Collectin 11 has a pivotal role in host defense against kidney and bladder infection in mice.

The urinary tract is constantly exposed to microorganisms. Host defense mechanisms in protection from microbial colonization and development of urinary tract infections require better understanding to control kidney infection. Here we report that the lectin collectin 11 (CL-11), particularly kidney produced, has a pivotal role in host defense against uropathogen infection. CL-11 was found in mouse urine under normal and pathological conditions. Mice with global gene ablation of Colec11 had increased susceptibility to and severity of kidney and to an extent, bladder infection. Mice with kidney-specific Colec11 ablation exhibited a similar disease phenotype to that observed in global Colec11 deficient mice, indicating the importance of kidney produced CL-11 for protection against kidney and bladder infection. Conversely, intravesical or systemic administration of recombinant CL-11 reduced susceptibility to and severity of kidney and bladder infection. Mechanism analysis revealed that CL-11 can mediate several key innate defense mechanisms (agglutination, anti- adhesion, opsonophagocytosis), and limit local inflammatory responses to pathogens. Furthermore, CL-11-mediated innate defense mechanisms can act on clinically relevant microorganisms including multiple antibiotic resistant strains. CL-11 was detectable in eight of 24 urine samples from patients with urinary tract infections but not detectable in urine samples from ten healthy individuals. Thus, our findings demonstrate that CL-11 is a key factor of host defense mechanisms in kidney and bladder infection with therapeutic potential for human application.

Roxadustat reduces left ventricular mass index compared to rHuEPO in haemodialysis patients in a randomized controlled trial.

BACKGROUND: Left ventricular hypertrophy (LVH) is highly prevalent in haemodialysis (HD) patients and is associated with an increased risk of death. Roxadustat and recombinant human erythropoietin (rHuEPO, abbreviated as EPO) are the main treatment strategies for renal anaemia in HD patients, but it has not been clear whether there is a difference in their effect on LVH. METHODS: In this multi-centre, prospective, randomized trial of 12-month duration, study participants were randomized in a 1:1 ratio to the roxadustat group or the EPO group. The doses of both treatment regimens were adjusted so that the patients had a haemoglobin level of 10.0-12.0 g per dL. The primary study endpoint was the change from baseline to 12 months in the left ventricular mass index (LVMI, g/m2) measured by echocardiography. RESULTS: In total, 114 patients were enrolled. The mean age was 50 years, and the median dialysis duration was 33 months. Sixty-one patients were men, and 24 were diabetic. LVMI decreased from 116.18 ± 27.84 to 110.70 ± 25.74 g/m2 in the roxadustat group. However, it increased from 109.35 ± 23.41 to 114.99 ± 28.46 g/m2 in the EPO group, with a significant difference in the change in LVMI between the two groups [-5.48 (-11.60 to 0.65) vs. 5.65 (0.74 to 10.55), p < 0.05]. Changes in left ventricular mass, end-diastolic volume and 6-min walk test seemed superior in the roxadustat group. There were no significant differences in other cardiac geometry, biochemical parameters and major adverse cardiovascular events between the two groups. CONCLUSIONS: Compared to EPO, roxadustat is more helpful in the regression of LVH in HD patients.

Decreased TAX1BP1 participates in systemic lupus erythematosus by regulating monocyte/macrophage function.

Systemic lupus erythematosus (SLE) involves disorders of innate and adaptive immune pathways. Tax1-binding protein 1 (TAX1BP1) modulates the production of antibodies in B cells and the T-cell cycle by regulating the NF-κB signaling pathway. However, the potential association of TAX1BP1 with SLE and its role in monocytes/macrophages have not been fully elucidated. In this study, we utilized whole-exome sequencing (WES) in combination with Sanger sequencing and identified 16 gene mutations, including in TAX1BP1, in an SLE family. TAX1BP1 protein expression with western blotting detection was reduced in SLE patients and correlated with disease activity negatively. Furthermore, RNA sequencing and 4D Label-Free Phosphoproteomic analysis were employed to characterize the transcriptome and phosphoproteome profiles in THP-1 and THP-1-differentiated M1 macrophages with TAX1BP1 knockdown. Silencing of TAX1BP1 in THP-1 and THP-1-differentiated M1 macrophages led to an increase in cluster of differentiation 80 (CD80) expression and differential changes in CD14 and CD16 expression, as assessed by flow cytometry. Additionally, western blot analysis showed that knockdown of TAX1BP1 led to a reduction in TRAF6 and p-p65 in THP-1-differentiated macrophages, with or without lipopolysaccharide (LPS) or tumor necrosis factor (TNF)-α stimulation. Taken together, our findings suggest that TAX1BP1 participates in SLE activity by regulating antigen presentation in monocytes and inflammatory responses in M1 macrophages.

Pathogenesis and histological changes of nephropathy associated with COVID-19.

Coronavirus disease 2019 (COVID-19) can cause damage to multiple organ, not only to the lungs, but also to the kidneys. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can cause acute and chronic kidney disease through direct viral infection, indirect injury, and vaccination-related injury. Like lung injury, kidney injury is also an important aspect affecting the severity and prognosis of SARS-CoV-2. This article summarizes the pathogenesis, pathological manifestations, and clinical features of SARS-CoV-2 direct or indirect renal injury. Including direct injury, indirect injury, special comorbidities (receiving kidney transplantation and chronic kidney disease), and vaccine-related renal injury, and exploring the possible therapeutic effect of anti-SARS-CoV-2 therapy on renal injury. The purpose is to provide reference for understanding COVID-19-related renal injury, guiding clinical and pathological diagnosis and treatment, and evaluating prognosis.

Protective role for C3aR in experimental chronic pyelonephritis.

Emerging evidence suggest that C3aR plays important roles in homeostasis, host defense and disease. Although it is known that C3aR is protective in several models of acute bacterial infections, the role for C3aR in chronic infection is largely unknown. Here we show that C3aR is protective in experimental chronic pyelonephritis. Global C3aR deficient (C3ar-/- ) mice had higher renal bacterial load, more pronounced renal histological lesions, increased renal apoptotic cell accumulation, tissue inflammation and extracellular matrix deposition following renal infection with uropathogenic E. coli (UPEC) strain IH11128, compared to WT control mice. Myeloid C3aR deficient (Lyz2-C3ar-/- ) mice exhibited a similar disease phenotype to global C3ar-/- mice. Pharmacological treatment with a C3aR agonist reduced disease severity in experimental chronic pyelonephritis. Furthermore, macrophages of C3ar-/- mice exhibited impaired ability to phagocytose UPEC. Our data clearly demonstrate a protective role for C3aR against experimental chronic pyelonephritis, macrophage C3aR plays a major role in the protection, and C3aR is necessary for phagocytosis of UPEC by macrophages. Our observation that C3aR agonist curtailed the pathology suggests a therapeutic potential for activation of C3aR in chronic infection.

First reported case of ANCA-associated vasculitis induced by oxaliplatin, capecitabine, and trastuzumab.

A 68-year-old male, who was undergoing XELOX plus trastuzumab therapy for gastric cancer, developed proteinuria, hematuria, and progressive increase in creatinine after 3 months. Subsequently, the patient also experienced hemoptysis, nasal bleeding. Chest CT examination shown pulmonary hemorrhage. The MRI of the nasopharynx ruled out nasopharyngeal cancer recurrence. The MPO and PR3 were elevated, and renal biopsy confirmed ANCA-related vasculitis, which affected the lungs, kidneys, and nasopharynx. Based on the review of the patient''s medical history and medication, it is believed that ANCA-related vasculitis was caused by XELOX plus trastuzumab chemotherapy, but it is difficult to confirm which specific drug caused it. After stopping XELOX plus trastuzumab chemotherapy, glucocorticoids and cyclophosphamide was given, the patient''s pulmonary hemorrhage and nasal bleeding stopped, and the lung lesions were absorbed. The renal function also improved. The patient later experienced pulmonary infection again, and tNGS indicated Legionella pneumophila and pulmonary tuberculosis infection. Despite anti-infection treatment, steroid dose was rapidly reduced. Ultimately, the patient gave up on treatment and eventually died.

LncRNA ENSMUST_147219 mediates the progression of ischemic acute kidney injury by targeting the miR-221-5p/IRF6 axis.

Although previous studies have revealed that long noncoding RNAs (lncRNAs) regulate the progression of ischemic acute kidney injury (AKI), the exact role and mechanism of lncRNA ENSMUST_147219 in ischemic AKI are not clear. In the present study, lncRNA ENSMUST_147219 was induced by ischemic injury in vitro and in vivo. Functionally, lncRNA ENSMUST_147219 mediated apoptosis in mouse proximal tubule-derived cell line (BUMPT). Mechanistically, lncRNA ENSMUST_147219 sponged the microRNA (miR)-221-5p to upregulate the expression of interferon regulatory factor 6 (IRF6) to drive apoptosis. Finally, knockdown of lncRNA ENSMUST_147219 markedly attenuated the ischemic AKI by targeting the miR-221-5p/IRF6 axis. Collectively, our data demonstrated that lncRNA ENSMUST_147219 promoted the development of ischemic AKI by regulating the miR-221-5p/IRF6 pathway, which could be considered a new therapeutic target for ischemic AKI.

The Role of NLRP3 Inflammasome in IgA Nephropathy.

Immunoglobulin A nephropathy (IgAN) is the most common primary glomerular disease worldwide today. The NLRP3 inflammasome is a polyprotein complex and an important participant in inflammation. Accumulating studies have shown that the NLRP3 inflammasome participates in a variety of kidney diseases, including IgAN. This review focuses on the role of the NLRP3 inflammasome in IgAN and summarizes multiple involved pathways, which may provide novel treatments for IgAN treatment.

ROBO2-mediated RALDH2 signaling is required for common nephric duct fusion with primitive bladder.

Congenital anomalies of the urinary tract are a significant cause of morbidity in infancy, and many congenital anomalies are linked to ureter development; however, the mechanism by which congenital anomalies control ureter development remains unknown. The loss of Robo2 can cause ureter defects and vesicoureteral reflux. However, how Robo2 impacts ureter development is unclear. We found that ROBO2 is expressed in the common nephric duct (CND) and primitive bladder, and impacts CND migration and fusion with the primitive bladder via its novel binding partner retinaldehyde dehydrogenase-2 (RALDH2). Delayed apoptosis that is due to the failure of CND fusion with the primitive bladder in the Robo2-/-embryo results in an abnormal ureter connection to the CND, which is required for ureter development. We define a novel pathway in which the CND is remodeled by ROBO2 and retinoic acid rescued the ureter anomalies in the Robo2-/-embryo. These findings may be relevant to diverse disease conditions that are associated with altered signaling in the primitive bladder.

Comparison of Three Methods Estimating Baseline Creatinine For Acute Kidney Injury in Hospitalized Patients: a Multicentre Survey in Third-Level Urban Hospitals of China.

BACKGROUND/AIMS: A lack of baseline serum creatinine (SCr) data leads to underestimation of the burden caused by acute kidney injury (AKI) in developing countries. The goal of this study was to investigate the effects of various baseline SCr analysis methods on the current diagnosis of AKI in hospitalized patients. METHODS: Patients with at least one SCr value during their hospital stay between January 1, 2011 and December 31, 2012 were retrospectively included in the study. The baseline SCr was determined either by the minimum SCr (SCrMIN) or the estimated SCr using the MDRD formula (SCrGFR-75). We also used the dynamic baseline SCr (SCrdynamic) in accordance with the 7 day/48 hour time window. AKI was defined based on the KDIGO SCr criteria. RESULTS: Of 562,733 hospitalized patients, 350,458 (62.3%) had at least one SCr determination, and 146,185 (26.0%) had repeat SCr tests. AKI was diagnosed in 13,883 (2.5%) patients using the SCrMIN, 21,281 (3.8%) using the SCrGFR-75 and 9,288 (1.7%) using the SCrdynamic. Compared with the non-AKI patients, AKI patients had a higher in-hospital mortality rate regardless of the baseline SCr analysis method. CONCLUSIONS: Because of the scarcity of SCr data, imputation of the baseline SCr is necessary to remedy the missing data. The detection rate of AKI varies depending on the different imputation methods. SCrGFR-75 can identify more AKI cases than the other two methods.

Diagnostic value of serum procalcitonin for acute pyelonephritis in infants and children with urinary tract infections: an updated meta-analysis.

PURPOSE: The aims were to assess (1) the diagnostic value of serum procalcitonin (PCT) for acute pyelonephritis (APN) in infants and children with urinary tract infections (UTIs) and (2) to compare the performance of two commonly used cutoff values. METHODS: A meta-analysis of serum PCT in the diagnosis of APN among pediatrics with lower UTIs was conducted. The process of search strategy, publications selection and data analysis was in accordance with the preferred reporting items for systematic reviews and meta-analyses guidelines. RESULTS: Eighteen high-quality studies with a total of 831 APN patients and 651 individuals with lower UTIs were analyzed. The overall performance of serum PCT ≥ 0.5 ng/mL was as follows: pooled sensitivity of 0.86 (95 % CI 0.73-0.93), pooled specificity of 0.76 (95 % CI 0.66-0.83), DOR of 18.90 (95 % CI 6.78-52.71) and AUROC of 0.86 (95 % CI 0.83-0.89), with significant heterogeneity. However, use of 1.0 ng/mL as a cutoff value produced an improved specificity of 0.91 (95 % CI 0.86-0.94), a DOR of 55.06 (95 % CI 22.57-115.48) and an AUROC of 0.94 (95 % CI 0.92-0.96), without obvious heterogeneity. CONCLUSION: In pediatrics with UTIs, the cutoff value of serum PCT, 1.0 ng/mL, has a preferable diagnostic performance compared with 0.5 ng/mL for APN. Additional prospective studies that propose an appropriate cutoff value and validate the performance of PCT for young with APN are needed in the future.

Impact of ER stress-regulated ATF4/p16 signaling on the premature senescence of renal tubular epithelial cells in diabetic nephropathy.

Premature senescence is an important event during diabetic nephropathy (DN) progression. Here, we investigated the role of endoplasmic reticulum (ER) stress-regulated activation of transcription factor 4 (ATF4)/p16 signaling in the premature senescence of renal tubular epithelial cells (RTECs) during DN development. In the renal tissues of Type 2 DN patients, we detected an increased number of senescent cells; elevated deposition of advanced glycation end products (AGEs); upregulated expression of ER stress marker, glucose-regulated protein 78; as well as overexpression of ATF4 and p16. Similarly, these phenomena were also observed in cultured mouse RTECs following AGE treatment. Interestingly, AGE-induced p16 expression and premature senescence were successfully attenuated by ER stress inhibitor and ATF4 gene silencing. Moreover, AGE-induced premature senescence was mimicked by ER stress inducers and ATF4 overexpression, while suppressed by p16 gene silencing. In addition, ER stress inducers can augment ATF4 expression. Therefore, our results demonstrate that the ER stress-regulated ATF4/p16 pathway is involved in the premature senescence of RTECs during DN progression.

miR-34a regulates mesangial cell proliferation via the PDGFR-ß/Ras-MAPK signaling pathway.

The main pathological characteristic of glomerulonephritis is diffuse mesangial cell proliferation. MiR-34a is associated with the proliferation of various organs and cancer cells. However, the role of miR-34a in renal proliferation diseases is not clear. Therefore, this study aimed to elucidate the mechanism of miR-34a in the regulation of renal mesangial cell proliferation. The miR-34a expression level at different time points in an anti-Thy1 mesangial proliferative nephritis rat model was determined by qRT-PCR. The cell proliferation rate and cell cycle changes were measured in the in vitro cultured rat mesangial cells (RMCs). Our results suggested that miR-34a expression was negatively correlated with the degree of cell proliferation in the anti-Thy1 nephritis model. MiR-34a could extend the G0/G1 phase and block cell proliferation in RMCs. Dual-luciferase assay results showed that there were binding sites of miR-34a at 3'-UTR of platelet-derived growth factor receptor-ß (PDGFR-ß). MiR-34a can inhibit PDGFR-ß protein expression at a post-transcriptional level, suppress Ras/MAPK signaling pathways, and down-regulate expression of cell cycle proteins at the G0/G1 phase, such as cyclin D1, CDK4/CDK6. In addition, miR-34a may also inhibit RMC proliferation by directly targeting cyclin E and CDK2. MiR-34a inhibits exogenous stimuli-induced proliferation of mesangial cells. Expression levels of phospho-PDGFR-ß and phospho-MEK1 (an important downstream molecule in PDGFR-ß-induced signaling pathway) were significantly increased in the anti-Thy-1 nephritis rat model. These results suggest that miR-34a may regulate RMC proliferation by directly inhibiting expressions of PDGFR-ß, MEK1, and cell cycle proteins, cyclin E and CDK2.

Ischemia-reperfusion induces renal tubule pyroptosis via the CHOP-caspase-11 pathway.

The apoptotic or necrotic death of renal tubule epithelial cells is the main pathogenesis of renal ischemia-reperfusion-induced acute kidney injury (AKI). Pyroptosis is a programmed cell death pathway that depends on the activation of the caspase cascade and IL-1 cytokine family members. However, the role of pyroptosis in AKI induced by ischemia-reperfusion remains unclear. In this study, we found that the levels of the pyroptosis-related proteins, including caspase-1, caspase-11, and IL-1ß, were significantly increased after 6 h of renal ischemia-reperfusion injury (IRI) and peaked at 12 h after IRI. Enhanced pyroptosis was accompanied by elevated renal structural and functional injury. Similarly, hypoxia-reoxygenation injury (HRI) also induced pyroptosis in renal tubule epithelial NRK-52E cells, which was characterized by increased pore formation and elevated lactate dehydrogenase release. In addition, obvious upregulation of the endoplasmic reticulum (ER) stress biomarkers glucose-regulated protein 78 and C/EBP homologous protein (CHOP) preceded the incidence of pyroptosis in cells treated with IRI or HRI. Pretreatment with a low dose of tunicamycin, an inducer of ER stress, relieved IRI-induced pyroptosis and renal tissue injury. Silencing of CHOP by small interfering RNA significantly decreased HRI-induced pyroptosis of NRK-52E cells, as evidenced by reduced caspase-11 activity and IL-1ß generation. Therefore, we conclude that pyroptosis of renal tubule epithelial cells is a key event during IRI and that CHOP-caspase-11 triggered by overactivated ER stress may be an essential pathway involved in pyroptosis.

Comprehensive Management of Blood Pressure in Patients with Septic AKI.

Acute kidney injury (AKI) is one of the serious complications of sepsis in clinical practice, and is an important cause of prolonged hospitalization, death, increased medical costs, and a huge medical burden to society. The pathogenesis of AKI associated with sepsis is relatively complex and includes hemodynamic abnormalities due to inflammatory response, oxidative stress, and shock, which subsequently cause a decrease in renal perfusion pressure and eventually lead to ischemia and hypoxia in renal tissue. Active clinical correction of hypotension can effectively improve renal microcirculatory disorders and promote the recovery of renal function. Furthermore, it has been found that in patients with a previous history of hypertension, small changes in blood pressure may be even more deleterious for kidney function. Therefore, the management of blood pressure in patients with sepsis-related AKI will directly affect the short-term and long-term renal function prognosis. This review summarizes the pathophysiological mechanisms of microcirculatory disorders affecting renal function, fluid management, vasopressor, the clinical blood pressure target, and kidney replacement therapy to provide a reference for the clinical management of sepsis-related AKI, thereby promoting the recovery of renal function for the purpose of improving patient prognosis.

The pathogenic role of intestinal flora metabolites in diabetic nephropathy.

With the increasing incidence of diabetes, diabetic kidney disease has become a major cause of chronic kidney disease. The role of the gut microbiota in diabetes and its related complications have been extensively investigated; the modulatory effect of the gut microbiota on the host depends on several gut microbial metabolites, particularly short-chain fatty acids, secondary bile acids, and trimethylamine N-oxide. In this review, we focused on the evidence related to the pathogenic role of each of the gut microbial metabolites in diabetic nephropathy. The main novel therapies targeting the gut microbiota include probiotics, dietary prebiotics, synbiotic supplements, and faecal microbiota transplants, although there is no standard treatment principle. Further research is therefore needed to elucidate the link between gut microbes and diabetic nephropathy, and more therapeutic targets should be explored to treat diabetic nephropathy with dysbiosis of the gut microbes.

The role and mechanism of the gut microbiota in the development and treatment of diabetic kidney disease.

Diabetic kidney disease (DKD) is a common complication in patients with diabetes mellitus (DM). Increasing evidence suggested that the gut microbiota participates in the progression of DKD, which is involved in insulin resistance, renin-angiotensin system (RAS) activation, oxidative stress, inflammation and immunity. Gut microbiota-targeted therapies including dietary fiber, supplementation with probiotics or prebiotics, fecal microbiota transplantation and diabetic agents that modulate the gut microbiota, such as metformin, glucagon-like peptide-1 (GLP-1) receptor agonists, dipeptidyl peptidase-4 (DPP-4) inhibitors, and sodium-glucose transporter-2 (SGLT-2) inhibitors. In this review, we summarize the most important findings about the role of the gut microbiota in the pathogenesis of DKD and the application of gut microbiota-targeted therapies.

A classifier based on 273 urinary peptides predicts early renal damage in primary hypertension.

OBJECTIVES: Renal diseases caused by primary hypertension (HTN) are often asymptomatic without sensitive markers for early diagnosis and prediction, easily progressing to severe and irreversible renal damage in patients with clinical manifestations. This study explored whether a classifier developed based on 273 urinary peptides (CKD273) could serve as a potential biomarker for early prediction of renal damage in HTN. METHODS: Urinary CKD273 level of healthy individuals, HTN + normoalbuminuric and HTN + albuminuria patients were compared, and 22 baseline data including sex, age, renal function, and hypertensive fundus lesions were collected. Patients diagnosed with HTN, albuminuria, and normal renal function were followed up. According to the follow-up results, the cut-off value of CKD273 in predicting hypertensive renal injury was calculated and analyzed in the high-risk and low-risk groups of HTN patients for its performance in detecting early hypertensive renal injury. RESULTS: Among a sum of 319 participants, average urinary CKD273 level was significantly higher in patients with HTN than in normal individuals. A total of 147 HTN patients with normal albuminuria were followed up for a mean of 3.8 years. Thirty-five patients showed urinary albumin-to-creatinine ratio (uACR) at least 30 mg/g for three consecutive times. The receiver-operating characteristic (ROC) curve showed that the urinary CKD273 cut-off value for evaluating new-onset proteinuria in patients with HTN was 0.097. Based on this cut-off value, 39 and 108 patients were included in the high-risk and low-risk groups, respectively. Specifically, compared with patients in the low-risk group, those in the high-risk group showed significantly longer duration of HTN, higher proportions of hypertensive fundus lesions and at least 30 mg/g uACR, and higher levels of homocysteine (Hcy), cystatin C (CysC), beta-2 microglobulin (ß2-MG), and uACR. 76.9% of high-risk patients had significantly higher new-onset proteinuria than the low-risk group. Correlation analysis demonstrated a positive correlation between urinary CKD273 and UACR ( r  = 0.494, P  = 0.000). The incidence of new-onset albuminuria was significantly higher in the high-risk group than in the low-risk group, as shown by Cox regression analysis. The areas under the curve of CKD273, Hcy, ß2-MG, and CysC were 0.925, 0.753, 0.796, and 0.769, respectively. CONCLUSION: Urinary CKD273 is a predictor of new-onset proteinuria in patients with HTN, therefore, it can be used for diagnosing patients with early renal injury in patients with HTN, contributing to early prevention and treatment of hypertensive nephropathy.

A set of urinary peptides can predict early renal damage in primary hypertension.

OBJECTIVES: Renal diseases caused by primary hypertension (HTN) are often asymptomatic without sensitive markers for early diagnosis and prediction, easily progressing to severe and irreversible renal damage in patients with clinical manifestations. This study explored whether a set of urinary peptides could serve as a potential biomarker for early prediction of renal damage in HTN. METHODS: Urinary peptides level of healthy individuals, HTN + normoalbuminuric and HTN + albuminuria patients were compared, and 22 baseline data including sex, age, renal function, hypertensive fundus lesions were collected. Patients diagnosed with HTN, albuminuria, and normal renal function were followed up. According to the follow-up results, the cut-off value of a set of urinary peptides in predicting hypertensive renal injury was calculated and analyzed in the high-risk and low-risk groups of HTN patients for its performance in detecting early hypertensive renal injury. RESULTS: Among a sum of 319 participants, average urinary peptides level was significantly higher in patients with HTN than in normal individuals. A total of 147 HTN patients with normal albuminuria were followed up for a mean of 3.8 years. Thirty-five patients showed urinary albumin-to-creatinine ratio (uACR) at least 30 mg/g for three consecutive times. The receiver-operating characteristic (ROC) curve showed that the urinary peptides cut-off value for evaluating new-onset proteinuria in patients with HTN was 0.097. Based on this cut-off value, 39 and 108 patients were included in the high-risk and low-risk groups, respectively. Specifically, compared with patients in the low-risk group, those in the high-risk group showed significantly longer duration of HTN, higher proportions of hypertensive fundus lesions and at least 30 mg/g uACR, and higher levels of homocysteine (Hcy), cystatin C (CysC), beta-2 microglobulin (ß2-MG), and uACR. 76.9% of high-risk patients had significantly higher new-onset proteinuria than the low-risk group. Correlation analysis demonstrated a positive correlation between urinary peptides and UACR ( r  = 0.494, P  < 0.001). The incidence of new-onset albuminuria was significantly higher in the high-risk group than in the low-risk group, as shown by Cox regression analysis. The areas under the curve of urinary peptides, Hcy, ß2-MG and CysC were 0.925, 0.753, 0.796 and 0.769, respectively. CONCLUSION: A set of urinary peptides is a predictor of new-onset proteinuria in patients with HTN, therefore, it can be used for diagnosing patients with early renal injury in patients with HTN, contributing to early prevention and treatment of hypertensive nephropathy.