared with small effusions (moderate: OR 1.47, 95%CI 1.11-1.94 p = 0.006; large: OR 1.86, 95%CI 1.05-3.20 p = 0.028). No significant modification effect was observed among age, gender, diabetes, bilateral effusions, and eGFR. Volume of effusions mediated 6.8% (p = 0.005), 4.0% (p = 0.046) and 4.6% (p < 0.001) of the effect of heart failure, pneumonia and low eGFR on the development of AKI respectively. CONCLUSION: The incidence of AKI is high among NMPE patients. Moderate and large effusion volume is independently associated with AKI compared to small size. The effusion size acts as a mediator in heart failure, pneumonia, and eGFR.

Urinary miR-185-5p is a biomarker of renal tubulointerstitial fibrosis in IgA nephropathy.

Background: For IgA nephropathy (IgAN), tubular atrophy/interstitial fibrosis is the most important prognostic pathological indicator in the mesangial and endocapillary hypercellularity, segmental sclerosis, interstitial fibrosis/tubular atrophy, and presence of crescents (MEST-C) score. The identification of non-invasive biomarkers for tubular atrophy/interstitial fibrosis would aid clinical monitoring of IgAN progression and improve patient prognosis. Methods: The study included 188 patients with primary IgAN in separate confirmation and validation cohorts. The associations of miR-92a-3p, miR-425-5p, and miR-185-5p with renal histopathological lesions and prognosis were explored using Spearman correlation analysis and Kaplan-Meier survival curves. Bioinformatics analysis and dual luciferase experiments were used to identify hub genes for miR-185-5p. The fibrotic phenotypes of tubular epithelial cells were evaluated in vivo and in HK-2 cells. Results: miRNA sequencing and cohort validation revealed that the expression levels of miR-92a-3p, miR-425-5p, and miR-185-5p in urine were significantly increased among patients with IgAN; these levels could predict the extent of tubular atrophy/interstitial fibrosis in such patients. The combination of the three biomarkers resulted in an area under the receiver operating characteristic curve of 0.742. The renal prognosis was significantly worse in the miR-185-5p high expression group than in the low expression group (P=0.003). Renal tissue in situ hybridization, bioinformatics analysis, and dual luciferase experiments confirmed that miR-185-5p affects prognosis in patients with IgAN mainly by influencing expression of the target gene tight junction protein 1 (TJP1) in renal tubular epithelial cells. In vitro experiment revealed that an miR-185-5p mimic could reduce TJP1 expression in HK-2 cells, while increasing the levels of α-smooth muscle actin, fibronectin, collagen I, and collagen III; these changes promoted the transformation of renal tubular epithelial cells to a fibrotic phenotype. An miR-185-5p inhibitor can reverse the fibrotic phenotype in renal tubular epithelial cells. In a unilateral ureteral obstruction model, the inhibition of miR-185-5p expression alleviated tubular atrophy/interstitial fibrosis. Conclusion: Urinary miR-185-5p, a non-invasive biomarker of tubular atrophy/interstitial fibrosis in IgAN, may promote the transformation of renal tubular epithelial cells to a fibrotic phenotype via TJP1.

Clinical phenotype of AAV, anti-GBM disease and double-positive patients after SARS-CoV-2 vaccination.

The number of anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV), anti-glomerular basement membrane (GBM) disease and double-positive patients (DPPs) following the coronavirus disease 2019 (COVID-19) vaccine reported in the literature is increasing, we reviewed the reported cases of AAV, anti-GBM disease and DPPs subsequent to COVID-19 vaccination, and compared the disparities in DPPs who received the COVID-19 vaccination and those who did not. We did not observe any differences in clinical phenotype of AAV, anti-GBM disease and DPPs before and after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination.

The effect of short-term remote ischemic preconditioning on endothelial function of patients with chronic kidney disease: A randomized pilot study.

AIM: Patients with chronic kidney disease (CKD) are more susceptible to endothelial dysfunction and cardiovascular disease (CV). Remote ischemic preconditioning (rIPC) has been proven efficient in improving endothelial function and lowering the risk of CV. However, the safety and effect of rIPC on endothelial function in patients with CKD have not been effectively assessed. METHODS: 45 patients with CKD (average estimated glomerular filtration rate: 48.4 mL/min/1.73 m2) were randomly allocated to either 7-day daily upper-arm rIPC (4 × 5 min 200 mmHg, interspaced by 5-min reperfusion) or control (4 × 5 min 60 mmHg, interspaced by 5-min reperfusion). Vascular endothelial function was assessed by natural log-transformed reactive hyperemia index (LnRHI) before and after a 7-day intervention. Arterial elasticity was assessed by augmentation index (AI). RESULTS: The results showed that LnRHI could be improved by rIPC treatment (Pre = 0.57 ± 0.04 vs. Post = 0.67 ± 0.04, p = .001) with no changes relative to control (Pre = 0.68 ± 0.06 vs. Post = 0.64 ± 0.05, p = .470). Compared with the control group, the improvement of LnRHI was greater after rIPC treatment (rIPC vs. Control: 0.10 ± 0.03 vs. -0.04 ± 0.06, between-group mean difference, -0.15 [95% CI, -0.27 to -0.02], p = .027), while there was no significant difference in the change of AI@75 bpm (p = .312) between the two groups. CONCLUSION: RIPC is safe and well tolerated in patients with CKD. This pilot study suggests that rIPC seems to have the potential therapeutic effect to improve endothelial function. Of note, further larger trials are still warranted to confirm the efficacy of rIPC in improving endothelial function in CKD patients.

The relationship between diabetic retinopathy and diabetic nephropathy in type 2 diabetes.

Context: Diabetic retinopathy (DR) and diabetic nephropathy (DN), are major microvascular complications of diabetes. DR is an important predictor of DN, but the relationship between the severity of DR and the pathological severity of diabetic glomerulopathy remains unclear. Objective: To investigate the relationship between severity of diabetic retinopathy (DR) and histological changes and clinical indicators of diabetic nephropathy (DN) in patients with type 2 diabetes mellitus (T2DM). Methods: Patients with T2DM (n=272) who underwent a renal biopsy were eligible. Severity of DR was classified as non-diabetic retinopathy, non-proliferative retinopathy, and proliferative retinopathy (PDR). Relationship between DN and DR and the diagnostic efficacy of DR for DN were explored. Results: DN had a higher prevalence of DR (86.4%) and DR was more severe. The sensitivity and specificity of DR in DN were 86.4% and 78.8%, while PDR was 26.4% and 98.5%, respectively. In DN patients, the severity of glomerular lesions (p=0.001) and prevalence of KW nodules (p<0.001) significantly increased with increasing severity of DR. The presence of KW nodules, lower hemoglobin levels, and younger age were independent risk factors associated with more severe DR in patients with DN. Conclusion: DR was a good predictor of DN. In DN patients, the severity of DR was associated with glomerular injury, and presence of KW nodules, lower hemoglobin levels and younger age were independent risk factors associated with more severe DR. Trial registration: ClinicalTrails.gov, NCT03865914.

Validity and applicability of the global leadership initiative on malnutrition criteria in non-dialysis patients with chronic kidney disease.

Introduction: There are no standardized assessment criteria for selecting nutritional risk screening tools or indicators to assess reduced muscle mass (RMM) in the Global Leadership Initiative on Malnutrition (GLIM) criteria. We aimed to compare the consistency of different GLIM criteria with Subjective Global Assessment (SGA) and protein-energy wasting (PEW). Methods: In this study, nutritional risk screening 2002 first four questions (NRS-2002-4Q), Nutritional Risk Screening 2002 (NRS-2002), Malnutrition Universal Screening Tool (MUST), and Mini-Nutritional Assessment Short-Form (MNA-SF) tools were used as the first step of nutritional risk screening for the GLIM. The RMM is expressed using different metrics. The SGA and PEW were used to diagnose patients and classify them as malnourished and non-malnourished. Kappa (κ) tests were used to compare the concordance between the SGA, PEW, and GLIM of each combination of screening tools. Results: A total of 157 patients were included. Patients with Chronic kidney disease (CKD) stage 1-3 accounted for a large proportion (79.0%). The prevalence rates of malnutrition diagnosed using the SGA and PEW were 18.5% and 19.7%, respectively. The prevalence of GLIM-diagnosed malnutrition ranges from 5.1% to 37.6%, depending on the different screening methods for nutritional risk and the different indicators denoting RMM. The SGA was moderately consistent with the PEW (κ = 0.423, p < 0.001). The consistency among the GLIM, SGA, and PEW was generally low. Using the NRS-2002-4Q to screen for nutritional risk, GLIM had the best agreement with SGA and PEW when skeletal muscle index (SMI), fat-free mass index (FFMI), and hand grip strength (HGS) indicated a reduction in muscle mass (SGA: κ = 0.464, 95% CI 0.28-0.65; PEW: κ = 0.306, 95% CI 0.12-0.49). Conclusion: The concordance between the GLIM criteria and the SGA and PEW depended on the screening tool used in the GLIM process. The inclusion of RMM in the GLIM framework is important. The addition of HGS could further improve the performance of the GLIM standard compared to the use of body composition measurements.

Progress in the study of aging marker criteria in human populations.

The use of human aging markers, which are physiological, biochemical and molecular indicators of structural or functional degeneration associated with aging, is the fundamental basis of individualized aging assessments. Identifying methods for selecting markers has become a primary and vital aspect of aging research. However, there is no clear consensus or uniform principle on the criteria for screening aging markers. Therefore, we combine previous research from our center and summarize the criteria for screening aging markers in previous population studies, which are discussed in three aspects: functional perspective, operational implementation perspective and methodological perspective. Finally, an evaluation framework has been established, and the criteria are categorized into three levels based on their importance, which can help assess the extent to which a candidate biomarker may be feasible, valid, and useful for a specific use context.

Arterial stiffness is associated with handgrip strength in relatively healthy Chinese older adults.

Background: Increased arterial stiffness and low handgrip strength (HGS) are associated with poor health outcomes and are a severe health risk for older adults. However, there is limited evidence and mixed results on whether there is an association between them. Therefore, this study focused on the association between arterial stiffness and HGS in relatively healthy older adults in Beijing, China. Methods: In 2016, 2,217 adult volunteers were recruited in Beijing. Brachial-ankle pulse wave velocity (baPWV) and the ankle-brachial index were measured using an automatic vascular profiling system. Carotid artery intima-media thickness and common carotid artery-internal diameter (CCAID) were evaluated using Doppler ultrasound, and HGS was measured with a dynamometer. Low HGS was determined using the Asian Sarcopenia Working Group 2019 criteria. Multivariate linear and logistic regressions evaluated the relationship between arterial stiffness and HGS. Results: Ultimately, 776 relatively healthy older adults (mean age 69.05 ± 6.46 years) were included. Based on the AWGS2019 criteria, 137 participants were defined as having low HGS. Compared to the normal HGS group, the low HGS group was older and had higher baPWV (p < 0.001) but lower CCAID, body mass index (BMI) and hemoglobin (Hb) (p < 0.05). The multiple linear regression analysis revealed that baPWV was negatively correlated with HGS (ß = -0.173, t = -2.587, p = 0.01). Multivariate logistic regression analysis showed that baPWV and CCAID were associated with an increased risk of low HGS (odds ratio (OR) per SD increase: 1.318, p = 0.007; OR per SD increase: 0.541, p < 0.001). Conclusion: Arterial stiffness and HGS were significantly negatively correlated in relatively healthy Chinese older adults. Low HGS is associated with increased arterial stiffness. Encouraging exercise training to improve HGS, thereby reducing arterial stiffness and the risk of cardiovascular events, may be a simple and effective intervention.

Enhanced TRPC3 transcription through AT1R/PKA/CREB signaling contributes to mitochondrial dysfunction in renal tubular epithelial cells in D-galactose-induced accelerated aging mice.

Aging-associated renal dysfunction promotes the pathogenesis of chronic kidney disease. Mitochondrial dysfunction in renal tubular epithelial cells is a hallmark of senescence and leads to accelerated progression of renal disorders. Dysregulated calcium profiles in mitochondria contribute to aging-associated disorders, but the detailed mechanism of this process is not clear. In this study, modulation of the sirtuin 1/angiotensin II type 1 receptor (Sirt1/AT1R) pathway partially attenuated renal glomerular sclerosis, tubular atrophy, and interstitial fibrosis in D-galactose (D-gal)-induced accelerated aging mice. Moreover, modulation of the Sirt1/AT1R pathway improved mitochondrial dysfunction induced by D-gal treatment. Transient receptor potential channel, subtype C, member 3 (TRPC3) upregulation mediated dysregulated cellular and mitochondrial calcium homeostasis during aging. Furthermore, knockdown or knockout (KO) of Trpc3 in mice ameliorated D-gal-induced mitochondrial reactive oxygen species production, membrane potential deterioration, and energy metabolism disorder. Mechanistically, activation of the AT1R/PKA pathway promoted CREB phosphorylation and nucleation of CRE2 binding to the Trpc3 promoter (-1659 to -1648 bp) to enhance transcription. Trpc3 KO significantly improved the renal disorder and cell senescence in D-gal-induced mice. Taken together, these results indicate that TRPC3 upregulation mediates age-related renal disorder and is associated with mitochondrial calcium overload and dysfunction. TRPC3 is a promising therapeutic target for aging-associated renal disorders.

Local Renal Treatments for Acute Kidney Injury: A Review of Current Progress and Future Translational Opportunities.

Acute kidney injury (AKI) constitutes a significant public health concern, with limited therapeutic options to mitigate injury or expedite recovery. A novel therapeutic approach, local renal treatment, encompassing pharmacotherapy and surgical interventions, has exhibited positive outcomes in AKI management. Peri-renal administration, employing various delivery routes, such as the renal artery, intrarenal, and subcapsular sites, has demonstrated superiority over peripheral intravenous infusion. This review evaluates different drug delivery methods, analyzing their benefits and limitations, and proposes potential improvements. Renal decapsulation, particularly with the availability of minimally invasive techniques, emerges as an effective procedure warranting renewed consideration for AKI treatment. The potential synergistic effects of combined drug delivery and renal decapsulation could further advance AKI therapies. Clinical studies have already begun to leverage the benefits of local renal treatments, and with ongoing technological advancements, these modalities are expected to increasingly outperform systemic intravenous therapy.

Identification of common and specific fibrosis-related genes in three common chronic kidney diseases.

BACKGROUND: Kidney fibrosis is the common final pathway of virtually all advanced forms of chronic kidney disease (CKD) including diabetic nephropathy (DN), IgA nephropathy (IgAN) and membranous nephropathy (MN), with complex mechanism. Comparative gene expression analysis among these types of CKD may shed light on its pathogenesis. Therefore, we conducted this study aiming at exploring the common and specific fibrosis-related genes involved in different types of CKD. METHODS: Kidney biopsy specimens from patients with different types of CKD and normal control subjects were analyzed using the NanoString nCounter® Human Fibrosis V2 Panel. Genes differentially expressed in all fibrotic DN, IgAN and MN tissues compared to the normal controls were regarded as the common fibrosis-related genes in CKD, whereas genes exclusively differentially expressed in fibrotic DN, IgAN or MN samples were considered to be the specific genes related to fibrosis in DN, IgAN and MN respectively. Quantitative real-time PCR (qRT-PCR) was performed to validate the expression of the selected genes. RESULTS: Protein tyrosine phosphatase receptor type C (PTPRC), intercellular cell adhesion molecule-1 (ICAM1), vascular cell adhesion molecule-1 (VCAM1), interleukin 10 receptor alpha (IL10RA) and CC chemokine receptor 2 (CCR2) were identified as the potential common genes for kidney fibrosis in different types of CKD, while peroxisome proliferator-activated receptor alpha (PPARA), lactate oxidase (LOX), secreted phosphoprotein 1 (SPP1) were identified as the specific fibrosis-associated genes for DN, IgAN and MN respectively. qRT-PCR demonstrated that the expression levels of these selected genes were consistent with the NanoString analysis. CONCLUSIONS: There were both commonalities and differences in the mechanisms of fibrosis in different types of CKD, the commonalities might be used as the common therapeutic targets for kidney fibrosis in CKD, while the differences might be used as the diagnostic markers for DN, IgAN and MN respectively. Inflammation was highly relevant to the pathogenesis of fibrosis. This study provides further insight into the pathophysiology and treatment of fibrotic kidney disease.

Integrin ß1-rich extracellular vesicles of kidney recruit Fn1+ macrophages to aggravate ischemia-reperfusion-induced inflammation.

Ischemia-reperfusion injury-induced (IRI-induced) acute kidney injury is accompanied by mononuclear phagocyte (MP) invasion and inflammation. However, systematic analysis of extracellular vesicle-carried (EV-carried) proteins mediating intercellular crosstalk in the IRI microenvironment is still lacking. Multiomics analysis combining single-cell RNA-Seq data of kidney and protein profiling of kidney-EV was used to elucidate the intercellular communication between proximal tubular cells (PTs) and MP. Targeted adhesion and migration of various MPs were caused by the secretion of multiple chemokines as well as integrin ß1-rich EV by ischemic-damaged PTs after IRI. These recruited MPs, especially Fn1+ macrophagocyte, amplified the surviving PT's inflammatory response by secreting the inflammatory factors TNF-α, MCP-1, and thrombospondin 1 (THBS-1), which could interact with integrin ß1 to promote more MP adhesion and interact with surviving PT to further promote the secretion of IL-1ß. However, GW4869 reduced MP infiltration and maintained a moderate inflammatory level likely by blocking EV secretion. Our findings establish the molecular bases by which chemokines and kidney-EV mediate PT-MP crosstalk in early IRI and provide insights into systematic intercellular communication.

Comparison of the effects of peritoneal dialysis and hemodialysis on spontaneous brain activity in CKD patients: an rs-fMRI study.

OBJECTIVE: To compare the effects of peritoneal dialysis and hemodialysis on spontaneous brain activity in patients with end-stage renal disease. METHODS: A total of 52 dialysis patients with end-stage renal disease, including 25 patients with chronic kidney disease undergoing hemodialysis (HD-CKD) and 27 patients with chronic kidney disease undergoing peritoneal dialysis (PD-CKD), and 49 healthy controls (normal control) were included. All participants underwent neuropsychological testing (Mini-Mental State Examination and Montreal cognitive assessment) and resting-state functional magnetic resonance imaging. Fractional amplitude of low frequency fluctuations and Regional Homogeneity algorithms were employed to evaluate spontaneous brain activity. Statistical analysis was performed to discern differences between the groups. RESULTS: When compared with the normal control group, the PD-CKD group exhibited significant alterations in fractional amplitude of low frequency fluctuations in various cerebellum regions and other brain areas, while the HD-CKD group showed decreased fractional amplitude of low frequency fluctuations in the bilateral pericalcarine cortex. The Regional Homogeneity values in the PD-CKD group were notably different than those in the normal control group, particularly in regions such as the bilateral caudate nucleus and the right putamen. CONCLUSION: Both peritoneal dialysis and hemodialysis modalities impact brain activity, but manifest differently in end-stage renal disease patients. Understanding these differences is crucial for optimizing patient care.

Characteristics of hospitalized elderly patients with CKD: a comparison between elderly and non-elderly CKD based on a multicenter cross-sectional study.

PURPOSE: We undertook a multicenter epidemiological survey among hospitalized patients with chronic kidney disease (CKD), aiming to reveal the characteristics of elderly CKD by comparing it with non-elderly CKD. METHODS: Medical records were obtained from 18 military hospitals across China from 1 January 2009 to 31 December 2011. The characteristics of chronic kidney disease in the elderly were analyzed through comparing with those in younger patients with chronic kidney disease. RESULTS: A total of 380,461 hospitalized patients were included in the database, with 25,826 (6.8%) diagnosed with CKD. Unlike non-elderly, the top-three causes of chronic kidney disease among elderly patients were diabetic nephropathy (24.1%), hypertension-related renal impairment (20.9%), and primary glomerular disease (11.1%). 71.6% of the elderly patients with CKD had more than one comorbidities and the number of morbidities increased with age. In-hospital mortality of the elderly was significantly higher than those of younger patients (3.3% vs. 1.0%). Multiple logistic regression analysis showed that age, CKD 5 stage, acidosis, cardiovascular and cerebrovascular diseases, infection disease, neoplasm, and dementia were independent risk factors for death from CKD in the elderly. The median length of stay (LOS) was similar between elderly and younger CKD patients. The median cost was higher for elderly CKD patients than for younger CKD patients. Among elderly individuals with CKD, LOS, and hospitalization costs also increased with an increase in the number of coexisting diseases. CONCLUSIONS: Diabetic nephropathy,  and hypertension-related kidney injury were the leading causes of chronic kidney disease in elderly patients, which is different from the non-elderly. Elderly patients with chronic kidney disease were more likely to have a higher burden of comorbidities, which were associated with worse in-hospital outcomes.

Serum levels of sonic hedgehog in patients with IgA nephropathy are closely associated with intrarenal arteriolar lesions.

BACKGROUND: Intrarenal arteriolar disease is a major risk factor for poor prognosis in immunoglobulin A nephropathy (IgAN). The morphologic factor sonic hedgehog (SHH) plays an important role in a variety of vascular diseases, so it may be directly or indirectly involved in the process of renal arteriolar disease. The purpose of this study was to investigate the correlation between serum SHH levels and renal arteriole disease in patients with IgAN. METHODS: Subjects with primary IgAN diagnosed by renal biopsy performed between October 2018 and August 2019 at the First Medical Center of the Chinese PLA General Hospital were recruited. Blood specimens were collected from the patients within 1 week before renal biopsy after they signed an informed consent form, and healthy controls were recruited for blood specimen collection during the same period. The concentration of serum SHH was measured by enzyme-linked immunosorbent assay in this population. RESULTS: Serum SHH levels were significantly lower in the IgAN group than in the control group. 41 of the 94 subjects diagnosed with IgAN had severe renal arteriolosclerosis and, compared to their less severely affected counterparts, were older, more hypertensive, and characterized by lower levels of SHH, higher levels of tubular atrophy/interstitial fibrosis and a higher Lee's classification. Serum SHH concentration was found to be an independent predictor of severe intrarenal arteriolosclerosis in IgAN subjects after correction using multivariate analysis. CONCLUSION: In this study, serum SHH levels were found to be significantly lower in patients with IgAN than in healthy subjects. Serum SHH may serve as a noninvasive biomarker of intrarenal arteriolosclerosis in patients with IgAN.

Iron Supplements Concomitant within Hypoxia-Inducible Factor Prolyl Hydroxylase Domain Inhibitors in the Treatment of Chronic Kidney Disease Anemia.

Background: Anemia is a common and important complication in patients with chronic kidney disease (CKD). Accordingly, the current treatment is based on erythropoiesis-stimulating agents (ESAs) and iron. Hypoxia-inducible factor (HIF) prolyl hydroxylase domain inhibitors (HIF-PHIs) have been developed to treat renal anemia through a novel mechanism. HIF-PHIs increase erythropoietin at physiologic blood concentrations and also improve the supply of hematopoietic iron. Iron is the main component of hemoglobin, and ensuring efficient iron metabolism is essential in the treatment of anemia. Summary: HIF-PHIs may have advantages in improving iron utilization and mobilization compared to ESAs. Most HIF-PHI trials revealed a significant decline of hepcidin, increase in transferrin level and total iron binding capacity in patients. From a clinical point of view, improvements in iron metabolism should translate into reductions in iron supplementation. There are differences in the iron treatment regimentation currently used, so it is important to evaluate and timely iron supplementation across studies. Key Messages: This review summarizes the mechanism of HIF-PHIs on improved iron metabolism and the route of iron usage in the trials for dialysis-dependent CKD and non-dialysis CKD. And this review also makes an interpretation of the clinical practice guidelines in China and recommendation by Asia Pacific Society of Nephrology.

Rapid detection of pathogens of peritoneal dialysis-related peritonitis, especially in patients who have taken antibiotics, using metagenomic next-generation sequencing: a pilot study.

INTRODUCTION: Peritoneal dialysis (PD)-related peritonitis is a serious complication of PD. Improving the diagnostic rate of peritonitis pathogens may substantially benefit peritonitis patients. METHODS: The study was conducted in the People's Liberation Army (PLA) General Hospital from 1 June 2021 to 31 May 2022. Information about peritonitis, culture and metagenomic next-generation sequencing (mNGS) results and so on were collected. Patients were divided into antibiotic-use and antibiotic-free groups. The culture and mNGS results were compared using the paired χ2 test. RESULTS: Data from 26 patients with peritonitis were collected. 50% of the patients had used antibiotics before samples were obtained (antibiotic-use group). The positivity rate using culture was 92.3% (12 cases) in the antibiotic-free group and 38.5% (5 cases) in the antibiotic-use group (p = 0.011). However, the positivity rate using mNGS was 92.3% (12 cases) regardless of whether antibiotics were used (p = 1.000). After revising the mNGS results, the positivity rate was 84.6% (11 cases) in both groups (p = 1.000). A significant difference between culture and mNGS results of all groups was observed (p = 0.039). The difference no matter between culture and mNGS (p = 0.016) or between culture and modified mNGS (p = 0.031) of the antibiotic-use group was observed. CONCLUSION: For patients with PD-related peritonitis who previously received antibiotics, mNGS is suggested. For other patients, mNGS testing can be performed, but the results should be interpreted with caution. Much more research should be done to identify a powerful and ideal tool to detect pathogens underlying PD-related peritonitis.

Higher urinary glyphosate exposure is associated with increased risk of liver dysfunction in adults: An analysis of NHANES, 2013-2016.

Glyphosate (GLY) exposure, both exogenous and endogenous, is a global concern. Multiple studies of model systems in vitro and in vivo have demonstrated the potential toxic effects of GLY exposure on human organs, particularly the liver and renal system. However, there is currently limited epidemiological evidence establishing a link between GLY exposure and hepatorenal function in the general population. In this study, a multivariable linear regression model and forest plots were employed to evaluate the connection between urinary GLY and biomarkers of hepatorenal function in 2241 participants from the National Health and Nutrition Examination Survey 2013-2016. Additionally, subgroup analyses were conducted based on age, gender, race, BMI, and chronic kidney disease (CKD). Alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), AST/ALT and fibrosis 4 score (FIB-4) all increased with elevated urinary GLY concentrations after adjusting for potential confounders, while albumin (ALB) exhibited the opposite trend, particularly among younger, female, non-Hispanic white, overweight, and CKD participants. Furthermore, individuals in the third tertile had a greater risk of liver dysfunction than those in the first tertile after categorizing urinary GLY concentrations. However, our study showed no proof that GLY exposure affects the ratio of urine albumin to creatinine (ACR) or serum creatinine levels. Overall, these results imply that GLY exposure may have adverse effects on human liver function.